bluuebunny/crossref_metadata_2025 huggingface dataset:
GAN‐segNet: A deep generative adversarial segmentation network for brain tumor semantic segmentation
Authors: Cui Shaoguo , Wei Mingjun , Liu Chang , Jiang Jingfeng
Published: November 2021

In this study, we present a novel automatic segmentation method using a neural network model named GAN‐segNet, which can not only identify brain tumors from MRI images but also accurately delineate intratumor regions. Since brain tumors with varying shapes and sizes can appear anywhere in the brain and image quality and contrast of MRI could be inadequate, automatic segmentation remains challenging despite its importance in the clinical workflow. The proposed GAN‐segNet is an innovative modification of the Generative Adversarial Network (GAN) and can efficiently and accurately segment brain tumors. One key innovation of our GAN model is an autoencoder learning representation of input data that were added to the generative network of the above‐mentioned GAN. By doing so, information extracted through convolution operations can be meaningfully regularized. As a result, the scales of extracted features can be controlled by the added autoencoder to preserve detail. Additionally, we propose an innovative loss function based on the concept of focal loss to effectively mitigate the impact of label imbalance. The above‐mentioned combination enables the proposed GAN‐segNet model to improve the segmentation of small intratumor region(s). We demonstrate the proposed method using MRI data available from a public database, that is, Brain Tumor Segmentation Challenge 2018 database (BRATS 2018). Using the proposed GAN‐segNet model, the average Dice scores were 0.8280, 0.9022, and 0.814 for segmenting enhancing tumor core, whole tumor, and tumor core, respectively. Furthermore, positive predictive values for segmenting enhanced tumor core, whole tumor, and tumor core were 0.8496, 0.9270, and 0.8610, respectively.
Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment
Authors: Xu Jianwen , Lin Rongfang , Chen Yong , You Xiang , Huang Pinfang , Lin Cuihong
Published: November 2021

The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment‐related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36‐fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration–time curve was predicted to increase 1.25‐fold, 1.95‐fold, and 2.82‐fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12‐hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin.
Phase duration and resurgence
Authors: Smith Sean W. , Greer Brian D.
Published: November 2021

Resurgence, the recurrence of responding due to a worsening of reinforcement conditions for current behavior, is a prevalent form of treatment relapse. Resurgence as Choice in Context predicts that increasing the duration of exposure to reinforcement for target responding during Phase 1 will increase resurgence magnitude, whereas increasing the duration of exposure to reinforcement for alternative responding and extinction for target responding during Phase 2 will decrease resurgence magnitude. We conducted an experiment evaluating these predictions with human participants recruited through Amazon's Mechanical Turk platform. We varied Phase 1 and Phase 2 durations across 4 experimental groups. Resurgence as Choice in Context successfully predicted the differences in resurgence magnitude across these groups, and fitting the quantitative model to the obtained data yielded an exceptional coefficient of determination. We discuss the implications of these results for using Resurgence as Choice in Context to inform experiments with human participants and the feasibility of using human‐operant preparations to evaluate resurgence.
A histological and immunohistochemical study on the parabronchial epithelium of the domestic fowl's (Gallus gallus domesticus) lung with special reference to its scanning and transmission electron microscopic characteristics
Authors: Kandyel Ramadan M. , El Basyouny Hebat Allah , El Nahas Eman E. , Madkour Fatma , Haddad Seham , Massoud Diaa , Morsy Kareem , Madkour Naglaa , Abumandour Mohamed
Published: November 2021

The current study was designed to give complete histo‐and immunohistochemical features of the parabronchial epithelium of domestic fowl's (Gallus gallus domesticus) lung with special reference to Scanning electron microscope (SEM) and mean transmission electron microscope (TEM) features. The lung exhibited variable‐sized atrial openings encircled by exchange tissue zones. The parabronchial atrial chambers appeared as ovoid and polygonal‐shaped that separated by the well‐developed interatrial septum. The deep atrial lumens had blood vessels pierced by openings that represent the infundibula. The parabronchial blood capillaries meshwork was branched and exhibited ovoid‐shaped air capillaries with numerous extravasated blood vessels. By TEM, there were several air capillaries and groups of squamous and endothelial respiratory cells and the squamous cells had oval nucleus with evenly distributed chromatin. The endothelial respiratory cells had few microvilli on their free surfaces. The parabronchial tubes opened into a group of widened atria that had smooth muscle bundles at the interatrial septa. The atrial chambers led to narrow infundibula. Moreover, the lining epithelium of parabronchi, atria, infundibula, and air capillaries was formed by simple squamous epithelium. Air capillary walls were lined by two types of respiratory cells (Types‐I and II). Collagen fibers were concentrated within the tunica externa layers of the parabronchial blood vessels as well as, they were observed in CT interparabronchial septa. Immunohistochemically, the elastin immunoreactivity was detected around the parabronchial blood vessels, at the base of each parabronchial atria, and in the area encircling the alveolar‐capillary walls. Our work concluded that there are a relation between the fowl's lifestyle and the surrounding environmental conditions.
Mixed Associations Between Grit and transformational Leadership Behavior
Authors: Caza Arran , Posner Barry Z.
Published: November 2021

