Neuromuscular medicine is being revolutionized by new genetic and molecular therapies. The purpose of this Special Issue is to present an overview of these new therapies, to examine their cardiopulmonary effects, and to consider the future of neuromuscular cardiopulmonary care. The emphasis will be on Duchenne muscular dystrophy (DMD) and, to a lesser extent, spinal muscular atrophy (SMA), as these are the diseases with the most robust new drug development and related cardiopulmonary outcome data. This Special Issue contains articles on a number of relevant topics, including an overview of new genetic and molecular therapies for DMD, examining the currently available cardiopulmonary outcome data; and a critical examination of pulmonary outcome measures, assessing which outcomes should be used in treatment studies. We will provide an overview of cardiopulmonary phenotypic variability and discordance and their implications for assessing patient prognosis and response to therapies, and present a new perspective on neuromuscular-induced sleep-disordered breathing, viewed in the context of new and emerging therapies. Finally, we will consider which cardiac imaging modalities should be used as outcome measures in studies assessing DMD heart function, and take a look at novel therapeutic approaches to DMD heart disease, including management of rhythm disorders and heart failure, and the use of left ventricular assist devices.

Clinical ImageSimultaneous hot and cold thyroid nodules: Which is malignant?Yuki Otsuka, M.D.1, Yasuhiro Nakano, M.D.1, Daisuke Omura, M.D., Ph.D.1, Takayuki Iwamoto, M.D., Ph.D.2, Ruiko Hayashi, M.D.3 and Fumio Otsuka, M.D., Ph.D.11Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

In this study, effect of swirling addition on the liquid mixing behavior of multi-orifice-impinging transverse jet mixer has been investigated by planar laser induced fluorescence as well as large eddy simulation (LES). In the case of swirling addition into the jet flow, there exists an optimized swirling jet angle or optimized jet-to-cross velocity ratio for the fixed mixer configuration. A larger swirling jet angle will make the flow dominated by the swirling, resulting in a slower mixing process. Interaction of swirling crossflow with no-swirling injected streams, or with swirling injected streams in the opposite direction is beneficial for the mixing. LES predictions show that many small vortices are produced homogenously due to intensified impingement in the case of opposite swirling directions, leading to a relative fast mixing process in several milliseconds. Whereas the mixing is restrained when the swirling directions of two flows are the same.

In this era of evidence-based practice, scholarly work such as peer-reviewed scientific publications play a vital role in policy and decision-making at an individual, organization, and country-level. Alongside being considered an essential means of communicating scholarly work, scientific publications also investigate the specific domains that lack well-established literature and thereby inform scientists and researchers to thrive for the betterment of the publics' well-being. Thus, the main purpose of articulating the scientific, scholarly work should be to make it understandable and accessible to everyone, including the lay audience. However, oftentimes, researchers overlook the lay summaries while publishing the research findings.

A benchmark of anisotropic polarizabilities has been carried out for 14 (hetero)-aromatic molecules using the methods: RPA, RPA(D), HRPA, HRPA(D), SOPPA, SOPPA(CC2), SOPPA(CCSD), CC2, CCSD and CC3. While this benchmark, to a large extend, shows similar tendencies as found for isotropic polarizabilities, it also reveals some differences between isotropic and anisotropic polarizabilities. CCSD is found to be the method performing closest to CC3 as it also was for isotropic polarizabilities. For static anisotropic polarizabilities SOPPA(CCSD) performs incredibly close to CCSD, however, the less demanding HRPA(D) follows shortly after in precision. For dynamic anisotropic polarizabilities SOPPA(CCSD) is again the method least deviating from CC3, beside CCSD, but its standard deviation is worse than for RPA, which gives results only slightly more deviating from the CC3 results than SOPPA(CCSD). While the HRPA model is seen to perform incomparably worse than any of the other methods, the simpler RPA is on the other hand thus performing notably well. The finding of this good performance of the relatively simpler and cheaper methods, RPA and HRPA(D), permits calculation of much larger systems without sacrificing the quality of the calculation.

This article describes how a step-stress accelerated life test (SSALT) can be designed for testing the fatigue life and reliability of structural components with a single failure mode. With simple numerical simulations of the crack’s propagation in the notched area of the structural part for different loading levels, the slope of the S-N curve for a structural component is initially estimated. Then, a very few fatigue-life experiments are carried out in the high-cycle domain to determine the intercept of the structure’s S-N curve. By considering the scatter from the material’s P-S-N curve, different SSALT designs for the structural component can be composed and checked for their expected acceleration factor. The procedure is experimentally validated for the case of a notched specimen and two different SSALT designs. From the results it can be concluded that the predicted durations of the SSALT experiments correlate well with the real experiments.

