bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Lipase Immobilization Conditions and Support Materials for the Production of Structured Triacylglycerols
Authors: Causevic Ariana , Olofsson Kim , Adlercreutz Patrick , Grey Carl 
Published: December 2022

AbstractStructured triacylglycerols (STAG) with desired properties can be synthesized by transesterification using immobilized lipases. Herein, the effect of immobilization conditions and support material on the immobilization yield, specific activity and regioselectivity of lipases from Rhizomucor miehei (RML) and Rhizopus oryzae (ROL) in the production of STAG, are evaluated. Four different support materials utilizing adsorption and one with covalent binding are investigated. Ammonium sulfate is found to significantly increase the activity‐based immobilization yield (12% and 38% for RML and ROL, respectively) and specific activity on Accurel MP1000 (MP1000) when used as the immobilization buffer. Furthermore, the immobilization principle and support material influenced both the activity and regiospecificity. Immobilization by adsorption is found to result in higher catalytic activity, while covalent binding resulted in lipase inactivation. For RML, the highest specific activity of 43 µmol STAG min−1 g−1 (U) is obtained on MP1000, while ROL, which exhibited higher activities in general, results in a maximum activity of 120 U on Lifetech ECR8806. The obtained specific activites are comparable to the commercial preparations Novozym 40086 (45 U) and Lipase DF “Amano” IM (147 U) while the regiospecificity of the developed preparations is even higher, forming at least 64% less byproduct.Practical applications: There is an increasing need for lipids with specific nutritional and physical properties in health, nutrition, and food applications. In this context, STAG are highly promising products due to the possibility to tailor the composition to obtain the desired properties. Immobilized lipases are the catalyst of choice for the production of STAG, in which activity and regioselectivity are particularly important parameters for the process performance. In this study, it is shown that these parameters can be affected by the immobilization conditions and support material. Immobilized preparations with high activity and excellent regiospecificity are created on commercially available supports. This shows the possibility of STAG synthesis with high purity and beneficial properties.
Gold(I)‐Catalyzed and PTSA‐Promoted Cycloisomerization of Ynamides to Access Pyrrole Substituted α,β‐Unsaturated Ketones**
Authors: Choudhary Shivani , Gayyur  , Ghosh Nayan 
Published: December 2022

AbstractSubstituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold‐catalyzed and para‐toluenesulfonic acid (PTSA)‐assisted cascade cycloisomerization reaction for the synthesis of β‐pyrrole substituted α,β‐unsaturated ketones. Notably, the reaction is stereoselective, offering E‐isomer as major product with low to moderate yield.
The temporal expression of circulating microRNAs after acute experimental pain in humans
Authors: Giordano Rocco , Gerra Maria Carla , Okutani Hiroai , Lo Vecchio Silvia , Stensballe Allan , Petersen Kristian Kjær‐Staal , Arendt‐Nielsen Lars 
Published: December 2022

