bluuebunny/crossref_metadata_2025 huggingface dataset:
Aplastic anemia, cellular and molecular aspects
Authors: Javan Mohammad R. , Saki Najmaldin , Moghimian‐Boroujeni Bahareh
Published: August 2021

Aplastic anemia (AA) is an autoimmune disorder characterized by bone marrow and peripheral blood pancytopenia. Different environmental and genetical conditions could be effective in an outbreak of this disease. The exact pathogenesis of this disease, however, is still idiopathic. The present study is based on Pubmed database information (2002–2021) using the words “Aplastic Anemia,” “Hematopoietic Stem Cells niche,” “Signaling pathway,” “Cytokines,” and “Immuno cells.” In this disease, both hematopoietic stem cells and mesenchymal stromal cells are impaired, which is associated with impaired hematopoiesis and decreased hematopoietic cells. Inflammatory cytokines increase, which changes the ratio of T lymphocytes and leads to disease progression. In addition, the most common mechanism of AA is damage by the immune system, which leads to increased apoptosis in progenitor cells. We have shown in this review that the disease involves quantitative defects in stem cell numbers and qualitative abnormalities in the function of these cells and the activity of many different cellular and molecular factors can damage hematopoietic cells and the protective substrate of these cells in this disease.
Effects of the functional Gpc‐B1 allele on soft durum wheat grain, milling, flour, dough, and breadmaking quality
Authors: Kiszonas Alecia M. , Ibba Maria Itria , Boehm Jeffrey D. , Morris Craig F.
Published: August 2021

Background and objectives

Utilization of durum wheat (Triticum turgidum subsp. durum) can be enhanced by increasing grain and flour protein content. One strategy to increase protein content is by introducing the functional Gpc‐B1 allele from wild emmer (Triticum turgidum subsp. dicoccoides).

Findings

Introduction of the functional Gpc‐B1 allele into soft kernel durum increased grain and flour protein by 17 g/kg, increased dough strength as evidenced by SDS sedimentation volume and Mixograph dough mixing parameters, and increased straight‐dough pan bread volume. When grown under arid conditions, high protein (151 g/kg) samples had decreased loaf volumes indicative of inelastic doughs. The functional Gpc‐B1 allele was associated with decreased test weight, a small increase in SKCS hardness, and a modest increase in flour ash; otherwise, milling performance was not affected.

Conclusions

Introgression of the Gpc‐B1 functional allele from dicoccoides into durum wheat can improve dough strength and breadmaking quality. The effect tends to be consistent over environments but overall, Gpc‐B1 made only a modest improvement in durum wheat breadmaking quality. Further studies with concomitant selection at other loci are needed to see the effects of Gpc‐B1 among elite germplasm.

Significance and novelty

Durum wheat production and consumption will increase as bread quality improves. The functional Gpc‐B1 allele contributed to improved breadmaking quality. The present report is the first to examine the effect of this allele on breadmaking in durum wheat.
Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)‐Containing Heterocycles
Authors: Souza João Pedro A. , Menezes Leociley R. A. , Garcia Francielle P. , Scariot Débora B. , Bandeira Pamela T. , Bespalhok Mateus B. , Giese Siddhartha O. K. , Hughes David L. , Nakamura Celso V. , Barison Andersson , Oliveira Alfredo R. M. , Campos Renan B. , Piovan Leandro
Published: August 2021

Inspired by the synthetic and biological potential of organotellurium substances, a series of five‐ and six‐membered ring organotelluranes containing a Te−O bond were synthesized and characterized. Theoretical calculations elucidated the mechanism for the oxidation‐cyclization processes involved in the formation of the heterocycles, consistent with chlorine transfer to hydroxy telluride, followed by a cyclization step with simultaneous formation of the new Te−O bond and deprotonation of the OH group. Moreover, theoretical calculations also indicated anti‐diastereoisomers to be major products for two chirality center–containing compounds. Antileishmanial assays against Leishmania amazonensis promastigotes disclosed 1,2λ4‐oxatellurane LQ50 (IC50=4.1±1.0; SI=12), 1,2λ4‐oxatellurolane LQ04 (IC50=7.0±1.3; SI=7) and 1,2λ4‐benzoxatellurole LQ56 (IC50=5.7±0.3; SI=6) as more powerful and more selective compounds than the reference, being up to four times more active. A stability study supported by 125Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous‐organic media or at temperatures up to 65 °C.
Investigation of Masked N‐Acyl‐N‐isocyanates: Support for Oxadiazolones as Blocked N‐Isocyanate Precursors
Authors: Gagné‐Monfette William , Vincent‐Rocan Jean‐François , Lutes Owen C. , O'Keefe Geneviève F. , Jeanneret Alexandria D. M. , Blanger Claire , Ivanovich Ryan A. , Beauchemin André M.
Published: August 2021