Hematologic malignancies are becoming more prevalent, manifesting in various clinical scenarios. Chronic myelogenous leukemia (CML) is usually diagnosed on routine complete blood count as it is typically asymptomatic. However, it can cause multiple signs and symptoms. We present a patient with appendicitis revealing CML during his workup for abdominal pain.

Abstract Background/aim: Two-dimensional speckle-tracking echocardiography (2D-STE) is a novel method that allows the assessment of regional myocardial function. The aim of our study was to use 2D-STE to assess left ventricular deformation in patients with coarctation of the aorta (CoA). Methods: In this prospective study, patients with CoA (n = 42) and healthy controls (n = 39) were recruited. Children with CoA who visited the outpatient clinic between 2013 and 2014 were included. The data were compared with those obtained from the sex- and age-matched controls. Results: The mean age of the patients was 5.8 ± 4.5 years. Global longitidinal strain based on all three apical views and total global strain values did not appear to be different between the patient and the control group (p = 0.59, p = 0.51, p = 0.15, p = 0.38). Hypertension was detected in 14 (33.3%) patients with CoA. There were significant differences between the global longitudinal strain values of the normotensive CoA subgroup and the hypertensive CoA subgroup (p < .05). Conclusions: In our study, we found that 2D-STE total strain analysis of patients with CoA was not different from comparative healthy controls. However, we determined that 2D-STE parameters were lower in the hypertensive CoA subgroup compared to the normotensive CoA subgroup.

Background Normal values (>80%) of Forced Expiratory Volume in one second (FEV1) in patients with Cystic fibrosis (CF) may lead to the interpretation that there is no lung disease. This study is a comprehensive analysis of lung involvement in CF patients having normal FEV1. Methods Patients were recruited from two CF Centers: Hadassah Medical Center, Jerusalem and Vall d’ Hebron Hospital, Barcelona. Lung disease was assessed by lung clearance index (LCI), chest CT-Brody Score, respiratory cultures, number of pulmonary exacerbations (PEx) and days of antibiotic treatment in the year prior to the assessment. Results Of the 247 patients, 89 (36%) had FEV1 ≥80% and were included in the study (mean age 17.6 range 4.25-49 years). Chronic P. aeruginosa infection was found in 21%, and 31% had at least one major PEx in the year prior to the study. Abnormally elevated LCI was found in 86% of patients, ranging between 7.52-18.97, and total Brody score (TBS) was abnormal in 92% (range 5.0-96.5). Patients with chronic P. aeruginosa had significantly higher LCI (p=0.01) and TBS (p=0.01) which were associated with more major PEx (p = 0.04 and p<0.001, respectively) and more days of intravenous (IV) antibiotic treatment in the preceding year (p=0.03 and p=0.002, respectively). Conclusions Most CF patients with normal FEV1 have already physiological and structural lung abnormalities which were associated with more PEx and IV antibiotic treatment.

Soil freeze-thaw events have important implications for water resources, flood risk, land productivity, and climate change. A property of these phenomena is the relationship between unfrozen water content and sub-freezing temperature, known as the soil freezing characteristic curve (SFC). It is documented that this relationship exhibits hysteretic behaviour when frozen soil thaws, leading to the definition of the soil thawing characteristic curve (STC). Although explanations have been given for SFC/STC hysteresis, the effect that “scale”—particularly “measurement scale”—may have on these curves has received little attention. The most commonly used measurement scale metric is the “grain” or “support,” which is the spatial (or temporal) unit within which the measured variable is integrated—in this case, the soil volume sampled. We show (1) measurement support can influence the range and shape of the SFC and (2) hysteresis can be, at least partially, attributed to the support and location of the measurements comprising the SFC/STC. We simulated lab measured temperature, volumetric water content (VWC), and permittivity from soil samples undergoing freeze-thaw transitions using Hydrus-1D and a modified Dobson permittivity model. To assess the effect of measurement support and location on SFC/STC, we masked the simulated temperature and VWC/permittivity extent to match the instrument’s grain and location. By creating a detailed simulation of the intra- and inter-grain variability associated with the penetration of a freezing front, we demonstrate how measurement support and location can influence the temperature range over which water freezing events are captured. We show it is possible to simulate hysteresis in homogenous media with purely geometric considerations, suggesting that SFC/STC hysteresis may be more of an apparent phenomenon than mechanistically real. Lastly, we develop an understanding of how the location and support of soil temperature and VWC/permittivity measurements influence the temperature range over which water freezing events are captured.

