bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Printed Poly (Lactic-co-Glycolic Acid)-Magnesium Composite Scaffolds for the Promotion of Osteogenesis Through Immunoregulation
Authors: Ren Yuqing , Zheng Zheng , Yu Yanjun , Hu Rongrong , Xu Shanshan
Published: October 2023

Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1β, IL-6, and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-β, IL-10, and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes (ALP, COL-1, BMP2, and BSP) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.
Damage control resuscitation in adult trauma patients: What you need to know
Authors: Lammers Danny T. , Holcomb John B.
Published: October 2023

Death after injury is a worldwide epidemic. Hemorrhage as a cause of death represents the leading potentially preventable condition. Based on hard-won experience from the recent wars, and two decades of military and civilian research, damage-control resuscitation (DCR) is now widely used. This article will briefly describe the history of blood transfusion, outline “why we do DCR,” and then discuss “how we do DCR.” Modern DCR occurs both prehospital and in the hospital and has several main tenants. Currently, DCR focuses on the liberal use of temporary hemorrhage-control adjuncts, early use of whole blood or balanced blood product-based transfusions, mitigation of crystalloid use, hypotensive resuscitation to promote hemostasis and decrease coagulopathy, and correction of ongoing metabolic derangements, followed by rapid definitive hemorrhage control. These concepts have evolved from a series of lessons learned over time from both civilian and military trauma casualties, and DCR is now the standard of care in trauma resuscitation.
Avoidant-restrictive food intake disorder and autism: epidemiology, etiology, complications, treatment, and outcome
Authors: Keski-Rahkonen Anna , Ruusunen Anu
Published: October 2023

Purpose of review

There is considerable overlap between the features of avoidant-restrictive food intake disorder (ARFID) and autism. The purpose of this scoping review is to provide an overview of studies published on ARFID and autism in 2022 and the first half of 2023.

Recent findings

ARFID and autism are highly heritable conditions that often co-occur. In a large autism cohort, 21% of participants and 17% of their parents presented with avoidant-restrictive features. Of children diagnosed with ARFID, 8.2–54.8% are autistic. More than half of individuals with ARFID also have other neurodevelopmental, psychiatric, or somatic diagnoses. Anxiety, depression, sleep disorders, and learning difficulties are particularly common co-occurring issues. Various strategies have been developed to support autistic children with feeding difficulties. It appears that their feeding difficulties, particularly sensory sensitivities, food preferences, and mealtime rituals and routines frequently persist into adolescence and adulthood, but research on optimal support for adults and adolescents is still scarce. Untreated ARFID in autistic individuals may lead to serious complications.

Individuals seeking specialist care for autism, eating disorders, or gender dysphoria should be screened for ARFID. More research is needed on how to support autistic adolescents and adults with features of ARFID.
Updates in the care of youths with intellectual disability and autism spectrum disorder
Authors: Bertelli Marco O. , Forte Luciana , Bianco Annamaria
Published: October 2023

Purpose of review

Since the turn of the new millennium, care for people with intellectual disability/intellectual developmental disorders (IDD) and/or autism spectrum disorder (ASD) has drawn increasing attention because of the continuous prevalence increase of these two conditions, the high health vulnerability, especially mental vulnerability, and the crucial role of care provision in the setting of continued deinstitutionalization and the shift to community care. The present review addresses the main issues related to mental healthcare in youth with IDD and/or ASD with a specific focus on adolescence and transition to adulthood.

Recent findings

Despite the existence of specific recommendations, persons with IDD/ASD lack access to quality mental healthcare within communities, receive inadequate diagnosis and intervention, including medication overuse as well as ineffective residential, educational, employment, financial, and social support services. The lack of a unified care system that provides services across all domains and life ages may be the cause of users’ perceptions and experiences of inefficiencies.