In contrast to carbon‐substituted isocyanates that are common building blocks, N‐substituted isocyanates remain underdeveloped and reports on their N‐acyl derivatives (i. e. amido‐isocyanates) are exceedingly rare. Herein, amido‐isocyanates were investigated in the context of syntheses of aza‐tripeptide and hydantoins subunits starting from simple bench‐stable precursors. A key finding is that the amido‐isocyanate formed in situ cyclized to yield an oxadiazolone, and that under suitable reaction conditions this heterocycle is a traceless blocked (masked) N‐isocyanate. Using organic bases as catalysts and upon heating, oxadiazolone formation is observed, and various nucleophiles to provide the desired aza‐dipeptides or hydantoins in moderate to high yields. Further support for an amido‐isocyanate intermediate was obtained using carboxylic acids as nucleophiles, affording N‐acylhydrazide products.
Primary Sulfonamide Functionalization via Sulfonyl Pyrroles: Seeing the N−Ts Bond in a Different Light
Authors: Ozaki Tomoya , Yorimitsu Hideki , Perry Gregory J. P.
Published: August 2021

Despite common occurrence in molecules of value, methods for transforming sulfonamides are distinctly lacking. Here we introduce easy‐to‐access sulfonyl pyrroles as synthetic linchpins for sulfonamide functionalization. The versatility of the sulfonyl pyrrole unit is shown by generating a variety of products through chemical, electrochemical and photochemical pathways. Preliminary results on the direct functionalization of primary sulfonamides are also provided, which may lead to new modes of activation.
Excited State Charge Separation in an Azobenzene‐Bridged Perylenediimide Dimer – Effect of Photochemical Trans‐Cis Isomerization
Authors: Zink‐Lorre Nathalie , Seetharaman Sairaman , Gutiérrez‐Moreno David , Fernández‐Lázaro Fernando , Karr Paul A. , D'Souza Francis
Published: August 2021

Photoinduced charge transfer and separation events in a newly synthesized azobenzene‐bridged perylenediimide‐dimer (PDI‐dimer) are demonstrated. Trans‐to‐cis conversion (∼50 % efficiency) from the initial trans PDI‐dimer by 355 nm pulsed laser light, and its reversal, cis‐to‐trans, process by 435 nm laser light irradiation has been possible to accomplish. Efficient fluorescence quenching in the PDI‐dimer, more so for the cis isomer was witnessed, and such quenching increased with increasing solvent polarity. DFT‐calculated geometry and electronic structures helped in visualizing the charge transfer in the PDI‐dimer in both isomeric forms, and also revealed certain degree of participation of the azobenzene entity in the charge transfer events. Femtosecond transient absorption spectral studies confirmed occurrence of both charge transfer followed by charge separation in the studied PDI‐dimer in both trans and cis forms in polar solvents, and the evaluated time constants from Global target analysis revealed accelerated events in the cis PDI‐dimer due to proximity effects. The present study offers key insights on the role of the azobenzene bridge, and the dimer geometry in governing the excited state charge transfer and separation in symmetrically linked PDI dimer.
Integrative surgical oncology: A model of acute integrative oncology
Authors: Diller Maggie L. , Master Viraj A.
Published: August 2021

Integrative oncology has emerged as a recognized medical subspecialty because of growing interest in the use of integrative medicine in modern cancer care on behalf of both patients and providers. Acutherapy and mind‐body techniques, such as meditation and yoga, have been shown to aid in symptom control and improve quality of life in oncologic patient populations, and the Society of Integrative Oncology and American Society of Clinical Oncology have recently endorsed a set of guidelines for the implementation of these techniques specifically in patients with breast cancer. Although the current guidelines focus largely on the management of chronic symptoms, there exists evidence to support the use of these techniques in acute symptom management as well. With surgical resection representing the backbone of many cancer treatment regimens, symptoms that arise during the perioperative period are prime examples of the acute symptomatology common among patients with cancer. Here, the authors provide a detailed literature review of the current evidence supporting the use of integrative techniques during the perioperative period and demonstrate their applicability for acute symptom management within oncologic and surgical populations. In doing so, the authors introduce a new paradigm of surgical practice they call integrative surgical oncology and integrative surgery.
Autologous fat transfer—principles, techniques, and outcomes for facial rejuvenation, scars, breast, and buttocks
Authors: Roh Mi R. , Chung Kee Y. , Goyal Nilesh N. , Al Shehri Fatma
Published: August 2021

Autologous fat transfer is a common method to correct soft‐tissue defects. It has been used in various conditions with subcutaneous atrophy induced by trauma or inflammation. Recently, the use has become popular for cosmetic purposes such as facial rejuvenation andbody contouring. In this article, we review the science and method behind its practice and describe other possible indications for autologous fat transfer.
Patterns of flammability after a sequence of mixed‐severity wildfire in dry eucalypt forests of southern Australia
Authors: Barker James W. , Price Owen F. , Jenkins Meaghan E.
Published: August 2021

