bluuebunny/crossref_metadata_2025 huggingface dataset:
Paternal preconception exposure to non‐steroid anti‐inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry‐based cohort study
Authors: Lund Ken , Garvik Olav Sivertsen , Aagaard Signe Marie , Jølving Line Riis , Larsen Michael Due , Damkier Per , Nørgård Bente Mertz
Published: November 2023

Background and aim

Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non‐steroid anti‐inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations).

Methods

We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non‐steroid anti‐inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non‐steroid anti‐inflammatory drugs or opioids, and we performed a sub‐analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals.

Results

We identified 1,260,934 children, 45,667 children with paternal exposure to non‐steroid anti‐inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03–1.13) after paternal exposure to non‐steroid anti‐inflammatory drugs and 1.21 (95% confidence interval, 1.08–1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03–1.17) after paternal exposure to non‐steroid anti‐inflammatory drugs, and 1.03 (95% confidence interval, 0.88–1.21) after paternal exposure to opioids. We found null‐associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure.

Conclusions

Overall, we found null‐associations across the comparisons made. Weak associations were found for paternal exposure to non‐steroid anti‐inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.
Adoption of new medicines in primary care: A comparison between the uptake of new oral anticoagulants and diabetes medicines
Authors: Dankers Marloes , Hek Karin , Mantel‐Teeuwisse Aukje K. , van Dijk Liset , Nelissen‐Vrancken Marjorie H. J. M. G.
Published: November 2023

Aims

To gain insight in the uptake and practice variation in the prescription of 2 new medicine groups for common conditions in primary care (direct‐acting oral anticoagulants [DOACs] and incretin‐based therapies) from introduction, around 2007, to 2019 and the correlation between the adoption of those medicines in primary care.

Methods

Prescription data from general practices in the Dutch Nivel Primary Care Database from 2007 to 2019 were used. The percentage of patients with prescriptions for DOACs of all patients with prescriptions for DOACs and vitamin K antagonists was calculated per practice per year, as was the percentage of patients prescribed incretin‐based therapies as a proportion of all patients with diabetes medication. Multilevel models were used to estimate practice variation for DOACs and incretin‐based therapies, expressed as intraclass correlation coefficients. Linear regression analysis was used to study the association between the prescription of DOACs and incretin‐based therapies.

Results

Per year, 46–424 general practices and 179 933–1 654 376 patients were included. In 2019, the mean percentage of patients per practice using DOACs or incretin‐based therapies was 54.9 and 9.7%, respectively. The intraclass correlation coefficient decreased from 0.75 to 0.024 for DOACs and from 0.33 to 0.074 for incretin‐based medicines during the study period. No clear correlation was found between the prescription of DOACs and incretin‐based therapies.

Conclusion

DOACs and incretin‐based therapies have different adoption profiles and practice variation is large, especially in the years before these medicines were introduced in guidelines. Early adopters of both medicine classes differ.
Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup
Authors: Ramamoorthy Senthilkumar , Lebrecht Dirk , Schanze Denny , Schanze Ina , Wieland Ilse , Andrieux Geoffroy , Metzger Patrick , Hess Maria , Albert Michael H. , Borkhardt Arndt , Bresters Dorine , Buechner Jochen , Catala Albert , De Haas Valerie , Dworzak Michael , Erlacher Miriam , Hasle Henrik , Jahnukainen Kirsi , Locatelli Franco , Masetti Riccardo , Stary Jan , Turkiewicz Dominik , Vinci Luca , Wlodarski Marcin W. , Yoshimi Ayami , Boerries Melanie , Niemeyer Charlotte M. , Zenker Martin , Flotho Christian
Published: November 2023

Juvenile myelomonocytic leukaemia (JMML) is characterized by gene variants that deregulate the RAS signalling pathway. Children with neurofibromatosis type 1 (NF‐1) carry a defective NF1 allele in the germline and are predisposed to JMML, which presumably requires somatic inactivation of the NF1 wild‐type allele. Here we examined the two‐hit concept in leukaemic cells of 25 patients with JMML and NF‐1. Ten patients with JMML/NF‐1 exhibited a NF1 loss‐of‐function variant in combination with uniparental disomy of the 17q arm. Five had NF1 microdeletions combined with a pathogenic NF1 variant and nine carried two compound‐heterozygous NF1 variants. We also examined 16 patients without clinical signs of NF‐1 and no variation in the JMML‐associated driver genes PTPN11, KRAS, NRAS or CBL (JMML‐5neg) and identified eight patients with NF1 variants. Three patients had microdeletions combined with hemizygous NF1 variants, three had compound‐heterozygous NF1 variants and two had heterozygous NF1 variants. In addition, we found a high incidence of secondary ASXL1 and/or SETBP1 variants in both groups. We conclude that the clinical diagnosis of JMML/NF‐1 reliably indicates a NF1‐driven JMML subtype, and that careful NF1 analysis should be included in the genetic workup of JMML even in the absence of clinical evidence of NF‐1.
Phase 1/2 study of CPX‐351 for patients with Int‐2 or high risk International Prognostic Scoring System myelodysplastic syndromes and chronic myelomonocytic leukaemia after failure to hypomethylating agents
Authors: Montalban‐Bravo Guillermo , Jabbour Elias , Borthakur Gautam , Kadia Tapan , Ravandi Farhad , Chien Kelly , Pemmaraju Naveen , Hammond Danielle , Dong Xiao Qin , Huang Xuelin , Schneider Heather , John Rosmy , Kanagal‐Shamana Rashmi , Loghavi Sanam , Kantarjian Hagop , Garcia‐Manero Guillermo
Published: November 2023