The scientific community seems to converge on that care should be provided in accordance with principles of interdisciplinarity, life-span view, precision, personalization, and participation. Quality of life appears to be an ideal conceptual reference for care planning and outcome evaluation.
Efficacy and safety of agomelatine versus SSRIs/SNRIs for post-stroke depression: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Yicong , Li Jianle , Liao Mengshi , He Yinxin , Dang Chao , Yu Jian , Xing Shihui , Zeng Jinsheng
Published: October 2023

Agomelatine is effective in the treatment of depression, but its effect for post-stroke depression (PSD) remains unclear. This study was conducted to compare the efficacy and safety of agomelatine versus SSRIs/SNRIs in treating PSD. We systematically searched Embase, PubMed, Cochrane Library, WanFang Data, China National Knowledge Infrastructure, and Cqvip databases for double-blind randomized controlled studies comparing the efficacy and safety of agomelatine versus SSRIs/SNRIs for PSD until December 2022. The primary efficacy endpoint was the Hamilton Depression Rating Scale (HAMD) score, and the primary safety endpoint was the incidence of overall adverse reactions. Nine studies comprising 857 patients with PSD were included. After 6–12 weeks of treatment, the HAMD score (P = 0.16) and the overall response rates (P = 0.20) in the agomelatine group were comparable to that in the SSRIs/SNRIs group. Participants treated with agomelatine achieved higher Barthel Index scores compared with the SSRIs/SNRIs group (P = 0.02). There was a significantly lower incidence of overall adverse reactions (P = 0.008) and neurological adverse reactions (P < 0.0001) in the agomelatine group. The efficacy of agomelatine for treating PSD is probably comparable to that of SSRIs/SNRIs, and it may improve stroke outcomes with better safety.
Modeling the Evolution of Populations with Multiple Killer Meiotic Drivers
Authors: Hernández José Fabricio López , Rubinstein Boris Y , Unckless Robert L. , Zanders Sarah E.
Published: October 2023

Meiotic drivers are selfish genetic loci that can be transmitted to more than half of the viable gametes produced by a heterozygote. This biased transmission gives meiotic drivers an evolutionary advantage that can allow them to spread over generations until all members of a population carry the driver. This evolutionary power can also be exploited to modify natural populations using synthetic drivers known as ‘gene drives’. Recently, it has become clear that natural drivers can spread within genomes to birth multicopy gene families. To understand intragenomic spread of drivers, we model the evolution of two distinct meiotic drivers in a population. We employ thewtfkiller meiotic drivers fromSchizosaccharomyces pombe, which are multicopy in all sequenced isolates, as models. We find that a duplicatewtfdriver identical to the parent gene can spread in a population unless, or until, the original driver is fixed. When the duplicate driver diverges to be distinct from the parent gene, we find that both drivers spread to fixation under most conditions. Finally, we show that stronger drivers make weaker drivers go extinct in most, but not all, polymorphic populations with absolutely linked drivers. These results reveal the strong potential for natural meiotic drive loci to duplicate and diverge within genomes. Our findings also highlight duplication potential as a factor to consider in the design of synthetic gene drives.
Amphibian mast cells: barriers to chytrid fungus infections
Authors: Hauser Kelsey A. , Garvey Christina N. , Crow Ryley S. , Hossainey Muhammad R.H. , Howard Dustin T. , Ranganathan Netra , Gentry Lindsey K. , Yaparla Amulya , Kalia Namarta , Zelle Mira , Jones Elizabeth J. , Duttargi Anju N. , Rollins-Smith Louise A. , Muletz-Wolz Carly R. , Grayfer Leon
Published: October 2023

Global amphibian declines are compounded by deadly disease outbreaks caused by the chytrid fungus,Batrachochytrium dendrobatidis(Bd). Much has been learned about the roles of amphibian skin-produced antimicrobial components and microbiomes in controllingBd, yet almost nothing is known about the roles of skin-resident immune cells in anti-Bddefenses. Mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like skin. Accordingly, we investigated the roles ofXenopus laevisfrog mast cells duringBdinfections. Our findings indicate that enrichment ofX. laevisskin mast cells confers significant anti-Bdprotection and ameliorates the inflammation-associated skin damage caused byBdinfection. This includes a significant reduction inBd-infected skin infiltration by neutrophils. Augmenting frog skin mast cells promotes greater mucin content within cutaneous mucus glands and protects frogs fromBd-mediated changes to their skin microbiomes. Mammalian mast cells are known for their production of the pleiotropic interleukin-4 (IL4) cytokine and our findings suggest that the frog IL4 plays a key role in conferring the effects seen following frog skin mast cell enrichment. Together, this work underlines the importance of amphibian skin-resident immune cells in anti-Bddefenses and illuminates a novel avenue for investigating amphibian host-chytrid pathogen interactions.
Uncovering genes involved in pollinator-driven mating system shifts and selfing syndrome evolution inBrassica rapa
Authors: Kofler Xeniya V. , Grossniklaus Ueli , Schiestl Florian P. , Frachon Léa
Published: October 2023

