bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of N, N′‐Diboryl‐4, 4′‐bipyridinylidene in the Transition‐Metal‐Free Borylation of Aryl Halides and Direct C−H Arylation of Unactivated Benzene
Authors: Waghamare Akash B. , Raut Ravindra K. , Patel Niranjan , Majumdar Moumita
Published: July 2022

N,N′‐Diboryl‐4,4′‐bipyridinylidene (BBiPy) has been utilized in sub‐stoichiometric amounts along with anionic base as one electron donor species for both transition metal‐free borylation of aryl halides and arene C−H functionalization with aryl iodides for biaryl syntheses. Reaction between BBiPy and potassium tert‐butoxide or methoxide has led to the formation of 4,4′‐bipyridine radical anion (BiPy⋅−) with the release of an electron. The BiPy⋅− has been structurally characterized. The single electron released is transferred to aryl halides generating aryl radicals, which then react with diboron in the presence of methoxide to form aryl boronate and with unactivated benzene in the presence of tert‐butoxide to form biaryls. Substrate scopes studies showed that aryl iodides and bromides undergo borylation (1B–12B), while only aryl iodides undergo C−C bond formation with arene C−H (1C–8C) through radical chain reaction. Mechanisms for C−B and C−C bond formation have been proposed based on the experimental findings.
Metalation of 2‐Quinolyl‐Linked (Boranophosphinoyl)methane −Alkali Metal, Alkaline Earth Metal, and Ytterbium(II) Complexes of Monoanionic [CH(iPr2P−BH3)(C9H6N‐2)]− Ligand
Authors: Choi Tsz‐Hei , Leung Wing‐Por , Lee Hung Kay , Chan Yuk‐Chi
Published: July 2022

A series of alkali and alkaline earth metal complexes, and an ytterbium(II) complex of monoanionic [CH(iPr2P−BH3)(C9H6N‐2)]− ligand (abbreviated as LQPB−) were synthesized. Lithium complexes [Li(LQPB)(TMEDA)] (2, TMEDA=Me2NCH2CH2NMe2) and [Li(LQPB)(12‐crown‐4)] (3) were prepared by lithiation of 1 with LinBu in the presence of TMEDA and 12‐crown‐4 ether, respectively. Treatment of 2 with NaOtBu and KOtBu, respectively, followed by addition of 18‐crown‐6 ether yielded monomeric sodium complex [Na(LQPB)(18‐crown‐6)] (4) and polymeric potassium derivative [K(LQPB)(18‐crown‐6)]n (5). Metalation of 1 with MgnBu2/TMEDA afforded [Mg(LQPB)2(TMEDA)] (6). Heavier group 2 complexes [Ca(LQPB)2(DME)2] (7), [Sr(LQPB)2]2 (8) and [Ba(LQPB)2(DME)] (9) were synthesized by metalation of 1 with the corresponding alkaline earth metal amide M[N(SiMe3)2]2(DME)n (M=Ca or Ba, n=2; M=Sr, n=0) in toluene under reflux conditions. Treatment of YbI2(THF)2 with potassium complex 5 led to isolation of mononuclear Yb(II) complex [Yb(LQPB)2(18‐crown‐6)] (10).
Cerium(IV)‐Mediated Carbon‐Carbon Bond Formation for the Synthesis of Spirodienone Lactams
Authors: Adler Pauline , Perez Vincent , Roupnel Loïc , Fadel Antoine , Rabasso Nicolas
Published: July 2022

α‐Phosphorylated para‐methoxybenzyl allenamides were oxidised with cerium(IV) to produce spirodienone lactams through a 5‐endo‐dig cyclisation. By modulating the electronic effects on the phosphorus and nitrogen atoms we were able to overcome some of the limitations of our first‐generation approach. Moreover, replacement of α‐allenylphosphonates with ynamido‐phosphonates led, in two steps, to the same spirodienone core after oxidation with cerium(IV) hence overcoming other limitations of the previous method.
One‐Pot Divergent Synthesis of Benzoxazines and Dihydroquinolines from Morita‐Baylis‐Hillman Alcohols
Authors: Wang Tao , Chen Xuling , Li Pengfei
Published: July 2022

Benzoxazines and hydroquinolines have been prepared by a one‐pot process via catalyst‐controlled divergent annulations of Morita‐Baylis‐Hillman (MBH) alcohols. In the presence of diazabicyclo[2.2.2]octane, MBH alcohols reacted with Boc2O to form MBH carbonates, followed by intramolecular annulation to give 4H‐benzo[d][1,3]oxazines. Divergently, the combination of Bu4NBr and NaOH enabled the formation of 1,2‐dihydroquinolines from the same starting materials.
A Novel Electrochemical Method for the Sensitive Determination of Aflatoxin B1 Using a Bivalent Binding Aptamer‐cDNA Structure
Authors: Sameiyan Elham , Lavaee Parirokh , Ramezani Mohammad , Alibolandi Mona , Khoshbin Zahra , Abnous Khalil , Taghdisi Seyed Mohammad
Published: July 2022

In this study, a simple electrochemical sensing platform with the employment of a bivalent binding aptamer‐cDNA probe (BBA‐cDNA) structure is constructed for the detection of aflatoxin B1 (AFB1) as a mycotoxin. The BBA‐cDNA structure is composed of two strands of aptamer (Apts) and their complementary strand (CS). Using a simple but accurate design, the presented measurement approach showed enhanced sensitivity and selectivity for AFB1 detection with a LOD of 0.1 ng/mL. The approach presented in this study can be applied to the development of biosensors for the measurement of various toxins by substituting the proper aptamers and complementary strands.
Commercially Available Nitrate Ionophores in Potentiometric Sensors are not Superior to Common Ion‐exchangers
Authors: Damala Polyxeni , Zdrachek Elena , Bakker Eric
Published: July 2022