AbstractBackgroundMicroRNAs (miRNAs) can modulate several biological systems, including the pain system. This study aimed to evaluate the temporal expression of circulating miRNAs in the plasma of healthy volunteers as a marker for epigenetic changes before and after an acute, experimental, pain provocation by intramuscular hypertonic saline injection.MethodsTwenty volunteers were randomly allocated into two groups and received either hypertonic (pain) or isotonic (control) saline injection in the first dorsal interosseous muscle of their dominant hand. Pain intensity was continuously recorded for 20 minutes after injection on a VAS scale from 0 to 100 (0 indicates no pain and 100 the worst imaginable pain). Blood samples were taken at baseline, 30 minutes, 3 hours, and 24 hours post‐injection, and plasma was separated. MiRNA extracts were used for RNA sequencing with the Illumina NextSeq platform. MiRNA transcripts were compared between the pain and the no‐pain, control group at every time point. Significant differences were considered when folds were >2 and the False Discovery Rate wasp < 0.05.ResultsAfter 30 minutes, 4 miRNAs were significantly altered in the pain group compared to controls, which increased to 24 after 3 hours and to 42 after 24 hours from baseline (p < 0.0001). Two miRNAs were consistently upregulated throughout the experiment. Enrichment analysis showed significant miRNAs involved in brain perception of pain, brain signalling and response to stimuli.ConclusionsThis exploratory study is the first to report on the temporal expression of circulating miRNAs after an acute, human experimental muscle pain model.SignificanceThis exploratory study evaluated the temporal profile of circulating miRNAs in the plasma of healthy subjects after acute experimental pain. Several miRNAs were altered in subjects at the times of follow‐up after the acute pain model when compared to controls. MiRNAs previously associated with pain processes were altered in the pain group. Our results, by showing the fast and prolonged modifications of miRNA elicited by the acute experimental pain model, add new perspectives to the topic of epigenetics and pain.
Using natural killer cell‐derived exosomes as a cell‐free therapy for leukemia
Authors: Samara Aladin , Anbar Michael , Shapira Saar , Zemlyansky Anna , Zozovsky Alla , Raanani Pia , Granot Galit , Rozovski Uri 
Published: December 2022

AbstractNatural killer (NK) cells are components of the innate immune system which play a pivotal role in cancer cell surveillance. Despite promising results in clinical trials, the use of NK‐based therapies is limited due to unsatisfactory efficiencies and safety issues. In recent years, exosomes have emerged as a powerful, natural therapeutic tool. Since exosomes are known to carry cargos that reflect the cellular makeup of their cell of origin, we were prompted to test whether NK‐derived exosomes (NKexo) maintain the anti‐leukemia capacity of NK‐cells. We found NK92MI‐cells to secrete large amounts of 100–200 nm cap‐shaped particles expressing exosomal and NK biomarkers (CD63, CD81, CD56). We demonstrated that NKexo exert a potent, selective, anti‐leukemia effect on all leukemia cell‐lines tested. Furthermore, NKexo eliminated leukemia cells isolated from patients with acute and chronic leukemia and inhibited hematopoietic colony growth. While leukemia cells were targeted and severely affected by NKexo, healthy B‐cells remained unaffected, indicating a selective effect. This selectivity was further confirmed by demonstrating that NKexo were specifically taken up by leukemic cells but not by healthy B‐cells. Our in vivo data support our in vitro and ex vivo findings and demonstrate improved human‐CD45+ leukemia blast counts and overall survival in NKexo treated humanized acute myeloid leukemia (HL‐60) xenograft mice thus supporting the assumption that NKexo possess an anti‐leukemia effect. Pending further analyses, our findings provide the pre‐clinical evidence needed to test the NKexo approach in future pre‐clinical and clinical studies to ultimately develop an acellular “off‐the‐shelf” product to treat leukemia.
Testing the acceptability of stillbirth awareness messages in anSMSprogram for fathers
Authors: Fletcher Richard , Symonds Ian , StGeorge Jennifer , Warland Jane , Stark Michael 
Published: December 2022

AbstractIssue addressedTo raise expectant fathers' awareness of risk factors for stillbirth.MethodsA set of brief text messages was developed addressing recognised risk factors for stillbirth: avoidance of maternal cigarette smoking, maternal going to sleep on side messaging, awareness of the importance of noticing and reporting changes in foetal movement and fathers' involvement in shared decision making for timing of birth. Eight messages were inserted into the SMS4dads pilot program being conducted by NSW Health. Feedback on the messages was requested. Participants rated the quality of the messages on a three‐point Likert scale and provided comments.ResultsOverall, 2528 messages were sent to 626 fathers' mobile phones, 45% of fathers replied with 666 ratings and 115 comments evaluating the texts. The quantitative ratings indicated substantial overall approval of the messages. Within the coding category “Evaluation of Message Content,” three themes described fathers' reactions and feelings about the smoking, movement, side sleeping and birth timing messages: “important‐good information,” “not appropriate/anxiety provoking” and “not relevant‐obvious.” Three themes reflecting the attributes of the messages within the “Service Quality” category were “need more information,” “complements public health” and “child voice fit.”ConclusionsResults indicate that the messages are an acceptable way to provide information and suggested actions addressing stillbirth risk factors to fathers‐to‐be.So what?Fathers' awareness of the risk factors for stillbirth can assist mothers to take appropriate actions for a healthy birth. Information on risk factors can be provided to fathers via a father‐focused text messaging service.
Dyslexia with and without Irlen syndrome: A study of influence on abilities and brain‐derived neurotrophic factor level
Authors: Abdelraouf Ehab R. , Kilany Ayman , Elhadidy Mohamed E. , Zeidan Hala M. , Elsaied Amal , Eid Ola M. , El‐Saied Mostafa M. , Anwar Rasha , Nashaat Neveen H. 
Published: December 2022

