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INTRODUCTION: Although studies using mixed insurance populations suggest that chemotherapy use in men with advanced penile cancer (PC) is low, it is unclear what regimens are being utilized. In this study, we use a database of insured patients to better understand specific chemotherapy utilization in men with PC. METHODS: This is a retrospective cohort study of patients with stage IIIB or IV PC in the Surveillance, Epidemiology, and End Results-Medicare database (2004–2015). Standard of care (SOC) chemotherapy was defined by the National Comprehensive Cancer Network® guidelines: 4 cycles of paclitaxel, ifosfamide and cisplatin or 5-fluorouracil with cisplatin in the neoadjuvant, adjuvant or primary setting. We calculated what proportion of patients receive SOC or any chemotherapy within 2 years of diagnosis and analyzed what factors were associated with receiving chemotherapy. RESULTS: Our study included 147 patients—48 stage IIIB and 99 stage IV. Of these patients, 49 (33%) received chemotherapy. Less than 5% of men received SOC. About 10% received SOC chemotherapy but an insufficient number of cycles. Married men were more likely to undergo chemotherapy (OR 3.4, 95% CI 1.5–7.8). Less than 5% of the 24 Black or Hispanic patients received chemotherapy compared to 37% of white patients (p

On 23 March 2020, the UK Government announced a nationwide lockdown in response to the COVID-19 epidemic, with people banned from leaving their homes except for essential journeys and exercise., Impact of the UK lockdown on early COPD https://bit.ly/3laMsmi

Exertional respiratory discomfort is the most common symptom in patients with COPD [1]. Menthol has recently been proposed as an ergogenic aid to decrease the perception of dyspnoea during exercise [2–4]. Menthol activates the transient receptor potential melastatin 8 (TRPM8) channels in the sensory nerve fibres of the tongue, promoting a feeling of freshness and a cognitive illusion of airflow into the airways [2, 5, 6]. We hypothesised that chewing menthol-flavoured gum before exercise would decrease the perception of dyspnoea during walking in COPD patients., Chewing menthol gum prior to exercise is a safe, easy-to-implement, low-cost, non-pharmacologic intervention that provides a reduction in dyspnoea in a third of patients and decreases the perception of discomfort during exercise in two-thirds of patients https://bit.ly/3FoFHp1

Among 582 participants in Western Kenya who were retrospectively tested from January through March 2020, 19 (3.3%) had detectable SARS-CoV-2 antibodies. The prevalence of detectable SARS-CoV-2 antibodies was similar between participants with and without HIV (3.1% vs. 4.0%, p = 0.68). One participant reported a cough in the preceding week but others denied symptoms. These may represent cross-reactivity or asymptomatic infections that predated the first reported COVID-19 cases in Kenya.

Background The creatinine-based CKD EPI equation is the most widely used method to estimate glomerular filtration rate (eGFRcr) in clinical practice. Here, we focus on African American (AA) participants to determine whether the race eGFRcr calibration factor contributes to poor accuracy and bias in AAs living with HIV. Methods Annually, we measured GFR by iohexol disappearance from plasma (iGFR) and serum concentrations of creatinine and cystatin C. We calculated eGFRcr and the creatinine-cystatin C combination equation (eGFRcr-cys) with and without race adjustment. We used multilevel mixed models to account for the within-visit linked structure of the multiple GFR measures, further nested within repeated observations for individuals. We examined the association between lean mass, HIV status, and eGFRcr bias in a subset with body composition measures. Results 207 HIV-positive and 107 HIV-negative AA participants contributed 781 and 376 study visits, respectively, with valid measures of iGFR, creatinine, and cystatin C. Among PLWH, omitting the race adjustment (compared with retaining it) changed average eGFRcr bias from 9.1 to -3.9 ml/min/1.73 m2. Moreover, estimation accuracy improved significantly when race adjustment was omitted rather than retained: 86% vs. 78% for eGFRcr (P