Fire severity is the impact of a fire on the landscape, particularly the physical impact on vegetation. Previous studies have established that the severity of a fire can be influenced by the severity of previous fires. Many of these studies were conducted in mixed‐conifer forests, while little is known of this process in temperate eucalypt forests. Barker and Price in their 2018 publication (“Positive severity feedback between consecutive fires in dry eucalypt forests of southern Australia,” Ecosphere 9:e02110) found that high severity fire promotes high severity fire in eucalypt forests, but how is the severity of a fire in these systems affected by the severity of two sequential previous fires? This was investigated using remotely sensed and mapped fire severity data. We found that high severity fire is more likely after at least one previous high severity fire, regardless of its position in the sequence. A sequence of low or moderate severity fire followed by low severity fire resulted in the lowest proportion of high severity in the response fire. Our results suggest that low severity fire maintains the structure of forest fuels, so flammability remains relatively constant. A single high severity fire drives change, altering the structure and flammability of the vegetation and promoting more severe fire. However, the effects were small, so a cycle of high severity fire may be easily broken due to the influence of other variables, such as weather. Repeated high severity fire may also result in a decline in the ability of plants to recover from fire, leading to a compositional and structural change and potentially reducing the flammability of a forest.
α‐Amino Acids and α,β‐Dipeptides Intercalated into Hydrotalcite: Efficient Catalysts in the Asymmetric Michael Addition Reaction of Aldehydes to N‐Substituted Maleimides
Authors: Landeros José M. , Cruz‐Hernández Carlos , Juaristi Eusebio
Published: August 2021

In this work, a series of α‐amino acids (L‐Phe, D‐Phe, L‐Trp) and several α,β‐dipeptides (H2N‐L‐Val‐N‐Bn‐β‐Ala‐COOH and H2N‐L‐Leu‐N‐Bn‐β‐Ala‐COOH) intercalated into hydrotalcite (Mg/Al, x=0.333) were prepared by high speed ball milling (HSBM) assisted rehydration/reconstruction methods, followed by sonication and mechanical stirring. All organic‐inorganic hybrid samples were characterized by powder X‐ray diffraction (XRD) and FTIR‐ATR spectroscopy. The catalytic activity of the resulting hydrotalcite‐supported materials (natural and hybrid) was evaluated in the asymmetric Michael addition reaction of α,α‐disubstituted‐aldehydes to N‐substituted‐maleimides. Pristine (HTS), calcined (HTC) and water‐reconstructed (HTR‐l) hydrotalcite‐derived materials exhibited very low catalytic activities, affording racemic mixtures of the anticipated Michael adduct. By contrast, hybrid materials showed better activities, especially HTR‐α‐amino acid catalysts afforded Michael products in up to 94 % yield and with rather high enantioselectivity (enantiomeric ratio (e.r.) up to 99 : 1) at room temperature under neat reaction conditions. The effect of solvents and Brønsted basic or acidic additives was evaluated using the best hybrid catalyst, HTR‐L‐Phe. In addition, recycling and reuse of the catalyst (up to 4 cycles) and large‐scale experiments was successfully carried out.
Using an autonomous underwater vehicle with onboard stochastic advection‐diffusion models to map excursion sets of environmental variables
Authors: Foss Karine Hagesæther , Berget Gunhild Elisabeth , Eidsvik Jo
Published: August 2021

New robotic sensor platforms have computing resources that enable a rich set of tasks for adaptive monitoring of the environment. But to substantially augment the toolbox of environmental sensing, such platforms must be embedded with realistic statistical models and coherent methodologies for designing experiments and assimilating the data. In this article, we develop myopic and hybrid strategies for autonomous underwater vehicle sampling in space and time. These strategies are based on a stochastic advection‐diffusion Gaussian process model for the mine tailings concentration in a Norwegian fjord, and the goal is to monitor the excursion set (ES) of high concentrations. Closed form expressions for the expected misclassification probabilities of the ES enable real‐time operation on board the autonomous vehicle, and this is used to guide the spatio‐temporal sampling. Simulation studies show that the suggested strategies outperform other approaches that either (i) simplify the models for spatio‐temporal variation, or (ii) simplify the design criterion. A field test shows how autonomous underwater sampling is useful for refining an initial stochastic advection‐diffusion model. These experiments further show that the vehicle can adapt to focus on regions with intermediate concentrations where it is natural to improve the ES prediction.
A transient flow solution to describe fluid flow to horizontal fractures applied to frac‐packed wells
Authors: Guo Boyun , Fu Chunkai , Liu Ning
Published: August 2021

This paper presents an analytical model to describe the transient fluid flow to a horizontal fracture in frac‐packed vertical wells. A physical model is first established where a horizontal frac‐packed fracture is located in the middle of a cylindrical reservoir. The pressure distribution in the fracture is then derived concerning time and the distance to the wellbore. The analytical model assumes a homogeneous and isotropic reservoir where Darcy's law applies to a single‐phase fluid flow, a radial fracture with a radius much greater than pay zone thickness, and a constant fracture width. For ease of application, a Type Curve Matching approach is introduced which features the matching of a defined dimensionless pressure between field pressure data and model data, and some exemplar curves are illustrated in this paper. The principle of applying curve matching here is to tune model parameters to match the measured pressure/rate data. Once the curves are matched, the model parameters, that is, fracture permeability, etc, are naturally obtained. The validity of the derived model is informed in two ways. The results show that the model will degenerate to the classic radial flow equation for practical values of certain model parameters and upon reasonable simplification. Model validity is further verified by applying the type curve matching technique using field data. This model can be used as a quick and reasonable method to analyze the transient pressure/rate test data to reveal fundamental fracture and reservoir properties for a frac‐packed horizontal fracture at shallow depths where the vertical formation stress is the least in situ stress.
Implications of reworking processes on tephra distribution during volcanic eruptions: The case of Parícutin (1943–1952, western Mexico)
Authors: Bolós Xavier , Macias José Luis , Ocampo‐Díaz Yam Zul E. , Tinoco Claudio
Published: August 2021