Background

Shifts in pollinator occurrence and their pollen transport effectiveness drive the evolution of mating systems in flowering plants. A decline in pollinator numbers can lead to the phenotypic evolution of floral traits favoring self-pollination (selfing syndrome). Understanding the genomic basis involved in such shifts of the mating system is crucial for predicting a species’ persistence or extinction under changing biotic and abiotic stressors in natural populations. We investigated loci showing high genetic differentiation before and after selection in fast-cyclingBrassica rapathat were associated with rapid phenotypic evolution toward the selfing syndrome (reduction in petal width, stamen and pistil length, and herkogamy). Combining a genotyping-by-sequencing (GBS) approach with a genome-wide association study (GWAS), we shed light onto the genetic basis associated with the mating system shift over nine generations of pollination byEpisyphrus balteatus(hoverflies), an abundant pollinator ofB. rapa. Moreover, we functionally validated the involvement of candidate genes associated with changes in floral morphology by studying corresponding mutants in the model plantArabidopsis thaliana.

Results

We found that the mating system ofB. rapashifted from predominantly outcrossing to mixed mating with high rates of autonomous selfing, accompanied by a rapid reduction of floral morphological traits and herkogamy involving many loci. We found 31 candidate genes associated with the affected traits that were involved in a wide range of functions from DNA/RNA binding to transport. Our functional validation inA. thalianaconfirmed that four of the identified genes are indeed involved in regulating the size of floral organs. Interestingly, two genes, both coding for the same protein complex responsible for active DNA methylation were successfully validated and closely linked to two correlated phenotypic traits, namely pistil and stamen length.

Conclusions

Altogether, our study shows that hoverfly pollination leads to rapid evolutionary changes of the mating system through polygenic changes, highlighting the importance of using genomic approaches to understand pollinator-driven plant adaptation.
Regulation of astrocyte metabolism by mitochondrial translocator protein 18kDa
Authors: Firth Wyn , Robb Josephine L , Stewart Daisy , Pye Katherine R , Bamford Rosemary , Oguro-Ando Asami , Beall Craig , Ellacott Kate LJ
Published: October 2023

The mitochondrial translocator protein 18kDa (TSPO) has been linked to a variety of functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in the periphery using Leydig cells and hepatocytes, as well as work in microglia, indicate that the function of TSPO may vary between cells depending on their specialised roles. Astrocytes are critical for providing trophic and metabolic support in the brain as part of their role in maintaining brain homeostasis. Recent work has highlighted that TSPO expression increases in astrocytes under inflamed conditions and may drive astrocyte reactivity. However, relatively little is known about the role TSPO plays in regulating astrocyte metabolism and whether this protein is involved in immunometabolic processes in these cells. Using TSPO-deficient (TSPO-/-) mouse primary astrocytesin vitro(MPAs) and a human astrocytoma cell line (U373 cells), we performed metabolic flux analyses. We found that loss of TSPO reduced basal astrocyte respiration and increased the bioenergetic response to glucose reintroduction following glucopenia, while increasing fatty acid oxidation (FAO). Lactate production was significantly reduced in TSPO-/-astrocytes. Co-immunoprecipitation studies in U373 cells revealed that TSPO forms a complex with carnitine palmitoyltransferase 1a, which presents a mechanism wherein TSPO may regulate FAO in astrocytes. Compared to TSPO+/+cells, inflammation induced by 3h lipopolysaccharide (LPS) stimulation of TSPO-/-MPAs revealed attenuated tumour necrosis factor release, which was enhanced in TSPO-/-MPAs at 24h LPS stimulation. Together these data suggest that while TSPO acts as a regulator of metabolic flexibility in astrocytes, loss of TSPO does not appear to modulate the metabolic response of astrocytes to inflammation, at least in response to the stimulus/time course used in this study.
ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97
Authors: Pozner Amir , Verma Shiv Prakash , Li Li , Wang Shuxin , Barrott Jared J. , Nelson Mary L. , Yu Jamie S. E. , Negri Gian Luca , Colborne Shane , Hughes Christopher S. , Zhu Ju-Fen , Lambert Sydney L. , Carroll Lara S. , Smith-Fry Kyllie , Stewart Michael G. , Kannan Sarmishta , Jensen Bodrie , Mortenson Katelyn L. , John Cini , Sikdar Saif , Liu Hongrui , Dang Ngoc Ha , Bourdage Jennifer , Li Jinxiu , Vahrenkamp Jeffery M. , Groundland John S. , Wustrack Rosanna , Senger Donna L. , Zemp Franz J. , Mahoney Douglas J. , Gertz Jason , Zhang Xiaoyang , Lazar Alexander J. , Hirst Martin , Morin Gregg B. , Nielsen Torsten O. , Shen Peter S. , Jones Kevin B.
Published: October 2023