The relationship between grit and transformational leadership behavior was investigated, using both self‐reported behavior and behavioral ratings by followers, peers, and managers. A multi‐source sample of surveys from leaders (6,654) and their associates (47,159) from thousands of organizations in 78 countries and 22 industries was analyzed using mixed‐effect multilevel models. Grit predicted both self‐reported and observer‐reported transformational leadership behavior. The relationships were complex, with each component of grit (i.e., perseverance and consistency) having statistically significant but different behavioral associations both within and between raters. The findings reveal the potential for grit to predict transformational leadership behavior, highlighting the theoretical and practical implications of the trait of grit when identifying, developing, and supporting leaders.
Tracing the Palaeolithic settlement patterns in the Western Tian Shan piedmont: an example of predictive GIS modelling use
Authors: Leloch Michał , Kot Małgorzata , Pavlenok Galina , Szymczak Karol , Khudjanazarov Mukhiddin , Pavlenok Konstantin
Published: November 2021

The Western Tian Shan piedmont, due to its high mountainous nature, is an exceptionally difficult area in which to conduct systematic surface research. In response to the specificities of the landscape, we decided to attempt to use predictive modelling to select sites with the greatest potential for the occurrence and preservation of Pleistocene layers and Palaeolithic sites. The aim of the project was to determine to what extent the high‐mountain areas of the Tian Shan piedmont were penetrated and inhabited by Palaeolithic humans. On the basis of the devised model, areas were selected for further prospecting in the field, which allowed the search area to be narrowed by a factor of five. In the course of surveying carried out on the selected areas, it was possible to locate nine new Palaeolithic sites and 18 settlement spots within one season, significantly increasing the number of known open‐air sites in the region. The results presented show the usefulness of this method, revealing the potential for its application in other similar areas, but also indicate the intensity of, in particular, Middle Palaeolithic or Middle/Upper Palaeolithic transitional settlement in the high‐mountain regions of Central Asia.
The Impact of Median Model for End‐Stage Liver Disease at Transplant Minus 3 National Policy on Waitlist Outcomes in Patients With and Without Hepatocellular Carcinoma
Authors: Bernards Sarah , Hirose Ryutaro , Yao Francis Y. , Jin Chengshi , Dodge Jennifer L. , Huang Chiung‐Yu , Mehta Neil
Published: November 2021

As a result of ongoing regional disparities, the United Network for Organ Sharing (UNOS) implemented policy in May 2019 limiting exception points for waitlisted patients with hepatocellular carcinoma (HCC) to median Model for End‐Stage Liver Disease at transplant in the area surrounding a transplant center minus 3 points (MMAT‐3). The impact of this policy change remains unknown. We included adult patients with HCC (n = 4567) and without HCC (n = 19,773) in the UNOS database added to the waiting list before this policy change (May 7, 2017‐May 18, 2019) and after (May 19, 2019‐March 7, 2020). Cumulative incidence analysis estimated the probability of dropout within 1 year of listing decreased from 12.9% before the policy to 11.1% after the policy in candidates without HCC and from 14% to 10.7% in candidates with HCC. Incidence rates of liver transplantation (LT) and waitlist dropout varied significantly before the policy in patients with HCC and without HCC but nearly equalized in the postpolicy era. These effects were observed in both shorter and longer wait regions. With policy change being modeled as a time‐dependent covariate, competing risk regression analyses estimated a decreased risk of dropout after policy change in the non‐HCC group (cause‐specific hazard ratio, 0.91; P = 0.02) after adjusting for demographic variables. These results suggest that the MMAT‐3 policy has successfully reduced disparities in access to LT including across UNOS wait regions, although certain patients with HCC are now disadvantaged.
A Guideline for the Synthesis of Amino‐Acid‐Functionalized Monomers and Their Polymerizations
Authors: Leiske Meike N. , Kempe Kristian
Published: November 2021

Amino acids have emerged as a sustainable source for the design of functional polymers. Besides their wide availability, especially their high degree of biocompatibility makes them appealing for a broad range of applications in the biomedical research field. In addition to these favorable characteristics, the versatility of reactive functional groups in amino acids (i.e., carboxylic acids, amines, thiols, and hydroxyl groups) makes them suitable starting materials for various polymerization approaches, which include step‐ and chain‐growth reactions. This review aims to provide an overview of strategies to incorporate amino acids into polymers. To this end, it focuses on the preparation of polymerizable monomers from amino acids, which yield main chain or side chain‐functionalized polymers. Furthermore, postpolymerization modification approaches for polymer side chain functionalization are discussed. Amino acids are presented as a versatile platform for the development of polymers with tailored properties.
Free vascularized second metatarsophalangeal joint transfer for scaphotrapezial joint reconstruction after distal scaphoid excision and carpal collapse: A case report
Authors: del Piñal Francisco , Cromheecke Michiel , Chaves Camilo
Published: November 2021