Tobacco Free Ireland is an Irish Government policy which demands that the prevalence of tobacco smoking in Ireland be less than 5% by 2025. From 1995 to 2015, teen smoking decreased from 41% in 1995 to 13.1% in 2015, and SimSmoke modelling suggested that the 5% 2025 target was achievable in this group [1]. But, in 2019, current smoking (smoked in the past 30 days) increased overall from 13.1% in 2015 to 14.4% in 2019, with the increase being greater in boys than girls (16.2% versus 12.8%) [2]. This threatens the Tobacco Free Ireland endgame. Here, we draw on data from two waves (2015 and 2019) of the Irish ESPAD (European School Survey Project on Alcohol and other Drugs) to analyse the use of tobacco products by teenagers and offer an explanation for the change., Smoking prevalence decreased in Irish teenagers in all ESPAD survey waves from 1995 until 2015. However, in ESPAD 2019, current teen smoking and e-cigarette use increased, threatening Ireland's 5% prevalence tobacco endgame strategy. https://bit.ly/3yXVAyN

The Potts shunt has been proposed as a strategy to alleviate symptoms and to delay lung transplantation in paediatric patients with pulmonary arterial hypertension (PAH) [1]. In a similar way to patients with Eisenmenger physiology with a patent ductus arteriosus, the Potts shunt may confer protection to the pressure-overloaded right ventricle in patients with suprasystemic pulmonary pressures. The results, in selected paediatric patients, have been encouraging in terms of survival, World Health Organization (WHO) functional classification and need for transplantation [1–4]. Recently, modifications to the classic Potts shunt have been reported by creating a unidirectional central valved conduit to protect the pulmonary circulation from reverse shunting [5, 6]. We report a second adult patient who underwent placement of a central unidirectional (valved) Potts shunt for severe suprasystemic PAH. After 1 year of follow up, the patient demonstrated overall clinical improvement with a significant increase in exercise tolerance., For young adults with end-stage idiopathic pulmonary hypertension, a valved graft connecting the central pulmonary artery to the distal aortic arch can provide substantial palliation of symptoms and may defer lung transplantation https://bit.ly/2TvMFFC

Heparan sulfate (HS), a sulfated glycosaminoglycan (GAG), was reported to be a necessary host attachment factor that promotes SARS-CoV-2 infection. In this study, we developed GAG microarrays based on fluorescence detection for high-sensitivity screening of the GAG-binding specificity of proteins and applied it for the analysis of SARS-CoV-2 spike (S) protein. Among the 20 distinct GAGs, the S protein bound not only to heparin (HEP)/HS but also to chondroitin sulfate E (CSE) in a concentration-dependent manner. We then analyzed the specificity of each subunit of the S protein. While the S1 subunit showed exclusive binding to HEP, the S2 subunit also bound to CSE and HEP/HS. CSE might act as an alternative attachment factor for HS in SARS-CoV-2 infection.

Pulmonary arterial hypertension (PAH) is characterised by pathological pulmonary vascular remodelling and increased resistance leading to right heart failure and death [1]. It is thought that exercise intolerance in PAH arises from an impairment in oxygen transport and delivery, driven by a reduced stroke volume [2]., In precapillary pulmonary hypertension, exercising muscles extract oxygen to a similar level seen in healthy individuals. Exercise limitation is a result of impaired oxygen delivery, which is matched to any impairment in skeletal muscle oxygen extraction. https://bit.ly/3hQUY8m

Patch test reactions during dupilumab treatment showed a reproducibility rate of 29%. Reproducibility rates were higher for initially extreme (+++) or strong positive (++) reactions. Patch test reactions might be suppressed during dupilumab treatment, possibly leading to false negative reactions.

Aspiration during swallow may have devastating consequences in COPD. It is known that COPD can impair swallow efficiency and safety [1–3] and a better understanding of how patients with COPD swallow is essential to inform preventative strategies. To date, no studies have examined swallow of large liquid volumes representative of everyday fast-paced drinking in an ample number of patients with COPD. In this letter we detail swallow patterns evaluated by videofluoroscopy in patients with COPD, with and without evidence of aspiration., Few studies have examined swallow of large liquid volumes representative of everyday drinking in COPD. Swallow by cup-drinking was evaluated in COPD using videofluoroscopy. Slower swallow was linked to aspiration indicating altered swallow habits in COPD. https://bit.ly/3wpdnO3

Non-rotationally averaged 3D structures of fibers can be restored from their rotationally averaged diffraction patterns., X-ray fiber diffraction is potentially a powerful technique to study the structure of fibrous materials, such as DNA and synthetic polymers. However, only rotationally averaged diffraction patterns can be recorded and it is difficult to correctly interpret them without the knowledge of esoteric diffraction theories. Here we demonstrate that, in principle, the non-rotationally averaged 3D structure of a fibrous material can be restored from its fiber diffraction pattern. The method is a simple puzzle-solving process and in ideal cases it does not require any prior knowledge about the structure, such as helical symmetry. We believe that the proposed method has a potential to transform the fiber diffraction to a 3D imaging technique, and will be useful for a wide field of life and materials sciences.

