bluuebunny/crossref_metadata_2025 huggingface dataset:
Vorinostat in the acute neuroinflammatory form of X‐linked adrenoleukodystrophy
Authors: Zierfuss Bettina , Weinhofer Isabelle , Kühl Jörn‐Sven , Köhler Wolfgang , Bley Annette , Zauner Katharina , Binder Johannes , Martinović Ksenija , Seiser Christian , Hertzberg Christoph , Kemp Stephan , Egger Gerda , Leitner Gerda , Bauer Jan , Wiesinger Christoph , Kunze Markus , Forss‐Petter Sonja , Berger Johannes
Published: May 2020

Objective

To identify a pharmacological compound targeting macrophages, the most affected immune cells in inflammatory X‐linked adrenoleukodystrophy (cerebral X‐ALD) caused by ABCD1 mutations and involved in the success of hematopoietic stem cell transplantation and gene therapy.

Methods

A comparative database analysis elucidated the epigenetic repressing mechanism of the related ABCD2 gene in macrophages and identified the histone deacetylase (HDAC) inhibitor Vorinostat as a compound to induce ABCD2 in these cells to compensate for ABCD1 deficiency. In these cells, we investigated ABCD2 and pro‐inflammatory gene expression, restoration of defective peroxisomal β‐oxidation activity, accumulation of very long‐chain fatty acids (VLCFAs) and their differentiation status. We investigated ABCD2 and pro‐inflammatory gene expression, restoration of defective peroxisomal ß‐oxidation activity, accumulation of very long‐chain fatty acids (VLCFA) and differentiation status. Three advanced cerebral X‐ALD patients received Vorinostat and CSF and MRI diagnostics was carried out in one patient after 80 days of treatment.

Results

Vorinostat improved the metabolic defects in X‐ALD macrophages by stimulating ABCD2 expression, peroxisomal ß‐oxidation, and ameliorating VLCFA accumulation. Vorinostat interfered with pro‐inflammatory skewing of X‐ALD macrophages by correcting IL12B expression and further reducing monocyte differentiation. Vorinostat normalized the albumin and immunoglobulin CSF‐serum ratios, but not gadolinium enhancement upon 80 days of treatment.

Interpretation

The beneficial effects of HDAC inhibitors on macrophages in X‐ALD and the improvement of the blood‐CSF/blood‐brain barrier are encouraging for future investigations. In contrast with Vorinostat, less toxic macrophage‐specific HDAC inhibitors might improve also the clinical state of X‐ALD patients with advanced inflammatory demyelination.
A novel patient with White–Sutton syndrome refines the mutational and clinical repertoire of the POGZ‐related phenotype and suggests further observations
Authors: Pascolini Giulia , Agolini Emanuele , Fleischer Nicole , Gulotta Elisa , Cesario Claudia , D'Elia Gemma , Novelli Antonio , Majore Silvia , Grammatico Paola
Published: May 2020

A rare developmental delay (DD)/intellectual disability (ID) syndrome with craniofacial dysmorphisms and autistic features, termed White–Sutton syndrome (WHSUS, MIM#614787), has been recently described, identifying truncating mutations in the chromatin regulator POGZ (KIAA0461, MIM#614787). We describe a further WHSUS patient harboring a novel nonsense de novo POGZ variant, which afflicts a protein domain with transposase activity less frequently impacted by mutational events (DDE domain). This patient displays additional physical and behavioral features, these latter mimicking Smith–Magenis syndrome (SMS, MIM#182290). Considering sleep–wake cycle anomalies and abnormal behavior manifested by this boy, we reinforced the clinical resemblance between WHSUS and SMS, being both chromatinopathies. In addition, using the DeepGestalt technology, we identified a different facial overlap between WHSUS patients with mutations in the DDE domain (Group 1) and individuals harboring variants in other protein domains/regions (Group 2). This report further delineates the clinical and molecular repertoire of the POGZ‐related phenotype, adding a novel patient with uncommon clinical and behavioral features and provides the first computer‐aided facial study of WHSUS patients.
Association between glioblastoma cell‐derived vessels and poor prognosis of the patients
Authors: Mei Xin , Chen Yin‐Sheng , Zhang Qing‐Ping , Chen Fu‐Rong , Xi Shao‐Yan , Long Ya‐Kang , Zhang Ji , Cai Hai‐Ping , Ke Chao , Wang Jing , Chen Zhong‐Ping
Published: May 2020

Background

Vessels with different microcirculation patterns are required for glioblastoma (GBM) growth. However, details of the microcirculation patterns in GBM remain unclear. Here, we examined the microcirculation patterns of GBM and analyzed their roles in patient prognosis together with two well‐known GMB prognosis factors (O6‐methylguanine DNA methyltransferase [MGMT] promoter methylation status and isocitrate dehydrogenase [IDH] mutations).

Methods

Eighty GBM clinical specimens were collected from patients diagnosed between January 2000 and December 2012. The microcirculation patterns, including endothelium‐dependent vessels (EDVs), extracellular matrix‐dependent vessels (ECMDVs), GBM cell‐derived vessels (GDVs), and mosaic vessels (MVs), were evaluated by immunohistochemistry (IHC) and immunofluorescence (IF) staining in both GBM clinical specimens and xenograft tissues. Vascular density assessments and three‐dimensional reconstruction were performed. MGMT promoter methylation status was determined by methylation‐specific PCR, and IDH1/2 mutations were detected by Sanger sequencing. The relationship between the microcirculation patterns and patient prognosis was analyzed by Kaplan‐Meier method.

