bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Restoration Following Resection of Malignant Peripheral Nerve Sheath Tumour of the Median Nerve: A Case Report
Authors: Chan Chung Ming , Lim Aymeric YT. , Puhaindran Mark E.
Published: July 2020

Management of malignant peripheral nerve sheath tumours (MPNSTs) is primarily surgical, involving surgical resection with wide margins, and frequently radiation therapy. When a MPNST involves a major peripheral nerve, wide resection leads to significant distal neurologic deficits. A patient who underwent resection of a MPNST involving the median nerve above the elbow is presented. Staged tendon and nerve transfers were performed to restore sensation to the thumb and index finger, thumb opposition and flexion, finger flexion and forearm pronation. These included: 1. radial sensory nerve branches to digital nerves of thumb and index finger, 2. ulnar nerve branch of flexor carpi ulnaris to pronator teres, 3. brachioradialis to flexor pollicis longus, 4. side-to-side transfer of flexor digitorum profundus tendon of index finger to middle, ring and little fingers, 5. extensor indicis proprius to abductor pollicis brevis. The rationale, approach, and favourable results of functional reconstruction in this patient are detailed.
Star-Forming Galaxies at Cosmic Noon
Authors: Förster Schreiber Natascha M. , Wuyts Stijn
Published: July 2020

Ever deeper and wider look-back surveys have led to a fairly robust outline of the cosmic star-formation history, which culminated around [Formula: see text]; this period is often nicknamed “cosmic noon.” Our knowledge about star-forming galaxies at these epochs has dramatically advanced from increasingly complete population censuses and detailed views of individual galaxies. We highlight some of the key observational insights that influenced our current understanding of galaxy evolution in the equilibrium growth picture: ▪  Scaling relations between galaxy properties are fairly well established among massive galaxies at least out to [Formula: see text], pointing to regulating mechanisms already acting on galaxy growth. ▪  Resolved views reveal that gravitational instabilities and efficient secular processes within the gas- and baryon-rich galaxies at [Formula: see text] play an important role in the early buildup of galactic structure. ▪  Ever more sensitive observations of kinematics at [Formula: see text] are probing the baryon and dark matter budget on galactic scales and the links between star-forming galaxies and their likely descendants. ▪  Toward higher masses, massive bulges, dense cores, and powerful AGNs and AGN-driven outflows are more prevalent and likely play a role in quenching star formation.

We outline emerging questions and exciting prospects for the next decade with upcoming instrumentation, including the James Webb Space Telescope and the next generation of extremely large telescopes.
The Role of Immune Factors in Shaping Fetal Neurodevelopment
Authors: Lu-Culligan Alice , Iwasaki Akiko
Published: July 2020

Fetal neurodevelopment in utero is profoundly shaped by both systemic maternal immunity and local processes at the maternal–fetal interface. Immune pathways are a critical participant in the normal physiology of pregnancy and perturbations of maternal immunity due to infections during this period have been increasingly linked to a diverse array of poor neurological outcomes, including diseases that manifest much later in postnatal life. While experimental models of maternal immune activation (MIA) have provided groundbreaking characterizations of the maternal pathways underlying pathogenesis, less commonly examined are the immune factors that serve pathogen-independent developmental functions in the embryo and fetus. In this review, we explore what is known about the in vivo role of immune factors in fetal neurodevelopment during normal pregnancy and provide an overview of how MIA perturbs the proper orchestration of this sequence of events. Finally, we discuss how the dysregulation of immune factors may contribute to the manifestation of a variety of neurological disorders.
Electrochemical Behavior and LC-MS Analysis of Anthocyanin’s in Vaccinium Arctostaphylos L. Extract: The Molecular Modelling of Potential Inhibition to COVID-19 and ROS Generation Receptors
Authors: Jamshidi Mahdi , Torabi Sara , Tavan Mansoureh , Azizi Ali , Khazalpour Sadegh
Published: July 2020

Caucasian whortleberry (Vaccinium Arctostaphylos L.) is rich in anthocyanins, which possesses a wide range of biological and pharmaceutical activities. Electrochemical behavior of V. Arctostaphylos extract of dried fruit was performed by cyclic voltammetry and differential pulse voltammetry in aqueous solution. The results show that the level of delphinidin 3-O-glucoside (D3-OG) compound is higher than petunidin 3-O-glucoside (P3-OG) and malvidin 3-O-glucoside (M3-OG) level. This extract has a high solubility in water, and the potential-pH diagram indicates that the D3-OG capable oxidized to D3-OGOX with two electron/two proton process. D3-OG compound has a high antioxidant power because of the oxidation peak potential is low. Furthermore, total antioxidant capacity (1.475 C g−1) was determined by charges under of first oxidation peak. The antioxidant activity of three anthocyanins against Xanthine oxidase, Myeloperoxidase, NADPH oxidase, cytochrome P450 3A4 and 2B4 (ROS generation enzymes) has been performed through molecular docking studies. The results indicated that all the anthocyanins (D3-OG, P3-OG and M3-OG) bound exclusively to the binding site of ROS generation enzymes and have a remarkable role in suppressing the destructive effects of oxidative stress in the biological system of the human body. Also, D3-OG as a major anthocyanin of Vaccinium Arctostaphylos L. extract has an inhibition effect against the COVID-19 outbreak. Electrochemical approaches provided a simple, fast, low cost, green, and high sensitivity methods for investigation of electroactive compounds in plant extracts.
SLC26A7 constitutes the thiocyanate-selective anion conductance of the basolateral membrane of the retinal pigment epithelium
Authors: Cao Xu , Soleimani Manoocher , Hughes Bret A.
Published: July 2020