Failure after hypomethylating agents (HMAs) is associated with dismal outcomes in higher risk myelodysplastic syndromes (HR‐MDS) or chronic myelomonocytic leukaemia (CMML). We aimed to evaluate the safety and preliminary activity of lower doses of CPX‐351, a liposomal encapsulation of cytarabine and daunorubicin, in a single‐centre, phase 1/2 study for patients with HR‐MDS or CMML after HMA failure. Four doses of CPX‐351 (10, 25, 50 and 75 units/m2) administered on Days 1, 3 and 5 of induction and Days 1 and 3 of consolidation were evaluated. Between June 2019 and June 2023, 25 patients were enrolled (phase 1: n = 15; phase 2: n = 10) including 19 (76%) with HR‐MDS and 6 (24%) with CMML. Most common grade 3–4 non‐haematological treatment‐emergent adverse events were febrile neutropenia (n = 12, 48%) and lung infection (n = 5, 20%). Three patients (age >75) experienced cardiac toxicity at the 75 units/m2 dose. Further enrolment continued at 50 units/m2. Four‐ and 8‐week mortality were 0% and 8% respectively. The overall response rate was 56% with median relapse‐free and overall survivals of 9.2 (95% CI 3.2–15.1 months) and 8.7 months (95% CI 1.8–15.6 months) respectively. These data suggest that lower doses of CPX‐351 are safe. Further studies are needed to evaluate its activity.
Disentangling genetic and environmental influences on early language development: The interplay of genetic propensity for negative emotionality and surgency, and parenting behavior effects on early language skills in an adoption study
Authors: Cheung Rachael W. , Austerberry Chloe , Fearon Pasco , Hayiou‐Thomas Marianna E. , Leve Leslie D. , Shaw Daniel S. , Ganiban Jody M. , Natsuaki Misaki N. , Neiderhieser Jenae M. , Reiss David
Published: November 2023

Parenting and children's temperament are important influences on language development. However, temperament may reflect prior parenting, and parenting effects may reflect genes common to parents and children. In 561 U.S. adoptees (57% male) and their birth and rearing parents (70% and 92% White, 13% and 4% African American, and 7% and 2% Latinx, respectively), this study demonstrated how genetic propensity for temperament affects language development, and how this relates to parenting. Genetic propensity for negative emotionality inversely predicted language at 27 months (β = −.15) and evoked greater maternal warmth (β = .12), whereas propensity for surgency positively predicted language at 4.5 years (β = .20), especially when warmth was low. Parental warmth (β = .15) and sensitivity (β = .19) further contributed to language development, controlling for common gene effects.
Young children's adaptive partner choice in cooperation and competition contexts
Authors: Grueneisen Sebastian , Török Georgina , Wathiyage Don Anushari , Ruggeri Azzurra
Published: November 2023

Choosing adequate partners is essential for cooperation, but how children calibrate their partner choice to specific social challenges is unknown. In two experiments, 4‐ to 7‐year‐olds (N = 189, 49% girls, mostly White, data collection: 03.2021–09.2022) were presented with partners in possession of different positive qualities. Children then recruited partners for hypothetical tasks that differed with respect to the quality necessary for success. Children and the selected partner either worked together toward a common goal or competed against each other. From age 5, children selectively chose individuals in possession of task‐relevant qualities as cooperative partners while avoiding them as competitors. Younger children chose partners indiscriminately. Children thus learn to strategically adjust their partner choice depending on context‐specific task demands and different social goals.
Medikamente als Auslöser Bradykinin‐vermittelter Angioödeme – mehr als ACE‐Hemmer
Authors: Lochbaum Robin , Hoffmann Thomas K. , Greve Jens , Hahn Janina
Published: November 2023

Bradykinin‐vermittelte Angioödeme sind seltene, nichtallergische und potenziell lebensbedrohliche Krankheiten. Die beiden bekanntesten Formen sind das ACE‐Hemmer‐induzierte Angioödem und das hereditäre Angioödem (HAE). Die therapeutischen Möglichkeiten, die Pathophysiologie und die Diagnostik werden weiter erforscht, wobei beim HAE in den letzten Jahrzehnten erhebliche Fortschritte erzielt wurden. Für alle Patienten mit Bradykinin‐vermittelten Angioödemen gibt es Medikamente, die vermieden oder mit Vorsicht verabreicht werden sollten. Einige dieser auslösenden Medikamente sind gut bekannt, bei anderen wird ein Zusammenhang vermutet oder ihre Bedeutung ist unbekannt. Ein gemeinsamer Nenner ist, dass es keine zugelassene Therapie für das Bradykinin‐vermittelte Angioödem als Arzneimittelnebenwirkung gibt. Bei einigen Medikamenten, wie dem gewebespezifischen Plasminogenaktivator, ist die Inzidenz von Angioödemen mit möglicher Beeinträchtigung der Atemwege höher als bei ACE‐Hemmern, wobei diese Tatsache weitgehend unterschätzt wird. In dieser Übersichtsarbeit fassen wir zusammen, was derzeit über die Begleitmedikation bei HAE‐Patienten und die Interaktion mit anderen Bradykinin‐beeinflussenden Medikamenten bekannt ist und empfohlen wird.
Hautbeteiligung bei Infektionen mit Mycobacterium haemophilum: Zwei Fallberichte und eine aktualisierte Literaturübersicht
Authors: Yasen Dilidaer , Liu Chaocheng , Mei Xingxing , Zhou Hui , Tang Xuhua , Chen Xiaohong
Published: November 2023