Parícutin in western Mexico is considered one of the most studied monogenetic volcanoes worldwide. The volcano began its formation in the middle of a cornfield in February 1943 and lasted until March 1952. Descriptions of the eruption documented the remobilization of unconsolidated primary ashfall by rainfall and wind in minor proportions. Despite these descriptions, the resulting reworked deposits have not yet been described in stratigraphic sequence. We present the first stratigraphic study of interfingered primary pyroclastic and reworked deposits of Parícutin's succession. We identify 13 units, of which seven correspond to reworked deposits dispersed around the volcano. These deposits display sedimentary structures produced by tephra remobilization due to lahars and stream flows. In addition, some layers display dunes and ripples generated by dust storms. By using GIS tools, we integrated the existing data with our new composite stratigraphic column, the distribution map of the syn‐eruptive reworked deposits and a new isopach map. This new evaluation reveals that more than 70% of the total thicknesses around the volcano correspond to syn‐eruptive reworked deposits (R1–R4 units). Therefore, previous studies had overestimated the distribution of primary tephra from the Parícutin explosive phases. The lowest and flattest areas with wide rill networks, which are located 4–6 km north of the volcano, are composed of up to 90% reworked deposits. In contrast, proximal locations with gentler slopes located at medium altitudes better preserve pyroclastic deposits. This study brings new light to understanding the sedimentary processes that occur during volcanic eruptions and highlights the importance of recognizing pyroclastic and reworked deposits during monogenetic eruptions.
Low molecular weight polysialic acid prevents lipopolysaccharide‐induced inflammatory dopaminergic neurodegeneration in humanized SIGLEC11 transgenic mice
Authors: Liao Huan , Winkler Jonas , Wißfeld Jannis , Shahraz Anahita , Klaus Christine , Neumann Harald
Published: August 2021

Parkinson's disease is one of the most common neurodegenerative diseases in the elderly population, with a pathophysiology linked to neuroinflammation, complement activation, and oxidative damage. Soluble polysialic acid with an average degree of polymerization 20 (polySia avDP20) prevents inflammation and oxidative burst in human macrophages via sialic acid‐binding immunoglobulin like lectin‐11 (SIGLEC11) receptor and interferes with alternative complement activation. Here, we confirmed the anti‐inflammatory capacity of polySia avDP20 on cultured murine embryonic stem cell‐derived microglia and analyzed the effect of polySia avDP20 in a lipopolysaccharide‐triggered animal model of Parkinson's disease. We demonstrated a neuroprotective effect of intraperitoneally applied polySia avDP20 in humanized SIGLEC11 transgenic mice after repeated systemic challenge with lipopolysaccharide. Pathway enrichment analysis of the brain transcriptome on day 19 after disease initiation showed that intraperitoneal application of 10 μg/g body weight polySia avDP20 prevented excessive inflammation. In line with these data, polySia avDP20 attenuated the lipopolysaccharide‐triggered increase in mRNA levels of immune‐related genes (Il1b, Cd14, Myd88, Fcer1g, Itgam, C4, Cybb, Iba1 and Cd68) and cell death‐related genes (Casp8, Ripk1 and Ripk3) in the brains of SIGLEC11 transgenic mice on day 19, but not on day 5. Moreover, immunohistochemistry demonstrated that polySia avDP20 reduced the lipopolysaccharide‐induced increase in immunoreactivity of IBA1 and CD68 in the substantia nigra pars reticulata in SIGLEC11 transgenic and wild type mice on day 19. Furthermore, treatment with polySia avDP20 prevented the loss of dopaminergic neurons in the substantia nigra pars compacta induced by lipopolysaccharide challenge in both SIGLEC11 transgenic and wild type mice on day 19. Thus, our data demonstrate that polySia avDP20 ameliorates inflammatory dopaminergic neurodegeneration and therefore is a promising drug candidate to prevent Parkinson's disease‐related inflammation and neurodegeneration.
Cardiac biomarkers, cardiac injury, and comorbidities associated with severe illness and mortality in coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis
Authors: Zhu Zhengchuan , Wang Miaoran , Lin Wei , Cai Qiaoyan , Zhang Ling , Chen Daxin , Liu Fei , Xiong Xiaoman , Chu Jianfeng , Peng Jun , Chen Keji
Published: August 2021

Aims

To explore the correlation between cardiac‐related comorbidities, cardiac biomarkers, acute myocardial injury, and severity level, outcomes in COVID‐19 patients.

Method

Pubmed, Web of Science, Embase, CNKI, VIP, Wanfang, Cochrane Library databases, medRxiv, and Sinomed were reviewed systemically. Various types of clinical research reporting cardiac‐related comorbidities, cardiac biomarkers including lactate dehydrogenase (LDH), troponin I (TnI), high sensitivity troponin I (hs‐TnI), creatine kinase (CK), creatine kinase–MB (CK‐MB), myoglobin (Myo), N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) and acute cardiac injury grouped by severity of COVID‐19 were included. Outcome measures were events and total sample size for comorbidities, acute cardiac injury, and laboratory parameters of these biomarkers. The study was performed with Stata version 15.1.