The t(X,17) chromosomal translocation, generating the ASPSCR1-TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCC), frustrating efforts to identify therapeutic targets for these rare cancers. Proteomic analysis showed that VCP/p97, an AAA+ ATPase with known segregase function, was strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1-TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1-TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributed with ASPSCR1-TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrated the oncogenic transcriptional signature of ASPSCR1-TFE3, by facilitating assembly of higher-order chromatin conformation structures as demonstrated by HiChIP. Finally, ASPSCR1-TFE3 and VCP demonstrated co-dependence for cancer cell proliferation and tumorigenesisin vitroand in ASPS and RCC mouse models, underscoring VCP’s potential as a novel therapeutic target.
Matching maternal and paternal experiences underpin molecular thermal acclimation
Authors: Bonzi L.C. , Donelson J.M. , Spinks R.K. , Munday P.L. , Ravasi T. , Schunter C.
Published: October 2023

The environment experienced by one generation has the potential to affect the subsequent one through non-genetic inheritance of parental effects. Since both mothers and fathers can influence their offspring, questions arise regarding how the maternal, paternal and offspring experiences integrate into the resulting phenotype. We aimed to disentangle the maternal and paternal contributions to transgenerational thermal acclimation in a reef fish,Acanthochromis polyacanthus, by exposing two generations to elevated temperature (+1.5°C) in a full factorial design and analyzing the F2 hepatic gene expression. Paternal and maternal effects showed common but also parent-specific components, with the father having the largest influence in shaping the offspring transcriptomic profile. Fathers contributed to transgenerational response to warming through transfer of epigenetically controlled stress-response mechanisms while mothers influenced increased lipid metabolism regulation. However, the key to acclimation potential was matching thermal experiences of the parents. When both parents were exposed to the same condition, offspring showed increased structural RNA production and transcriptional regulation, whereas environmental mismatch in parents resulted in maladaptive parental condition-transfer, revealed by translation suppression and endoplasmic reticulum stress. Interestingly, the offspring’s own environmental experience had the smallest influence on their hepatic transcription profiles. Taken together, our results show the complex nature of the interplay between paternal, maternal and offspring cue integration, and reveal that acclimation potential to ocean warming depends not only on maternal and paternal contributions, but importantly on congruent parental thermal experiences.
Trends in caesarean section rates in Europe from 2015 to 2019 using Robson's Ten Group Classification System: A Euro‐Peristat study
Authors: Amyx Melissa , Philibert Marianne , Farr Alex , Donati Serena , Smárason Alexander K. , Tica Vlad , Velebil Petr , Alexander Sophie , Durox Mélanie , Elorriaga Maria Fernandez , Heller Günther , Kyprianou Theopisti , Mierzejewska Ewa , Verdenik Ivan , Zīle‐Velika Irisa , Zeitlin Jennifer ,   for the Euro‐Peristat Research Group
Published: October 2023

Objective

To assess changes in caesarean section (CS) rates in Europe from 2015 to 2019 and utilise the Robson Ten Group Classification System (TGCS) to evaluate the contribution of different obstetric populations to overall CS rates and trends.

Design

Observational study utilising routine birth registry data.

Setting

A total of 28 European countries.

Population

Births at ≥22 weeks of gestation in 2015 and 2019.