Mycobacterium haemophilum (MH) ist ein langsam wachsendes, nicht‐tuberkulöses Mykobakterium. Infektionen treten am häufigsten bei Patienten mit beeinträchtigtem Immunsystem auf; sie manifestieren sich meist an der Haut und kommen isoliert oder bei disseminierten Infektionen vor. Wir berichten hier über einen Fall mit isolierter MH‐Infektion an der Hand sowie über einen weiteren Fall von disseminierter MH‐Infektion mit multiplen Hautläsionen. Zusätzlich haben wir weitere Fallberichte über MH‐Infektionen mit kutaner Beteiligung aus den letzten zehn Jahren (2011–2022) ausgewertet. Die am häufigsten beobachteten Hautmanifestationen der insgesamt 79 Fälle waren Knötchen, Ulzera, Abszesse, Schwellungen und Pusteln. Patienten mittleren Alters mit iatrogener Immunsuppression durch Glucocorticoide, Mycophenolat‐Mofetil, Ciclosporin und Cyclophosphamid scheinen besonders anfällig für MH‐Infektionen zu sein und haben auch ein höheres Risiko für eine Dissemination in die inneren Organe. Disseminierte MH‐Infektionen manifestieren sich gewöhnlich als Tenosynovitis, Arthritis/Arthralgie oder Osteomyelitis. Derzeit gibt es keine starke Evidenz für bestimmte Therapeutika; in der Praxis wird am häufigsten eine Dreifachkombination aus Chinolon, Makroliden und Rifampicin eingesetzt. Die Prognose ist allgemein gut. Iatrogene Immunsuppression, Läsionen im proximalen Bereich der Extremitäten sowie disseminierte Manifestation sind mit schlechteren klinischen Verläufen assoziiert.
KI‐basierte Bestimmung des PRO‐Scores in aktinischen Keratosen anhand von LC‐OCT‐Bilddatensätzen
Authors: Thamm Janis R. , Daxenberger Fabia , Viel Théo , Gust Charlotte , Eijkenboom Quirine , French Lars E. , Welzel Julia , Sattler Elke C. , Schuh Sandra
Published: November 2023

Hintergrund

Mit Hilfe des histologischen PRO‐Scores (I–III) kann das Risiko einer malignen Transformation aktinischer Keratosen (AK) abgeschätzt werden, indem er das Ausmaß der Undulation und basalen Proliferation der dermoepidermalen Junktionszone (DEJ) bewertet. Die konfokale Line‐Field optische Kohärenztomographie (LC‐OCT) ermöglicht eine nichtinvasive Bestimmung des PRO‐Scores in Echtzeit. Anhand von LC‐OCT‐Bilddatensätzen kann eine künstliche Intelligenz (KI) mit Hilfe von Convolutional Neural Networks (CNN) zur automatischen Quantifizierung des PRO‐Scores von AK in vivo trainiert werden.

Patienten und Methodik

Convolutional Neural Networks wurden trainiert, um LC‐OCT‐Bilder von gesunder Haut und von AK zu segmentieren. PRO‐Score‐Modelle wurden in Übereinstimmung mit dem histopathologischen Goldstandard entwickelt und an einer Teilmenge von 237 LC‐OCT‐AK‐Bildern trainiert und an 76 Bildern getestet, wobei der von der KI‐berechnete PRO‐Score mit dem visuellen Konsens der Bildgebungsexperten verglichen wurde.

Ergebnisse

Eine signifikante Übereinstimmung wurde in 57/76 (75%) Fällen festgestellt. Die KI‐basierte Bewertung des PRO‐Scores korrelierte am besten mit dem visuellen Score für PRO II (84,8%) vs. PRO III (69,2%) vs. PRO I (66,6%). In 25% der Fälle kam es zu Fehlinterpretationen, die meist auf eine Verschattung der DEJ sowie störende Merkmale wie Haarfollikel zurückzuführen waren.

Schlussfolgerungen

Die Ergebnisse deuten darauf hin, dass CNN für die automatische Quantifizierung des PRO‐Scores in LC‐OCT‐Bilddatensätzen hilfreich sind. Dies könnte zur nichtinvasiven Bewertung des Proliferationsrisikos in der Diagnostik und Nachsorge von AK herangezogen werden.
Education in exile: Ukrainian refugee students in the schooling system in Poland following the Russian–Ukrainian war
Authors: Herbst Mikołaj , Sitek Michał
Published: November 2023

Following the Russian war of aggression in Ukraine since February 2022, Poland adopted institutional solutions and policies to facilitate the inclusion of Ukrainian refugees in the schooling system. We analyse geographical patterns and local determinants of the participation of children and young people from Ukraine in education in Poland. Applying a computer‐based geographic information system and statistical analysis to administrative data from schools and municipalities in Poland, we found that about 50% of the Ukrainian refugees at schools in Poland are of primary school age, while the rates for other age groups are significantly lower. Ukrainian refugees are more likely to attend public schools in affluent urban municipalities and places with more developed accommodation infrastructure. Clearly, the role of local resources was of key importance in the territorial distribution of refugee families in Poland during the first year of the war. Another factor that proved to be important in attracting refugees was the presence of pre‐war Ukrainian immigrants in schools. Observed patterns differ between spring and autumn 2022, which partly reflects the changes in migration to Poland and then back to Ukraine. We anticipate that much of the Ukrainian migration to Poland may outlast the current conflict. This situation creates further challenges for education in Poland—and even more so for Ukraine.
Metric error monitoring as a component of metacognitive processing
Authors: Öztel Tutku , Balcı Fuat
Published: November 2023