Results

Seventy studies, with a total of 15,354 cases were identified. The results showed that COVID‐19's severity was related to cardiovascular disease. Similar odds ratios (ORs) were achieved in hypertension except for severe versus critical group (OR = 1.406; 95% CI, 0.942–2.097; p = .095). The relative risk (RR) of acute cardiac injury is 7.01 (95% CI, 5.64–8.71) in non‐survivor cases. When compared with the different severity of cardiac biomarkers, the pool OR of CK, CK‐MB, TnI, Myo and LDH were 2.683 (95% CI, 0.83–8.671; p = .106; I2 = 0%), 2.263 (95% CI, 0.939–5.457; p = .069), 1.242 (95% CI, 0.628–2.457; p = .534), 1.756 (95% CI, 0.608–5.071; p = .298; I2 = 42.3%), 1.387 (95% CI, 0.707–2.721;  p = .341; I2 = 0%) in the critical versus severe group, whose trends were not similar to other groups. The standard mean differences (SMD) of CK and TnI in the critical versus severe group were 0.09 (95% CI, −0.33 to 0.50; p = .685; I2 = 65.2%), 0.478 (95% CI, −0.183 to 1.138; p = .156; I2 = 76.7%), which means no difference was observed in the serum level of these indicators.

Conclusion

Most of the findings clearly indicate that hypertension, cardiovascular disease, acute cardiac injury, and related laboratory indicators are associated with the severity of COVID‐19. What is now needed are cross‐national prospectively designed observational or clinical trials that will help improve the certainty of the available evidence and treatment decisions for patients.
Approach‐avoidance responses and categorical perception of ambiguous facial expressions
Authors: Ikeda Shinnosuke
Published: August 2021

Emotion perception of facial expressions involves two processes: quick approach‐avoidance responses and subsequent sorting into emotional categories (i.e., happiness, anger), considering the context. Sorting of morphed ambiguous facial expressions is known to occur categorically, but the occurrence of approach‐avoidance responses for morphed facial expressions is yet to be investigated. The present study used morphed angry and fearful facial expressions and measured approach‐avoidance responses among Japanese university students (Experiment 1, n = 29). Similar experiments with linguistic load (Experiment 2, n = 28) and visual load (Experiment 3, n = 29) were conducted. The results indicated categorical perception in the sorting of facial expressions but no approach‐avoidance response for morphed expressions. Furthermore, linguistic load affected the categorisation of facial expressions, but neither linguistic load nor visual load affected the approach‐avoidance response. These results support the idea that the non‐linguistic approach‐avoidance response and the linguistic categorisation of facial expressions are two different processes. The nature of the emotional perception process is also discussed.
IceCream, Transportable Software for Creating Friendly Human Interfaces
Authors: Linnainmaa Seppo
Published: August 2021

A new software package called IceCream (‘Interactive Command Executor, CREAting Modules‘) is described, which can be used as a frame when creating interactive text‐based user interfaces. Also, syntactically complicated command languages can be implemented easily. Several convenient properties are automatically included in the generated interfaces, including expansion of keywords to full width as soon as they can be uniquely identified, the impossibility of entering syntactically incorrect input, and an automatic help facility. The software is almost entirely written in totally portable standard Pascal. The small fraction of code which depends on the hardware is well isolated.
The Automatic Generation of Fast Lexical Analysers
Authors: Heuring V. P.
Published: August 2021

This paper describes lexical analyser generators that accept specifications for the basic symbols of a programming language, and produce directly executing lexical analysers in Pascal or C as output. The resulting analysers are up to five times as fast as the typical interpreted lexical analyser generated from arbitrary regular expressions and actions. An example is given showing how these tools may be combined with others in a compiler construction environment.
The first Chinese case of Vici syndrome with novel compound heterozygous sequence variants in EPG5
Authors: Dong Liping , Li Liangshan , Zhang Xiao , Xu Xin , Han Mengmeng , Liu Shiguo
Published: August 2021

Background

Vici syndrome (VICIS) refers to a clinical spectrum of multiple organ systems characterized by corpus callosum agenesis, hypopigmentation, cataracts, cardiomyopathy and immunodeficiency. The aims of this study were to describe detailed clinical and molecular features of two Chinese female siblings and to review several previous findings.

Methods

Targeted sequencing panel involving all known disease‐causing genes of monogenic disorders combined with Sanger sequencing validation were performed to identify the likely pathogenic sequence variants of the proband with VICIS.

Results

The proband diagnosed as VICIS presented with neonatal pneumonia, myocardial damage, hypotonia, maxillofacial malformations, hearing impairment, failure to thrive and died 40 days after birth. Two novel missense variants in ectopic P‐granules autophagy protein 5 homologue (EPG5, NM_020964.3) were identified in this proband. The two likely pathogenic variants c.1609G > A (p.(E537K)) and c.5764C>G (p.(P1922A)) were assessed as damaging by bioinformatic analysis. As these variants were absent in 150 unrelated Chinese normal controls and inherited from asymptomatic parents in the co‐segregation analysis, the compound heterozygous EPG5 variants were responsible for the clinical features of this patient. Finally, she was genetically diagnosed with VICIS.