Treatment of the destroyed scaphotrapezial (ST) joint in young patients is challenging due to the limited available options as they might not tolerate the stiffness, loss of grip strength and long‐term complications of partial fusions, bone resections, and interposition implants or arthroplasties. This report presents the results of a free osteocutaneous joint transfer used to reconstruct the ST joint in a young patient suffering from ST destruction and carpal collapse. This 34‐year‐old patient was previously treated for a right scaphoid nonunion with distal scaphoid excision and interposition implant that evolved to destruction of the ST space, symptomatic carpal collapse associated and a ST height loss of 7 mm. The DASH score was 34 and the grip strength of 32 kg. The patient was treated with an osteocutaneous vascularized free transfer from the second metatarsophalangeal joint vascularized by the first dorsal metatarsal artery and anastomosed to the palmar carpal branch of the radial artery and a palmar superficial vein. After 3.5 months, the patient returned to full duty work as a mechanic. At the last follow‐up, 3 years after the surgery, the patients had complete range of motion without clinical nor radiological degenerative changes. There were no postoperative complications. The DASH score was 3 and the grip strength was 53 kg. This reconstructive procedure allows to recreate a functional ST joint and to correct a carpal collapse avoiding degenerative wrist changes. It may be proposed to young patients who aim to recover a near normal function of their wrist.
A nonlinear version of the distributed Halanay inequality and its application
Authors: Tatar Nasser‐eddine , Sakthivel Rathinasamy
Published: November 2021

In this paper, first we prove a nonlinear version of Halanay inequality with distributed delay. Then, we use it to establish a local exponential stability result for a problem appearing in neural networks theory under the name Hopfield neural network system. This is done for activation functions violating the usual standard condition of Lipschitz continuity. One of the activation functions may be non‐Lipschitz continuous. Finally, an example is provided to illustrate the developed theory.
Optimization ofvirtually aperiodiclinear sparse arrays
Authors: Aslan Yanki
Published: November 2021

Multi‐port multi‐mode antenna elements have the ability to move their phase centers and modify their radiation patterns electronically. Arrays composed of such elements are referred to as virtually aperiodic arrays in this paper. Herein, optimization of the mode excitation coefficients in virtually aperiodic sparse linear arrays is proposed, by introducing novel design constraints with the aim of synthesizing wide‐angle scanning, reconfigurable patterns, with grating/side lobe reduction. A dual‐mode patch antenna is used for demonstration purposes. An efficient convex optimization based algorithm is adopted to optimize the excitation weight at each element mode port, while considering the mutual coupling effects. Through full‐wave simulations, the effectiveness of the optimization in suppressing the unwanted radiation and adapting to different fields‐of‐view is shown. A novel investigation on the impacts of defining different mode excitation ratios on the radiation pattern characteristics is conducted.
Transcutaneous CO2 monitoring as indication for inpatient non‐invasive ventilation initiation in patients with amyotrophic lateral sclerosis
Authors: Quigg Kellen H. , Wilson Matthew W. , Choi Philip J.
Published: November 2021

Introduction/Aims

Amyotrophic lateral sclerosis (ALS) is characterized by profound muscle weakness, including diaphragmatic weakness resulting in hypercapnic respiratory failure. While non‐invasive ventilation (NIV) is usually initiated in the home, patients presenting with hypercapnic respiratory failure may be at high risk of adverse outcomes with delays in treatment. We aim to describe the clinical utility of transcutaneous CO2 (TCO2) to assess the need for inpatient initiation of NIV.

Methods

Eight patients from the University of Michigan Pranger ALS clinic were directly admitted to the hospital for urgent initiation of NIV between May 2020–May 2021. A retrospective review of electronic medical records, including pre‐hospital pulmonary function assessments, hospitalization blood gases, and NIV use metrics was performed.

Results

All eight patients had symptoms of respiratory insufficiency at time of admission, although not all patients had forced vital capacity (FVC) measurements that would identify need for NIV. All patients had measured TCO2 > 45 mmHg. Seven of eight patients had worsening hypercapnia after admission, indicating advanced respiratory failure. All patients were titrated to tolerance of continuous nocturnal NIV while in the hospital, with an average length of stay of 6.5 days (range, 3–8). All patients demonstrated compliance with NIV, >4 h, at post‐hospital follow‐up.

Discussion

Many current ambulatory measurements underestimate, or incompletely evaluate, respiratory dysfunction, and arterial blood gases are not typically readily available. Outpatient TCO2 measurements can serve as a useful screening tool to identify ALS patients who would benefit from inpatient initiation and titration of NIV.
Length scale control schemes for bi‐directional evolutionary structural optimization method
Authors: Qiu Wenke , Jin Shaomeng , Xia Liang , Shi Tielin
Published: November 2021

This work develops length scale control schemes for bi‐directional evolutionary structural optimization method, enabling an enhanced and flexible control of the method on structural member sizes. Specifically, the maximum length scale control is achieved by constraining local material volumes below a threshold value, which is determined upon the allowed maximum length. The massive per‐element volume constraints are aggregated by the p‐norm global measure. The aggregated volume constraint is augmented to the conventional compliance design objective through a Lagrange multiplier. On the other hand, the minimum length scale control is achieved by a post‐processing modification of local feature according to the skeleton detected from a preliminarily optimized topology. The sensitivity numbers of the local structural features that violate the minimum length scale constraint are compensated during the post‐processing modification. Both 2D and 3D benchmark design results show that the proposed schemes are effective and efficient in controlling both the maximum and minimum structural length scales.
Racialised representations of Black African poverty in INGO communications and implications for UK African diaspora: Reflections, lessons and recommendations
Authors: Ademolu Edward
Published: November 2021