Metacognitive processing constitutes one of the contemporary target domains in consciousness research. Error monitoring (the ability to correctly report one's own errors without feedback) is considered one of the functional outcomes of metacognitive processing. Error monitoring is traditionally investigated as part of categorical decisions where choice accuracy is a binary construct (choice is either correct or incorrect). However, recent studies revealed that this ability is characterized by metric features (i.e., direction and magnitude) in temporal, spatial, and numerical domains. Here, we discuss methodological approaches to investigating metric error monitoring in both humans and non‐human animals and review their findings. The potential neural substrates of metric error monitoring measures are also discussed. This new scope of metacognitive processing can help improve our current understanding of conscious processing from a new perspective. Thus, by summarizing and discussing the perspectives, findings, and common applications in the metric error monitoring literature, this paper aims to provide a guideline for future research.
Climate change: Attitudes and concerns of, and learnings from, people with neurological conditions, carers, and health care professionals
Authors: Blenkinsop Stephen , Wardrope Alistair , Willis Joseph , Sisodiya Sanjay M.
Published: November 2023

Objective

Concern about climate change among the general public is acknowledged by surveys. The health care sector must play its part in reducing greenhouse gas emissions and adapting to a changing climate, which will require the support of its stakeholders including those with epilepsy, who may be especially vulnerable. It is important to understand this community's attitudes and concerns about climate change and societal responses.

Methods

A survey was made available to more than 100 000 people among a section of the neurological community (patients, carers, and clinicians), focused on epilepsy. We applied quantitative analysis of Likert scale responses supported by qualitative analyses of free‐text questions with crossover analyses to identify consonance and dissonance between the two approaches.

Results

A small proportion of potential respondents completed the survey; of 126 respondents, 52 had epilepsy and 56 explicitly declared no illness. The survey indicated concern about the impact of climate change on health within this neurological community focused on epilepsy. More than half of respondents considered climate change to have been bad for their health, rising to 68% in a subgroup with a neurological condition; over 80% expected climate change to harm their health in future. Most (>75%) believed that action to reduce greenhouse gas emissions will lead to improved health and well‐being. The crossover analysis identified cost and accessibility as significant barriers.

Significance

The high level of concern about climate change impacts and positive attitudes toward policies to reduce greenhouse gas emissions provide support for climate action from the epilepsy community. However, if policies are implemented without considering the needs of patients, they risk being exclusionary, worsening inequalities, and further threatening neurological health and well‐being.
Occurrence and evolutionary conservation analysis of α‐helical cationic amphiphilic segments in the human proteome
Authors: Costa Igor S. D. , Junot Tiago , Silva Fernanda L. , Felix Wanessa , Cardozo Fh José L. , Pereira de Araujo Antonio F. , Pais do Amaral Constança , Gonçalves Sónia , Santos Nuno C. , Leite José R. S. A. , Bloch Carlos , Brand Guilherme D.
Published: November 2023

The existence of encrypted fragments with antimicrobial activity in human proteins has been thoroughly demonstrated in the literature. Recently, algorithms for the large‐scale identification of these segments in whole proteomes were developed, and the pervasiveness of this phenomenon was stated. These algorithms typically mine encrypted cationic and amphiphilic segments of proteins, which, when synthesized as individual polypeptide sequences, exert antimicrobial activity by membrane disruption. In the present report, the human reference proteome was submitted to the software kamal for the uncovering of protein segments that correspond to putative intragenic antimicrobial peptides (IAPs). The assessment of the identity of these segments, frequency, functional classes of parent proteins, structural relevance, and evolutionary conservation of amino acid residues within their corresponding proteins was conducted in silico. Additionally, the antimicrobial and anticancer activity of six selected synthetic peptides was evaluated. Our results indicate that cationic and amphiphilic segments can be found in 2% of all human proteins, but are more common in transmembrane and peripheral membrane proteins. These segments are surface‐exposed basic patches whose amino acid residues present similar conservation scores to other residues with similar solvent accessibility. Moreover, the antimicrobial and anticancer activity of the synthetic putative IAP sequences was irrespective to whether these are associated to membranes in the cellular setting. Our study discusses these findings in light of the current understanding of encrypted peptide sequences, offering some insights into the relevance of these segments to the organism in the context of their harboring proteins or as separate polypeptide sequences.
Managing mineral phosphorus application with soil residual phosphorus reuse in Canada
Authors: Wang Jiaxin , Qi Zhiming , Bennett Elena M.
Published: November 2023