Methods

Using a federated model, individual‐level data from routine sources in each country were formatted to a common data model and transformed into anonymised, aggregated data.

Main Outcome Measures

By country: overall CS rate. For TGCS groups (by country): CS rate, relative size, relative and absolute contribution to overall CS rate.

Results

Among the 28 European countries, both the CS rates (2015, 16.0%–55.9%; 2019, 16.0%–52.2%) and the trends varied (from −3.7% to +4.7%, with decreased rates in nine countries, maintained rates in seven countries (≤ ± 0.2) and with increasing rates in 12 countries). Using the TGCS (for 17 countries), in most countries labour induction increased (groups 2a and 4a), whereas multiple pregnancies (group 8) decreased. In countries with decreasing overall CS rates, CS tended to decrease across all TGCS groups, whereas in countries with increasing rates, CS tended to increase in most groups. In countries with the greatest increase in CS rates (>1%), the absolute contributions of groups 1 (nulliparous term cephalic singletons, spontaneous labour), 2a and 4a (induction of labour), 2b and 4b (prelabour CS) and 10 (preterm cephalic singletons) to the overall CS rate tended to increase.

Conclusions

The TGCS shows varying CS trends and rates among countries of Europe. Comparisons between European countries, particularly those with differing trends, could provide insight into strategies to reduce CS without clinical indication.
Dry fractionation process operations in the production of protein concentrates: A review
Authors: Pulivarthi Manoj Kumar , Buenavista Rania Marie , Bangar Sneh Punia , Li Yonghui , Pordesimo Lester O. , Bean Scott R. , Siliveru Kaliramesh
Published: October 2023

The market for plant proteins is expanding rapidly as the negative impacts of animal agriculture on the environment and resources become more evident. Plant proteins offer competitive advantages in production costs, energy requirements, and sustainability. Conventional plant‐protein extraction is water and chemical‐intensive, posing environmental concerns. Dry fractionation is an energy‐efficient and environmentally friendly process for protein separation, preserving protein's native functionality. Cereals and pulses are excellent sources of plant proteins as they are widely grown worldwide. This paper provides a comprehensive review of the dry fractionation process utilized for different seeds to obtain protein‐rich fractions with high purity and functionality. Pretreatments, such as dehulling and defatting, are known to enhance the protein separation efficiency. Factors, such as milling speed, mill classifier speed, feed rate, seed type, and hardness, were crucial for obtaining parent flour of desired particle size distribution during milling. The air classification or electrostatic separation settings are crucial in determining the quality of the separated protein. The cut point in air classification is targeted based on the starch granule size of the seed material. Optimization of these operations, applied to different pulses and seeds, led to higher yields of proteins with higher purity. Dual techniques, such as air classification and electrostatic separation, enhance protein purity. The yield of the protein concentrates can be increased by recycling the coarse fractions. Further research is necessary to improve the quality, purity, and yield of protein concentrates to enable more efficient use of plant proteins to meet global protein demands.
New virtual approach to the study of metallurgy through the analysis of slice marks from the Chalcolithic site of Zanjillas (Torrejón de Velasco, Madrid, Spain)
Authors: Aramendi Julia , Estaca‐Gómez Verónica , Maté‐González Miguel Ángel , Blázquez Cristina Sáez , Morín Jorge , López German , Yravedra Sainz de los Terreros José
Published: October 2023

Although the discovery of metal objects is not common in Chalcolithic or Bronze Age sites, the study of bone surface microscopic grooves from animal butchering can yield evidence of the use of metal artefacts in these contexts. Additionally, the presence of slice marks made with metal objects in Chalcolithic and Bronze Age sites has highlighted the use of metal in common practices beyond their ornamental application, as usually expected at the early stages of metallurgy. Here, we present the study of the slice marks found at the Chalcolithic site of Zanjillas, using geometric morphometrics and machine learning algorithms, with the aim of identifying the nature of the tools used for carcass processing at the site. For this purpose, we replicate previous analyses considering slice marks produced with lint flakes and metal tools to generate a referential framework that serves as comparative to the Zanjillas sample. Our results suggest that most of the domestic activities related to carcass skinning, defleshing, or evisceration in Zanjillas were still performed with flint artefacts.
Imperfect public choice
Authors: de Palma André , Myers Gordon M. , Papageorgiou Yorgos Y.
Published: October 2023