While the role and implications of representations of global poverty and inequality in contemporary humanitarian and international development communications is well established in mainstream development studies. Less considered are the broader comprehensions around how racialised representations of Black African poverty in, for example, charity advertisements and attendant publicity materials uniquely affect UK‐situated African Diaspora communities, in ways that are complex and distinct from seemingly monoracial donor publics. Using interview and focus group evidence with UK Nigerian diaspora as a case study, this article engages in a reflective discussion on the multiple and differentiated ways that International Non‐Governmental Organisation (INGO) fundraising communications of Africa(ns) inform how, why and with what effects these Black racialised minorities adopt resistant and counterstereotypic identities. Taking lessons learned from these reflections, I suggest recommendations for how INGOs, specifically communication professionals, can adequately construe, negotiate and address perceived tensions around, and implications of, their visual communications for the UK African diaspora.
Thermal and mechanical properties of flax char/carbon fiber reinforced polyamide 66 hybrid composites
Authors: Biricik Gorkem Degirmen , Celebi Hande , Seyhan A. Tugrul , Ates Funda
Published: November 2021

In this study, flax fiber char (CH), a kind of biomass carbon material obtained by thermochemical conversion of flax fibers in a nitrogen environment in a fixed bed reactor, was used as a reinforcing constituent together with carbon fiber (CF) to produce polyamide 66 (PA66) hybrid composites. The potential use of biochar as a promising substitutional filler candidate for CF in composite applications was deemed in principle. Biochar and carbon fiber surfaces were treated with nitric acid followed by modification with a 3‐aminopropyltriethoxysilane coupling agent to improve their interfacial compatibility with PA66. The overall characterization of the composite materials was conducted by performing the thermal gravimetric analysis and differential scanning calorimetry measurements and tensile and water absorption tests. Scanning electron microscopy was further employed to examine the fracture surface of the specimens. The findings obtained revealed that silane ‐modified CF and CH altered composite material crystallization behavior, thus enhancing the ultimate composite tensile strength and Young's modulus. Moreover, the tailored interfacial interactions associated with enhanced thermal stability were determined to reduce water absorption capacity for composites with CH. In brief, CH may be substituted with CF, cost‐effectively, at a 50:50 w/w ratio of total reinforcement (10 wt%) in PA66 without compromising ultimate composite performance.
The indentation responses of composite Y‐type cores sandwich structure under various temperatures
Authors: Jiang Weimin , Zhu Xiaolan , Zhou Junmeng , Liu Jiayi , Liu Jingxi , Huang Wei
Published: November 2021

The influences of elevated and cryogenic temperature on the quasi‐static indentation responses and damage mechanism for composite Y‐type cores sandwich structure were studied by experiments in present paper. The quasi‐static indentation experiments were performed to explore the indentation performances for composite Y‐type cores sandwich structures under eight different temperature conditions. The influences of the testing environment temperature on the typical indentation force‐deformation curves, damage patterns and indentation failure load were investigated and analyzed. The experimental results demonstrated that the testing environment temperature made an important influence on the deformation mechanism, typical force‐deformation curves and failure load. Fiber fracture of the front panel was found when the testing environment temperature was below the glass transition temperature, while the fiber microbuckling of the front panel was also revealed when the testing environment temperature was above the glass transition temperature. The failure load increased with the decreasing of the testing environment temperature at cryogenic temperature. Nevertheless, at elevated temperature, the failure load decreased with the increasing of the testing environment temperature attributing to the weakening of the fiber‐matrix interface performances.
Microstructural analysis and multi‐response optimization of mechanical properties of bulk molding compound
Authors: Rajaee Pouya , Ashenai Ghasemi Faramarz , Fasihi Mohammad , Amini Nasrin
Published: November 2021

In this article, the mechanical properties of commercial bulk molding compounds (BMC) based on the unsaturated polyester resin were maximized by optimizing glass fiber weight (FW) and fiber length (FL). An empirical design was utilized to study the influence of each parameter and its interaction on responses. Accordingly, three levels of FW (10, 15, and 20 wt.%) and FL (3, 6, and 12 mm) were used. A full factorial design was utilized to investigate the effect of each variable and their interaction on all responses. The addition of FW improved all the results except flexibility. In addition, all responses increased except the modulus of composites by increasing FL. The compound with 15 wt.% FW and 12 mm FL was chosen as the best toughness‐stiffness‐strength equilibrium among the specimens based on optimization outcomes. In addition, the R2 obtained from the analysis of variance (ANOVA) and normal probability plots showed good compliance between the empirical results and those anticipated using a full factorial model.
Enhanced thermal and dielectric performance in ternary PVDF/PVP/Co3O4 nanocomposites
Authors: Taha Taha Abdel Mohaymen , Mahmoud Mohammed H , Hamdeh Hussein H
Published: November 2021