With limited phosphorus (P) supplies, increasing P demand, and issues with P runoff and pollution, developing an ability to reuse the large amounts of residual P stored in agricultural soils is increasingly important. In this study, we investigated the potential for residual soil P to maintain crop yields while reducing P applications and losses in Canada. Using a P cycling model coupled with a soil P dynamics model, we analyzed soil P dynamics over 110 years across Canada's provinces. We found that using soil residual P may reduce mineral P demand as large as 132 Gg P year−1 (29%) in Canada, with the highest potential for reducing P applications in the Atlantic provinces, Quebec, Ontario, and British Columbia. Using residual soil P would result in a 21% increase in Canada's cropland P use efficiency. We expected that the Atlantic provinces and Quebec would have the greatest runoff P loss reduction with use of residual soil P, with the average P loss rate decreasing from 4.24 and 1.69 kg ha−1 to 3.45 and 1.38 kg ha−1, respectively. Ontario, Manitoba, and British Columbia would experience relatively lower reductions in P loss through use of residual soil P, with the average runoff P loss rate decreasing from 0.44, 0.36, and 4.33 kg ha−1 to 0.19, 0.26, and 4.14 kg ha−1, respectively. Our study highlights the importance of considering residual soil P as a valuable resource and its potential for reducing P pollution.
Platform work‐lives in the gig economy: Recentering work–family research
Authors: James Al
Published: November 2023

Crowdwork platforms have been widely celebrated as challenging gendered labor market inequalities through new digitally mediated possibilities for reconciling work, home, and family. This paper interrogates those claims and explores the wider implications of digital labor platforms for an expansive work–family research agenda stubbornly rooted in formal modes of employment in the “analogue” economy. Based on ethnographic research with women platform workers in the UK (using PeoplePerHour, Upwork, Freelancer, Fiverr, and Copify), the paper asks: what are women crowdworkers' lived experiences of integrating paid work and family relative to formal employment? And what coping tactics have women developed to reduce gendered work–family conflicts on digital labor platforms? In response to these research questions, the paper makes three contributions. First, it offers a critical review of recent commentary to theorize how disruptive innovations by digital labor platforms to recast long‐standing definitions of “work”, “workers”, “managers”, and “employers” have served to position platforms and platform workers as somehow outside the analytical gaze of the expansive work–family research agenda. Second, it extends a growing alternative work–family analysis of platform work to examine the kinds of “work–life balance” (WLB) provision available to women crowdworkers in the absence of an employer; and how women's experiences of algorithmically mediated and contradictory work–family outcomes further challenge widespread claims of new platform work–life “flexibilities”. Third, the paper points to exciting and urgent possibilities for advancing and recentering work–family research through new engagements with platforms, algorithmic management, and “independent” platform workers in support of feminist activism and campaigning around WLB.
Effect of transglutaminase cross‐linking on debittering of Alaska pollock frame hydrolysate
Authors: Shan Chunyu , Wu Guoqiang , Bu Ying , Zhu Wenhui , Li Jianrong , Li Xuepeng
Published: November 2023

The present study aimed to investigate the impact of TGase cross‐linking on the flavour characteristics, particularly focusing on its ability to reduce bitterness in enzymatically digested Alaska Pollock framework (APF) hydrolysates using Protease A ‘Amano’ 2SD (A2SD) and Protease A ‘Amano’ 6SD (A6SD). Electronic tongue results showed that the umami was enhanced, accompanied by a reduction in both bitterness and bitter aftertaste. The contents of glutamic acid (Glu) and nucleotides (AMP, IMP and GMP) exhibited significant differences among all treatment groups (P < 0.05). There was a notable increase in the types and relative concentrations of alcohols, ketones, alkanes and aldehydes in the cross‐linked APF enzymatic hydrolysate. The Fourier transform infrared spectroscopy, ultraviolet spectrum and fluorescence spectrum analyses indicate that TGase cross‐linking leads to a reduction in the exposure of hydrophobic amino acid residues. The surface hydrophobicity of HA2SD‐C and HA6SD‐C exhibited a significantly lower level compared with that of HA2SD and HA6SD. The present study presents an effective approach for mitigating the bitter taste of aquatic hydrolysate, thereby positively contributing to the advancement and utilisation of this valuable resource.
Effect of segmental versus lobectomy in minimally invasive surgery on postoperative wound complications in lung cancer patients: A meta‐analysis
Authors: Zhou Jin , Wang Wei
Published: November 2023

It is still a matter of debate whether the surgical segmentectomy and lobectomy of lung cancer are comparable in the incidence of perioperative wound complications. An extensive review of the literature through August 2023 was carried out with a critical review of four databases. Following the acceptance and elimination criteria set out in the trial, as well as a qualitative assessment of the literature, this resulted in a review of related research that compared the results of both lobectomy and partial resection in the management of lung cancer. The analysis of the data was performed with the RevMan 5.3 software, and the 95% confidence interval [CI] and odds ratio [OR] were performed with either stationary or random‐effect models. It is concluded that the operation time of lobectomy is shorter than that of sectioning in the treatment of segmentectomy (mean difference [MD], −38.62; 95% CI, −41.96, −35.28; p < 0.0001). But the rate of postoperative wound infection (OR, 0.62; 95% CI, 0.18, 2.15; p = 0.45) and intraoperative blood loss (MD, 17.54; 95% CI, −4.19, 39.26; p = 0.11) were not significantly different for them. Thus, for those who have received a pulmonary carcinoma operation, different operative methods might not have an impact on the incidence of postoperative wound infections. The operative procedure appears to have a major impact on the length of the operation in patients.
The practical histochemical demonstration of catecholamines by formaldehyde‐induced fluorescence
Authors: ERÄNKÖ OLAVI
Published: November 2023

SYNOPSIS

Catecholamines become intensely fluorescent when exposed to formaldehyde. This is due to closure of the side chain by a methylene bridge and subsequent dehydrogenation, which results in the formation of intensely fluorescent isoquinolines. Exposing freeze‐dried tissue to formaldehyde vapour makes it possible to study the distribution of catecholamines by fluorescence microscopy. The present paper deals with the practical performance of the formaldehyde‐induced fluorescence.