AbstractThe presence of comorbid Irlen syndrome (IS) in children with developmental dyslexia (DD) may have an impact on their reading and cognitive abilities. Furthermore, the brain‐derived neurotrophic factor (BDNF) was reported to be expressed in brain areas involved in cognitive and visual processing. The aim of this study was to evaluate some cognitive abilities of a group of dyslexic children with IS and to measure and compare the plasma BDNF level to dyslexic children without IS and neurotypical (NT) children. The participants were 60 children with DD (30 in the DD + IS group; 30 in the DD group) and 30 NT children. The Irlen reading perceptual scale, the Stanford Binet intelligence scale, 4th ed, the dyslexia assessment test, and the Illinois test of psycholinguistic abilities were used. The BDNF level was measured using the enzyme‐linked immunosorbent assay. One‐minute writing and visual closure deficits were more prevalent, while phonemic segmentation deficits were less prevalent in the DD + IS group compared to the DD group. The BDNF level in the DD groups was lower than that in NT children (p < 0.001). Some reading and non‐reading tasks were influenced by the presence of a coexisting IS. The reduced BDNF level could play a role in the deficits noticed in the abilities of children with DD.
Immunotherapies targeting neoantigens are effective in PD‐1 blockade‐resistant tumors
Authors: Sun Changbo , Nagaoka Koji , Kobayashi Yukari , Maejima Kazuhiro , Nakagawa Hidewaki , Nakajima Jun , Kakimi Kazuhiro 
Published: December 2022

AbstractOnly a small fraction of tumor‐infiltrating lymphocytes can specifically recognize and attack cancer cells in PD‐1/PD‐L1 blockade therapy. Here, we investigate approaches to expand the neoantigen‐specific CD8+ T cells to overcome the difficulties in treating PD‐1/PD‐L1 blockade‐resistant tumors. Mutation‐associated neoepitopes of murine nonsmall cell lung cancer ASB‐XIV were estimated by whole‐exome and RNA sequencing and predicted by MHC‐I binding affinity (FPKM >1) in silico. Using ASB‐XIV‐specific CD8+ T cells, we screened a panel of 257 neoepitope peptides derived from ASB‐XIV missense and indel mutations. Mutated Phf3 peptide (mPhf3) was successfully identified as an immunogenic neoepitope. Prophylactic mPhf3‐DC vaccination inhibited ASB‐XIV tumor growth through CD8+ T cell‐mediated antitumor immunity. Combining the mPhf3‐DC vaccine and anti‐PD‐1 treatment elicited robust antitumor activity through the induction of mPhf3‐specific CD8+ T cells in the tumor microenvironment. Furthermore, the adoptive transfer of mPhf3‐specific CD8+ T cells eradicated ASB‐XIV tumors. Likewise, the combination of mutated Cdt1 peptide (mCdt1)‐DC vaccine and anti‐PD‐1 treatment or adoptive transfer of mCdt1‐specific CD8+ T cells also led to significant regression of PD‐1 blockade‐resistant murine gastric YTN16 tumors. In conclusion, a novel immunogenic neoepitope of ASB‐XIV was identified for immunotherapy targeting neoantigens. Identification of immunogenic neoantigens can extend the therapeutic strategies by increasing the frequency of neoantigen‐specific T cells, even for PD‐1/PD‐L1 blockade‐resistant tumors.
Association between a polymorphic variant in the CDKN2B‐AS1/ANRIL gene and pancreatic cancer risk
Authors: Giaccherini Matteo , Farinella Riccardo , Gentiluomo Manuel , Mohelnikova‐Duchonova Beatrice , Kauffmann Emanuele Federico , Palmeri Matteo , Uzunoglu Faik , Soucek Pavel , Petrauskas Dalius , Cavestro Giulia Martina , Zykus Romanas , Carrara Silvia , Pezzilli Raffaele , Puzzono Marta , Szentesi Andrea , Neoptolemos John , Archibugi Livia , Palmieri Orazio , Milanetto Anna Caterina , Capurso Gabriele , van Eijck Casper H. J. , Stocker Hannah , Lawlor Rita T. , Vodicka Pavel , Lovecek Martin , Izbicki Jakob R. , Perri Francesco , Kupcinskaite‐Noreikiene Rita , Götz Mara , Kupcinskas Juozas , Hussein Tamás , Hegyi Péter , Busch Olivier R. , Hackert Thilo , Mambrini Andrea , Brenner Hermann , Lucchesi Maurizio , Basso Daniela , Tavano Francesca , Schöttker Ben , Vanella Giuseppe , Bunduc Stefania , Petrányi Ágota , Landi Stefano , Morelli Luca , Canzian Federico , Campa Daniele 
Published: December 2022