Anion channels in the retinal pigment epithelium (RPE) play an essential role in the transport of Cl− between the outer retina and the choroidal blood to regulate the ionic composition and volume of the subretinal fluid that surrounds the photoreceptor outer segments. Recently, we reported that the anion conductance of the mouse RPE basolateral membrane is highly selective for the biologically active anion thiocyanate (SCN−), a property that does not correspond with any of the Cl− channels that have been found to be expressed in the RPE to date. The purpose of this study was to determine the extent to which SLC26A7, a SCN− permeable-anion exchanger/channel that was reported to be expressed in human RPE, contributes to the RPE basolateral anion conductance. We show by quantitative RT-PCR that Slc26a7 is highly expressed in mouse RPE compared with other members of the Slc26 gene family and Cl− channel genes known to be expressed in the RPE. By applying immunofluorescence microscopy to mouse retinal sections and isolated cells, we localized SLC26A7 to the RPE basolateral membrane. Finally, we performed whole cell and excised patch recordings from RPE cells acutely isolated from Slc26a7 knockout mice to show that the SCN− conductance and permeability of its basolateral membrane are dramatically smaller relative to wild-type mouse RPE cells. These findings establish SLC26A7 as the SCN−-selective conductance of the RPE basolateral membrane and provide new insight into the physiology of an anion channel that may participate in anion transport and pH regulation by the RPE.
Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice
Authors: Tsui Hung-Chang , Decaesteker Tatjana , Jonckheere Anne-Charlotte , Vande Velde Greetje , Cremer Jonathan , Verbeken Erik , Hoet Peter H. M. , Nemery Benoit , Vanoirbeek Jeroen A. J.
Published: July 2020

Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. BALB/c mice received epicutaneous applications (25 μL/ear) with 5% CoCl2*6H2O (Co) or the vehicle (Veh) dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal challenges with 0.05% CoCl2*6H2O or saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh, Veh/Co, and Co/Co. To detect early respiratory responses noninvasively, we performed sequential in vivo microcomputed tomography (µCT). One day after the last challenge, we assessed airway hyperreactivity (AHR) to methacholine, inflammation in bronchoalveolar lavage (BAL), innate lymphoid cells (ILCs) and dendritic cells (DCs) in the lungs, and serum IgE. Compared with the Veh/Veh group, the Co/Co group showed increased µCT-derived lung response, increased AHR to methacholine, mixed neutrophilic and eosinophilic inflammation, elevated monocyte chemoattractant protein-1 (MCP-1), and elevated keratinocyte chemoattractant (KC) in BAL. Flow cytometry in the Co/Co group demonstrated increased DC, type 1 and type 2 conventional DC (cDC1/cDC2), monocyte-derived DC, increased ILC group 2, and natural cytotoxicity receptor-ILC group 3. The Veh/Co group showed only increased AHR to methacholine and elevated MCP-1 in BAL, whereas the Co/Veh group showed increased cDC1 and ILC2 in lung. We conclude that dermal sensitization to cobalt may increase the susceptibility of the lungs to inhaling cobalt. Mechanistically, this enhanced susceptibility involves changes in pulmonary DCs and ILCs.
Using electrodermal activity to validate multilevel pain stimulation in healthy volunteers evoked by thermal grills
Authors: Posada-Quintero Hugo F. , Kong Youngsun , Nguyen Kimberly , Tran Cara , Beardslee Luke , Chen Longtu , Guo Tiantian , Cong Xiaomei , Feng Bin , Chon Ki H.
Published: July 2020

We have tested the feasibility of thermal grills, a harmless method to induce pain. The thermal grills consist of interlaced tubes that are set at cool or warm temperatures, creating a painful “illusion” (no tissue injury is caused) in the brain when the cool and warm stimuli are presented collectively. Advancement in objective pain assessment research is limited because the gold standard, the self-reporting pain scale, is highly subjective and only works for alert and cooperative patients. However, the main difficulty for pain studies is the potential harm caused to participants. We have recruited 23 subjects in whom we induced electric pulses and thermal grill (TG) stimulation. The TG effectively induced three different levels of pain, as evidenced by the visual analog scale (VAS) provided by the subjects after each stimulus. Furthermore, objective physiological measurements based on electrodermal activity showed a significant increase in levels as stimulation level increased. We found that VAS was highly correlated with the TG stimulation level. The TG stimulation safely elicited pain levels up to 9 out of 10. The TG stimulation allows for extending studies of pain to ranges of pain in which other stimuli are harmful.
Applying Complex Network and Cell‐Cell Communication Network Diagram Methods to Explore the Key Cytokines and Immune Cells in Local Acupoint Involved in Acupuncture Treating Inflammatory Pain
Authors: Zhang Kuo , Zhao Xue , Ding Shasha , Liu Yangyang , Xu Yuan , Yan Yawen , Hong Shouhai , Yang Fuming , Wang Shenjun , Xu Zhifang , Guo Yongming , Guo Yi , Pang Guangchang , Wang Jiang , Guo Xinmeng , Zhao Miao
Published: July 2020