The technique consists of the following steps:

Freezing. This must be rapid. An apparatus is proposed for freezing at maximum rate, in which the tissue slice comes into sudden contact with a cold metal surface.

Drying. The tissue must be dried at a temperature below −40°C, using an efficient apparatus. The types of apparatus are described and discussed. Small tissue pieces can be dried overnight with an efficient apparatus.

Formaldehyde condensation. Formaldehyde is generated by warming paraformaldehyde powder in a glass vessel containing the freeze‐dried tissue pieces. The temperature of exposure and the water content of the paraformaldehyde powder must be properly adjusted for each tissue. Exposure for 1 hour at 50°C to paraformaldehyde powder equilibriated with 60 p.c. relative humidity is recommended as a start.

Embedding, sectioning, and mounting. The formaldehyde‐treated tissue pieces are embedded in paraffin wax or, for better resolution, in epoxy resin. Sections must be spread on the slide without using water. Xylene, paraffin oil, and Entellan are suitable mounting media.

Fluorescence microscopy. Any microscope fitted with non‐fluorescent optics is suitable for fluorescence work. A sufficiently intense light source is necessary; the high pressure mercury vapour lamp HBO 200 (Osram) is suitable. Special effects can be obtained with different filter combinations. The Schott filters BG 12 and OG 1 are suitable for most practical studies of catecholamines.
The aging gut: Symptoms compatible with disorders of gut‐brain interaction (DGBI) in older adults in the general population
Authors: Busby‐Whitehead Jan , Whitehead William E. , Sperber Ami D. , Palsson Olafur S. , Simrén Magnus
Published: November 2023

Background

Little is known about changes in gastrointestinal symptoms compatible with disorders of gut‐brain interaction (DGBI) with increasing age at the population level. The objective of this study was to describe the patterns of DGBI in individuals 65 years of age and above and contrasting them with those of younger adults.

Methods

A community sample of 6300 individuals ages 18 and older in the US, UK, and Canada completed an online survey. Quota‐based sampling was used to ensure equal proportion of sex and age groups (40% aged 18–39, 40% aged 40–64, 20% aged 65+) across countries, and to control education distributions. The survey included the Rome IV Diagnostic Questionnaire for DGBI, demographic questions, questionnaires measuring overall somatic symptom severity and quality of life, and questions on healthcare utilization, medications, and surgical history.

Results

We included 5926 individuals in our analyses; 4700 were 18–64 years of age and 1226 were ages 65+. Symptoms compatible with at least one DGBI were less prevalent in participants ages 65+ vs. ages 18–64 years (34.1% vs. 41.3%, p < 0.0001). For symptoms compatible with upper GI DGBI, lower prevalence for most disorders was noted in the 65+ group. For lower GI DGBI, a different pattern was seen. Prevalence was lower in ages 65+ for irritable bowel syndrome and anorectal pain, but no differences from younger participants for the disorders defined by abnormal bowel habits (constipation and/or diarrhea) were seen. Fecal incontinence was the only DGBI that was more common in ages 65+. Having a DGBI was associated with reduced quality of life, more severe non‐GI somatic symptoms, and increased healthcare seeking, both in younger and older participants.

Conclusion

Symptoms compatible with DGBI are common, but most of these decrease in older adults at the population level, with the exception of fecal incontinence which increases. This pattern needs to be taken into account when planning GI health care for the growing population of older adults.
Efficacy and safety of surgical excision and reconstruction combined with radiotherapy for huge keloids: A 13‐year experience
Authors: Dong Wenfang , Xiao Xiaodi , Yang Xin , Zhao Zhenmin
Published: November 2023

Background

Surgical excision combined with radiotherapy is considered an effective treatment for keloids, while the efficacy and safety of this regimen for huge keloids in patients who need reconstruction after excision is still unclear. Therefore, this study aimed to evaluate the efficacy and safety of surgical excision and reconstruction combined with radiotherapy for huge keloids in a single center with 13 years of experience.

Methods

All consecutive patients with huge keloids who underwent surgical excision and reconstruction combined with radiotherapy were identified. Demographic information, prior interventions for keloids, parameters and complications, and recurrence rates were documented.

Results

Twenty‐one patients (10 males; mean age, 43.19 ± 18.15 years) were included, 14 patients reconstructed with z‐plasties, 5 with skin grafts, and 2 with skin flaps. During a mean follow‐up of 75 months, one patient developed local necrosis without the need for revision surgery and two patients developed temporary hyperpigmentation. Two patients with the z‐plasties suffered partial keloids recurrence, which was healed with corticosteroid injection. No wound infection, hematoma, telangiectasia, or new keloids at donor sites were observed. The overall appearance of reconstructed defects was aesthetically acceptable.

Conclusion

Surgical excision and reconstruction combined with radiotherapy may be safe and effective for huge keloids.
Effect of denture cleansers on color stability and surface properties of denture base material containing titanium dioxide nanoparticles
Authors: Ansarifard Elham , Mohaghegh Mina , Saadat Mohammad Hossein , Taghva Masumeh
Published: November 2023

Purpose

To investigate the effect of different denture cleansers on color stability, surface roughness, and hardness of polymethylmethacrylate (PMMA) infused with titanium dioxide nanoparticles (TiO2 NPs) at concentrations of 1% and 2% by weight on each.