The main objective of this research was to prepare high thermal and dielectric performance PVDF/PVP/Co3O4 nanocomposites (PVDF, oply(vinylidene fluoride); PVP, polyvinylpyrrolidone) using the method of solution mixing. The structural properties and thermal stability of the samples were examined through measurements of XRD, SEM, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). From the XRD measurements, the cubic crystal structure of the Co3O4 nanoparticles was revealed with an average size of 17 nm. Also, diffraction peaks of the α‐phase were seen in PVDF/PVP/Co3O4 nanocomposite spectra. The SEM images for the surface of the films showed a homogeneous distribution of the nanoparticles. The absorption peaks of both α‐ and β‐phases were confirmed by measurements of the FTIR spectra. The nanocomposite films grafted with Co3O4 nanoparticles possess high thermal stability. The dielectric permittivity and energy density of the nanocomposites improved significantly at 4.0 wt% Co3O4. Finally, the increase in Co3O4 content caused an improvement in dielectric response function as well as electrical conductivity. © 2021 Society of Industrial Chemistry.
Lung ultrasound to detect cardiopulmonary interactions in acutely ill children
Authors: Buonsenso Danilo , De Rose Cristina , Ferro Valentina , Morello Rosa , Musolino Annamaria , Valentini Piero
Published: November 2021

Objective and design

Our prospective observational study is the first study that evaluates the lung ultrasound (LUS) findings of cardiopulmonary interactions in acutely ill children with elevated pro‐brain natriuretic peptide (BNP) levels, with the aim of establishing the specific LUS pattern in this category of patients without primary lung diseases.

Methodology

We prospectively analyzed epidemiological, clinical, laboratory, instrumental, and lung ultrasound parameters in acutely ill children aged 1 month to 18 years admitted to the Department of Pediatrics between March 2020 to August 2020. Among the acutely ill patients evaluated, only patients with pro‐BNP > 300 pg/ml and who underwent LUS before the start of any treatment were included. They were stratified into three subcategories based on the diagnosis (A) cardiac disease, (B) systemic inflammatory disease/sepsis without functional and/or organic alterations of the myocardium, and (C) systemic inflammatory disease/sepsis and cardiac disease, and were classified into two groups based on the level of pro‐BNP. We also enrolled patients belonging to two other categories (patients with primary infectious lung disease and completely healthy patients) analyzing their epidemiological, clinical, laboratory, instrumental parameters, and lung ultrasound findings and comparing them with those of acutely ill children.

Results and Conclusion

We found that LUS findings in these acutely ill children are different from the ultrasound pattern of other categories of children and in particular (1) children with acute lower respiratory tract infections and (2) healthy infants.

The finding in a child of a sonographic interstitial syndrome with multiple, bright, long, separate, and nonconfluent B‐lines/long vertical artifacts deriving from a normal and regular pleural line, in the absence of subpleural consolidations, is strongly predictive of cardiogenic pulmonary edema or pulmonary congestion in the course of systemic inflammatory disease/sepsis.
SAXSMoW 3.0: New advances in the determination of the molecular weight of proteins in dilute solutions from SAXS intensity data on a relative scale
Authors: de Oliveira Neto Mario , de Freitas Fernandes Adriano , Piiadov Vassili , Craievich Aldo Felix , de Araújo Evandro Ares , Polikarpov Igor
Published: November 2021

SAXSMoW (SAXS Molecular Weight) is an online platform widely used over the past few years for determination of molecular weights of proteins in dilute solutions. The scattering intensity retrieved from small‐angle X‐ray scattering (SAXS) raw data is the sole input to SAXSMoW for determination of molecular weights of proteins in liquid. The current updated SAXSMoW version 3.0 determines the linear dependence of the true protein volume on their apparent protein volume, based on SAXS curves calculated for 67,000 protein structures selected from the Protein Data Bank. SAXSMoW 3.0 was tested against 43 experimental SAXS scattering curves from proteins with known molecular weights. Our results demonstrate that most of the molecular weights determined for the nonglycosylated and also for the glycosylated proteins are in good agreement with their expected molecular weights. Additionally, the average discrepancies between the calculated molecular weights and their nominal values for glycosylated proteins are similar to those for nonglycosylated ones.
Robust response of pulmonary pleomorphic carcinoma to pembrolizumab and sequential radiotherapy: A case report
Authors: Kim Tae‐Hun , Park Sun Hyo , Hwang Ilseon , Lee Jin Hee , Kim Jin Hee , Kim Hae Won , Kim Hyun Jung
Published: November 2021

Pulmonary pleomorphic carcinoma (PPC) is a rare type of non‐small cell lung cancer (NSCLC) with a more aggressive clinical course and a worse outcome than other types of NSCLC. Pembrolizumab, a monoclonal antibody targeting programmed cell death‐1 (PD‐1), has been approved as the first‐line treatment for advanced NSCLC with robust PD‐L1 expression in at least 50% of tumour cells, without epidermal growth factor receptor gene (EGFR) mutations or anaplastic lymphoma kinase gene (ALK) rearrangement. Here, we report the case of an 81‐year‐old man with multiple comorbidities who was diagnosed with PPC and showed a robust response to pembrolizumab followed by radiation therapy without adverse effects. In the absence of randomized clinical trials for PPCs, our case report demonstrates the potential application of pembrolizumab and radiation therapy for the treatment of PPCs.
A curious case of asphyxiating thoracic dystrophy in an adult
Authors: Stranks Lachlan , Barry Simone , Yeo Aeneas
Published: November 2021