Manual acupuncture (MA) can effectively treat a variety of diseases, but its specific mechanism remains unclear. The “acupoint network” activated by MA participates in MA signal transduction, in which immune‐related cells and cytokines play an important role. However, which cells and cytokines in the acupoint have changed after MA? What is the network relationship between them? Which cells and cytokines may play the most important role in MA effect? These problems are unclear. In this study, on the basis of affirming the analgesic, detumescence, and anti‐inflammatory effect of MA, the concentration of 24 cytokines in ST36 acupoint in rats with inflammatory pain after MA treatment was detected by multiplex immunoassay technology. Then, using statistical and complex network and cell‐cell communication (CCC) network diagram method to analyze the detected data depicts the network relationship between the cytokines and related cells objectively and establishes cytokine connection network and CCC network, respectively. The results showed that MA reinforced communication intensity between cells while reducing the overall correlation intensity. On this basis, the key cytokines and key cells at three MA time‐points were screened out, cytokines IL‐6, MCP‐1, fibroblasts cell, and monocyte macrophage screened by the three methods at three MA time‐points might be the key cytokines or key cells. After that, we detected the macrophages in ST36 acupoint by flow cytometry and immunofluorescence and found that the relative amount of macrophages increased significantly after MA, especially the macrophage of the dermis of skin. This study provided a basis for revealing the initiated mechanism of MA effect.
Memory-Enhancing Effect of a Phytosome Containing the Combined Extract of Mulberry Fruit and Ginger in an Animal Model of Ischemic Stroke with Metabolic Syndrome
Authors: Wattanathorn Jintanaporn , Palachai Nut , Thukham-mee Wipawee , Muchimapura Supaporn
Published: July 2020

The prevalence of dementia following cerebral ischemia in metabolic syndrome (MetS) condition is increasing, and most of the cases are often severe. Unfortunately, no effective strategy for treating this condition is available. Based on the positive modulation effect of a polyphenol-rich substance on dementia and the improvement in bioavailability and stability of polyphenols induced by the phytosome technique together with the use of the synergistic concept, we hypothesized that a phytosome containing the combined extract of mulberry fruit and ginger (PMG) should mitigate dementia and memory impairment following ischemic stroke in MetS. MetS was induced in male Wistar rats weighing 180-200 g by exposure to a 16-week feeding period of high-carbohydrate high-fat (HCHF) diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg·kg-1BW 21 days before and 21 days after the occlusion of the right middle cerebral artery (Rt. MCAO). Then, their spatial memory was determined and the possible underlying mechanisms explored via the alterations of acetylcholinesterase (AChE), neuron density, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and signal transduction via extracellular signal-regulated kinase (ERK) pathway in both the cerebral cortex and the hippocampus. It was found that PMG significantly enhanced memory. It also decreased AChE, IL-6, and MDA but increased SOD, CAT, GSH-Px, neuron density, and phosphorylation of ERK. These data suggested the cognitive enhancing effect of PMG. The possible underlying mechanisms might occur partly via the improvement of cholinergic function via the ERK pathway together with the decrease in neurodegeneration induced by the reduction of oxidative stress and inflammation. However, a subchronic toxicity study is also required to assure the safety of PMG consumption before moving forward to a clinical trial study.
Relationship between Serum Indirect Bilirubin Level and Insulin Sensitivity: Results from Two Independent Cohorts of Obese Patients with Impaired Glucose Regulation and Type 2 Diabetes Mellitus in China
Authors: Zhang Fan , Guan Wei , Fu Zhenzhen , Zhou Li , Guo Wen , Ma Yizhe , Gong Yingyun , Jiang Wanzi , Liang Hui , Zhou Hongwen
Published: July 2020

Background. Serum bilirubin is an endogenous antioxidant that has protective effects against obesity-related metabolic diseases. Objectives. This study aimed to evaluate the characteristics of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) and their relationships with insulin sensitivity in obese patients with impaired glucose regulation and type 2 diabetes mellitus (IGR/T2DM) in China. Patients and Methods. Cohort 1 comprised obese patients (n = 71) was divided into the IGR/T2DM group (n = 38, obesity with IGR/T2DM) and control group (n = 33, obesity without IGR/T2DM). Insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique (HEC) with glucose disposal rate (GDR, M value). Cohort 2 comprised obese patients with IGR/T2DM who underwent metabolic surgery (n = 109) as complementary to cohort 1. Insulin sensitivity was evaluated with the Matsuda Index and homeostatic model assessment of insulin sensitivity (HOMA-IS). Results. In cohort 1, TBIL, DBIL, and IBIL were higher within the physiological range in the IGR/T2DM group compared with the control group; IBIL was positively correlated with M value (r = 0.342, p=0.044) in the IGR/T2DM group, and multivariate logistic regression showed that IBIL might be independent protective factors against insulin resistance (odds ratio (OR) = 0.602; 95% confidence interval (CI): 0.413–0.878; p=0.008). In cohort 2, at 1 month after metabolic surgery, serum bilirubin levels (TBIL, DBIL, and IBIL) increased, and the percentage change in IBIL was positively correlated with the change of the Matsuda Index (r = 0.195, p=0.045). Conclusions. The relationships between different types of bilirubin and insulin sensitivity varied. Serum indirect bilirubin might be a protective factor that enhances insulin sensitivity.
The Role of Gender in the Importance of Risk Factors for Coronary Artery Disease
Authors: Gheisari Farshid , Emami Melika , Raeisi Shahraki Hadi , Samipour Saeid , Nematollahi Parastoo
Published: July 2020