Nitrate sensing is an important application for potentiometry in environmental applications. Its recognition is by ion‐exchangers whose selectivity is governed by the lipophilicity of the ions in solution. Yet, considerable research efforts have been dedicated to the development of such ionophores and some have already been commercialized. This work examines two commercially available nitrate ionophores, nitrate ionophores V and VI, and compares their performance with widely used ion‐exchangers by determining the resulting membrane selectivity and complexation to nitrate. Unfortunately, adding a nitrate ionophore to the membrane did not result in improved selectivity. Sandwich membrane experiments indicated that binding interaction is too weak to be measurable, with a logarithmic formation constant of just 1.36±0.14 for ionophore V with nitrate. Ways to improve the reporting of relevant data are suggested.
Epidemic trend analysis of SARS‐CoV‐2 in South Asian Association for Regional Cooperation countries using modified susceptible‐infected‐recovered predictive model
Authors: Dey Samrat Kumar , Rahman Md. Mahbubur , Shibly Kabid Hassan , Siddiqi Umme Raihan , Howlader Arpita
Published: July 2022

A novel coronavirus causing the severe and fatal respiratory syndrome was identified in China, is now producing outbreaks in more than 200 countries around the world, and became pandemic by the time. In this article, a modified version of the well‐known mathematical epidemic model susceptible‐infected‐recovered (SIR) is used to analyze the epidemic's course of COVID‐19 in eight different countries of the South Asian Association for Regional Cooperation (SAARC). To achieve this goal, the parameters of the SIR model are identified by using publicly available data for the corresponding countries: Afghanistan, Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka. Based on the prediction model, we estimated the epidemic trend of COVID‐19 outbreak in SAARC countries for 20, 90, and 180 days, respectively. A short‐mid‐long term prediction model has been designed to understand the early dynamics of the COVID‐19 epidemic in the southeast Asian region. The maximum and minimum basic reproduction numbers (R0 = 1.33 and 1.07) for SAARC countries are predicted to be in Pakistan and Bhutan. We equate simulation results with real data in the SAARC countries on the COVID‐19 outbreak, and predicted different scenarios using the modified SIR prediction model. Our results should provide policymakers with a method for evaluating the impacts of possible interventions, including lockdown and social distancing, as well as testing and contact tracking.
Effect of fenfluramine on seizures and comorbidities in SCN8A‐developmental and epileptic encephalopathy: A case series
Authors: Aledo‐Serrano Ángel , Cabal‐Paz Borja , Gardella Elena , Gómez‐Porro Pablo , Martínez‐Múgica Otilia , Beltrán‐Corbellini Alvaro , Toledano Rafael , García‐Morales Irene , Gil‐Nagel Antonio
Published: July 2022

SCN8A‐developmental and epileptic encephalopathy is caused by pathogenic variants in the SCN8A gene encoding the Nav1.6 sodium channel, and is characterized by intractable multivariate seizures and developmental regression. Fenfluramine is a repurposed drug with proven antiseizure efficacy in Dravet syndrome and Lennox–Gastaut syndrome. The effect of fenfluramine treatment was assessed in a retrospective series of three patients with intractable SCN8A epilepsy and severe neurodevelopmental comorbidity (n = 2 females; age 2.8–13 years; 8–16 prior failed antiseizure medications [ASM]; treatment duration: 0.75–4.2 years). In the 6 months prior to receiving fenfluramine, patients experienced multiple seizure types, including generalized tonic–clonic, focal and myoclonic seizures, and status epilepticus. Overall seizure reduction was 60%–90% in the last 3, 6, and 12 months of fenfluramine treatment. Clinically meaningful improvement was noted in ≥1 non‐seizure comorbidity per patient after fenfluramine, as assessed by physician‐ratings of ≥“Much Improved” on the Clinical Global Impression of Improvement scale. Improvements included ambulation in a previously non‐ambulant patient and better attention, sleep, and language. One patient showed mild irritability which resolved; no other treatment‐related adverse events were reported. There were no reports of valvular heart disease or pulmonary arterial hypertension. Fenfluramine may be a promising ASM for randomized clinical trials in SCN8A‐related disorders.
Nematode Community of a Natural Grassland Responds Sensitively to the Broad-Spectrum Fungicide Mancozeb in Soil Microcosms
Authors: Höss Sebastian , Reiff Nicola , Asekunowo Jennifer , Helder Johannes
Published: July 2022

Fungicides make up the largest part of total pesticide use, with the dithiocarbamate mancozeb being widely applied as a nonsystemic contact pesticide to protect a wide range of field crops against fungal diseases. Although nematodes are key drivers of soil functioning, data on effects of fungicides, and especially mancozeb, on these nontarget organisms are scarce. Therefore, the effects of mancozeb on a soil nematode community from a natural grassland were assessed in small-scale soil microcosms. Nematodes were exposed to mancozeb-spiked soil in six nominal concentrations (7–133 mg/kg dry soil) and analyzed after 14, 56, and 84 days in terms of densities, genus composition, and functional traits. Because this fungicide is known to quickly degrade in soils (50% degradation time <1 day), mancozeb concentrations were analyzed for all sampling occasions. Chemical analysis revealed considerably lower measured concentrations compared with the aimed nominal soil concentrations at the beginning of the exposure (1–18 mg/kg dry soil), suggesting fast degradation during the spiking process. Nevertheless, the native nematode community responded sensitively to the fungicide mancozeb, revealing lower no-observed-effect concentration and 10% effect concentration (EC10) values than reported for other soil invertebrates such as springtails and earthworms. Using the EC10 for the most sensitive nematode community endpoint (percentage of predators and omnivores: 1.2 mg/kg dry soil), the risk assessment exhibited a toxicity exposure ratio of 0.66 and, thus, a high risk of mancozeb for soil nematodes. Keeping in mind their abundance and their central roles in soil food-web functioning, the demonstrated sensitivity to a widely applied fungicide underscores the relevance of the inclusion of nematodes into routine risk-assessment programs for pesticides. Environ Toxicol Chem 2022;41:2420–2430. © 2022 SETAC
Collembola are Among the Most Pesticide-Sensitive Soil Fauna Groups: A Meta-Analysis
Authors: Joimel Sophie , Chassain Juliette , Artru Maxime , Faburé Juliette
Published: July 2022