Results

All 4 microcirculation patterns were observed in both GBM clinical specimens and xenograft tissues. EDVs were detected in all tissue samples, while the other three patterns were observed in a small number of tissue samples (ECMDVs in 27.5%, GDVs in 43.8%, and MVs in 52.5% tissue samples). GDV‐positive patients had a median survival of 9.56 months versus 13.60 months for GDV‐negative patients (P = 0.015). In MGMT promoter‐methylated cohort, GDV‐positive patients had a median survival of 6.76 months versus 14.23 months for GDV‐negative patients (P = 0.022).

Conclusion

GDVs might be a negative predictor for the survival of GBM patients, even in those with MGMT promoter methylation.
Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase
Authors: Shivakumaraswamy Santosh , Pandey Nivedita , Ballut Lionel , Violot Sébastien , Aghajari Nushin , Balaram Hemalatha
Published: May 2020

GMP synthetase catalyses the conversion of XMP to GMP through a series of reactions that include hydrolysis of Gln to generate ammonia in the glutamine amidotransferase (GATase) domain, activation of XMP to adenyl‐XMP intermediate in the ATP pyrophosphatase (ATPPase) domain and reaction of ammonia with the intermediate to generate GMP. The functioning of GMP synthetases entails bidirectional domain crosstalk, which leads to allosteric activation of the GATase domain, synchronization of catalytic events and tunnelling of ammonia. Herein, we have taken recourse to the analysis of structures of GMP synthetases, site‐directed mutagenesis and steady‐state and transient kinetics on the Plasmodium falciparum enzyme to decipher the molecular basis of catalysis in the ATPPase domain and domain crosstalk. Our results suggest an arrangement at the interdomain interface, of helices with residues that play roles in ATPPase catalysis as well as domain crosstalk enabling the coupling of ATPPase catalysis with GATase activation. Overall, the study enhances our understanding of GMP synthetases, which are drug targets in many infectious pathogens.
A Step toward Molecular Evolution of RNA: Ribose Binds to Prebiotic Fatty Acid Membranes, and Nucleosides Bind Better than Individual Bases Do
Authors: Xue Mengjun , Black Roy A. , Cornell Caitlin E. , Drobny Gary P. , Keller Sarah L.
Published: May 2020

A major challenge in understanding how biological cells arose on the early Earth is explaining how RNA and membranes originally colocalized. We propose that the building blocks of RNA (nucleobases and ribose) bound to self‐assembled prebiotic membranes. We have previously demonstrated that the bases bind to membranes composed of a prebiotic fatty acid, but evidence for the binding of sugars has remained a technical challenge. Here, we used pulsed‐field gradient NMR spectroscopy to demonstrate that ribose and other sugars bind to membranes of decanoic acid. Moreover, the binding of some bases is strongly enhanced when they are linked to ribose to form a nucleoside or – with the addition of phosphate – a nucleotide. This enhanced binding could have played a role in the molecular evolution leading to the production of RNA.
A Multilevel investigation into the effect of cultural distance on bilateral trade: The roles of product type and uncertainty avoidance
Authors: Wang Ying , Yang Zhiyong , Yasar Mahmut
Published: May 2020

Previous research shows mixed findings about how cultural distance may affect bilateral trade. To reconcile the mixed findings, we examine how key moderators at both the country‐pair level (product type) and the country level (uncertainty avoidance) affect the magnitude of the effect of cultural distance on bilateral trade. Using trade data on electronic products from 90 nations during 2008–2 014, we show that cultural distance in general has a negative impact on bilateral trade. However, the effect is more pronounced when the trade is on experience (versus search) products, or if the importing country is low (versus high) in uncertainty avoidance. Apart from its moderating effect, experience (versus search) product also has a negative main effect on bilateral trade, but its impact is stronger for countries low (versus high) in uncertainty avoidance.
Copper‐Catalyzed Carbocyclization of Silyl Enol Ether Tethered Ynamides for Efficient and Practical Synthesis of 2‐Azabicyclo[3.2.0] Compounds†
Authors: Huang En‐He , Zhang Zhi‐Xin , Ye Si‐Han , Chen Yang‐Bo , Luo Wen‐Feng , Qian Peng‐Cheng , Ye Long‐Wu
Published: May 2020

Summary of main observation and conclusion

An efficient copper‐catalyzed carbocyclization of silyl enol ether tethered ynamides has been developed, allowing rapid and practical construction of diverse 2‐azabicyclo[3.2.0] compounds in generally good to excellent yields with broad substrate scope under mild reaction conditions. Importantly, this protocol not only constitutes a rare example of non‐noble metal‐catalyzed alkyne carbocyclization, but also represents a rare cyclization on the β‐position of π‐tethered ynamides. The possibility of asymmetric carbocyclization via kinetic resolution also emerges.
On water‐use efficiency, boundary functions, and yield gaps: French and Schultz insight and legacy
Authors: Sadras Victor O.
Published: May 2020

This article is part of a series of brief commentaries to highlight papers that have resulted in important and distinctly new perspectives in crop science. Here, we outline a series of two papers by French and Schultz (F&S) on water use efficiency of wheat (Triticum aestivum L.) published in 1984. The insight of F&S was not to draw a regression line across their yield‐evapotranspiration data. Instead they saw an upper limit of 20 kg ha−1 mm−1 that, less than a decade after publication, was widely used by Australian farmers to benchmark their crops and identify causes of yield gaps. Over the last two decades, F&S‐type benchmarks have been expanded beyond wheat and beyond Australia to include sunflower (Helianthus annuus L.) in Argentina, maize (Zea mays L.) and wheat in the United States and China, and millet [Pennisetum glaucum (L.) R. Br.] in West Africa, among others. More recently, the concept of yield gap analysis based on a upper limit of yield per unit resource uptake has been successfully extrapolated to N. The N uptake per millimeter of water required to meet the water‐limited yield potential (0.65 kg N ha−1 mm−1 under their original conditions) is a hidden insight in the work of French and Schultz; it has been recently rediscovered in the context of crop improvement, co‐limitation theory, and drought‐induced N deficit. Perhaps more deeply, French and Schultz shifted farmers mindset from the mildly fatalistic idea of “drought” to the notion that many other factors were typically limiting crop yield, and the quantitative challenge of attaining a plausible benchmark.
Severe and enduring anorexia nervosa: Update and observations about the current clinical reality
Authors: Wonderlich Stephen A. , Bulik Cynthia M. , Schmidt Ulrike , Steiger Howard , Hoek Hans W.
Published: May 2020