Identification of risk factors and their importance in different genders is essential in order to prevent, diagnose, and manage coronary artery disease (CAD) properly. The present study aims to investigate the role of gender in the distribution of different risk factors in ischemic heart disease. This study is a cross-sectional study. More than one thousand (N = 1012) patients referring to the Nuclear Medicine Department in Namazi Hospital, Shiraz, Iran, from March 2017 to March 2018 were studied. The patients’ demographic data and their clinical history were collected. The results of the myocardial perfusion scan were recorded and compared between groups. Statistical analysis was implemented by SPSS version 18.0, and P values below 0.05 were considered statistically significant. Out of the 1012 patients participating in this study, 698 (69%) were female and 314 (31%) were male. Ischemic heart disease (IHD) was significantly higher in men compared to women (19.1% versus 14.2%). The higher levels of systolic and diastolic blood pressures, along with older age, were a significant risk factor in women P<0.05. Previous myocardial infarction (MI), diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia (HLP) had a strong correlation with IHD in our female population. Regarding the male subjects, previous MI and HLP had a lower correlation with IHD. Based on our logistic regression models, investigation of the simultaneous effects of risk factors on IHD showed that previous MI is the most effective risk factor in females (OR = 3.93) mostly in terms of residual ischemia in the infarcted myocardium. In the male population, on the other hand, HTN was identified as the most effective risk factor for IHD (OR = 2). In conclusion, we found that older age, higher blood pressure, DM, previous MI, HTN, and HLP have a significant association with IHD in the female population, whereas older age, DM, and HTN were significant risk factors for IHD in males. Also, the most effective factor for women was previous MI, while it was HTN for the male population.
Abraded Glass Strength: An Ad Hoc Fitting Protocol Based on the Change of Variable Theorem
Authors: Ferretti Camilla , Ganugi Piero , Pisano Gabriele , Zammori Francesco
Published: July 2020

This work tackles the problem of finding a suitable statistical model to describe relevant glass properties, such as the strength under tensile stress. As known, glass is a brittle material, whose strength is strictly related to the presence of microcracks on its surface. The main issue is that the number of cracks, their size, and orientation are of random nature, and they may even change over time, due to abrasion phenomena. Consequently, glass strength should be statistically treated, but unfortunately none of the known probability distributions properly fit experimental data, when measured on abraded and/or aged glass panes. Owing to these issues, this paper proposes an innovative method to analyze the statistical properties of glass. The method takes advantage of the change of variable theorem and uses an ad-hoc transforming function to properly account for the distortion, on the original probability distribution of the glass strength, induced by the abrasion process. The adopted transforming function is based on micromechanical theory, and it provides an optimal fit of the experimental data.
High-Gain SIR Dual-Band Antenna Based on CSRR-Enhanced SIW for 2.4/5.2/5.8 GHz WLAN
Authors: Feng Caixia , Kang Yongqiang , Dong Lijuan , Wang Lihong
Published: July 2020

This paper presents a dual-band step impedance resonator (SIR) antenna based on metamaterial-inspired periodic structure of coupled complementary split-ring resonators substrate-integrated waveguide (CSRR-SIW). The antenna supports wireless local area networks (WLAN) bands at 2.4/5.2/5.8 GHz. The CSRRs and two branches of the SIR element are etched on the top and bottom metal surfaces of the substrate. The SIR element produces a fundamental frequency f1 at 2.4 GHz and a second harmonic frequency fs2 at 5.7 GHz. Meanwhile, the CSRRs produces a resonant frequency at high-frequency band around 5.2 GHz, which can be combined with the second harmonic frequency fs2 at 5.7 GHz. The high-frequency bandwidth can then be broadened. The simulated and measured results show that the dual operation bands with bandwidths of 16% from 2.25 GHz to 2.64 GHz and 18.2% from 5 GHz to 6 GHz for |S11| < −10 dB are achieved. Meanwhile, the proposed antenna has peak gains ranging from 6.5 dBi to 7 dBi and from 7 dBi to 7.7 dBi in the lower and upper bands, respectively. Compared with many previously reported dual-band antenna designs, the proposed antenna achieves comparable bandwidth performance and larger gain per unit area with a relatively smaller size. Moreover, the simple structure renders the proposed antenna has the advantage of easy-processable and cost-effective implementation.
Multibacillary Leprosy Presenting as Anetoderma in a Young Teenager
Authors: Parajuli Niraj , Shrestha Shraddha , Lama Laila , Shrestha Rushma , Tiwari Sumida , Karki Anupama
Published: July 2020

Anetoderma presents as a circumscribed area of slack skin. It can present as either primary or secondary, if associated with other conditions. Leprosy is one of the causes of secondary anetoderma, but it is not commonly reported, especially in multibacillary leprosy. Here, we report a case of a 16-year-old young girl who presented with fever, joint pain, and only three anetodermic plaques. A slit skin smear from the lesion showed multiple acid-fast bacilli with a bacillary index of 3+, thus confirming the diagnosis of leprosy. This case is unique since multibacillary leprosy presented with only few anetoderma lesions in a young teenager girl from a leprosy-eliminated country.
The Response of Urban Travel Mode Choice to Parking Fees considering Travel Time Variability
Authors: Ding Ling , Yang Xu
Published: July 2020