Materials and Methods

In this in vitro study, 90 disc‐shaped specimens (10×10×2 mm) were divided into 3 main groups: the non‐containing nanoparticle group (0wt% concentration), 1wt% concentration, and 2wt% concentration TiO2 NPs groups. Each group was further assorted into 3 subgroups (n = 10): immersed in distilled water, oxygenating tablet (Corega), and 0.5% sodium hypochlorite. Color change, surface roughness, and hardness values were assessed after 90 and 180 days of storage. Color changes (∆E) were measured with a spectrophotometer (VITA, Easy Shade V, Germany) and assessed using the CIE L*a*b* colorimetric system and the American National Bureau of Standards (NBS = 0.92×∆E). The surface roughness and surface hardness values were measured using a profilometer device and Vickers hardness tester, respectively. First, ANOVA‐repeated measurements were performed, followed by the Tukey test. The significance level in this study was considered 0.05.

Results

At all concentrations, there were significant differences in the mean color changes of samples immersed in cleansers compared to distilled water (p < 0.01). Moreover, hypochlorite caused a significant increase compared to Corega at 0wt% concentration after 90 days and at 1wt% concentration after 90 and 180 days. Evaluations also showed that the mean NBS values in all cleanser groups were in the range of appreciable change, except the water group. In addition, only hypochlorite changed the color higher than the clinically acceptable range (∆E >3.7). The mean roughness of samples immersed in hypochlorite at 0wt% concentration was significantly higher than the samples containing TiO2 NPs (p = 0.006). No significant difference was observed in surface roughness of samples containing different concentrations of TiO2 NPs immersed in different cleansers; however, hypochlorite increased the surface roughness of samples without TiO2 NPs compared to samples containing TiO2 NPs after 180 days. The immersion time in cleansers had a significant influence on the surface roughness and hardness while having no effect on the color.

Conclusion

In general, the cleansers had a significant effect on color change in all groups compared to distilled water. The adverse effect of hypochlorite was more than Corega. The cleansers in the samples containing TiO2 NPs did not make a significant difference in surface roughness in comparison with the distilled water groups. Surface hardness of the samples was not affected in a steady pattern by the cleansers.
Performance of tunnelled, non‐cuffed central venous catheters in infants: A scoping review
Authors: Dean Anna , Doyle Rebecca , Ullman Amanda
Published: November 2023

Aim

To summarise and critique existing knowledge and evidence relating to the utility, and post‐insertion complications surrounding tunnelled non‐cuffed central venous catheters (tncCVCs) in infants.

Methods

A scoping review of original research studies reporting the use of, and post‐insertion complications associated with, tncCVCs in infants was completed. MeSH terms were used to formulate a systematic search, and data were extracted using a customised data extraction form. Data were analysed descriptively across key themes based on the research questions. Study quality was evaluated using the Mixed Methods Appraisal Tool.

Results

The systematic search generated 3994 studies, of which 9 studies met final inclusion criteria. Studies included 644 tncCVCs in infants based in the USA, Europe and Australia. Most studies were retrospective cohort studies. The most common vein of insertion, where individually specified, was the internal jugular (n = 177). Tunnel length, where reported, was 2.5–5 cm. Infection rates were most commonly reported (eight studies), with results ranging from 0 to 12.8%, and device dislodgements of up to 20% reported. Participant follow‐up and definition of complications varied greatly between studies. Study quality across all papers was sound.

Conclusions

This review has identified only a small number of studies, with small participant numbers, reporting the performance of tncCVCs in infants. Definitions of complications measured varied significantly between studies, and vastly different patient follow‐up protocols were reported. Further larger‐scale studies on the performance of tncCVC, employing internationally recognised reporting standards is warranted to ensure clinicians can make informed choices for medication and infusion delivery.
Effects of intravenous administration of ascorbic acid (vitamin C) on oxidative status in healthy adult horses
Authors: Taylor Sandra D. , Hart Kelsey A. , Vaughn Sarah , Giancola Shyla C. , Serpa Priscila B. S. , Santos Andrea P.
Published: November 2023

Background

Ascorbic acid (AA) is an antioxidant that might be beneficial for adjunctive treatment of sepsis in horses. The optimal dose and effects on oxidative status are unknown.

Hypothesis

Ascorbic acid administration will increase plasma AA concentrations and decrease determinants of reactive oxygen metabolites (dROM), basal and stimulant‐induced intraerythrocytic reactive oxygen species (ROS) concentrations, and stimulant‐induced neutrophil ROS production, and increase plasma antioxidant capacity (PAC) in a dose‐dependent manner.

Animals

Eight healthy horses.

Methods

Randomized placebo‐controlled crossover study. Each horse received 4 single‐dose IV treatments including AA at 25, 50, and 100 mg/kg and saline (placebo) with each treatment separated by ≥1 week. Blood was collected at baseline, 2 and 6 hours for assessment of plasma dROM and PAC via photometer, intraerythrocytic ROS by flow cytometry, and stimulant‐induced neutrophil ROS by a fluorometric assay. Plasma AA concentrations were measured by high‐performance liquid chromatography/electrochemical detection.