Several objectives underlie the current article. First, to review historical diagnostic issues and clinical strategies for treating SE‐AN. Second, to provide an overview of recent evidence informed strategies and clinical innovations for the treatment of SE‐AN. Third, based on the authors' collective clinical and research experience, we offer eight observations that we believe capture the current clinical experience of patients with SE‐AN. Some of these observations represent empirically testable hypotheses, but all are designed to generate a meaningful discussion about the treatment of this group of individuals with eating disorders. Finally, we hope to call clinicians, scientists, professional organizations, advocates, and policy makers to action to attend to critical issues related to the care of individuals with SE‐AN. We believe that an international discussion could clarify areas of need for these patients and identify opportunities for clinical innovation that would enhance the lives of individuals with SE‐AN and their families.
Echocardiographic analysis of acute effects of percutaneous mitral annuloplasty on severity of secondary mitral regurgitation
Authors: Stöbe Stephan , Kreyer Kristin , Jurisch Daniel , Pfeiffer Dietrich , Lavall Daniel , Farese Gerardo , Laufs Ulrich , Hagendorff Andreas
Published: May 2020

Aims

Percutaneous mitral annuloplasty (PMA) represents a new treatment option for secondary mitral regurgitation (SMR) being associated with higher morbidity and mortality. The present study was aimed to evaluate whether or not acute effects on SMR severity can quantitatively be assessed after PMA.

Methods and results

PMA was performed in 30 patients (mean age 76 ± 9; 37% males) with moderate (n = 14) or severe (n = 16) SMR. Vena contracta (VC), left ventricular (LV) velocity‐time‐integral ratio (VTIMV/LVOT), effective regurgitant orifice area (EROA) by two‐dimensional proximal isovelocity surface area (PISA), regurgitant volume (RVolPISA) and regurgitant fraction (RFPISA) by PISA, RVolvolume and RFvolume by LV volume analyses, and parameters describing LV morphology, function, and cardiac performance were assessed by transthoracic echocardiography prior to and after PMA. According to RFPISA/RFvolume, 14 patients showed mild, 15 moderate, and 1 severe SMR after PMA. Mean RF, RVol, EROA, VC, and VTIMV/LVOT were lower directly after PMA (RFPISA: 49% ± 11 vs. 34% ± 13, P < 0.001; RFvolume: 46% ± 10 vs. 34% ± 13, P < 0.001; RVolPISA: 33 mL ± 13 vs. 25 mL ± 12, P < 0.001; RVolvolume: 28 mL ± 17 vs. 20 mL ± 14, P < 0.05; EROAPISA: 0.24 cm2 ± 0.1 vs. 0.19 cm2 ± 0.1, P < 0.05; VC: 5.2 ± 0.1 vs. 4.1 ± 0.2, P < 0.001; VTIMV/LVOT: 1.9 ± 0.4 vs. 1.6 ± 0.5, P < 0.05). Parameters of LV morphology, function, and cardiac performance did not change directly after PMA.

Conclusions

PMA leads to a reduction of MR severity in >80% of SMR patients. Acute effects of PMA can quantitatively be assessed by transthoracic echocardiography.
Structural Versatility and Supramolecular Isomerism in Redox‐Active Tetra‐ and Hexaruthenium Macrocycles
Authors: Fink Daniel , Orth Nicole , Linseis Michael , Ivanović‐Burmazović Ivana , Winter Rainer F.
Published: May 2020

We report on six macrocyclic tetra‐ and hexaruthenium complexes formed by the self‐assembly of 2,5‐divinylthiophene‐ or 2,5‐divinylfuran‐bridged diruthenium and 2,5‐thiophene‐, ‐furan‐ or ‐pyrroledicarboxylate linkers. All complexes were scrutinized by NMR spectroscopy and UHR ESI‐MS, cyclic and square wave voltammetry and, in five cases, by X‐ray diffraction analyses. Although the utilized building blocks differ only slightly with respect to their intrinsic bite angles, the resulting macrocycles exhibit remarkable structural versatility. Electrolysis inside an optically transparent electrochemical (OTTLE) cell provided their associated di‐/tri‐ and tetra‐/hexacations, which were studied by IR, UV/Vis/NIR and EPR spectroscopy. The divinylthiophene‐furandicarboxylate complex 2‐TF provides a rare example of supramolecular isomerism in metallamacrocyclic complexes. Thus, hexanuclear 2‐TF6 is initially formed as a kinetic isomer, which subsequently transforms slowly and cleanly into tetranuclear 2‐TF4.
Quick stabilization of capillary for rapid determination of potassium ions in the blood of epilepsy patients by capillary electrophoresis without sample pretreatment
Authors: Zhao Litao , Luo Fanghong , Wang Anting , Zhang Jing , Wang Yuanhang , Zhao Liangtao , Wang Zhaoyan , Pu Qiaosheng
Published: May 2020