AbstractGenes carrying high‐penetrance germline mutations may also be associated with cancer susceptibility through common low‐penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high‐penetrance PDAC‐associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B‐AS1/ANRIL, showed a genome‐wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07‐1.15, P = 5.25 × 10−9). CDKN2B‐AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases.
Safety of COVID‐19 vaccination in pregnant women: A study of the adverse perinatal outcomes
Authors: Kugelman Nir , Riskin Arieh , Kedar Reuven , Riskin‐Mashiah Shlomit 
Published: December 2022

AbstractObjectiveTo compare adverse perinatal outcome among coronavirus disease 2019 (COVID‐19)–vaccinated and –unvaccinated pregnant women.MethodRetrospective equivalence cohort study comparing 930 women who received at least one BNT162b2 (Pfizer/BioNTech) COVID‐19 vaccine during the second or third trimester of pregnancy and 964 unvaccinated women. The primary outcome was a composite adverse perinatal outcome including at least one of the following: preterm delivery <35 weeks of gestation, intrauterine fetal death >23 weeks of gestation, intrauterine growth restriction defined as birth weight < 10th percentile, 5‐min APGAR score ≤ 7, and neonatal care unit admission.ResultsThe authors found no effect of the COVID‐19 vaccine on the rate of the individual adverse perinatal outcomes. At least one adverse perinatal outcome was found in 108 (11.25%) of unvaccinated women versus 82 (8.82%) of vaccinated pregnant women (P = 0.080). The observed proportion difference (unvaccinated minus vaccinated) was 0.024. In the equivalence analysis with a margin of 0.05, the 90% confidence interval (0.01–0.05) was entirely within the equivalence zone (−0.05 to 0.05) with a P value of 0.032.ConclusionThe present study demonstrated an equivalent rate of adverse perinatal outcomes among vaccinated and unvaccinated women, thus supporting vaccine safety during the second and third trimesters of pregnancy. The authors believe this information is useful in counseling pregnant women regarding COVID‐19 vaccination during pregnancy.
Deviant peer affiliation mediates the prospective association from impulsivity to alcohol use in late adolescence
Authors: Wilhoit Sarah A. , Goodnight Jackson A. 
Published: December 2022