Increasing automobile use leads to higher costs for traveling associated with emissions, congestion, noise, and other impacts. One option to address this is to introduce high parking charges to reduce the demand for automobile use and encourage the travel mode switch to public transport. To estimate commuters’ mode choice behavior in response to high parking fees, commuters from Nanjing completed an individually customized discrete choice survey in which they chose between driving and taking the bus or metro when choices varied in terms of time and cost attributes. Multinomial logit models were used to estimate commuters’ responses to high parking charges. In the models, the variability of travel times is considered and analyzed in the stated mode choice models. The results suggest that increases in costs of driving will lead to a great reduction in driving demand. The travel time reliability ratio is 0.50 and the value of each minute late is almost 5.0 times more than the average travel time with the restriction of the maximum allowed delays. The methods used in this study could be adopted to estimate the effect of variable pricing strategies on mode choice responses for different trip purposes. The high value given to travel time variability has implications for transport policy in terms of decision making with respect to new pricing strategies. Moreover, the valuation of travel time savings taken into account in this study would be helpful to better understand the effect of high parking fees.
Nut and Peanut Butter Consumption and the Risk of Total Cancer: A Prospective Cohort Study
Authors: Nieuwenhuis Lisette , van den Brandt Piet A.
Published: July 2020

Background:

Nut intake has been associated with reduced cancer-related mortality, but there is very limited evidence on total cancer risk. We investigated the associations of nut and peanut butter intake with the risk of total cancer and smoking- and alcohol-related cancer subgroups.

Methods:

In the prospective Netherlands Cohort Study, 120,852 men and women aged 55 to 69 years provided information on lifestyle and dietary habits at baseline in 1986. After 20.3 years of follow-up, 19,255 total cancer cases and 3,499 subcohort members were included in multivariable-adjusted Cox regression analyses, using a case–cohort approach.

Results:

No significant associations were found between total nut, tree nut, peanut, and peanut butter intake and total cancer risk in men and women. There were also no significant associations with smoking-(un)related and alcohol-(un)related cancers in both sexes.

Conclusions:

Our findings suggest that nut and peanut butter intake are not associated with a reduced risk of total cancer in men or women.

Impact:

Nut and peanut butter consumption are not related to the risk of total cancer.
Interleukin-17A Expression Correlated with the Prognosis of Chronic Rhinosinusitis with Nasal Polyps and the Anti-Interleukin-17A Effect in a Murine Nasal Polyps Model
Authors: Huang Jian-Cong , Chen Xiao-Hong , Wang Zhi-Yuan , Li Xia , Chang Li-Hong , Zhang Ge-Hua
Published: July 2020

Objective: To investigate the expression of interleukin-17A (IL-17A) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and to analyze its effect on prognosis and to explore the role and mechanism of anti-IL-17A effect in vivo by establishing a murine nasal polyps (NP) model. Methods: Patients with CRSwNP who underwent endoscopic sinus surgery and matched control subjects were collected. We investigated IL-17A expression in human NP tissues using immunohistochemistry and analyzed their clinical features, including Lund-Mackay computed tomography scoring (LMCS) before surgery, Lund-Kennedy endoscopic scoring (LKES) before surgery (LKES B), LKES 6 months after surgery (LKES A), and reduction of LKES (LKES R). Then, after establishing the murine NP model to detect the expression and correlation of IL-17A and matrix metalloproteinase-9 (MMP-9) in nasal tissue, we studied nasal lavage fluid and serum by PCR and enzyme-linked immunosorbent assay in vivo. Anti-IL-17A treatment was administered in the murine NP model to confirm the function of IL-17A during the pathogenic processes. Results: IL-17A expression was upregulated in NP tissues from patients with CRSwNP compared with control subjects (p < 0.001). The number of IL-17A+ cells was significantly negatively correlated with LKES R in patients with CRSwNP (p < 0.01). However, there was no significant correlation between IL-17A and LMCS or LKES B (all p < 0.05). Further, IL-17A and MMP-9 were more abundant in nasal mucosa of the murine NP model compared with that of control mice (all p < 0.05), and severe polypoid lesions were apparently observed in murine NP models. Anti-IL-17A treatment downregulated the mRNA and protein expression of MMP-9 in nasal mucosa and reduced the number of polypoid lesions in the murine NP model (all p < 0.05). Conclusion: Our results suggest that IL-17A plays a crucial role and may affect the prognosis of CRSwNP. Anti-IL-17A treatment may reduce the formation of polypoid lesions through inhibition of MMP-9 expression.
Transient Pleural Fluid Infiltration by Clonal Plasma Cells Associated with Pulmonary Tuberculosis
Authors: Sameh Soliman Dina , Ali Mohammad , Akikki Susanna , Ibrahim Feryal , El-Omari Halima , Al-Sabbagh Ahmad , Okar Lina
Published: July 2020