Pesticides are a major concern because of their deleterious impacts on biodiversity and on the ecological functions provided by living organisms. Although earthworms are well studied, smaller-sized organisms, such as Collembola, also contribute to the agroecosystem functioning, and their sensitivity to pesticides makes them good bioindicators of soil quality. Using data from 21 publications, we performed a meta-analysis to compare the pesticide sensitivity of Collembola with other soil invertebrate groups and discuss the relevance of including tests on representatives of this microarthropods group in European regulation tests. We defined a paired observation as the median lethal concentration or the median effect concentration values for both Collembola species and another soil fauna group (Acari, enchytraeids, earthworms, isopods, and nematodes) under a unique combination of author, year, substance, and type of soil (61 and 57 paired observations for reproduction and lethal effects). In some studies, paired comparisons were available for several groups of soil fauna. We demonstrated that Collembola are among the most sensitive soil fauna groups to a variety of pesticides, notably for effects on reproduction, mostly compared with earthworms and enchytraeids. Because there are several modes of exposure and explaining factors, we suggest moving from a single-species study to a food-chain approach integrating different taxonomic groups. Differences between soil fauna groups in sensitivity or response to pesticides could have effects on soil communities and also on soil functions. Environ Toxicol Chem 2022;41:2333–2341. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Atomic cerium modulated palladium nanoclusters exsolved ferrite catalysts for lean methane conversion
Authors: Yang Yanling , Wang Si , Tu Xin , Hu Zhiwei , Zhu Yinlong , Guo Hongquan , Li Zhishan , Zhang Li , Peng Meilan , Jia Lichao , Yang Meiting , Yang Guangming , Qiao Xurong , Sun Jiahui , Liang Xiaolu , Zhang Zhen , Zhu Yanru , Shi Lei , Jiang Chenxing , Zhao Yingru , Li Jianhui , Shao Zongping , Zhang Xin , Sun Yifei
Published: July 2022

The active and stable palladium (Pd) based catalysts for CH4 conversion are of great environmental and industrial significance. Herein, we employed N2 as an optimal activation agent to develop a Pd nanocluster exsolved Ce‐incorporated perovskite ferrite catalyst toward lean methane oxidation. Replacing the traditional initiator of H2, the N2 was found as an effective driving force to selectively touch off the surface exsolution of Pd nanocluster from perovskite framework without deteriorating the overall material robustness. The catalyst showed an outstanding T50 (temperature of 50% conversion) plummeting down to 350°C, outperforming the pristine and H2‐activated counterparts. Further, the combined theoretical and experimental results also deciphered the crucial role that the atomically dispersed Ce ions played in both construction of active sites and CH4 conversion. The isolated Ce located at the A‐site of perovskite framework facilitated the thermodynamic and kinetics of the Pd exsolution process, lowering its formation temperature and promoting its quantity. Moreover, the incorporation of Ce lowered the energy barrier for cleavage of C─H bond, and was dedicated to the preservation of highly reactive PdOx moieties during stability measurement. This work successfully ventures uncharted territory of in situ exsolution to provide a new design thinking for a highly performed catalytic interface.
Parental emotional support trajectories and the risk of adolescent overweight or obesity
Authors: Tabet Maya , Xaverius Pamela K.
Published: July 2022

We used data from the National Longitudinal Survey of Youth (n = 6108; 50.9% males; 16.7% Black, 8.1% Hispanic, 75.2% Non‐Black, Non‐Hispanic) to examine associations between parental emotional support trajectories at 0–15 years and overweight or obesity at 15–19 years and explore the effects of timing and cumulative exposure to low parental emotional support on overweight or obesity. Parental emotional support was assessed using the Home Observation Measurement of the Environment and adolescent overweight or obesity was defined using the International Obesity Task Force cut‐offs. Latent Class Analysis was used to identify parental emotional support trajectories and Poisson regression was used to examine associations under study. Low parental emotional support in childhood increased the risk of adolescent overweight or obesity, with gender‐based differences.