Asphyxiating thoracic dystrophy (ATD), also known as Jeune syndrome, is a rare autosomal recessive chondrodysplasia that most commonly manifests as shortening of long bones and ribs, as well as frequent extra‐skeletal organ involvement. It is typically diagnosed in infancy or early childhood following episodes of respiratory distress or failure, in conjunction with characteristic physical findings, and is often fatal. The genetic heterogeneity of this disease, however, means there is varying severity of symptoms and physical manifestations. In this report, we describe a 57‐year‐old man with his first presentation of respiratory failure, with a history and physical findings consistent with ATD, a diagnosis previously unknown to the patient.
Temperature‐Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma
Authors: Prawatborisut Mongkhol , Oberländer Jennifer , Jiang Shuai , Graf Robert , Avlasevich Yuri , Morsbach Svenja , Crespy Daniel , Mailänder Volker , Landfester Katharina
Published: November 2021

Apolipoproteins are an important class of proteins because they provide a so‐called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well‐defined poly(N‐isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label‐free quantitative liquid chromatography‐mass spectrometry that the nanoparticles are largely enriched with apolipoprotein J (clusterin) at 25 °C while they are enriched with apolipoprotein A1 and apolipoprotein E at 37 °C. The temperature‐dependent protein binding is found to significantly influence the uptake of the nanoparticles by RAW264.7 and HeLa cells. The findings imply that the functionalization of nanoparticles with temperature‐responsive materials is a suitable method for imparting stealth properties to nanocarriers for drug‐delivery.
Boosting Alkaline Hydrogen and Oxygen Evolution Kinetic Process of Tungsten Disulfide‐Based Heterostructures by Multi‐Site Engineering
Authors: Zeng Jinsong , Zhang Long , Zhou Qian , Liao Liling , Qi Ying , Zhou Haiqing , Li Dongyang , Cai Fengming , Wang Hui , Tang Dongsheng , Yu Fang
Published: November 2021

Alkaline water electrolysis is an advanced technology for scalable H2 production using surplus electricity from intermittent energy sources, but it remains challenging for non‐noble electrocatalysts to split water into hydrogen and oxygen efficiently, especially for tungsten disulfide (WS2)‐based catalysts. Density functional theory calculations in combination with experimental study are used to establish a multi‐site engineering strategy for developing robust WS2‐based hybrid electrocatalyst on mesoporous bimetallic nitride (Ni3FeN) nanoarrays for bifunctional water splitting. This ingenious design endows the catalyst with numerous edge sites chemically bonded with the conductive scaffold, which are favorable for water dissociation and hydrogen adsorption. Benefiting from the synergistic advantages, the N‐WS2/Ni3FeN hybrid exhibits exceptional bifunctional properties for hydrogen and oxygen evolution reactions (HER and OER) in base with excellent large‐current durability, requiring 84 mV to afford 10 mA cm−2 for HER, and 240 mV at 100 mA cm−2 for OER, respectively. Assembling the catalytic materials as both the anode and cathode to construct an electrolyzer, it is actualized very good activities for overall water splitting with only 1.5 V to deliver 10 mA cm−2, outperforming the IrO2(+)//Pt(−) coupled electrodes and many non‐noble bifunctional electrocatalysts thus far. This work provides a promising avenue for designing WS2‐based heterogeneous electrocatalysts for water electrolysis.
Beitrag zu Kranbahnkonsolen im Stahlhochbau – Ermüdungsnachweis für die Lasteinleitung in den Konsolensteg
Authors: Euler Mathias , Kuhlmann Ulrike , Steinmann Ralf
Published: November 2021

Kranbahnkonsolen stellen typische Unterstützungskonstruktionen von Kranbahnträgern im Stahlhochbau dar und fallen in den Anwendungsbereich der Bemessungsnorm DIN EN 1993‐6. Die Kranbahnkonsolen erfahren durch den Kranbetrieb zyklische Beanspruchungen und müssen daher ausreichenden Widerstand gegen Ermüdung aufweisen. In der Vergangenheit wurde in der Regel für die Konsolen kein Nachweis gegen Ermüdung geführt. Dieser Beitrag behandelt die Ermüdungsbeanspruchung von Kranbahnkonsolen durch den Kranbetrieb und beschreibt konstruktive Randbedingungen, bei deren Einhaltung kein besonderer Nachweis der Lasteinleitung in den Konsolensteg gegen Ermüdung erforderlich wird.
Sox2 Controls Neural Stem Cell Self-Renewal Through a Fos-Centered Gene Regulatory Network
Authors: Pagin Miriam , Pernebrink Mattias , Giubbolini Simone , Barone Cristiana , Sambruni Gaia , Zhu Yanfen , Chiara Matteo , Ottolenghi Sergio , Pavesi Giulio , Wei Chia-Lin , Cantù Claudio , Nicolis Silvia K.
Published: November 2021

The Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSCs). Its mechanism of action is still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, into Sox2-deleted NSC, genes whose expression is strongly downregulated following Sox2 loss (Fos, Jun, Egr2), individually or in combination. Fos alone rescued long-term proliferation, as shown by in vitro cell growth and clonal analysis. Furthermore, pharmacological inhibition by T-5224 of FOS/JUN AP1 complex binding to its targets decreased cell proliferation and expression of the putative target Suppressor of cytokine signaling 3 (Socs3). Additionally, Fos requirement for efficient long-term proliferation was demonstrated by the reduction of NSC clones capable of long-term expansion following CRISPR/Cas9-mediated Fos inactivation. Previous work showed that the Socs3 gene is strongly downregulated following Sox2 deletion, and its re-expression by lentiviral transduction rescues long-term NSC proliferation. Fos appears to be an upstream regulator of Socs3, possibly together with Jun and Egr2; indeed, Sox2 re-expression in Sox2-deleted NSC progressively activates both Fos and Socs3 expression; in turn, Fos transduction activates Socs3 expression. Based on available SOX2 ChIPseq and ChIA-PET data, we propose a model whereby Sox2 is a direct activator of both Socs3 and Fos, as well as possibly Jun and Egr2; furthermore, we provide direct evidence for FOS and JUN binding on Socs3 promoter, suggesting direct transcriptional regulation. These results provide the basis for developing a model of a network of interactions, regulating critical effectors of NSC proliferation and long-term maintenance.
Multifaceted Involvement of Microglia in Gray Matter Pathology in Multiple Sclerosis
Authors: Tsouki Foteini , Williams Anna
Published: November 2021

In the inflammatory demyelinating neurodegenerative disease multiple sclerosis (MS), there is increasing interest in gray matter pathology, as neuronal loss and cortical atrophy correlate with disability and disease progression, and MS therapeutics fail to significantly slow or stop neurodegeneration. Microglia, the central nervous system (CNS)-resident macrophages, are extensively involved in white matter MS pathology, but are also implicated in gray matter pathology, similar to other neurodegenerative diseases, for which there is synaptic, axonal, and neuronal degeneration. Microglia display regional heterogeneity within the CNS, which reflects their highly plastic nature and their ability to deliver context-dependent responses tailored to the demands of their microenvironment. Therefore, microglial roles in the MS gray matter in part reflect and in part diverge from those in the white matter. The present review summarizes current knowledge of microglial involvement in gray matter changes in MS, in demyelination, synaptic damage, and neurodegeneration, with evidence implicating microglia in pathology, neuroprotection, and repair. As our understanding of microglial physiology and pathophysiology increases, we describe how we are moving toward potential therapeutic applications in MS, harnessing microglia to protect and regenerate the CNS.
Engineered Human Cardiac Microtissues: The State-of-the-(He)art
Authors: Soon Kayla , Mourad Omar , Nunes Sara S.
Published: November 2021

Due to the integration of recent advances in stem cell biology, materials science, and engineering, the field of cardiac tissue engineering has been rapidly progressing toward developing more accurate functional 3D cardiac microtissues from human cell sources. These engineered tissues enable screening of cardiotoxic drugs, disease modeling (eg, by using cells from specific genetic backgrounds or modifying environmental conditions) and can serve as novel drug development platforms. This concise review presents the most recent advances and improvements in cardiac tissue formation, including cardiomyocyte maturation and disease modeling.
Bone Marrow-Derived Mesenchymal Stem Cells Improve Rat Islet Graft Revascularization by Upregulating ISL1
Authors: Wang Ying , Wang Jing-Wen , Li Yang , Tian Xiao-Hui , Feng Xin-Shun , Zhang Shu-Cong , Liu Pei-Jun , Xue Wu-Jun , Zheng Jin , Ding Xiao-Ming
Published: November 2021

Revascularization of the islet transplant is a crucial step that defines the success rate of patient recovery. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to promote revascularization; however, the underlying cellular mechanism remains unclear. Moreover, our liquid chromatography-tandem mass spectrometry results showed that BMSCs could promote the expression of insulin gene enhancer binding protein-1 (ISL1) in islets. ISL1 is involved in islets proliferation and plays a potential regulatory role in the revascularization of islets. This study identifies the ISL1 protein as a potential modulator in BMSCs-mediated revascularization of islet grafts. We demonstrated that the survival rate and insulin secretion of islets were increased in the presence of BMSCs, indicating that BMSCs promote islet revascularization in a coculture system and rat diabetes model. Interestingly, we also observed that the presence of BMSCs led to an increase in ISL1 and vascular endothelial growth factor A (VEGFA) expression in both islets and the INS-1 rat insulinoma cell line. In silico protein structure modeling indicated that ISL1 is a transcription factor that has four binding sites with VEGFA mRNA. Further results showed that overexpression of ISL1 increased both the abundance of VEGFA transcripts and protein accumulation, while inhibition of ISL1 decreased the abundance of VEGFA. Using a ChIP-qPCR assay, we demonstrated that direct molecular interactions between ISL1 and VEGFA occur in INS-1 cells. Together, these findings reveal that BMSCs promote the expression of ISL1 in islets and lead to an increase in VEGFA in islet grafts. Hence, ISL1 is a potential target to induce early revascularization in islet transplantation.
miR-351-3p Promotes Rat Amniotic Fluid-Derived Mesenchymal Stromal Cell Proliferation via Targeting the Coding Sequence of Abca4
Authors: Huang Jieting , Zhao Qi , Wei Xiaowei , Ma Wei , Luo Wenting , Gu Hui , Liu Dan , He Yiwen , Huang Tianchu , Liu Yusi , Wang Chenfei , Yuan Zhengwei
Published: November 2021