Pleural effusion is a rare presentation of plasma cell myeloma, occurring in around 6% of patients during the course of their disease, most commonly as a consequence of a concurrent disease process like heart failure secondary to amyloid deposition. Direct infiltration of the pleural fluid by malignant cells leading to myelomatous pleural effusion is a rare mechanism occurring in less than 1% of patients with plasma cell myeloma, and it is associated with a worse prognosis. There are few case reports of myelomatous pleural effusion as an initial presentation of multiple myeloma. Pleural fluid infiltration by monoclonal plasma cells in the absence of an underlying plasma cell myeloma was not reported before in the literature. Tuberculosis is a known cause of polyclonal gammaglobulinemia, however few case reports described the coexistence of monoclonal gammopathy of undetermined significance and tuberculosis. Here we present an interesting case of pleural fluid infiltration by an abnormal looking clonal plasma cells associated with active pulmonary tuberculosis and parapneumonic effusion in a patient with a background of acute myeloid leukemia. Interestingly, the clonal plasma cell proliferation was confined to the pleural fluid without any evidence of an underlying plasma cell neoplasms (including monoclonal gammopathy of undetermined significance and plasmacytomas). Since our patient had an underlying meyloid neoplasm, we though about the possibility of secondary malignancy. However, in almost all patients with coexisting myeloid and plasma cell neoplasms, myeloid neoplasms developed following chemotherapeutic treatment of plasma cell neoplasms not the other way around. Given that, one must conclude localized extramedullary (pleural) plasma cell proliferation probably represents a transient reactive process to pulmonary tuberculosis which is an extremely rare phenomenon and not described before.
Excellent Response to Olaparib in a Patient with Metastatic Pancreatic Adenocarcinoma with Germline BRCA1 Mutation after Progression on FOLFIRINOX: Case Report and Literature Review
Authors: Pimenta Jefferson Rios , Ueda Serli Kiyomi Nakao , Peixoto Renata D’Alpino
Published: July 2020

Metastatic pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Until recently, cytotoxic chemotherapy was the only treatment option. Currently, there are subgroups of patients with PDAC either with somatic or germline mutations who are candidates for targeted agents. Germline mutations in the BRCA1 and BRCA2 genes promote the incapacity of tumor cells to recover from DNA-accumulated damage caused by cytotoxic drugs, like platinum agents, and, most recently, through a diverse process by poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). A 59-year-old female who was treated for a triple negative breast cancer 8 years ago with surgery, adjuvant chemotherapy and radiotherapy, presented with increasing back pain. Investigation revealed multiple liver nodules and a large mass in the head of the pancreas. Biopsy confirmed PDAC. She received 13 cycles of FOLFIRINOX, achieving partial response both in the liver and pancreatic lesion, with resolution of symptoms. Due to increasing neuropathy, chemotherapy was stopped, and the patient was followed. Sixteen months later, her CA19-9 levels increased. Given limiting neuropathy, the patient was restarted on FOLFIRI only. After 8 cycles, there was disease progression plus uncontrolled back pain. A mutational test was requested and confirmed a BRCA1 germline mutation. The patient was started on olaparib. After 3 cycles, images showed a significant response and after 6 cycles, it remained stable, with persistent fall in CA19-9 levels. She is currently on treatment, with ongoing response. In conclusion, patients with metastatic PDAC and BRCA mutation may benefit from PARPi even after progression on chemotherapy. We hypothesize that olaparib works even in the setting of disease progression and not solely as a maintenance therapy following platinum-based therapy. Randomized trials are needed investigating the role of olaparib following disease progression in PDAC.
Supervised Exercise Training in Patients with Chronic Thromboembolic Pulmonary Hypertension as Early Follow-Up Treatment after Pulmonary Endarterectomy: A Prospective Cohort Study
Authors: Nagel Christian , Nasereddin Mohammed , Benjamin Nicola , Egenlauf Benjamin , Harutyunova Satenik , Eichstaedt Christina A. , Xanthouli Panagiota , Mayer Eckhard , Grünig Ekkehard , Guth Stefan
Published: July 2020

Background: Data on exercise training in chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA) as well as data on clinical and haemodynamic changes shortly after PEA are lacking. Objective: The objective of this prospective study was to analyse the safety, feasibility, and the effectiveness of combined supervised inpatient rehabilitation in patients with CTEPH directly after PEA. Methods: CTEPH patients started a 19-week rehabilitation program (3 weeks as inpatients and continued at home for another 16 weeks) with supervised exercise training as follow-up treatment shortly after PEA. Haemodynamics were assessed by right heart catheterisation before PEA and 22 weeks after PEA. Non-invasive assessments as transthoracic echocardiography and 6-min walking distance (6MWD) were performed before PEA and after 3 (that is, beginning of rehabilitation), 6, and 22 weeks following PEA. Adverse events were recorded throughout the study. Results: Forty-five CTEPH patients were included (49% female, 57.6 ± 12.4 years old, 60% WHO functional class III). Rehabilitation was started 3.3 ± 0.9 weeks after PEA. Exercise training was well tolerated in all patients without severe side effects. Haemodynamics measured by right heart catheterisation significantly improved from pre-PEA to 22 weeks post-PEA in cardiac output (+1.2 ± 1.5 L/min, 33.4%, p = 0.001) and mean pulmonary arterial pressure (–19 ± 13 mm Hg, –39.6%, p < 0.0001). Right heart size measured by echocardiography, 6MWD, quality of life, and oxygen saturation significantly improved not only within the first 3 weeks after PEA but also during the following 19 weeks of exercise training. Conclusions: Supervised exercise training was feasible as early follow-up treatment after PEA. Further controlled studies are needed to discriminate the effects of PEA and early follow-up rehabilitation. Trial Registration: The study was registered at clinicaltrials.gov (NCT01393327) on July 13, 2011. The study start date was January 2010, and completion date was December 2013.
Comparison of Intravascular Ultrasound Virtual Histology Parameters in Diabetes versus Non-Diabetes with Acute Coronary Syndrome
Authors: Reddy Sreenivas , Kadiyala Vikas , Kashyap Jeet Ram , Rao Raghavendra , Reddy Hithesh , Kaur Jaspreet , Kaur Naindeep , Ramalingam Vadivelu
Published: July 2020