Highlights

We examined associations between parental emotional support at 0–15 years and overweight or obesity at 15–19 years

We used Latent Class Analysis to identify parental emotional support trajectories and Poisson regression to examine associations under study

Low parental emotional support in childhood increased the risk of adolescent overweight or obesity, with gender‐based differences
Human iPSC‐Vascular smooth muscle cell spheroids demonstrate size‐dependent alterations in cellular viability and secretory function
Authors: Islam Sara , Parker Jackson , Dash Biraja C. , Hsia Henry C.
Published: July 2022

Human‐induced pluripotent stem cells (hiPSC) and their differentiated vascular cells have been revolutionizing the field of regenerative wound healing. These cells are shown to be rejuvenated with immense potentials in secreting paracrine factors. Recently, hiPSC‐derived vascular smooth muscle cells (hiPSC‐VSMC) have shown regenerative wound healing ability via their paracrine secretion. The quest to modulate the secretory function of these hiPSC‐VSMC is an ongoing effort and involves the use of both biochemical and biophysical stimuli. This study explores the development and optimization of a reproducible, inexpensive protocol to form hiPSC‐VSMC derived spheroids to investigate the implications of spheroid size on viability and paracrine secretion. Our data show the successful formation of different sizes of spheroids using various amount of hiPSC‐VSMC. The hiPSC‐VSMC spheroids formed with 10,000 cells strike an ideal balance between overall cell health and maximal paracrine secretion. The conditioned medium from these spheroids was found to be bioactive in enhancing human dermal fibroblast cell proliferation and migration. This research will inform future studies on the optimal spheroid size for regenerative wound healing applications.
Targeted Long-Read Sequencing Identifies a Retrotransposon Insertion as a Cause of Altered GNAS Exon A/B Methylation in a Family With Autosomal Dominant Pseudohypoparathyroidism Type 1b (PHP1B)
Authors: Miller Danny E , Hanna Patrick , Galey Miranda , Reyes Monica , Linglart Agnès , Eichler Evan E , Jüppner Harald
Published: July 2022

Pseudohypoparathyroidism type Ib (PHP1B) is characterized predominantly by resistance to parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. These laboratory abnormalities are caused by maternal loss-of-methylation (LOM) at GNAS exon A/B, which reduces in cis expression of the stimulatory G protein α-subunit (Gsα). Paternal Gsα expression in proximal renal tubules is silenced through unknown mechanisms, hence LOM at exon A/B reduces further Gsα protein in this kidney portion, leading to PTH resistance. In a previously reported PHP1B family, affected members showed variable LOM at exon A/B, yet no genetic defect was found by whole-genome sequencing despite linkage to GNAS. Using targeted long-read sequencing (T-LRS), we discovered an approximately 2800-bp maternally inherited retrotransposon insertion nearly 1200 bp downstream of exon XL not found in public databases or in 13,675 DNA samples analyzed by short-read whole-genome sequencing. T-LRS data furthermore confirmed normal methylation at exons XL, AS, and NESP and showed that LOM comprising exon A/B is broader than previously thought. The retrotransposon most likely causes the observed epigenetic defect by impairing function of a maternally derived NESP transcript, consistent with findings in mice lacking full-length NESP mRNA and in PHP1B patients with deletion of exon NESP and adjacent intronic sequences. In addition to demonstrating that T-LRS is an effective strategy for identifying a small disease-causing variant that abolishes or severely reduces exon A/B methylation, our data demonstrate that this sequencing technology has major advantages for simultaneously identifying structural defects and altered methylation. © 2022 American Society for Bone and Mineral Research (ASBMR).
Domestic cat embryos reveal unique transcriptomes of developing incisor, canine, and premolar teeth
Authors: Woodruff Emily D. , Kircher Bonnie K. , Armfield Brooke A. , Levy Julie K. , Bloch Jonathan I. , Cohn Martin J.
Published: July 2022

Division of the dentition into morphologically distinct classes of teeth (incisors, canines, premolars, and molars) and the acquisition of tribosphenic molars facilitated precise occlusion between the teeth early in mammal evolution. Despite the evolutionary and ecological importance of distinct classes of teeth with unique cusp, crest, and basin morphologies, relatively little is known about the genetic basis for the development of different tooth classes within the embryo. Here we investigated genetic differences between developing deciduous incisor, canine, and premolar teeth in the domestic cat (Felis catus), which we propose to be a new model for tooth development. We examined differences in both developmental timing and crown morphology between the three tooth classes. Using RNA sequencing of early bell stage tooth germs, we showed that each of the three deciduous tooth classes possess a unique transcriptional profile. Three notable groups of genes emerged from our differential expression analysis; genes involved in the extracellular matrix (ECM), Wnt pathway signaling, and members of multiple homeobox gene families (Lhx, Dlx, Alx, and Nkx). Our results suggest that ECM genes may play a previously under‐appreciated role in shaping the surface of the tooth crown during development. Differential regulation of these genes likely underlies differences in tooth crown shape and size, although subtle temporal differences in development between the tooth germs could also be responsible. This study provides foundational data for future experiments to examine the function of these candidate genes in tooth development to directly test their potential effects on crown morphology.
Downregulation of indolethylamine N‐methyltransferase is an early event in the rat hepatocarcinogenesis and is associated with poor prognosis in hepatocellular carcinoma patients
Authors: López‐Torres Carlos David , Torres‐Mena Julia Esperanza , Castro‐Gil María Paulette , Villa‐Treviño Saúl , Arellanes‐Robledo Jaime , del Pozo‐Yauner Luis , Pérez‐Carreón Julio Isael
Published: July 2022

Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide, often preceded by cirrhosis and usually diagnosed at advanced stages; therefore, identifying molecular changes at early stages is an attractive strategy for detection and timely treatment. Here, we investigated the progressive transcriptomic changes during experimental hepatocarcinogenesis to identify novel early tumor markers in an HCC model induced by chronic administration of sublethal doses of diethylnitrosamine. An analysis of differentially expressed genes showed that four processes associated with oxidation–reduction and detoxification were significantly over‐represented during hepatocarcinogenesis progression, of which the Nuclear Factor, Erythroid 2 Like 2 pathway showed several dysregulated genes. Interestingly, we also identified 91 genes dysregulated at early HCC stages, but the expression of the indolethylamine N‐methyltransferase gene (INMT), as well as the level of its encoding protein, were strongly downregulated. INMT was increased in perivenular hepatocytes of normal livers but decreased in livers of experimental HCC. Furthermore, a gene expression and survival analysis performed using data from the liver hepatocellular carcinoma project of The Cancer Genome Atlas Program revealed that INMT is also significantly downregulated in human HCC and is associated with poor overall survival. In conclusion, by performing a transcriptome analysis of the HCC progression, we identified that INMT is early downregulated in the rat hepatocarcinogenesis and is associated with poor prognosis in human HCC, suggesting that INMT downregulation may be a promising prognostic marker for HCC in high‐risk populations.
IL-17A aggravates asthma-induced intestinal immune injury by promoting neutrophil trafficking
Authors: Hong Yanfei , Chu Zhulang , Kong Jingwei , Li Qiuyi , Li Na , Liu Liting , Wu Tong , Liu Jiajing , Ge Dongyu , Li Jie , Peng Guiying
Published: July 2022

With the concept of the gut–lung axis reinforced in recent years, emerging evidence has shown that intestinal homeostasis is vital for lung health. Nevertheless, the impacts of lung homeostasis on intestinal tracts and their mechanism are rarely studied. Our results showed that papain-induced asthmatic mice exhibited apparent colonic injuries compared with controls, including increased intestinal permeability, neutrophil and Th17 infiltration in the colonic lamina propria. Moreover, the intranasal administration of papain aggravated such colonic injuries in mice with dextran sulfate sodium-induced colitis, as evidenced by increased occult blood scores, shortened colon length, and accumulated neutrophils. The level of IL-17A was also higher in the serum of asthmatic mice than wild-type mice. Interestingly, the pathologic scores, the proportion of Th17 cells, and neutrophil infiltration in the colon were markedly reduced after IL-17A blocking. Similarly, longer length, lower pathologic scores, and fewer neutrophils were also observed in the colon of IL-17-deficient asthmatic mice. More importantly, we demonstrated that severe gastrointestinal symptoms could accompany clinical asthmatics. The frequencies of Th17 cells and the mRNA expression of IL-17A in the peripheral blood of these patients were significantly enhanced. Besides, the gastrointestinal symptom rating scale scores positively correlated with the frequencies of Th17 in asthmatics. These findings enlighten that IL-17A aggravates asthma-induced intestinal immune injury by promoting neutrophil trafficking, which facilitates the exploration of new potential biomarkers to treat asthma.
Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS‐CoV‐2 from 946 whole‐exome sequencing data in the Turkish population
Authors: Duman Nilgun , Tuncel Gulten , Bisgin Atil , Bozdogan Sevcan Tug , Sag Sebnem Ozemri , Gul Seref , Kiraz Aslihan , Balta Burhan , Erdogan Murat , Uyanik Bulent , Canbek Sezin , Ata Pinar , Geckinli Bilgen Bilge , Arslan Ates Esra , Alavanda Ceren , Yesim Ozdemir Sevda , Sezer Ozlem , Ozgon Gulay Oner , Gurkan Hakan , Guler Kubra , Boga Ibrahim , Kaya Niyazi , Alemdar Adem , Sayan Murat , Dundar Munis , Ergoren Mahmut Cerkez , Temel Sehime Gulsun
Published: July 2022

Heterogeneity in symptoms associated with COVID‐19 in infected patients remains unclear. ACE2 and TMPRSS2 gene variants are considered possible risk factors for COVID‐19. In this study, a retrospective comparative genome analysis of the ACE2 and TMPRSS2 variants from 946 whole‐exome sequencing data was conducted. Allele frequencies of all variants were calculated and filtered to remove variants with allele frequencies lower than 0.003 and to prioritize functional coding variants. The majority of detected variants were intronic, only two ACE2 and three TMPRSS2 nonsynonymous variants were detected in the analyzed cohort. The main ACE2 variants that putatively have a protective or susceptibility effect on SARS‐CoV‐2 have not yet been determined in the Turkish population. The Turkish genetic makeup likely lacks any ACE2 variant that increases susceptibility to SARS‐CoV‐2 infection. TMPRSS2 rs75603675 and rs12329760 variants that were previously defined as common variants that have different allele frequencies among populations and may have a role in SARS‐CoV‐2 attachment to host cells were determined in the population. Overall, these data will contribute to the formation of a national variation database and may also contribute to further studies of ACE2 and TMPRSS2 in the Turkish population and differences in SARS‐CoV‐2 infection among other populations.
COVID‐19 vaccine breakthrough infection among fully vaccinated healthcare workers in Duhok governorate, Iraqi Kurdistan: A retrospective cohort study
Authors: Almufty Hind B. , Mamani Masoud M. Ameen , Ali Ali H. , Merza Muayad A.
Published: July 2022