Mutations in the potassium channel genes may be linked to the development of epilepsy and affect the blood potassium levels. Therefore, accurate determination of potassium in the blood will be critical to diagnose the cause of epilepsy. CE is a competent technique for the fast detection of multiple ions, but complicated matrices of a blood sample may cause significant variation of migration times and the peak shape. In this work, a procedure for rapid stabilization of the capillary inner surface through preflushing of a blood sample was employed. The process takes only 40 min for a capillary and then it can be used for more than 2 weeks. No pretreatment of the blood sample or other surface modification of the capillary is needed for the analysis. The RSDs of the migration time and peak area were reduced to 1.5 and 5.1% from 12.6 and 14.5%, respectively. The proposed method has been successfully applied to the determination of the potassium contents in the blood sample of patients with epilepsy at different stages. The recoveries of potassium ions in these blood samples are in a range from 86.5 to 104.5%.
Synthesis of humidity‐conditioning mesoporous molecular sieves by using liquid‐crystal display waste glass
Authors: Cheng Ta‐Wui , Lin Ya‐Wen , Lo Kang‐Wei , Chen Chiao‐Ying , Lin Kae‐Long
Published: May 2020

During this analysis, liquid‐crystal display (LCD) waste glass containing high SiO2 and Al2O3 contents was investigated as an alternative source for the synthesis of a humidity‐conditioning Al‐MCM‐41 mesoporous molecular sieve (HC‐Al‐MCM‐41). The hydrothermal method of synthesis involved the use of supernatants of LCD glass waste and the cationic surfactant cetyltrimethylammonium bromide as a structural controller. Chemically examined LCD waste glass was used in the HC‐Al‐MCM‐41 preparation. Silicates were used as a matrix and as a source of Si and Al precursors in HC‐Al‐MCM‐41 preparation. HC‐Al‐MCM‐41 has a uniform pore network and a transparent, hexagonal arrangement of pores or honeycomb‐like structures synthesized at a hydrothermal temperature of 105°C. At 105°C and 120°C, the N2 adsorption‐desorption isotherms are commonly type IV, with the HC‐Al‐MCM‐41 sampling characteristics of the hysteresis chain. The HC‐Al‐MCM‐41 samples synthesized from LCD waste glass showed higher equilibrium moisture contents than mortars (0.8‐1.6 m3/m3) and bricks (0.3‐0.8 m3/m3) due to the ordered structure. When the hydrothermal reaction temperature was 105°C (relative humidity = 95%), HC‐Al‐MCM‐41 exhibited favorable mechanical properties and met JIS A 1475 intensity building materials specifications (equilibrium moisture content >5 m3/m3); therefore, HC‐Al‐MCM‐41 can be used in several applications, especially as a humidity‐conditioning material in construction.
Removal of ammonia from industrial wastewater using novel heterogeneous nanocomposite of nickel, strontium, and zirconia oxides decorated graphene oxide
Authors: Mousavi Seyed Vahid , Nabi Bidhendi Gholamreza , Mehrdadi Naser
Published: May 2020

In this study, a novel adsorbent was developed based on nickel oxide, strontium oxide and zirconia oxide and was anchored onto graphene oxide to produce a heterogeneous nanocomposite (NiSr–ZrO2/GO) for efficient removal of ammonia from industrial wastewater. The proposed nanocomposite was characterized using FTIR, XRD, SEM, EDX, BET, and TEM techniques. Effects of changing important parameters on the ammonia adsorption such as pH, adsorbent dosage, contact time, and initial concentration of ammonia were investigated. Different models were conducted to study the kinetics and isotherms equilibrium data of the adsorption process. The results revealed that the adsorption kinetics was well‐fitted to the second‐order model. The equilibrium data were well fitted on Langmuir isotherm model with a maximum monolayer adsorption capacity of 181.81 mg g−1 (R2 = 0.997). Adding metal‐containing species to graphene oxide can favorably interact with ammonia.
Lifetime health care costs of oropharyngeal cancer for commercially insured patients in the United States
Authors: Wu Chi‐Fang , Lairson David R. , Dahlstrom Kristina R. , Fokom Domgue Joël , Fu Shuangshuang , Sturgis Erich M. , Chan Wenyaw
Published: May 2020

Background

Incidence of oropharyngeal cancer (OPC) is expected to increase but its health care cost is unknown. The purpose for this study was to estimate the phase‐specific lifetime health care costs of OPC for commercially insured individuals in the United States.

Methods

We used the Truven MarketScan Commercial Claims and Encounter Database to identify our patient population. Cox survival analysis was used to estimate patients' monthly survival probabilities. We determined the ratios of the cumulative costs up to a particular survival probability and the costs from that time point to death for all subjects who died before end of the 5‐year follow‐up period. This relationship was then used to predict phase‐specific lifetime health care costs.

Results

Our study included 2445 patients with OPC. The predicted phase‐specific lifetime health care costs attributable to OPC were $88 872, $24 038, and $1537 in the initial, continuous, and terminal phases, respectively, among commercially insured patients.
Tracheostomy during COVID‐19 pandemic—Novel approach
Authors: Chow Velda Ling Yu , Chan Jimmy Yu Wai , Ho Valerie Wai Yee , Pang Sherby Suet Ying , Lee George Chung Ching , Wong Melody Man Kuen , Lo Arthur Shing Ho , Lui Frances , Poon Clara Ching Mei , Wong Stanley Thian Sze
Published: May 2020

Background

This study describes a novel approach in reducing SARS‐CoV‐2 transmission during tracheostomy.

Methods

Five patients underwent tracheostomy between April 1, 2020 and April 17, 2020. A clear and sterile plastic drape was used as an additional physical barrier against droplets and aerosols. Operative diagnosis; droplet count and distribution on plastic sheet and face shields were documented.