Introduction: The progression and pattern of coronary atherosclerosis in diabetes mellitus (DM) is different from non-DM, leading to a higher rate of vascular complications in DM. Objective: This study aims to assess and compare the high-risk plaque characteristics in the culprit artery of DM and non-DM patients with acute coronary syndrome (ACS) using virtual histology intravascular ultrasound (VH-IVUS). Methods: A total of 158 ACS patients were included, 63 of whom were known to have DM. IVUS analysis was done in the de novo target vessel and culprit lesion for which percutaneous coronary intervention was planned. Culprit lesions with a visual-estimate angiographic stenosis of <70% were excluded. Results: The mean age of patients was 52.4 ± 11.6 years. The study group comprised 82% men, 31% with hypertension, and 39.87% with DM. No significant difference was observed between the DM and non-DM groups in relation to quantitative IVUS parameters like lesion length, minimal lumen area, and plaque area. However, there was a significant difference in VH-IVUS parameters like higher necrotic core and dense calcium in the DM patients than in the non-DM patients (p < 0.01). The occurrence of VH-derived thin-cap fibroatheroma (VH-TCFA) in the culprit vessel was significantly higher in the DM group than in the non-DM group (25.3 vs. 5.2%; p < 0.01). Positive vessel-wall remodeling was noted in both groups without any significant difference (p = 0.74). Conclusion: The DM patients had high-risk plaque composition features like a higher necrotic core, which is a marker of plaque vulnerability. Thus, aggressive medical therapy targeting vascular inflammation using high-dose statins would help in the stabilization of unstable plaque morphology and the reduction of major cardiovascular events.
Hydrophobicity and the Physico-Chemical Basis of Immunotolerance
Authors: Kanduc Darja
Published: July 2020

This study analyzes the primary electrostatic interaction between the membrane-bound B-cell receptor and antigen peptide determinants, and identifies peptide frequency and hydrophobicity as the main factors that govern and shape immunotolerance versus immunoreactivity.
A Novel Duplication Mutation in the Myelin Protein Zero Gene Causing Mild, Nonprogressive Demyelinating Neuropathy
Authors: Oberoi Kinsi , Grewal Alam S. , Peddareddygari Leema Reddy
Published: July 2020

Mutations in the myelin protein zero (MPZ) gene can cause a variety of clinical and electrophysiological forms of genetic neuropathies including Charcot-Marie-Tooth (CMT) type 1B disease which is characterized by demyelinating features. We present a father and daughter with neuropathy carrying a novel 31 base pair duplication mutation in the 5′ untranslated region of the MPZ gene, c.-23_8dup31. Genetic analysis and protein modeling indicated that this is a frameshift mutation resulting in premature truncation of the encoded protein. The daughter underwent repeat neurological examination and electromyography testing over an 11-year time span demonstrating no clinical or electrophysiological change. Our study expands the clinical and genetic spectrum of mutations that can cause CMT type 1B disease and demonstrates the value of sequence analysis of noncoding portions of a gene that are not intronic.
JAK/STAT Pathway Inhibition May Be a Promising Therapy for COVID-19-Related Hyperinflammation in Hematologic Patients
Authors: Rojas Patricio , Sarmiento Mauricio
Published: July 2020

COVID-19 has rapidly become a major concern for the health systems worldwide. Its high contagiousness and associated mortality demand the discovery of helpful interventions with promising safety profile. Here, we report 3 severe COVID-19 cases, which achieved rapid and sustained improvement in outcome with the use of ruxolitinib, a JAK/STAT pathway inhibitor.
Obese-Inflammatory Phenotypes in Heart Failure With Preserved Ejection Fraction
Authors: Sabbah Michael S. , Fayyaz Ahmed U. , de Denus Simon , Felker G. Michael , Borlaug Barry A. , Dasari Surendra , Carter Rickey E. , Redfield Margaret M.
Published: July 2020

Background:

Comorbidity-driven microvascular inflammation is posited as a unifying pathophysiologic mechanism for heart failure with preserved ejection fraction (HFpEF). Obesity is proinflammatory and common in HFpEF. We hypothesized that unique obesity-inflammation HFpEF phenotypes exist and are associated with differences in clinical features, fibrosis biomarkers, and functional performance.

Methods:

Patients (n=301) from 3 HFpEF clinical trials were studied. Unsupervised machine learning (hierarchical clustering) with obese status and 13 inflammatory biomarkers as input variables was performed. Associations of clusters with HFpEF severity and fibrosis biomarkers (PIIINP [procollagen III N-terminal peptide], CITP [C-telopeptide for type I collagen], IGFBP7 [insulin-like growth factor-binding protein-7], and GAL-3 [galectin-3]) were assessed.