AbstractIntroductionPrevious research has found that impulsivity and deviant peer affiliation predict alcohol use among adolescents. However, it remains unclear to what extent these risk factors predict alcohol use in conjunction with one another, and to what extent they predict over and above correlated risk factors, such as pre‐existing externalizing problems and sociodemographic characteristics. The present study tested the hypothesis that deviant peer affiliation would mediate the prospective association between impulsivity and alcohol use in adolescence (ages 13–18 years), controlling for a wide range of family and child‐level covariates.MethodsAnalyses were conducted using data from 2318 participants from the Longitudinal Cohort Study of the Project on Human Development in Chicago Neighborhoods. Participants were approximately 9, 12, or 15 years of age at wave 1 of the study, with waves 2 and 3 taking place at approximately 2‐year intervals. The sample composition was 50.3% male, 46.1% Hispanic, 35.6% Black, non‐Hispanic, 14.4% White, non‐Hispanic, and 3.9% other race/ethnicity.ResultsResults from path analyses indicated that the prospective association between impulsivity and alcohol use was mediated by peer deviance, but only for the oldest (age 15) cohort.ConclusionsFindings from the present study suggest that despite impulsivity being a dispositional characteristic, its effects on alcohol use in later adolescence are achieved through a social pathway, via affiliation with deviant peers. It further suggests that this pathway, especially the link from impulsivity to affiliation with deviant peers, may not operate until late adolescence. Findings suggest that alcohol use may be prevented or reduced among impulsive adolescents by reducing their exposure to delinquent peers.
Release of drugs used in the treatment of osteoporosis from zeolites with divalent ions—Influence of the type of ion and drug on the release profile
Authors: Sandomierski Mariusz , Jakubowski Marcel , Ratajczak Maria , Pokora Monika , Zielińska Monika , Voelkel Adam 
Published: December 2022

AbstractBisphosphonates are drugs that are used to treat osteoporosis that causes the low mineral density of the bones. These drugs can be delivered in several ways, but each method has disadvantages. Materials with high potential as carriers of these drugs are zeolites with divalent ions. The aim of this study was to investigate the effect of divalent cations (calcium, magnesium, zinc) and drug type (risedronate, zoledronate) on sorption and release of the drug for osteoporosis. It was proved that drug sorption occurs on all zeolites presented in this work. Risedronate sorption was highest in zinc zeolite and lowest in calcium zeolite. In the case of zoledronate, sorption was most effective in magnesium zeolite and the least effective in zinc zeolite. Very large differences in drug release profiles were also observed. Risedronate was released several times longer than zoledronate. The diversity of the results indicates that the examined materials can be used in different types of drug delivery systems. They can be used, for example, intravenously or in the form of implants due to the different release profiles. Furthermore, the proposed carriers also release magnesium and calcium ions which are used in the prevention of osteoporosis, and zinc ions which have antibacterial properties.
Population Pharmacokinetics and Exposure‐Response for Dapirolizumab Pegol From a Phase 2b Trial in Patients With Systemic Lupus Erythematosus
Authors: Acharya Chayan , Magnusson Mats O. , Vajjah Pavan , Oliver Ruth , Zamacona Miren 
Published: December 2022