Results

Tracheostomy was performed for patients with carcinoma of tonsil (n = 2) and nasopharynx (n = 1), and aspiration pneumonia (n = 2). Droplet contamination was noted on all plastic sheets (n = 5). Droplet contamination was most severe over the central surface at 91.5% (86.7%‐100.0%) followed by the left and right lateral surfaces at 5.2% (6.7%‐10.0%) and 3.3% (6.7%‐10.0%), respectively. No droplet contamination was noted on all face shields.

Conclusion

Plastic drapes can help reduce viral transmission to health care providers during tracheostomy. Face shields may be spared which in turn helps to conserve resources during the novel coronavirus disease 2019 pandemic.
Head and neck survivorship care in the times of the SARS‐CoV‐2 pandemic
Authors: Huang Victoria W. , Imam Sarah A. , Nguyen Shaun A.
Published: May 2020

With the arrival of the coronavirus disease (SARS‐CoV‐2) in the United States, care practice paradigms have drastically changed. Data from China suggest that the new virus poses additional risks as case fatality of patients with cancer was higher at 5.6% compared to 2.3% of the general population. There are three proposed major strategies to address care for patients with cancer in this SARS‐CoV‐2 pandemic with postponing treatment for those with stable cancer, increasing personal protection provisions for patients with cancer, and increasing monitoring if a patient becomes infected with SARS‐CoV‐2. In this present commentary, we discuss the unique mental health challenges and burdens of patients with head and neck cancer in the times of the SARS‐CoV‐2 pandemic and approaches to mitigate these stressors through telemedicine to reduce future burdens to the patient and the health care system.
Optimization of applied irrigation water and nitrogen fertilizer for barley in a semi‐arid region: a case study in Iran
Authors: Naghdyzadegan Jahromi Mojtaba , Razzaghi Fatemeh , Zand‐Parsa Shahrokh
Published: May 2020

This study was conducted to estimate the optimal amounts of water and nitrogen of barley production under water‐ and land‐limited conditions. Two years of field experiments were performed with two treatments using a spilt plot design with three replications. The treatments included four levels of irrigation regimes (0, 50, 75 and 100% of water requirement) as the main plots and four nitrogen fertilizer levels (0, 70, 140 and 210 kg N ha−1) as the subplots. Straw yield income was about 35% of total income, indicating the important role of both grain and straw yield in the economic analysis. The optimal amounts of water and nitrogen considering the rainfall and residual amount of nitrogen in the soil were estimated using a generalized reduced gradient nonlinear method as 0.758 m and 236 kg N ha−1 for maximum income per unit area, while these values were obtained as 0.758 m and 232 kg N ha−1 for maximum profit under land‐limited and 0.56 m and 293 kg N ha−1 for maximum profit under water‐limited conditions, respectively. The results show that the highest profit was obtained under land‐limited, maximum income and water‐limited criteria, respectively. © 2020 John Wiley & Sons, Ltd.
Cardiotoxicity danger in immunotherapy
Authors: Jagielska Beata , Ozdowska Patrycja , Gepner Katarzyna , Kubala Szymon , Siedlecki Janusz A. , Sarnowski Tomasz J. , Sarnowska Elzbieta
Published: May 2020

Immunotherapy based on immune checkpoint inhibitors (ICIs) is currently broadly used in the treatment of different types of cancer. The treatment targeting programmed cell death protein 1/programmed death‐ligand 1 axis is already approved by Food and Drug Administration for numerous cancers. These kinds of therapy brought spectacular results in the treatment of non‐small cell lung cancer where systemic therapy was ineffective. However, a wide range of applied therapies based on ICIs in the clinic have led to unexpected side effects, such as severe cardiotoxicity. It needs to be underlined that the molecular mechanism of myocarditis in response to ICIs is still not fully understood. Lack of sufficient knowledge, especially concerning the kind of risk factors increasing probability of myocarditis, poses currently a large clinical problem. Continuous cardiac monitoring of patients who undergo ICI treatment presents another problem as it is cost‐ineffective for the healthcare system. Herein, we highlight the risks of use of anticancer therapy based on ICIs. We also stress that detailed monitoring of any event of cardiotoxicity following ICIs treatment should be carefully investigated and registered to give a global overview of the frequency of myocarditis occurrence. Moreover, we propose that the extension of molecular and systemic knowledge of etiology of myocarditis as a side effect, including the role of protein kinases, will be highly beneficial for the medical field. Last but not least, better understanding of mechanisms of cardiotoxicity induction will improve the safety of cancer patients and will help clinicians in prediction of unexpected side effect occurrence.
MPC‐grafted highly cross‐linked polyethylene liners retrieved from short‐term total hip arthroplasty: Further evidences for the unsuitability of the MPC method
Authors: Hosoi Takashi , Hasegawa Masahiro , Tone Shine , Nakasone Satoshi , Kishida Narifumi , Marin Elia , Zhu Wenliang , Pezzotti Giuseppe , Sudo Akihiro
Published: May 2020

An analysis is presented of four short‐term retrieved highly crosslinked polyethylene (HXLPE) hip liners grafted with 2‐methacryloyloxyethyl phosphorylcholine (MPC) on their bearing surfaces, which were recently commercialized as a new generation of artificial hip joints. Straightforward evidences by X‐ray photoelectron spectroscopy (XPS) confirmed that the MPC layer peeled off on the bearing surface of all short‐term liners in both main wear and nonwear zones. Analyses by Fourier‐transform infrared spectroscopy with attenuated total reflection assessed the extent of surface oxidation and revealed the type of oxidative species. Electron spin resonance analyses, which compared retrievals and as‐received samples, revealed the presence of different species of alkoxyl CO• radicals. This study suggests that MPC grafts on polyethylene do not offer any additional protection from oxidation and can delaminate prematurely after short‐term in vivo exposure.
Sex‐dependent aberrant PFC development in the adolescent offspring rats exposed to variable prenatal stress
Authors: Niu Yunxia , Wang Tao , Liang Shan , Li Wei , Hu Xu , Wu Xiaoli , Jin Feng
Published: May 2020