The aims of this study were: to determine the incidence of Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) infection among vaccinated healthcare workers (HCWs), assess risk factors associated with the vaccine breakthrough (BT), and compare the effectiveness of vaccine manufacturers against SARS‐CoV‐2 variant of concern among HCWs in Duhok governorate. It is a multicenter retrospective cohort study, which enrolled 944 HCWs through March 2022. COVID‐19 vaccinated HCWs aging 18 and above were included. A random sampling process was performed by asking the participants to fill out a standardized questionnaire by means of interviews or participant‐completed surveys. Fully vaccinated HCWs with positive polymerase chain reaction tests were considered to have vaccine BT infection. Two hundred and eighty‐four (30.1%) out of 944 vaccinated HCWs had SARS‐CoV‐2 infection postvaccination, of whom 241 (84.9%) were fully vaccinated, concluding that the incidence of BT infection is 25.5%. There were 422 (44.7%) males and 522 (55.3%) females. Most vaccine BT infections had developed in SARS‐CoV‐2 Omicron variant (53.5%). The majority of BT infections were mild to moderate (95.5%). Occupation, namely dentist was a significant risk factor, with a p value of 0.001. HCWs with a history of SARS‐CoV‐2 infection prevaccination were more prone to a vaccine BT infection (p value =0.002). Pfizer vaccine manufacturers revealed the highest effectiveness against BT infection (p value =0.0001). Paramedics showed a significant association with the disease severity (p value =0.02). The three available vaccine manufacturers in the Duhok governorate are effective against COVID‐19 BT infections. Dentists and paramedics were significantly associated with poor COVID‐19 outcomes.
Rhinovirus persistence during the COVID‐19 pandemic—Impact on pediatric acute wheezing presentations
Authors: Teo Kah Wee , Patel Deepa , Sisodia Shilpa , Roland Damian , Gaillard Erol A. , Tang Julian W.
Published: July 2022

Rhinoviruses have persisted throughout the COVID‐19 pandemic, despite other seasonal respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, adenoviruses, human metapneumovirus) being mostly suppressed by pandemic restrictions, such as masking and other forms of social distancing, especially during the national lockdown periods. Rhinoviruses, as nonenveloped viruses, are known to transmit effectively via the airborne and fomite route, which has allowed infection among children and adults to continue despite pandemic restrictions. Rhinoviruses are also known to cause and exacerbate acute wheezing episodes in children predisposed to this condition. Noninfectious causes such as air pollutants (PM2.5, PM10) can also play a role. In this retrospective ecological study, we demonstrate the correlation between UK national sentinel rhinovirus surveillance, the level of airborne particulates, and the changing patterns of pediatric emergency department presentations for acute wheezing, before and during the COVID‐19 pandemic (2018–2021) in a large UK teaching hospital.
Relevant SARS‐CoV‐2 viremia is associated with COVID‐19 severity: Prospective cohort study and validation cohort
Authors: Cardeñoso Domingo Laura , Roy Vallejo Emilia , Zurita Cruz Nelly D. , Chicot Llano Marta , Ávalos Pérez‐Urria Elena , Barrios Ana , Hernando Santos Julia , Ortiz Javier , Rodríguez García Sebastián C. , Martín Ramírez Alexandra , Ciudad Sañudo Marianela , Marcos Celeste , García Castillo Elena , Fontán García‐Rodrigo Leticia , González Begoña , Méndez Rosa , Iturrate Isabel , Sanz García Ancor , Villa Almudena , Sánchez Azofra Ana , Quicios Begoña , Arribas David , Álvarez Rodríguez Jesús , Patiño Pablo , Trigueros Marina , Uriarte Miren , Triguero Martínez Ana , Arévalo Cristina , Galván Román José M. , García‐Vicuña Rosario , Ancochea Julio , Soriano Joan B. , Canabal Alfonso , Muñoz Calleja Cecilia , De la Cámara Rafael , Suarez Fernández Carmen , González Álvaro Isidoro , Rodríguez‐Serrano Diego A. ,   the PREDINMUN‐COVID Group
Published: July 2022

Early kinetics of SARS‐CoV‐2 viral load (VL) in plasma determined by quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single‐center study including consecutive adult patients hospitalized with COVID‐19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT‐PCR was performed to assess SARS‐CoV‐2 VL. The main outcomes were in‐hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID‐19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU‐admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1–15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3–28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8–22]; p < 0.0001). Relevant SARS‐CoV‐2 viremia in the first week of hospitalization was associated with higher in‐hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort.
The Deltacron conundrum: Its origin and potential health risks
Authors: Farheen Saria , Araf Yusha , Tang Yan‐Dong , Zheng Chunfu
Published: July 2022

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), since its outbreak in December 2019, has been capable of continuing the pandemic by mutating itself into different variants. Mass vaccinations, antibiotic treatment therapy, herd immunity, and preventive measures have reduced the disease's severity from the emerging variants. However, the virus is undergoing recombination among the current two variants: Delta and Omicron, resulting in a new variant, informally known as “Deltacron,” which was controversial as it might be a product of lab contamination between Omicron and Delta samples. However, the proclamation was proved wrong, and the experts are putting more effort into better understanding the variant's epidemiological characteristics to control potential outbreaks. This review has discussed the potential mutations in the novel variant and prospective risk factors and therapeutic options in the context of this new variant. This study could be used as a guide for implementing appropriate controls in a sudden outbreak of this new variant.
Tropical cyclone activity in the Solomon Islands region: Climatology, variability, and trends
Authors: Haruhiru Alick , Chand Savin S. , Turville Christopher , Ramsay Hamish
Published: July 2022