Results:

Hierarchical clustering revealed 3 phenotypes: pan-inflammatory (n=129; 64% obese), noninflammatory (n=83; 55% obese), and obese high CRP (C-reactive protein; n=89; 98% obese). The pan-inflammatory phenotype had more comorbidities and heart failure hospitalizations; higher left atrial volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and fibrosis biomarkers; and lower glomerular filtration rate, peak oxygen consumption, 6-minute walk distance, and active hours/day (
P
<0.05 for all). The noninflammatory phenotype had the most favorable values for all measures. The obese high CRP phenotype resembled the noninflammatory phenotype except for isolated elevation of CRP and lower functional performance. Hierarchical cluster assignment was independent of CRP genotype combinations that alter CRP levels and more biologically plausible than other clustering approaches. Multiple traditional analytic techniques confirmed and extended the hierarchical clustering findings.

Conclusions:

Unique obesity-inflammation phenotypes exist in HFpEF and are associated with differences in comorbidity burden, HFpEF severity, and fibrosis. These data support comorbidity-driven microvascular inflammation as a pathophysiologic mechanism for many but not all HFpEF patients.
Phylogenetic relationships of Leptolaimus de Man, 1876 (Plectida: Leptolaimidae) with description of two new species from the Persian Gulf, Iran
Authors: Gharahkhani Azadeh , Pourjam Ebrahim , Holovachov Oleksandr , Pedram Majid
Published: July 2020

Members of the family Leptolaimidae are reported for the first time from Iran with description of two new species of Leptolaimus from the Persian Gulf in the south of the country. Leptolaimus hormozganensis sp. n. is described based upon three populations. It differs from other Leptolaimus species in the position of the pharyngeal supplement and the number of precloacal tubular supplements and has a single sickle-shaped tubular pharyngeal supplement at mid-pharynx level in both sexes, 9-12 male precloacal supplements and one female preanal supplement. Leptolaimus dimorphus sp. n. is characterised by the presence of a pharyngeal tubular supplement only in some adults, one female preanal supplement and four male precloacal supplements. It differs from other species in that the pharyngeal supplement is only present in some specimens, presence of four male precloacal supplements, tail 50-59 μm long and ventrosublateral position of vulva on either the right or left side of the body. Near full length SSU rDNA sequences are provided for L. hormozganensis sp. n. and two different males (one with, and one without, a pharyngeal supplement) of L. dimorphus sp. n. COI sequences for three populations of L. hormozganensis sp. n. from different regions of the Persian Gulf are also obtained. New sequences of two Leptolaimus species formed a clade with other sequenced Leptolaimus spp. and representatives of two genera of Leptolaimidae, i.e., Aphanolaimus and Paraplectonema in a phylogeny based on SSU rDNA gene with 1.00/81 Bayesian posterior probability/maximum likelihood bootstrap (BPP/BS) values. Molecular phylogeny confirmed the synonymy of Leptolaimus and Halaphanolaimus that was formerly proposed based only on morphology. Based on SSU sequences and morphological characters, the presence of a pharyngeal supplement may not be a species-specific character and should not be used to differentiate genera.
Hannah Arendt and Philosophical Influence
Authors: Fry Karin
Published: July 2020

Over the years, many scholars have focused on the hierarchical and overpowering influence of Martin Heidegger upon Hannah Arendt’s thought. This view follows the stereotype concerning philosophical influence in which an all-knowing teacher affects the thought of the student, particularly if the student is a woman. In this paper, I argue that the story of philosophical influence is more complicated. In this case, the biographical archive establishes how Karl Jaspers, Martin Heidegger, and Hannah Arendt mutually influenced one another throughout their lives and careers. This evidence contests the typical view of philosophical influence which is hierarchical and often gendered and suggests a new model for understanding philosophical influences as dynamic and reciprocal.
Labor as Action: the Human Condition in the Anthropocene
Authors: Hyvönen Ari-Elmeri
Published: July 2020

The Anthropocene has become an umbrella term for the disastrous transgression of ecological safety boundaries by human societies. The impact of this new reality is yet to be fully registered by political theorists. In an attempt to recalibrate the categories of political thought, this article brings Hannah Arendt’s framework of The Human Condition (labor, work, action) into the gravitational pull of the Anthropocene and current knowledge about the Earth System. It elaborates the historical emergence of our capacity to “act in the mode of laboring” during fossil-fueled capitalist modernity, a form of agency relating to our collectively organized laboring processes reminiscent of the capacity of modern sciences to “act into nature” discussed by Arendt. I argue that once read from an energy/ecology-centric perspective, The Human Condition can help us make sense of the Anthropocene predicament, and rethink the modes of collectively organizing the activities of labor, work, and action.
Body and Place as the Noetic-Noematic Structure of Geographical Experience
Authors: Schmidt Stefan W.
Published: July 2020

In this paper, I use Husserl’s phenomenological analyses of noesis and noema to investigate the connection between experience and place, a relation which I call “geographical experience,” using a term coined by Edward Relph. Following the correlative structure of lived experience, geographical experience is enabled by the lived body as the noetic part and place as the respective noematic part. Both parts belong together necessarily. However, in this experiential field, distortions and an eluding aspect of place appear in the relationship between body and place. These distortions point to an aspect of geographical experience that cannot be fully grasped by the noetic-noematic structure of experience. They indicate that the reality of place is not completely constituted by this correlative structure but nevertheless becomes apparent in and through it.