The strategy to eliminate tuberculosis (TB) in low-incidence countries includes the investigation of the contacts of TB cases [1]. This recognises that whilst most TB disease in these settings is due to reactivation [2], local transmission also occurs [3]. In the UK, TB networks (TBN), which support and coordinate local and regional TB services, typically follow the National Institute of Health and Care Excellence guidance which recommends screening close contacts (predominantly household) but not routinely for social or non-household contacts [4]. Many studies from low TB burden countries report contact investigation for specific congregate settings including outbreaks in childcare centres [5], homeless facilities [6] and methadone treatment clinics [7]. However, the comprehensive application of contact investigation across multiple non-household locations is rarely reported. Therefore, we evaluated a systematic approach to managing people potentially exposed to TB in congregate settings., A systematic approach to nonhousehold TB contact identified a similar number of LTBI cases to household screening over the same time period https://bit.ly/2Tq96LN

The monocarboxypeptidase angiotensin-converting enzyme 2 (ACE2) is a major player in the the renin–angiotensin system (RAS) as it converts the decapeptide angiotensin (Ang) I to Ang-(1–9) and Ang II to Ang-(1–7) (figure 1a) [1]. ACE2 is also a target for the new human coronavirus SARS-CoV-2, which is responsible for the dramatic ongoing COVID-19 pandemic [2]. It has been suggested that following SARS-CoV-2/ACE2 internalisation, Ang II level increases [3] in parallel to a decrease of Ang-(1–7) level [4]. These changes would be expected both at tissue and circulatory levels. Considering that Ang-(1–7) has many beneficial effects, including anti-inflammatory, antithrombogenic and antifibrotic activities [1], it has been hypothesised that Ang-(1–7) administration would improve the clinical outcome of COVID-19 patients. Aiming to test this hypothesis, a phase I/II clinical trial (www.clinicaltrials.gov identifier NCT04633772) has been initiated with a planned phase III clinical trial (NCT04332666)., This letter reports an unexpected increase of the ACE2 product angiotensin-(1–7) and a parallel decrease of its substrate angiotensin II, suggesting a dysregulation of the renin–angiotensin system towards angiotensin-(1–7) formation in #COVID19 patients https://bit.ly/3xFXuTU

The SARS‐CoV‐2 spike glycoprotein (spike) mediates viral entry by binding ACE2 receptors on host cell surfaces. Spike glycan processing and cleavage, which occur in the Golgi network, are important for fusion at the plasma membrane, promoting both virion infectivity and cell‐to‐cell viral spreading. We show that a KxHxx motif in the cytosolic tail of spike weakly binds the COPβ’ subunit of COPI coatomer, which facilitates some recycling of spike within the Golgi, while releasing the remainder to the cell surface. Although histidine (KxHxx) has been proposed to be equivalent to lysine within di‐lysine endoplasmic reticulum (ER) retrieval sequences, we show that histidine‐to‐lysine substitution (KxKxx) retains spike at the ER and prevents glycan processing, protease cleavage, and transport to the plasma membrane.

Physicians still have great difficulty in diagnosing asthma. Over- and under diagnosis both occur for this lung disease from which around 300 million people suffer worldwide.1 For diagnosing asthma, after careful history taking, lung function testing is considered the most relevant investigation. However, other parameters could also assist in completing the asthma jigsaw. Since atopy is one of the predisposing factors for asthma, measurement of specific IgE (sIgE) could be of assistance. This statement only applies to sIgE and not to total IgE measurement, which cannot be used as crucial evidence for allergy diagnosis.2.

A 2.0 Å resolution cryo-EM structure of a thermostable bacterial nanocompartment is reported, with the high-resolution structure allowing the visualization of key details and new proposed biological functions., Protein nanocompartments are widespread in bacteria and archaea, but their functions are not yet well understood. Here, the cryo-EM structure of a nanocompartment from the thermophilic bacterium Thermotoga maritima is reported at 2.0 Å resolution. The high resolution of this structure shows that interactions in the E-loop domain may be important for the thermostability of the nanocompartment assembly. Also, the channels at the fivefold axis, threefold axis and dimer interface are assessed for their ability to transport iron. Finally, an unexpected flavin ligand was identified on the exterior of the shell, indicating that this nanocompartment may also play a direct role in iron metabolism.