This study examines the climatology, variability, and trends of tropical cyclones (TCs) affecting the Solomon Islands (SI) territory, in the wider southwest Pacific (SWP), using the South Pacific Enhanced Archive for Tropical Cyclones (SPEArTC) database. During the period 1969/1970–2018/2019, 168 TCs were recorded in the SI territory. A cluster analysis is used to objectively partition these tracks into three clusters of similar TC trajectories to obtain better insights into the effects of natural climate variability, particularly due to the El Niño–Southern Oscillation (ENSO) phenomenon, which otherwise is not very apparent for TCs when considered collectively in the SI region. We find that TCs in clusters 1 and 3 show enhanced activity during El Niño phase, whereas TCs in cluster 2 are enhanced during La Niña and neutral phases. In addition to being modulated by ENSO, TCs in clusters 2 and 3 show statistically significant modulation at an intraseasonal timescale due to the Madden–Julian Oscillation (MJO) phenomenon. There are also some indications through sophisticated Bayesian modelling that TCs in clusters 2 and 3 are slightly influenced by the Interdecadal Pacific Oscillation (IPO). These results can have substantial implications for cluster‐specific development of TC prediction schemes for the SI region.
Effect of soy protein isolate on physical properties of quinoa dough and gluten‐free bread quality characteristics
Authors: Bian Xin , Xing Tong‐Lin , Yang Yang , Fan Jing , Ma Chun‐Min , Liu Xiao‐Fei , Wang Yan , He Yin‐Yuan , Wang Li‐Dong , Wang Bing , Zhang Na
Published: July 2022

BACKGROUND

Quinoa is a good gluten‐free resource for food processing, especially bread making, and can improve and prevent the development of complications associated with celiac disease (CD). However, lack of gluten affects quinoa bread quality. Previous research showed that soy protein isolate (SPI) could improve gluten‐free bread quality to some extent. Therefore, this study investigated the effects of SPI on the physical properties of quinoa dough and gluten‐free bread quality characteristics.

RESULTS

Results showed that, with appropriate SPI substitution, the farinograph properties of quinoa flour significantly improved (P < 0.05). The sample with 8% SPI substitution showed a better development time (DT, 3.30 ± 0.20 min), stability time (ST, 8.80 ± 0.10 min) and softening degree (SD, 8.80 ± 0.10 FU), which were close to those of wheat flour, although more water absorption (WA, 76.40 ± 2.10%) was needed than for wheat flour (66.30 ± 3.10%). The extensograph properties of quinoa flour also significantly improved after 8% SPI substitution (P < 0.05). Furthermore, SPI substitution increased G′ moduli of quinoa dough and decreased tan δ to some extent, providing better rheological properties closer to those of wheat dough. SPI substitution also improved the quality and texture of quinoa bread and reduced the gap with wheat bread. When SPI substitution was 8%, the specific volume, hardness and springiness of quinoa bread were 2.29 ± 0.05 mL g−1, 1496.47 ± 85.21 g and 0.71 ± 0.03%, respectively.

CONCLUSION

These results suggested that SPI substitution would be an effective way to develop higher‐quality gluten‐free bread. © 2022 Society of Chemical Industry.
Evaluation of Intracranial Structures of Fetuses With Congenital Heart Defects
Authors: Turgut Ezgi , Özdemir Halis , Turan Gokce , Karcaaltıncaba Deniz , Bayram Merih
Published: July 2022

Objectives

We classified congenital heart defects (CHDs) according to cerebral blood flow oxygenation and aimed to evaluate the effect on the size of brain structures in these fetuses.

Methods

The study which was designed retrospectively, included 28 patients with fetal CHDs and 76 patients without fetal anomalies.

Results

The width and length of the cavum septum pellucidum significantly increased in the CHD group (P = .002, P = .004). The biparietal diameter and z scores were significantly lower in the single ventricle (SV) (P = .006, P = .019), and the head circumference (HC) and z scores were significantly lower in the transposition of great arteries (TGA) (P = .013, P = .038). The transverse cerebellar diameter, the cerebellar HC and the cerebellar hemisphere area values were lower in the SV (P = .005, P = .017, P = .044).

Conclusions

Brain structure changes are more pronounced in groups with low cerebral oxygenation, especially in the SV and the TGA.
Management of patients with positive margin after conization for high‐grade cervical intraepithelial lesions
Authors: Zhang Yingcui , Su Yuehui , Tang Yujie , Qin Lihong , Shen Yan , Wang Bingjie , Zhou Yingying , Zhang Mengzhen , Zhang Ting
Published: July 2022

Background and Objective

To evaluate the clinical efficacy and safety of 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) in the treatment of patients with positive margin in comparison to regular follow‐up, and a repeat cervical conization.

Materials and Methods

A retrospective analysis was conducted using 83 patients with pathologically confirmed high‐grade cervical intraepithelial neoplasia (CIN) with a positive margin after conization. The management methods and patient prognosis were analyzed and compared.

Results

Thirty‐five, 33, and 15 patients were treated for regular follow‐up, ALA‐PDT, and a repeat cervical conization, respectively. About 33.3% (5/15) patients had residual lesions of low‐grade CIN and above after recognization. The clinical characteristics of patients in the three groups were similar. The residual lesion rates of patients selected for follow‐up, ALA‐PDT, and recognization were 34.3% (12/35), 9.1% (3/33), and 0% (0/15), respectively, at 6‐month follow‐up (p = 0.004). The HPV clearance rates were 31.3%, 66.7%, and 84.6%, respectively (p = 0.01). Further analysis showed that a positive margin in the inscribed margin of the cervical canal (p = 0.022) and persistent HR‐HPV positive tests after initial conization (p = 0.003) significantly increased the risk of residual disease. At 2‐year follow‐up, the recurrence rates of lesions were 3.3% and 26.1% in the ALA‐PDT and follow‐up groups, respectively (p = 0.021). Notably, the recurrence rates were not significantly different between the ALA‐PDT and recognization groups (3.3% vs. 6.7%) (p = 0.561).