AbstractSystemic lupus erythematosus (SLE) is a systemic, autoimmune disease characterized by chronic inflammation and organ damage. Dapirolizumab pegol inhibits CD40 ligand (CD40L) and is currently undergoing phase 3 trials for the treatment of SLE. To describe the pharmacokinetic characteristics of dapirolizumab pegol and the relationship between exposure and probability of achieving a British Isles Lupus Assessment Group‐based Composite Lupus Assessment (BICLA) response, a population pharmacokinetic (popPK) model and an exposure‐response model were developed, based on results of the phase 2b trial (RISE; NCT02804763) of dapirolizumab pegol in SLE. Dapirolizumab pegol pharmacokinetics were found to be dose proportional and well described by a 2‐compartment model with first‐order elimination from the central compartment. In the popPK model, body weight was the only significant covariate. The average concentration of dapirolizumab pegol, derived from the popPK model, was incorporated into the exposure‐response model. Overall, the exposure‐response model showed that treatment with dapirolizumab pegol increased the probability of transitioning from BICLA “Nonresponder” to “Responder.” No significant covariates on BICLA responder status were identified. Notably, the half maximal effective concentration was greater for the transition from “Responder” to “Nonresponder” (150 µg/mL) than the transition from “Nonresponder” to “Responder” (12 µg/mL), indicating that sustained dapirolizumab pegol concentrations may be required to maintain BICLA response. In conclusion, dapirolizumab pegol pharmacokinetics were as expected for a PEGylated molecule and results from the exposure‐response model indicate that a favorable dapirolizumab pegol effect was identified for both BICLA “Nonresponder” to “Responder” and “Responder” to “Nonresponder” transition probabilities.
COVID–19ワクチン接種後に副腎クリーゼ，たこつぼ心筋症を発症しショックとなり多腺性自己免疫症候群2型の診断に至った1例(A patient with post COVID–19 vaccination presented with convulsions and cardiogenic shock due to adrenal crisis and Takotsubo cardiomyopathy diagnosed with autoimmune polyendocrine syndromes type II and Addison’s disease)
Authors: 晶子 久下 , 幸治 森下 , 慎平 朝田 , 啓太 中堤 , 渉 高山 , 英美 木内 , 康裕 大友 
Published: December 2022

要旨若年時にバセドウ病，白斑病の既往のある49歳女性。COVID–19ワクチン接種後からめまい，嘔気，体動困難が出現し，5日後に意識障害，心原性ショック状態で救急搬送された。低ナトリウム血症に伴う重症意識障害，たこつぼ心筋症の診断で，挿管人工呼吸管理，電解質補正，大動脈バルーンパンピングを含む心不全治療を開始した。副腎不全を鑑別に直ちにステロイド補充を開始したところ全身状態は改善傾向となり，第7病日に抜管した。状態回復後の内分泌機能精査で，原発性副腎機能不全，多腺性自己免疫症候群2型の診断に至った。副腎クリーゼは初発だと診断がつきづらいが，重症意識障害やたこつぼ心筋症を合併し致命的となりうる重症病態であり，早期ステロイド補充が救命に不可欠である。今回，COVID–19ワクチン接種を契機に初発の副腎クリーゼを発症したが，集学的治療を行い救命しえた多腺性自己免疫症候群2型の1例を経験したため報告する。
救急外来における小児魚骨異物症例の臨床的特徴(Clinical characteristics of accidental fish bone ingestion in children)
Authors: 侑画 神谷 , 由典 松岡 , 大介 水 , 葉子 浅香 , 孝一 有吉 
Published: December 2022

要旨　魚骨による咽頭異物（以下，魚骨異物）は救急外来で頻繁に遭遇するが，小児にかかる診療内容をまとめた報告はみられない。本研究では，小児の魚骨異物症例の診療実態を明らかにすることを目的とする。2013年から2017年の5年間に，魚骨異物を主訴に救急外来を受診した15歳以下の小児を対象とし記述検討を行った。全115例が対象となり，年齢中央値は5歳（四分位，3−8）であった。約8割の症例は口腔内観察のみで終了し，追加検査は21例（18.3%）において施行されていた。追加検査はX線が6例，CTが2例，鼻咽喉ファイバーが13例であり，それぞれ年齢を考慮して施行される傾向にあった。異物摘出については，魚骨が発見された40例中38例で成功しており，救急医による摘出34例，耳鼻咽喉科医による摘出4例であった。その後の経過は，救急外来で魚骨を視認できなかった，または摘出できなかった77例中，71例で電話での追跡が可能であった。翌日再受診を要したものが3例，それ以外は数日で症状は軽快し，重篤な合併症は認めなかった。小児の魚骨異物症例は，多くの症例が口腔内観察のみで診察が終了し，診断的な追加検査を必要としなかった。救急外来から帰宅する際は，重篤な合併症は稀であり自然に症状が消失することを伝え，同程度以上の症状が持続する場合には，合併症を考慮し耳鼻咽喉科受診を指示することが適切である。