Adolescence is a remarkable period of brain development. Prenatal stress can increase the risk of various neuropsychiatric disorders. This research investigated neurochemical and behavioural changes in the offspring rats (especially adolescences) who were treated with repeated variable prenatal stress (PNS) during the third week of gestation. The study tested the concentration of brain‐derived neurotrophic factor (BDNF), cluster of differentiation 68 (CD68), synaptotagmin‐1(Syt‐1), 5‐hydroxytryptamine (5‐HT), dopamine (DA), glucocorticoid receptors (GRs) and oestrogen receptors (ERs) in the PFC (prefrontal cortex). We also tested prepulse inhibition (PPI) of the acoustic startle reflex (ASR) (a measure of sensorimotor gating). The main results were as follows: PNS increased the BDNF and CD68 concentrations in adolescent females, and increased the Syt‐1 concentration in adolescent males. The increases in BDNF/CD68 concentration (in females) and Syt‐1/DA concentration (in males) with age were disturbed by PNS, and PNS changed the sex differences in CD68 concentration in adolescence and disturbed the sex differences in the Syt‐1 concentration (in adolescence) and DA concentration (in adults). In conclusion, we found that PNS lead to Sex‐dependent aberrant PFC development, and might accelerate the development of the adolescent PFC, and so that lessened the age difference (between adolescence and adulthood) and the sex difference.
Tumor marker recovery rather than major pathological response is a preferable prognostic factor in patients with pancreatic ductal adenocarcinoma with preoperative therapy
Authors: Yamada Suguru , Yokoyama Yukihiro , Sonohara Fuminori , Yamaguchi Junpei , Takami Hideki , Hayashi Masamichi , Onoe Shunsuke , Fujii Tsutomu , Nagino Masato , Kodera Yasuhiro
Published: May 2020

Background/Purpose

A pathological response of the primary tumor by preoperative therapy is a prognostic factor in various malignancies, and several histologic grading systems have been proposed for pancreatic ductal adenocarcinoma (PDAC). However, the prognostic value remains unclear. We explored the clinical implication of a major pathological response following preoperative therapy in patients with PDAC.

Methods

Of 415 patients with resected PDAC, 137 who had undergone preoperative therapy were examined. Cox proportional hazards models were used to determine the predictors of a major pathological response, and survival analyses were performed.

Results

Twenty patients exhibited a major pathological response (≥90% tumor reduction). Significant associations were observed between a major pathological response and resectability (P = .001), the period of preoperative therapy (P < .001), RECIST best response (P < .001), the tumor size after preoperative therapy (P = .02), and tumor marker recovery (P < .001). Multivariate analysis of progression‐free survival (PFS) revealed that both body mass index (≥20 kg/m2) (P = .035) and tumor marker recovery (P = .046) were independent prognostic factors. The median survival time (MST) of PFS for a ≥90% pathological response was better than that of a <90% response (P = .25); however, the MST for tumor marker recovery was significantly better than that without tumor marker recovery (P = .0054).

Conclusions

In our study, a major pathological response was not extracted as a prognostic factor. Rather, tumor marker recovery was a preferable prognostic factor in patients with PDAC who had undergone preoperative therapy.
A Sex‐Stratified Prognostic Nomogram Incorporating Body Compositions for Long‐Term Mortality in Cirrhosis
Authors: Hou Lijun , Deng You , Fan Xiaofei , Zhao Tianming , Cui Binxin , Lin Lin , Hou Junjie , Mao Lihong , Zhao Wei , Jiang Kui , Wang Bangmao , Zhang Jie , Sun Chao
Published: May 2020

Background

Alterations in body compositions are related to poor outcomes and the presence of complications in cirrhosis. However, no predictive tools combining all these anthropometric parameters are applicable in the clinical setting. We aimed to clarify the potential utility of body compositions and develop a nomogram incorporating any independent factor for prognosticating long‐term mortality in cirrhosis.

Methods

A total of 414 patients were randomized into primary (n = 274) and validation (n = 140) cohorts. X‐tile was performed to identify optimal cut points for stratifying participants. Multivariate Cox regression was performed, and nomogram incorporating body compositions were generated. The utility of developed models was evaluated by Harrell concordance index (C‐index), calibration curve, and decision curve analysis (DCA).

Results

Stratifying by X‐tilederived cut points, low skeletal muscle index (myopenia), high intramuscular adipose tissue content (myosteatosis), and the ratio of high visceral to subcutaneous adipose tissue area (adiposity) was independently associated with 3‐year mortality. A sex‐stratified nomogram incorporating anthropometric indices and clinical factors resulted in moderate discriminative accuracy, with a C‐index of 0.787 (95% CI, 0.736–0.838) and 0.789 (95% CI, 0.727–0.851) in males and females, respectively. The calibration curve showed predictive survival corresponding optimally with the actual outcomes. Our models were feasible in the clinical settings based on DCA. Similar results were observed in the validation cohort. Additionally, participants could be classified into 3 distinct risk groups by the nomogram.

Conclusions

Our proposed nomogram embedding body compositions rendered an individualized predictive tool for long‐term mortality in cirrhosis.
Clinical significance of lymphatic invasion in the esophageal region in patients with adenocarcinoma of the esophagogastric junction
Authors: Sugita Shizuki , Kuwata Takeshi , Tokunaga Masanori , Kaito Akio , Watanabe Masahiro , Tonouchi Akiko , Kinoshita Takahiro , Nagino Masato
Published: May 2020

Background and Objectives

The lymphatic flow around the esophagogastric junction is complicated. Therefore, it is unclear whether lymphatic invasion in the esophageal region (eLI) and in the gastric region (gLI) in patients with adenocarcinoma of the esophagogastric junction (AEG) equally affect the incidence of lymph node metastases (LNM), and consequently, survival.