Conclusions

To our knowledge, this is the first Chinese case of VICIS. Our report identified novel compound heterozygous EPG5 sequence variants in the proband with VICIS, highlighting the rarity and high mortality rate of VICIS and emphasizing on the importance of high‐throughput sequencing in confirmed diagnosis of monogenic diseases, which could further facilitate the development of genetic counselling and prenatal diagnosis.
Efficacy of Nd:YAG laser‐assisted periodontal therapy for the management of periodontitis: A double‐blind split‐mouth randomized controlled clinical trial
Authors: Dortaj Dorara , Bassir Seyed Hossein , Hakimiha Neda , Hong Houlin , Aslroosta Hoori , Fekrazad Reza , Moslemi Neda
Published: August 2021

Background

This study aimed to explore the efficacy of Nd:YAG laser‐assisted periodontal therapy for management of patients with stage II‐IV periodontitis.

Methods

Patients who presented with residual periodontal pockets were enrolled. After non‐surgical periodontal therapy (NSPT), test sites received Nd:YAG laser (first entrance to pocket: 3 W, 100 μs, 20 Hz; second entrance: 4 W, 600 μs, 20 Hz) and control sites received placebo (laser off). Periodontal probing depth (PPD), clinical attachment level (CAL), gingival recession (GR), bleeding on probing (BOP), and plaque index (PI) were recorded at baseline and 1, 2, 3, 4 and 6‐month visits.

Results

Twenty patients completed the 6‐month period. Significant reductions in PPD, CAL, BOP, and PI values and a significant increase in GR at all follow‐up visits compared to the baseline (all P < 0.001) were revealed in both groups. Test sites showed significantly greater improvement in PPD (P = 0.0002) and greater increase in GR (P < 0.0001) compared to the control sites at 6‐month visit. There was no difference between two groups regarding CAL gain through the study period (P = 0.23).

Conclusion

NSPT+Nd:YAG laser with the current protocol results in greater PPD reduction compared to NSPT alone. However, this reduction is likely because of greater GR rather than attachment gain. Therefore, the adjunction of Nd:YAG laser (with the current setting) to the NSPT for the treatment of residual periodontal pockets did not ameliorate the clinical outcomes (ClinicalTrials.gov ID: NCT03365167).
Fermentability of select polyphenol‐rich substrates in the canine faecal inoculum and their interaction with a canine‐origin probiotic: anin vitroappraisal
Authors: Ashwin Kandathil , Pattanaik Ashok K , Paladan Varsha , Singh Asmita , Sahoo Jatin K , Jose Tony , Jadhav Sunil E , Dutta Narayan
Published: August 2021

BACKGROUND

Thisin vitrostudy aimed to compare the hindgut fermentability and digestibility of four different sources of polyphenols, namely orange (Citrus sinensis) peel (ORP), pomegranate (Punica granatum) peel (PMP), Indian blackberry (Syzygium cumini) pulp (IBP), and Jerusalem artichoke (Helianthus tuberosus) tuber (JAT), and their influence on the viability of a canine‐origin probiotic,Lactobacillus johnsoniiCPN23.

RESULTS

Anin vitrogas production test carried out using the four substrates for a period of 72 h with dog faecal inoculum indicated that the total gas production, dry matter, and organic matter digestibility were significantly (P < 0.001) higher with JAT, whereas they were lowest for PMP. Short‐chain fatty acids production was significantly higher (P < 0.001) with ORP and JAT, with the least values recorded for PMP. The ammonia‐nitrogen production was significantly (P < 0.001) higher with JAT than with ORP, IBP, and PMP, and a lower (P < 0.001) pH was evident with ORP, JAT, and IBP than with PMP. Viability ofL. johnsoniiCPN23 was tested in the presence of the polyphenol‐rich extract from each of the four sources at varying doses (50, 500, 1000, 2500, and 5000 μg mL−1). PMP extract showed the highest inhibitory effect on the probiotic bacteria's growth in a dose‑ and time‐dependent manner (P < 0.001). ORP and IBP extracts were stimulatory at the optimum dosage, whereas JAT reduced probiotic activity significantly at all doses tested.

CONCLUSION

Overall, the results indicate a higher hindgut fermentability of JAT, ORP, and IBP, suggesting their potential beneficial effects for gut health application. An interaction study between polyphenol extract andL. johnsoniiCPN23 showed a stimulatory effect of polyphenolic extracts from ORP and IBP on probiotic growth at optimal dosage. Consistent with the fermentation study findings, PMP extract reduced the growth ofL. johnsoniiCPN23 irrespective of the doses tested. © 2021 Society of Chemical Industry.
A survey of surgical management of the sentinel node positive melanoma patient in the post‐MSLT2 era
Authors: Downs Jennifer S. , Subramaniam Suren , Henderson Michael A. , Paton Elizabeth , Spillane Andrew J. , Mathy Jon A. , Gyorki David E.
Published: August 2021

Background

The evidence‐based management of melanoma patients with a positive sentinel lymph node biopsy (SLNB) has undergone a dramatic shift following publication of practice‐changing surgical trials demonstrating no melanoma‐specific survival advantage for completion lymph node dissection (CLND) in this scenario. We aimed to survey how surgeons' clinical practice had shifted in response to new evidence from these trials, and at a time when there was starting to become available systemic adjuvant treatments for AJCC Stage III melanoma patients.