We model imperfect governments with public choices that are sequential, myopic and not free of error. We first use this framework to explore governmental incremental budgeting. We argue that a model of bounded rationality is required to capture the empirical reality of incremental budgeting. We then provide a model that integrates bounds errors and systematic errors. We argue that the empirical evidence is that bounds errors and systematic errors are inextricably intertwined—some level of bounded rationality is required for systematic errors to emerge. We use this to explore political information lobbying. A testable hypothesis is that lobbyists will focus efforts on policy‐makers of low ability. We show that choosing leaders with high ability, that is Madison's wisdom to discern, is important, especially when policy decisions concern dangerous products (rifles) or dangerous environments (pandemics).
Lidocaine as an anti‐arrhythmic drug: Are there any indications left?
Authors: Güler Sati , Könemann Hilke , Wolfes Julian , Güner Fatih , Ellermann Christian , Rath Benjamin , Frommeyer Gerrit , Lange Philipp Sebastian , Köbe Julia , Reinke Florian , Eckardt Lars
Published: October 2023

Lidocaine is classified as a class Ib anti‐arrhythmic that blocks voltage‐ and pH‐dependent sodium channels. It exhibits well investigated anti‐arrhythmic effects and has been the anti‐arrhythmic of choice for the treatment of ventricular arrhythmias for several decades. Lidocaine binds primarily to inactivated sodium channels, decreases the action potential duration, and increases the refractory period. It increases the ventricular fibrillatory threshold and can interrupt life‐threatening tachycardias caused by re‐entrant mechanisms, especially in ischemic tissue. Its use was pushed into the background in the era of amiodarone and modern electric device therapy. Recently, lidocaine has come back into focus for the treatment of acute sustained ventricular tachyarrhythmias. In this brief overview, we review the clinical pharmacology including possible side effects, the historical course, possible indications, and current Guideline recommendations for the use of lidocaine.
Trans‐anal Foley catheter facilitates endoscopic submucosal dissection of a distal rectal tumor
Authors: Kagaya Yuka , Hayashi Yoshikazu , Morikawa Takaaki
Published: October 2023

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Design Management and Business Success: The Emerging Connection
Authors: Machado Romeu Biscaia
Published: October 2023

What does it look like when a company becomes design‐led? Where might this journey take your organization?

Companies using strategic design post a 219 percent better result than their peers? How do I bring some of this design value into my organization?
Design to Launch
Authors: Nicholson Jamie , Breneman Mark , Hui Gordon
Published: October 2023

Successful startups have learned to start building solutions early in the innovation process. If corporations could shift their focus away from costly pilot projects and instead use their resources on diverse and incremental experiments, they might be able to behave more nimbly and risk less.

Large corporates that want to take advantage of new technologies tend to stand by and watch as small startups move more nimbly. Design to Launch helps big companies learn to experiment and iterate in new ways that avoid typical innovation bottlenecks.
Astrocytic NKCC1 inhibits seizures by buffering Cl− and antagonizing neuronal NKCC1 at GABAergic synapses
Authors: Nguyen Trong Dao , Ishibashi Masaru , Sinha Adya Saran , Watanabe Miho , Kato Daisuke , Horiuchi Hiroshi , Wake Hiroaki , Fukuda Atsuo
Published: October 2023

Objective

A pathological excitatory action of the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) has been observed in epilepsy. Blocking the Cl− importer NKCC1 with bumetanide is expected to reduce the neuronal intracellular Cl− concentration ([Cl−]i) and thereby attenuate the excitatory GABA response. Accordingly, several clinical trials of bumetanide for epilepsy were conducted. Although NKCC1 is expressed in both neurons and glial cells, an involvement of glial NKCC1 in seizures has not yet been reported. Astrocytes maintain high [Cl−]i with NKCC1, and this gradient promotes Cl− efflux via the astrocytic GABAA receptor (GABAAR). This Cl− efflux buffers the synaptic cleft Cl− concentration to maintain the postsynaptic Cl− gradient during intense firing of GABAergic neurons, thereby sustaining its inhibitory action during seizure. In this study, we investigated the function of astrocytic NKCC1 in modulating the postsynaptic action of GABA in acute seizure models.