Amniotic fluid-derived mesenchymal stromal cells (AFMSCs) present different features, depending on the isolation timing and culture conditions. The lack of uniform experimental standards hinders the comparison of results from different studies on AFMSCs. Moreover, understanding the molecular mechanisms that underlie the features of AFMSCs isolated at different embryonic developmental stages might allow the obtention of more viable and highly proliferative AFMSCs through genetic modification. We isolated AFMSCs from pregnant rats at embryonic day (E)12, E15, E18, and E21 and compared their cell proliferation capacity and transcriptome. The cell counting kit-8 assay and RNA sequencing revealed that E12 and E15 AFMSCs showed different characteristics from E18 and E21 AFMSCs. Therefore, AFMSCs were divided into two groups: early (E12 and E15) and late (E18 and E21) pregnancy-stage groups. Next, we screened the gene/microRNA pair Abca4/miR-351-3p that was related to cell proliferation. Abca4 knockdown/overexpression suggested that this gene represses the proliferation of AFMSCs, which is a newly discovered function of this gene. Finally, dual luciferase reporter gene assays confirmed that miR-351-3p targeted the coding sequence of Abca4 and regulated AFMSC proliferation. miR-351-3p promotes AFMSC proliferation via targeting the coding sequence of Abca4. Our findings provide a molecular foundation for further research for obtaining AFMSCs with a higher proliferation capacity.
Directly Reprogrammed Huntington's Disease Neural Precursor Cells Generate Striatal Neurons Exhibiting Aggregates and Impaired Neuronal Maturation
Authors: Monk Ruth , Lee Kevin , Jones Kathryn S. , Connor Bronwen
Published: November 2021

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by the progressive loss of striatal medium spiny neurons. Using a highly efficient protocol for direct reprogramming of adult human fibroblasts with chemically modified mRNA, we report the first generation of HD induced neural precursor cells (iNPs) expressing striatal lineage markers that differentiated into DARPP32+ neurons from individuals with adult-onset HD (41-57 CAG). While no transcriptional differences between normal and HD reprogrammed neurons were detected by NanoString nCounter analysis, a subpopulation of HD reprogrammed neurons contained ubiquitinated polyglutamine aggregates. Importantly, reprogrammed HD neurons exhibited impaired neuronal maturation, displaying altered neurite morphology and more depolarized resting membrane potentials. Reduced BDNF protein expression in reprogrammed HD neurons correlated with increased CAG repeat lengths and earlier symptom onset. This model represents a platform for investigating impaired neuronal maturation and screening for neuronal maturation modifiers to treat HD.
Characterization in Mice of the Resident Mesenchymal Niche Maintaining At2 Stem Cell Proliferation in Homeostasis and Disease
Authors: Taghizadeh Sara , Heiner Monika , Vazquez-Armendariz Ana Ivonne , Wilhelm Jochen , Herold Susanne , Chen Chengshui , Zhang Jin San , Bellusci Saverio
Published: November 2021

Resident mesenchymal cells (rMCs defined as Cd31NegCd45NegEpcamNeg) control the proliferation and differentiation of alveolar epithelial type 2 (AT2) stem cells in vitro. The identity of these rMCs is still elusive. Among them, Axin2Pos mesenchymal alveolar niche cells (MANCs), which are expressing Fgf7, have been previously described. We propose that an additional population of rMCs, expressing Fgf10 (called rMC-Sca1PosFgf10Pos) are equally important to maintain AT2 stem cell proliferation. The alveolosphere model, based on the AT2-rMC co-culture in growth factor-reduced Matrigel, was used to test the efficiency of different rMC subpopulations isolated by FACS from adult murine lung to sustain the proliferation and differentiation of AT2 stem cells. We demonstrate that rMC-Sca1PosFgf10Pos cells are efficient to promote the proliferation and differentiation of AT2 stem cells. Co-staining of adult lung for Fgf10 mRNA and Sftpc protein respectively, indicate that 28% of Fgf10Pos cells are located close to AT2 cells. Co-ISH for Fgf7 and Fgf10 indicate that these two populations do not significantly overlap. Gene arrays comparing rMC-Sca1PosAxin2Pos and rMC-Sca1PosFgf10Pos support that these two cell subsets express differential markers. In addition, rMC function is decreased in obese ob/ob mutant compared to WT mice with a much stronger loss of function in males compared to females. In conclusion, rMC-Sca1PosFgf10Pos cells play important role in supporting AT2 stem cells proliferation and differentiation. This result sheds a new light on the subpopulations of rMCs contributing to the AT2 stem cell niche in homeostasis and in the context of pre-existing metabolic diseases.