Methods

A web‐based survey consisting of practice‐based questions and hypothetical clinical scenarios about current melanoma practice with regard to positive sentinel node biopsy was developed and sent to the surgical members of a Melanoma and Skin Cancer (MASC) Trials group in December 2018. Responses were analysed using descriptive statistics.

Results

There were 212 invitations sent and 65 respondents (31%). Respondents were from 17 countries, 94% of whom practice in specialist melanoma centres or at referral centres. Of these 97% were familiar with the MSLT2 and DeCOG‐SLT clinical trials. At survey, 5% of respondents reported routinely recommending CLND and 55% recommend CLND in selected cases. Respondents were most likely to recommend CLND when multiple SLNs were positive. Important factors for surgical decision‐making mentioned included size of SLN deposit, number of positive SLNs and likely compliance with the recommended surveillance regimen.

Conclusion

In line with rapid adoption of published evidence, surgical management of Stage III melanoma has altered significantly, with few surgeons within the cohort now performing routine CLNDs after positive SLNB.
Deep learning based synthetic‐CT generation in radiotherapy and PET: A review
Authors: Spadea Maria Francesca , Maspero Matteo , Zaffino Paolo , Seco Joao
Published: August 2021

Recently,deep learning (DL)‐based methods for the generation of synthetic computed tomography (sCT) have received significant research attention as an alternative to classical ones. We present here a systematic review of these methods by grouping them into three categories, according to their clinical applications: (i) to replace computed tomography in magnetic resonance (MR) based treatment planning, (ii) facilitate cone‐beam computed tomography based image‐guided adaptive radiotherapy, and (iii) derive attenuation maps for the correction of positron emission tomography. Appropriate database searching was performed on journal articles published between January 2014 and December 2020. The DL methods' key characteristics were extracted from each eligible study, and a comprehensive comparison among network architectures and metrics was reported. A detailed review of each category was given, highlighting essential contributions, identifying specific challenges, and summarizing the achievements. Lastly, the statistics of all the cited works from various aspects were analyzed, revealing the popularity and future trends and the potential of DL‐based sCT generation. The current status of DL‐based sCT generation was evaluated, assessing the clinical readiness of the presented methods.
Prediction of 15N chemical shifts by machine learning
Authors: Gerrard Will , Yiu Calvin , Butts Craig P.
Published: August 2021

We demonstrate the potential for machine learning systems to predict three‐dimensional (3D)‐relevant NMR properties beyond traditional 1H‐ and 13C‐based data, with comparable accuracy to density functional theory (DFT) (but orders of magnitude faster). Predictions of DFT‐calculated 15N chemical shifts for 3D molecular structures can be achieved using a machine learning system—IMPRESSION (Intelligent Machine PREdiction of Shift and Scalar information Of Nuclei), with an accuracy of 6.12‐ppm mean absolute error (∼1% of the δ15N chemical shift range) and an error of less than 20 ppm for 95% of the chemical shifts. It provides less accurate raw predictions of experimental chemical shifts, due to the limited size and chemical space diversity of the training dataset used in its creation, coupled with the limitations of the underlying DFT methodology in reproducing experiment.
Experiences of women with breast cancer undergoing chemotherapy: A study at Ho Teaching Hospital, Ghana
Authors: Kudjawu Senam , Agyeman‐Yeboah Joana
Published: August 2021

Aim

The study explored the experiences of women with breast cancer undergoing chemotherapy at Ho Teaching Hospital.

Design

A qualitative design which was exploratory and descriptive in nature was employed.

Methods

Purposive sampling was used to recruit participants. Data were collected using a semi‐structured interview guide. Saturation of data was reached after the eighth participant was interviewed. The interviews were audio‐recorded and lasted between 30–70 min, and the data were analysed concurrently with data collection using content analysis. Three major themes emerged.

Results

Participants experienced hair loss, changes in skin and nail pigmentation and social isolation. The study further revealed that inadequate access to information from healthcare providers and lack of resources coupled with financial constraints were among the major challenges participants faced. However, varied supports from significant others were of much help which enabled participants to go through their chemotherapy successfully.
The Occasional Reader
Authors: Chabner Bruce A.
Published: August 2021

The editors of The Oncologist offer suggestions for summer reading of books that provide insight into our field of endeavor, our civil discourse, and our personal lives.
Immune response to SARS‐CoV‐2 in children: A review of the current knowledge
Authors: Filippatos Filippos , Tatsi Elizabeth‐Barbara , Michos Athanasios
Published: August 2021

Host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID‐19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS‐C) associated with SARS‐CoV‐2 infection. The deciphering of children’s immune responses during COVID‐19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID‐19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS‐CoV‐2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS‐CoV‐2 infection and adaptive memory immunity is vital to prevent reinfection.
De novo design of metal‐binding cleft in a Trp‐Trp stapled thermostable β‐hairpin peptide
Authors: Lella Muralikrishna , Mahalakshmi Radhakrishnan
Published: August 2021