Acute attacks could occur during the convalescent phase of COVID-19 illness, more commonly in patients with a history of frequent attacks. However it is unclear whether the acute attacks during the convalescent phase are specifically triggered by COVID-19 or not.

eGFR from serum creatinine–based equations informs diagnosis and staging of CKD. The guideline-recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation includes age, sex, and race (Black versus non-Black) variables and increases the eGFR estimate by

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have a devastating effect on patients receiving hemodialysis. To what extent infection-induced antibody responses are maintained, or protective, is unknown. This study describes the evolution of antibodies against the SARS-CoV-2 spike protein in a cohort of 990 patients on hemodialysis. During the first wave of the pandemic, 26% of patients had developed antispike SARS-CoV-2 antibodies. Fewer PCR-confirmed second-wave infections were observed in patients with pre-existing antibodies (4.2%) than those without antibodies (11.4%). This study shows that SARS-CoV-2 antibodies in patients on hemodialysis are well maintained and associate with reduced risk of subsequent SARS-CoV-2 infection.

The interference of solute self-assembly caused by the interactions between pimelic acid and a series of homologous additives is closely related to the ability to induce the form II compound with similar packing but a different conformation to that of form I. The novel use of additives demonstrates the direct link between solute aggregation in solution and molecular conformation in crystals., Understanding the nucleation pathway and achieving regulation to produce the desired crystals are mutually beneficial. The authors previously proposed a nucleation pathway of conformational polymorphs in which solvation and solute self-assembly could affect the result of the conformational rearrangement and further nucleation outcomes. Based on this, herein α,ω-alkanedi­carb­oxy­lic acids (DAn, where n represents the number of carbon atoms in the molecule, n = 2–6, 8–11) were designed as homologous additives to interfere with the self-assembly of pimelic acid (DA7) to further induce the form II compound, which differs from form I only in conformation. Interestingly, longer-chain additives (DA6–11) have a stronger form II-inducing ability than short-chain ones (DA2–4). In addition, an apparent gradient of the degree of interference with solute self-assembly, consistent with form II-inducing ability, was detected by infrared and nuclear magnetic resonance spectroscopy. The calculated molecular electrostatic potential charges also clearly indicate that additive–solute electrostatic interactions gradually increase with increasing carbon chain length of the additives, reaching a maximum value with DA6–11. This novel use of additives demonstrates a direct link between solute aggregation and conformational polymorph nucleation.

The prevalence of IgE-mediated food allergy diagnosed by clinical history and positive serology in adults across Europe ranges from 0.3-6% (1). Almost half of the food allergic adults are confronted with accidental allergic reactions yearly (2). Especially moderate and severe reactions require medical consultation and treatment, which can have a high impact on economic costs (3).

openaire: EC/H2020/648925/EU//BHIVE Glucuronoxylans represent a significant fraction of woody biomass, and its decomposition is complicated by the presence of lignin–carbohydrate complexes (LCCs). Herein, LCCs from birchwood were used to investigate the potential coordinated action of a glucuronoyl esterase (TtCE15A) and two α-glucuronidases (SdeAgu115A and AxyAgu115A). When supplementing α-glucuronidase with equimolar quantities of TtCE15A, total MeGlcpA released after 72 h by SdeAgu115A and AxyAgu115A increased from 52% to 67%, and 61% to 95%, respectively. Based on the combined TtCE15A and AxyAgu115A activities, ~ 34% of MeGlcpA in the extracted birchwood glucuronoxylan was occupied as LCCs. Notably, insoluble LCC fractions reduced soluble α-glucuronidase concentrations by up to 70%, whereas reduction in soluble TtCE15A was less than 30%, indicating different tendencies to adsorb onto the LCC substrate.

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that are driven by impaired growth of denervated muscles. A rare form of NBPI, which maintains afferent muscle innervation despite motor denervation, does not cause contractures. As afferent innervation regulates various aspects of skeletal muscle homeostasis through NRG/ErbB signaling, our current study investigated the role of this pathway in modulating contracture development. Through pharmacologic modification with an ErbB antagonist and NRG1 isoforms, we discovered that NRG/ErbB signaling does not modulate the development of contractures in neonatal mice. Instead, ErbB inhibition impeded growth in nondenervated skeletal muscles, whereas increased ErbB activation exacerbated denervation-induced skeletal muscle atrophy. This potential regulatory effect of NRG/ErbB signaling on neonatal muscle growth warrants deeper investigation.