Methods

We used the astrocyte‐specific conditional NKCC1 knockout (AstroNKCC1KO) mice. The seizurelike events (SLEs) in CA1 pyramidal neurons were triggered by tetanic stimulation of stratum radiatum in acute hippocampus slices. The SLE underlying GABAAR‐mediated depolarization was evaluated by applying the GABAAR antagonist bicuculline. The pilocarpine‐induced seizure in vivo was monitored in adult mice by the Racine scale. The SLE duration and tetanus stimulation intensity threshold and seizure behavior in AstroNKCC1KO mice and wild‐type (WT) mice were compared.

Results

The AstroNKCC1KO mice were prone to seizures with lower threshold and longer duration of SLEs and larger GABAAR‐mediated depolarization underlying the SLEs, accompanied by higher Racine‐scored seizures. Bumetanide reduced these indicators of seizure in AstroNKCC1KO mice (which still express neuronal NKCC1), but not in the WT, both in vitro and in vivo.

Significance

Astrocytic NKCC1 inhibits GABA‐mediated excitatory action during seizures, whereas neuronal NKCC1 has the converse effect, suggesting opposing actions of bumetanide on these cells.
Baseline characteristics of a prospective cohort study of aging and cardiovascular diseases among people living with HIV
Authors: Giguère Katia , Chartrand‐Lefebvre Carl , Baril Jean‐Guy , Conway Brian , El‐Far Mohamed , Falutz Julian , Harris Marianne , Jenabian Mohammad‐Ali , Leipsic Jonathon , Loutfy Mona , Mansour Samer , MacPherson Paul , Margolese Shari , McMillan Jacqueline M. , Monteith Ken , Murray Melanie C. M. , Pick Neora , Thomas Réjean , Trottier Benoît , Trottier Sylvie , Tsoukas Christos , Walmsley Sharon , Wong Alex , Tremblay Cécile , Durand Madeleine ,   The Canadian HIV And Aging Cohort Study Group
Published: October 2023

Objectives

Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol.

Methods

CHACS is a multi‐centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow‐up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender—gender roles, gender identity, gender relationships, and institutionalized gender—will be measured using the GENESIS‐PRAXY questionnaire. Diet will be assessed using a validated, web‐based, self‐administered food frequency questionnaire.

Results

A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50–61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail.

Conclusions

The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio‐economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses.
The composition, characterisation, and health impacts of human milk lipid medium‐ and long‐chain TAGs
Authors: Karrar Emad , Albakry Zainab , Mohamed Ahmed Isam A. , Chen Chaoxiang , Yan Youchun , Brennan Charles S. , Li Jian
Published: October 2023

Medium‐chain fatty acids (MCFAs) are naturally associated with human milk lipids and can also be associated with MCTs (medium‐chain triacylglycerols). Healthy lipids could be constructed from medium‐ and long‐chain triacylglycerols (MLCTs) composed of MCFAs. Biochemical and chemical catalysts catalyse many chemical and enzymatic processes, such as acidolysis, interesterification, and esterification. Due to their potential health benefits, MCTs and MLCTs are widely used as nutraceuticals in the pharmaceutical and food industries. This comprehensive overview of MLCTs evaluates their structures, compositions, nutritional properties, and supposed health benefits. This review identifies the key research gaps to overcome the MCFA‐TAG use when compared to human milk and infant formulas.
Systematic review and meta‐analysis of the impact of decontamination interventions on the prevalence and concentration of Salmonella in broiler chickens during primary processing
Authors: Gichure Josphat Njenga , Coorey Ranil , Njage Patrick Murigu Kamau , Wambui Joseph M. , Dykes Gary A. , Buys Elna M.
Published: October 2023