­­Editorial: Natural Sciences is debuting“There’s a way to do it better – find it.” –Thomas A. EdisonWelcome to Wiley’s new flagship journal, Natural Sciences. Our aim is to meet the challenge of publishing top-tier papers in an open-science environment and thereby contribute to innovating the ways scientists communicate with one another and with society at large. We encourage you to partake in this transformative endeavor.Natural Sciences is an inter- and multidisciplinary journal that publishes outstanding research from the global community spanning biology, chemistry, and physics and their interfaces, as well as seminal works from related fields such as engineering and biomedical research. The journal’s aspiration is to promote the sharing and hybridization of disciplinary perspectives and thereby to foster crossing of the traditional boundaries that have previously separated disciplines. The journal will feature Research Articles of all lengths and formats, Commentaries, and Reviews, as well as Editorials, Highlights, Book Reviews, and News items.In contrast to many other high-ranking “elite” journals, Natural Sciences is run by practicing academic scientists who will treat submitted papers just like they wish their own papers would be treated – fairly, quickly, and without bias. That’s why our tagline readsA Journal of, by, and for scientists .By embracing open science, Natural Sciences will promote the global scientific community’s shared goal of enriching society with freely accessible prime scientific research. With open-science in general and open-access publishing in particular, the cost of scientific publishing will be carried by funding agencies or research institutions, and not the reader. Subscription-model-based academic publishing will be relegated to the sidelines, and scientific publications made freely accessible and re-usable for all.Moreover, Natural Sciences supports the cultural changes in the research community that call for increased transparency and openness in communicating and sharing the results of scientific research. Open science encompasses not only open-access publishing but also open peer review and sharing of primary scientific data. These, along with reviewer recognition, are key innovations effecting such a transformation and will be espoused by Natural Sciences .In developing the concept of Natural Sciences , we worked closely with Wiley to ensure efficient editorial practices. Wiley’s international network of experienced professionals steeped in scientific publishing are there for us 24/7. Together, we are committed to open-science publishing that is timely and rigorous – and to embracing open-science innovations in the process.The ideas and values that led us to envision Natural Sciences are summarized in our Manifesto [link to https://onlinelibrary.wiley.com/page/journal/26986248/homepage/manifesto].Natural Sciences is now open for submissions [link to https://mc.manuscriptcentral.com/naturalsciences]. The Article Processing Charge (APC) will be waived during the first two years.Looking forward to your submissions,Bretislav Friedrich, Executive EditorMarianne Bronner, Chief Biology EditorVivian Yam, Chief Chemistry EditorGerard Meijer, Chief Physics Editor [link all the names to https://onlinelibrary.wiley.com/page/journal/26986248/homepage/editorial-board]

On magnetic resonance imaging (MRI), a butterfly lesion is most commonly described in Glioblastoma Multiforme (GBM), however we report an unusual case of Cryptococcus Meningoencephalitis with the butterfly lesion on MRI. This infection is generally diagnosed via lumbar puncture, however MRI may reveal perivascular space involvement, dilation and leptomeningeal enhancement.

All people including those with Haemoglobinopathies are at risk of COVID-19 infection. Though those patients were considered vulnerable, a clear prognosis, as well as the possibility of reinfection, was not mentioned before. We report here the first case of Thalassemia beta major who had COVID-19 reinfection detected by screening.

We experienced a successful case of cardiopulmonary arrest due to left ventricular free wall rupture treated with venoarterial extracorporeal membrane oxygenation and immediate induction of targeted temperature management.

An 18-year-old female presented with hypopigmentation, ulcerative skin changes and masses of both breasts for over a year. She was referred to the Uganda Cancer Institute (UCI) with suspected inflammatory breast cancer. Radiological findings and trucut biopsy were consistent with secondary CD3+ CD20- T-cell NHL of both breasts.

This report supports the feasibility of surgical pulmonary thromboendarterectomy in thalassemic patients with chronic thromboembolic pulmonary hypertension, and highlights the need for a comprehensive evaluation for both the presence and cause of pulmonary arterial hypertension prior to determining the likelihood of surgical cure.

The purpose of this study is to investigate the outcomes of an alternative method for large defects reconstruction after mastectomy by applying negative pressure wound therapy onto the grafts.

Nodular pulmonary amyloidosis is a rare and localized manifestation of amyloid deposition in the lungs. This rare entity, though asymptomatic, is often misdiagnosed on imaging alone, due to its resemblance to metastatic pulmonary nodules. This report highlights the significance of histologic confirmation before treatment, as a preventive measure against overtreatment.