Despite development of multiple technologies, distinguishing benign from malignant lung nodules when they are still small in size is challenging. A high yield and minimally invasive bronchoscopic technology with low cost for diagnosis of small lung lesions is needed in pulmonary and lung cancer clinical practice. Peripheral airway bronchoscopy using thin and most recently ultrathin bronchoscopes improve visualization of small airways. The novel mobile 2D/3D C-Arm fluoroscopy system is a complementary tool along with radial endobronchial ultrasound in detecting small lung nodules with real-time high-quality multidimensional image confirmation during bronchoscopy. This combined technology can be easily acquired in any bronchoscopy room, and potentially affect lung nodule practice significantly.

The tobacco variant Nicotiana benthamiana has recently emerged as a versatile host for the manufacturing of protein therapeutics, but the fidelity of many recombinant proteins generated in this system is compromised by inadvertent proteolysis. Previous studies have revealed that the anti-HIV-1 antibodies 2F5 and PG9 as well as the protease inhibitor α1 -antitrypsin (A1AT) are particularly susceptible to N. benthamiana proteases. Here, we identify two subtilisin-like serine proteases (NbSBT1 and NbSBT2) whose combined action is sufficient to account for all major cleavage events observed upon expression of 2F5, PG9 and A1AT in N. benthamiana. We propose that downregulation of NbSBT1 and NbSBT2 activities could constitute a powerful means to optimize the performance of this promising platform for the production of biopharmaceuticals. DATABASES: NbSBT sequence data are available in the DDBJ/EMBL/GenBank databases under the accession numbers MN534996 to MN535005.

Respiratory disease, characterized by changes in the cells of the lung, can affect molecular phenotype of cells and the intercellular interactions, resulting in a disbalance in the relative proportions of individual cell types. Understanding these changes is essential to understand the pathophysiology of lung disease. Conventional 'bulk' RNA-sequencing (RNA-seq), analyzing the entire transcriptome of the tissue sample, provides information about average expression levels of each gene in the mixed cell population; whereas it does not consider the cellular heterogeneity in samples composed of more than one cell type 1 . Single-cell RNA-seq (scRNA-seq) assesses the transcriptome of a complex biological sample with single-cell resolution, allowing identification of the relative frequency of discrete cell-types and analysis of their transcriptomes 1 . Nevertheless, analyzing the transcriptomic signature in large numbers of patients by scRNA-Seq is currently limited by its high costs. Mast cells are key regulatory cells driving the inflammatory process in asthma2 . Since they can be quantified by immunohistochemical staining for validation purposes, we used mast cells as an example of a rare cell population to assess the validity of our deconvolution approach. Recently, a number of bulk RNA-seq deconvolution methods have become available 3 , for instance of two deconvolution methods, namely support vector regression (SVR) 4 , the machine-learning method implemented in CYBERSORT, and Non-Negative Least Square (NNLS) 5 , using a matrix of cell-type selective genes identified with AutoGeneSc 6 . Both approaches are designed to estimate relative proportion of the main, common cell types present in the sample. When we used these methods to estimate the number of mast cells, we found a poor correlation with the number of mast cells stained by immunohistochemistry in the biopsies, suggesting the CIBERSORT and NNLS are less reliable in the case of rare cell types. We explored the possibility to use scRNA-Seq data from small numbers of subjects to specifically interrogate the relative cell type frequency of a rare cell population in a bulk RNA-Seq dataset obtained from a large asthma cohort.

Barium titanate (BTO) is a ferroelectric perovskite with potential in energy storage applications. Previous research suggests that BTO dielectric constant increases as nanoparticle diameter decreases. This report recounts an investigation of this relationship. Injection-molded nanocomposites of 5 vol% BTO nanoparticles incorporated in a low-density polyethylene matrix were fabricated and measured. Finite-element analysis was used to model nanocomposites of all BTO sizes and the results were compared with experimental data. Both indicated a negligible relationship between BTO diameter and dielectric constant at 5 vol%. However, a path for fabricating and testing composites of 30 vol% and higher is presented here. Supplementary material The supplementary material for this article can be found at 10.1557/mrc.2020.69