Methods

We retrospectively reviewed clinicopathological data of 175 patients with AEG between January 2008 and July 2017. Risk factors for LNM and impacts of eLI or gLI on survival outcomes were investigated.

Results

eLI was identified in 34% of the patients (59/175). By multivariate analysis, eLI was associated with an increased risk of both mediastinal LNM (odds ratio [OR] = 2.98, 95% confidence interval [CI]: 1.26‐7.05) and abdominal LNM (OR = 5.44, 95% CI: 1.95‐15.20). The 5‐year overall survival for patients with eLI (53%) was significantly worse than for patients without eLI (76%) (hazard ratio = 2.45, 95% CI: 1.37‐10.01). gLI was not selected in either of these analyses.

Conclusions

Positive eLI was strongly associated with mediastinal and abdominal LNM and worse survival in patients with AEG compared with gLI. In the histopathological examination, it seems to make sense to assess eLI and gLI separately.
Genetics of pediatric hearing loss: A functional perspective
Authors: Khela Harmon , Kenna Margaret A.
Published: May 2020

Objectives

This article reviews the current role of genetics in pediatric hearing loss (HL).

Methods

A review of the current literature regarding the genetic basis of HL in children was performed.

Results

To date, 119 nonsyndromic genes have been associated with HL. There are also hundreds of syndromic causes that have HL as part of the clinical phenotype.

Conclusions

Identifying HL genes coupled with clinical characteristics (“genotype‐phenotype”) yields a more accurate diagnosis and prognosis. Although the complexity of the auditory apparatus presents challenges, gene therapy is emerging and may be a viable management option in the future.
Integro‐differential equations linked to compound birth processes with infinitely divisible addends
Authors: Beghin Luisa , Gajda Janusz , Maheshwari Aditya
Published: May 2020

Stochastic modelling of fatigue (and other material's deterioration), as well as of cumulative damage in risk theory, are often based on compound sums of independent random variables, where the number of addends is represented by an independent counting process. We consider here a cumulative model where, instead of a renewal process (as in the Poisson case), a linear birth (or Yule) process is used. This corresponds to the assumption that the frequency of “damage” increments accelerates according to the increasing number of “damages”. We start from the partial differential equation satisfied by its transition density, in the case of exponentially distributed addends, and then we generalize it by introducing a space derivative of convolution type (i.e., defined in terms of the Laplace exponent of a subordinator). Then we are concerned with the solution of integro‐differential equations, under proper initial conditions, which, in a special case, reduce to a fractional one. Correspondingly, we analyze the related cumulative jump processes under a general infinitely divisible distribution of the (positive) jumps. Some special cases (such as the stable, tempered stable, gamma, and Poisson) are presented.
Frequency of pathogenic/likely pathogenic germline variants in cancer‐related genes among children with acute leukemia in Saudi Arabia
Authors: Alsultan Abdulrahman , Essa Mohammed , Aljefri Abdullah , Ayas Mouhab , Alharbi Musa , Alkhayat Nawaf , Al‐Anzi Faisal , Yassin Fawwaz , Alkasim Fawaz , Alharbi Qasim , Abdullah Shaker , Jastaniah Wasil
Published: May 2020

Background

The frequency of pathogenic/likely pathogenic (P/LP) germline mutations in cancer‐related genes among children with cancer in highly consanguineous populations is not well studied.

Methods

Whole‐exome sequencing of germline DNA was performed in 60 children with acute leukemia. We used the St. Jude Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) data portal for the classification of germline variants by the St. Jude Medal Ceremony pipeline.

Results

Fifty‐seven patients had acute lymphoblastic leukemia (ALL) and three patients had acute myeloid leukemia. Parental consanguinity was present in 27 (45%) patients. All patients were of Arab ancestry. Three patients (5%) had a history of cancer in their siblings. Five patients (8.3%) had P/LP germline mutations in cancer‐related genes. Three patients with B‐ALL had heterozygous pathogenic mutations in TP53, BRCA1, and BRCA2; one patient with B‐ALL had homozygous pathogenic mutation in PMS2; and one patient with T‐ALL had LP homozygous mutation in AK2 that was associated with reticular dysgenesis. Among patients who had history of parental consanguinity, three (11%) had P/LP germline mutations compared with two (8%) in the absence of parental consanguinity. Fourteen (23%) patients had gold medal variants in cancer‐related genes, 13 were heterozygous, and one was homozygous. Silver medal variants were present in 35 (58%) patients; all were heterozygous except one homozygous.

Conclusions

Children with acute leukemia in Saudi Arabia had low frequency of P/LP mutations in cancer‐related genes despite the high rate of consanguinity. Larger studies using whole‐genome sequencing are needed to further explore the heritability of childhood leukemia.
Training paraprofessionals who work with students with intellectual and developmental disabilities: What does the research say?
Authors: Brock Matthew E. , Anderson Eric J.
Published: May 2020