Conclusion

ALA‐PDT is an effective treatment for patients with a positive margin after cervical conization for high‐grade CIN. Compared with regular follow‐up, ALA‐PDT can reduce residual and recurrence rate. Moreover, there was no significant difference in the efficacy between AlA‐PDT and recognization.
Primers for the Adhesion of Gellan Gum‐Based Hydrogels to the Cartilage: A Comparative Study
Authors: Trucco Diego , Riacci Laura , Vannozzi Lorenzo , Manferdini Cristina , Arrico Lorenzo , Gabusi Elena , Lisignoli Gina , Ricotti Leonardo
Published: July 2022

A stable adhesion to the cartilage is a crucial requisite for hydrogels used for cartilage regeneration. Indeed, a weak interface between the tissue and the implanted material may produce a premature detachment and thus the failure of the regeneration processes. Fibrin glue, cellulose nanofibers and catecholamines have been proposed in the state‐of‐the‐art as primers to improve the adhesion. However, no studies focused on a systematic comparison of their performance. This work aims to evaluate the adhesion strength between ex vivo cartilage specimens and polysaccharide hydrogels (gellan gum and methacrylated gellan gum), by applying the mentioned primers as intermediate layer. Results show that the fibrin glue and the cellulose nanofibers improve the adhesion strength, while catecholamines do not guarantee reaching a clinically acceptable value. Stem cells embedded in gellan gum hydrogels reduce the adhesion strength when fibrin glue is used as a primer, being anyhow still sufficient for in vivo applications.
Stimuli‐Responsive Miktoarm Polymer‐Based Formulations for Fisetin Delivery and Regulatory Effects in Hyperactive Human Microglia
Authors: Baghbanbashi Mojhdeh , Yong Hui Wen , Zhang Issan , Lotocki Victor , Yuan Zhuoer , Pazuki Gholamreza , Maysinger Dusica , Kakkar Ashok
Published: July 2022

Branched star polymers offer exciting opportunities in enhancing the efficacy of nanocarriers in delivering biologically active lipophilic agents. It is demonstrated that the star polymeric architecture can be leveraged to yield soft nanoparticles of vesicular morphology with precisely located stimuli‐sensitive chemical entities. Amphiphilic stars of AB2 (A = PEG, B = PCL) composition with/without oxidative stress or reduction responsive units at the core junction of A and B arms, are constructed using synthetic articulation. Fisetin, a natural flavonoid with remarkable anti‐inflammatory and antioxidant properties, but of limited clinical value due to its poor aqueous solubility, is physically encapsulated into miktoarm star‐derived aqueous polymersomes. Polymersomes and fisetin are evaluated separately, and in combination, in human microglia (HMC3), to show if i) polymersomes are toxic; ii) fisetin reduces the abundance of reactive oxygen species (ROS); and iii) fisetin modulates the activation of ERK1/2. These signaling molecules and pathways are implicated in inflammatory processes and cell survival. Fisetin, both incorporated and nonincorporated into polymersomes, reduces ROS and ERK1/2 phosphorylation in lipopolysaccharide‐treated human microglia, normalizing excessive oxidative stress and ERK‐mediated signaling.
Next‐generation pathology practices with mass spectrometry imaging
Authors: Chung Hsin‐Hsiang , Huang Penghsuan , Chen Chih‐Lin , Lee Chuping , Hsu Cheng‐Chih
Published: July 2022

Mass spectrometry imaging (MSI) is a powerful technique that reveals the spatial distribution of various molecules in biological samples, and it is widely used in pathology‐related research. In this review, we summarize common MSI techniques, including matrix‐assisted laser desorption/ionization and desorption electrospray ionization MSI, and their applications in pathological research, including disease diagnosis, microbiology, and drug discovery. We also describe the improvements of MSI, focusing on the accumulation of imaging data sets, expansion of chemical coverage, and identification of biological significant molecules, that have prompted the evolution of MSI to meet the requirements of pathology practices. Overall, this review details the applications and improvements of MSI techniques, demonstrating the potential of integrating MSI techniques into next‐generation pathology practices.
Anisotropic Navier Kirchhoff problems with convection and Laplacian dependence
Authors: Rădulescu Vicenţiu D. , Vetro Calogero
Published: July 2022

We consider the Navier problem

driven by the sign‐changing (degenerate) Kirchhoff type
‐biharmonic operator, and involving a
‐dependent nonlinearity
. We prove the existence of solutions, in weak sense, defining an appropriate Nemitsky map for the nonlinearity. Then, the Brouwer fixed point theorem assessed for a Galerkin basis of the Banach space
leads to the existence result. The case of nondegenerate Kirchhoff type
‐biharmonic operator is also considered with respect to the theory of pseudo‐monotone operators, and an asymptotic analysis is derived.
Cavity length dependence on strain sensitivity for Fabry–Perot sensors
Authors: Rodrigues António V. , Reis João , Martins António José M. , Monteiro Catarina S. , Silva Susana O. , Caridade Cristina M. R. , Tavares Sérgio O. , Frazão Orlando
Published: July 2022

This study presents the dependence of strain sensitivity on cavity length in conventional Fabry–Perot (F‐P) sensors. A high number of F‐P sensors were required and to ensure their reproducibility, a manufacturing process was developed to obtain similar sensors but with different types of lengths. A hollow‐core silica tube was used to fabricate several F‐P cavities by fusion splicing it between two sections of SMF28 fiber. The fabricated F‐P has a varying length ranging from 15 to 2500 μm. The cavities were measured under a microscope and the reflected spectrum was acquired for each one. Strain measurements were performed for a maximum strain of 1000 με. The strain sensitivity showed a highly linear correlation with ∆λFSR. Small length variations for short cavities heavily affect the FSR value. The smallest and longest cavities present sensitivities of 8.71 and 2.68 pm/με, respectively. Thermal characterization for low‐ and high‐temperature regimes was also performed and is constant for tested sensors.