Metals are important molecules in protein biochemistry, as they are involved in various essential biochemical processes. Inspired by the coordination chemistry of metal‐binding proteins, and to improvise the stability of recognition motifs, here we present the design of hyperstable stapled β‐hairpin with a defined metal‐binding cleft. We achieved this by establishing Trp‐Trp covalent cross‐linking in a long‐chain 16‐residue β‐hairpin scaffold, and incorporating a stereospecific Cys2‐His2 tetrad as the metal‐binding cleft. This water‐soluble peptide showed broad metal‐binding properties, with Cu2+ specificity. Importance of the Cys‐His tetrad in metal ion selectivity was established with Asp/Glu substitutions. We propose that such predefined hyperstable β‐hairpins with recognition motifs are useful versatile tools for developing peptide‐based catalysts, and in biomarker design.
Investigate the interaction of testosterone/progesterone with ionic liquids on varying the anion to combat COVID‐19: Density functional theory calculations and molecular docking approach
Authors: Kumari Kamlesh , Kumar Ajay , Bahadur Indra , Singh Prashant
Published: August 2021

Hormones like testosterone and progesterone in the humans play significant role in the regulation of various biological processes like the body growth, reproduction, and others. In last two decades, researchers are using ionic liquids (ILs) extensively in different areas of sciences, and they are a novel class of compounds as well as their polarity can be tuned. ILs are multidisciplinary in nature and can be used in chemistry, materials science, chemical engineering, and environmental science. Further, ILs are being explored to increase the solubility of drugs or biological potential molecules. Testosterone and progesterone are found to be not very polar in nature; therefore, the authors attempt to increase the solubility of testosterone and progesterone via interaction with ILs. It was studied with density functional theory calculations using Gaussian, and an increase in the value of dipole moment is observed for the complex of testosterone/progesterone with the ILs in comparison of individual one. The optimization energy and other thermodynamic energies of the ILs (IL1‐IL3), testosterone (T), testosterone‐IL (T‐IL1 to T‐IL3), progesterone (P), and progesterone‐ILs (P‐IL1 to P‐IL3) are found to be negative. Further, the change in free energy for the formation of complexes at room temperature is calculated. Further, the authors have investigated the synergistic effect of testosterone and progesterone against the main protease of new coronavirus using molecular docking. It is observed that the testosterone‐IL1 {IL1‐3‐(2‐hydroxyethyl)‐1‐methyl‐1H‐imidazol‐3‐ium 2,4,6‐trinitrophenolate} is found to be prominent against the main protease of SARS‐CoV‐2.
Effect of human milk and other neonatal variables on lung function at three months corrected age
Authors: Beretta Francesco , Lavizzari Anna , Pesenti Nicola , Arkhangelskaia Taja , Ciuffini Francesca , Ophorst Marijke , Gangi Silvana , Colnaghi Mariarosa , Morniroli Daniela , Mosca Fabio , Giannì Maria L.
Published: August 2021

Objective

To evaluate the impact of human milk and different neonatal variables on tidal breathing flow‐volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing <1500 g.

Methods

We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) <1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018.

We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and >1000 g).

Results

The mean(SD) z‐score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively −4.3 (2.5) and −0.8 (2.0) for the overall population with no significant differences between infants <1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg.

Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW < 1000 gr, tPTEF/tE was positively associated with HMF.

Conclusion

An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW <1000 g has emerged, which deserves further investigation.
Effects of tracheostomy on mothers of children with cerebral palsy
Authors: Mavi Deniz , Onay Zeynep Reyhan , Karatoprak Elif Yuksel , Oksay Sinem Can , Ayhan Yetkin , Bulut Irem , Bilgin Gülay , Bikmazer Alperen , Girit Saniye
Published: August 2021

Objective

We aimed to investigate psychosocial changes such as burnout, caregiver burden, depression, and coping in mothers of children with cerebral palsy (CP) after tracheostomy placement.

Design

A total of 48 children with CP and chronic respiratory insufficiency and their mothers participated in the study. The children with tracheostomy were classified as T (+) (n = 26) and those who did not have tracheostomy were classified as T (−) (n = 22). The patients with tracheostomy through invasive mechanical ventilation were classified as TIV (+). The data about the clinical conditions of the patients and the sociodemographic characteristics of the mothers were recorded. Zarit caregiver burden, Maslach burnout, Beck depression, and Coping Orientation to Problems Experienced (COPE) questionnaires were applied to all mothers.

Findings

Beck depression score was 14 ± 8.24 in T (+) group and 16.09 ± 9.65 in T (−) group (p = .576). There was no significant difference between the T (+) and T (−) groups in the Maslach burnout inventory, Zarit caregiver burden scale, and their subgroups. The first two methods from the COPE scales were identical. In the T (+) group, the third coping method was found as “planning” and in the T (−) group as “active coping”. Maslach burnout inventory, Zarit 1, and Zarit 2 scores were higher in patients with only tracheostomy compared to those with TIV (p = .002, p = .018, p = .021).

Conclusion

In the study presented, the placement of tracheostomy in children with CP does not increase mother's depression tendencies and mood changes.