Federal law allows for paraprofessionals to provide instruction to students with developmental disabilities if they are adequately trained and supervised, but how to best provide this training and support remains unclear. In this paper, we update a systematic review of experimental studies that test the efficacy of paraprofessional‐implemented interventions for students with developmental disabilities. We identified 36 studies published 2012–2019. An exciting development is that some researchers are shifting to testing teacher‐implemented training, therefore beginning to address important questions about the feasibility of widespread implementation under real‐world conditions. Based on findings across studies, recommendations for practice include that (a) paraprofessional roles be well‐defined and focused on the implementation of evidence‐based practices; (b) paraprofessional training should feature modeling, an implementation checklist, and performance feedback that is sustained over time; and (c) administrators should ensure that teachers have the time and support that are required for effective paraprofessional training and supervision.
A Comparison of the Armeo to Tabletop‐assisted Therapy Exercises as Supplemental Interventions in Acute Stroke Rehabilitation: A Randomized Single Blind Study
Authors: Esquenazi Alberto , Lee Stella , Watanabe Thomas , Nastaskin Alexey , McKee Casey , O'Neill James , Scheponik Katherine , May Jaun
Published: May 2020

Objectives

To evaluate the feasibility of an additional therapeutic upper limb exercise (ULE) intervention in early phase post‐stroke rehabilitation and to assess outcomes of therapy using the Armeo Spring (ARMEO) versus Therapist‐assisted Table Top (TAT) interventions.

Design

Randomized, single‐blind trial.

Setting

Stroke acute inpatient rehabilitation unit.

Participants

Forty‐five participants early after first stroke, Fugl‐Meyer Assessment (FMA) score >8, Modified Ashworth score (MAS) of <3.

Interventions

Participants were randomized to TAT or ARMEO ULE in addition to the required 3 hours of 1:1 standard of care provided in an inpatient rehabilitation facility (IRF).

Main Outcome Measures

Completed number of treatments; withdrawals; serious/adverse events; Functional Independence Measure (FIM) motor; FIM efficiency; FMA; MAS; elbow active (A) and passive (P) range of motion (ROM); and therapist effort measured by the Modified Borg Rating of Perceived Exertion Scale (RPE).

Results

Post‐intervention FIM and FMA scores increased but did not demonstrate any statistically significant differences between the intervention groups (P = .585, .962, partial n2 = .001, .001, respectively). There were no statistically significant differences in post‐intervention MAS elbow flexion and extension (P = .332, .252, partial n2 = .009, .007, respectively) and A/P ROM elbow extension between training groups (P = .841, .731, partial n2 = .001, .003, respectively). There was a statistically significant difference in post‐intervention A/P ROM elbow flexion between groups (P = .031, .018, partial n2 = .123, .146). Post‐intervention RPE did not show any statistically significant differences between the training groups (P = .128, partial n2 = .063). Total elbow range showed larger adjusted mean gains for the ARMEO. No serious adverse events were reported.

Conclusions

This study demonstrates that additional therapeutic ULE in the early phase of post‐stroke inpatient rehabilitation is feasible and that both interventions showed positive changes in selected outcomes.
Integrated qualitative analysis of polymer sample by pyrolysis–gas chromatography combined with high‐resolution mass spectrometry: Using accurate mass measurement results from both electron ionization and soft ionization
Authors: Ubukata Masaaki , Kubo Ayumi , Nagatomo Kenji , Hizume Takuhiro , Ishioka Haruki , Dane A. John , Cody Robert B. , Ueda Yoshihisa
Published: May 2020

Rationale

Gas chromatography/mass spectrometry (GC/MS) is a powerful analytical tool used to separate and then identify volatile compounds through library database searches. However, as not all compounds are registered in these databases, it is not uncommon to detect unregistered components. Therefore, new analytical techniques were developed that utilize methods of identification beyond database searches alone.

Methods

Acquire data by using electron ionization (EI) and soft ionization (SI) with high‐resolution mass spectrometry (HRMS). Use the EI mass spectra to library search for matches. Use the SI mass spectra for accurate mass analysis of the EI molecular ions. Conduct an isotope pattern analysis of the molecular ion to refine the possible candidate compositions. Use these compositions as a constraint for the accurate mass analysis of the EI fragment ions. If a given molecular ion formula is not correct, the EI fragment ions will not show good matches. Finally, all analytical results are integrated into a color‐coded qualitative analysis report.

Results

The capabilities of this new integrated analytical method were assessed for a polymer resin sample that was measured by using pyrolysis–gas chromatography/high resolution time‐of‐flight mass spectrometry. A total of 161 compounds were detected in the total ion current chromatogram, and 154 of these compounds were identified as having only one chemical formula candidate with this new integrated qualitative analysis method.

Conclusions

This new integrated qualitative analysis method gives analytical results independent of library search results. It can be applied to a variety of SI methods including chemical ionization, photoionization, field ionization, and low‐energy EI.
β‐Carotene Stability and Some Physicochemical Properties of Apricot Juice Powders Obtained by Using Maltodextrins with Different Dextrose Equivalents
Authors: Arslan Tamer , Durmaz Gökhan
Published: May 2020

In this study, apricot juice powders (AJPs) are obtained via freeze‐drying using different maltodextrins (MDs) as carrier agents. The Hacıhaliloğlu cultivar, which is the most common variety in Turkey, is used as an apricot sample. Three different MDs: low (4–7), medium (13–17), and high (17–20) dextrose equivalence (DE) are used as the carrier agent. The powders obtained are subjected to accelerated oxidation at 55 °C, and the stability of β‐carotene in the AJPs is determined. Some physicochemical properties, such as the glass transition temperature, microstructure, bulk density, color, moisture, solubility, degree of caking, and hygroscopicity, are also determined. The results show that after a 20 day period of oxidation, the remaining β‐carotene in the control sample is 24% of the initial value, whereas for low, medium, and high DE MD samples, it is measured to be 47%, 60%, and 57% of the initial concentration, respectively. There is no significant difference in the content of surface carotenoids between the control and the samples with added MD. In contrast, according to other quality attributes like hygroscopicity, caking, moisture content, and solubility, the best results are obtained from the low DE MD sample.