Results

Ascorbic acid at 100 mg/kg resulted in decreased dROM 2 hours after treatment (P = .03, 95% CI 5.51‐121.2, point estimate 63.3). There was no effect of AA on basal or stimulant‐induced intraerythrocytic ROS (P = .88, 95% CI −0.156 to 0.081, point estimate −0.037; P = .93, 95% CI −0.123 to 0.112, point estimate −0.006, respectively), basal or stimulant‐induced neutrophil ROS (P ≥ .12, 95% CI −644.9 to 56.2, point estimate −294.4), or PAC (P ≥ .64, 95% CI −1567 to 463.4, point estimate −552.0) at any dose or timepoint. Plasma AA concentrations increased in a dose‐dependent manner.

Conclusions and Clinical Importance

High‐dose administration of AA might provide antioxidant benefits in horses.
Temporal colonization of macadamia tree roots by Phytophthora cinnamomi based on a newly developed quantitative real‐time PCR assay
Authors: McLeod Adele , Hamza Zizipho , Schoeman Maritha H. , Moyo Lindani , Akinsanmi Olufemi A.
Published: November 2023

Phytophthora cinnamomi is an important soilborne pathogen causing root rot and stem cankers on macadamia in South Africa and other countries. It is unknown whether a temporal pattern exists in the colonization of macadamia tree roots by P. cinnamomi. To investigate this, three macadamia orchards were studied bimonthly for 2 years. The study also examined whether two types of feeder roots contained varying levels of P. cinnamomi DNA. A new sensitive P. cinnamomi‐specific quantitative real‐time PCR (qPCR) assay was used to conduct the assessments. Only symptomatic trees were studied in two of the orchards (ZC and ZD), while symptomatic and asymptomatic trees were assessed in the third orchard (ZA). In the ZC and ZD orchards, white non‐suberized feeder roots from a new root flush had higher levels of P. cinnamomi DNA than suberized feeder roots. In orchard ZD, autumn and winter yielded the highest P. cinnamomi root quantities in suberized roots. The symptomatic and asymptomatic trees in orchard ZA generally contained higher P. cinnamomi root quantities in winter than in summer. However, in orchard ZC, no significant temporal pattern was evident, although a trend was noticeable towards higher P. cinnamomi root colonization in autumn, winter and spring. Principal component analyses supported autumn and winter as the months yielding the highest P. cinnamomi root colonization levels. The study has contributed to a better understanding of the temporal nature of P. cinnamomi root colonization, and feeder root types that are optimal for qPCR quantifying the pathogen in macadamia.
Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma
Authors: Vasilijic Sasa , Atai Nadia A. , Hyakusoku Hiroshi , Worthington Steven , Ren Yin , Sagers Jessica E. , Sahin Mehmet I. , Brown Alyssa , Reddy Rohan , Malhotra Charvi , Fujita Takeshi , Landegger Lukas D. , Lewis Richard , Welling D. Bradley , Stankovic Konstantina M.
Published: November 2023

Vestibular schwannoma (VS) is an intracranial tumor arising from neoplastic Schwann cells and typically presenting with hearing loss. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. We conducted profiling of patients’ plasma for 66 immune-related factors in patients with sporadic VS (
N
> 170) and identified and validated candidate biomarkers associated with tumor size (S100B) and hearing (MCP-3). We further identified a nine-biomarker panel (TNR-R2, MIF, CD30, MCP-3, IL-2R, BLC, TWEAK, eotaxin, and S100B) with outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS, providing a unique diagnostic tool that may predict hearing change and tumor growth in VS patients, and may inform the timing of tumor resection to preserve hearing.
Alpha-frequency feedback to early visual cortex orchestrates coherent naturalistic vision
Authors: Chen Lixiang , Cichy Radoslaw M. , Kaiser Daniel
Published: November 2023

During naturalistic vision, the brain generates coherent percepts by integrating sensory inputs scattered across the visual field. Here, we asked whether this integration process is mediated by rhythmic cortical feedback. In electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) experiments, we experimentally manipulated integrative processing by changing the spatiotemporal coherence of naturalistic videos presented across visual hemifields. Our EEG data revealed that information about incoherent videos is coded in feedforward-related gamma activity while information about coherent videos is coded in feedback-related alpha activity, indicating that integration is indeed mediated by rhythmic activity. Our fMRI data identified scene-selective cortex and human middle temporal complex (hMT) as likely sources of this feedback. Analytically combining our EEG and fMRI data further revealed that feedback-related representations in the alpha band shape the earliest stages of visual processing in cortex. Together, our findings indicate that the construction of coherent visual experiences relies on cortical feedback rhythms that fully traverse the visual hierarchy.
Optimal control pulses for the 1.2-GHz (28.2-T) NMR spectrometers
Authors: Joseph David , Griesinger Christian
Published: November 2023

The ability to measure nuclear magnetic resonance (NMR) spectra with a large sample volume is crucial for concentration-limited biological samples to attain adequate signal-to-noise (S/N) ratio. The possibility to measure with a 5-mm cryoprobe is currently absent at the 1.2-GHz NMR instruments due to the exceedingly high radio frequency power demands, which is four times compared to 600-MHz instruments. Here, we overcome the high-power demands by designing optimal control (OC) pulses with up to 20 times lower power requirements than currently necessary at a 1.2-GHz spectrometer. We show that multidimensional biomolecular NMR experiments constructed using these OC pulses can bestow improvement in the S/N ratio of up to 26%. With the expected power limitations of a 5-mm cryoprobe, we observe an enhancement in the S/N ratio of more than 240% using our OC sequences. This motivates the development of a cryoprobe with a larger volume than the current 3-mm cryoprobes.