Systematic review and meta‐analysis aggregate quantitative data from different studies into unified effect size estimates with better statistical power in risk assessment model parameterisation. This study uses systematic review and meta‐analysis to estimate Salmonella decontamination during broiler slaughter from scalding to post‐chilling, with meta‐regression applied to explore modifier variables. Data from 161 studies published between 1998 and 2022 was extracted from thirty‐five articles identified in the systematic review process with meta‐analysis and meta‐regression performed using the metafor package (version 2.0‐0) in R statistical environment (version 3.6.0). The analysis revealed carcass wash (1.31 log10 CFU/carcass reduction in odds; P < 0.01) and chilling (121.50% reduction in relative risk; P < 0.01) had significant reduction on Salmonella concentration and prevalence, respectively. Chemical additives reduced the concentration (0.98 log10 CFU/carcass; P < 0.01) and prevalence (64.74% relative risk; P < 0.01) but the efficacy of physical methods was not conclusive. Application of decontaminants through immersion was superior (0.90 log10 CFU/carcass; P < 0.01) to spraying (0.72 log10 CFU/carcass; P < 0.01). Adjusting the pH sequentially of electrolysed water, acetic acid and trisodium phosphate reduced the odds of Salmonella concentration by more than 2 log cycles and the relative risk by more than 100%. The results provide trends in the concentration and prevalence of Salmonella during the broilers slaughter process with application of decontamination interventions and provide a basis for control decision‐making and quantitative microbial risk assessment.
Effect of refining on the quality of oils extracted by cold press from black cumin (Nigella sativa L.) seed and by solvent from its cake
Authors: Abedinzadeh Solmaz , Torbati Mohammadali , Azadmard‐Damirchi Sodeif , Savage Geoffrey P.
Published: October 2023

Black cumin seed oil, known for its bioactive compounds and health benefits, faces challenges due to its high peroxide value and free fatty acid content, limiting its applications. The study investigates oil extraction from black cumin seeds using cold pressing and solvent extraction. The oil extraction yields were found to be 32% from the seeds and 13% from the cake. Subsequently, the study investigated the impact of different refining steps on the quality of these oils. The oil extracted from the cake exhibited higher free fatty acid, chlorophyll, and carotenoid contents compared to the oil extracted from the seeds, with increases of 84%, 73%, and 66%, respectively. Conversely, the peroxide value, total phenol, and thymoquinone content of the cake‐derived oil were lower than those of the seed‐derived oil, with reductions of 74%, 69%, and 95%, respectively. The refining process resulted in general reductions in peroxide value, free fatty acid, and p‐anisidine levels. However, no significant effect on the fatty acid composition was observed. The refining led to a decrease in the bioactive content, including total phenolic compounds (6%–68%), carotenoids (86%–85%), and thymoquinone (50%–90%). These results contribute to a better understanding of the potential applications and refining requirements for black cumin seed oil.
Risk‐taking in pension and crashes: Firm‐level evidence
Authors: Park Heejin , Noh Jung‐Hee
Published: October 2023

Our study, using a large sample of U.S. firms between 1990 and 2013, found a positive association between pension risk‐taking and future stock price crash risk. The impact of pension risk‐taking on future crash risk is particularly significant in firms with low funding ratios and high default risks. Overall, our findings provide robust evidence that risk‐taking in defined benefit (DB) pension asset management can predict future crash risk. Our study offers valuable insights for stakeholders and shareholders in evaluating firms with DB pension plans and for policymakers in protecting workers' retirement benefits and shareholder wealth.
Retail Trading in Options and the Rise of the Big Three Wholesalers
Authors: BRYZGALOVA SVETLANA , PAVLOVA ANNA , SIKORSKAYA TAISIYA
Published: October 2023

We document a rapid increase in retail trading in options in the United States. Facilitated by payment for order flow (PFOF) from wholesalers executing retail orders, retail trading recently reached over 60% of total market volume. Nearly 90% of PFOF comes from three wholesalers. Exploiting new flags in transaction‐level data, we isolate wholesaler trades and build a novel measure of retail options trading. Our measure comoves with equity‐based retail activity proxies and drops significantly during U.S. brokerage platform outages and trading restrictions. Retail investors prefer cheaper, weekly options with average bid‐ask spread of 12.6%, and lose money on average.
Perpetuating and protective factors in insomnia across racial/ethnic groups of veterans
Authors: Rubi Sofia , Monk J. Kale , Shoemaker Sydney , Miller Colten , Prabhu Nivedita , Flores Lisa Y. , Bernard Donte , McCrae Christina S. , Borsari Brian , Miller Mary Beth
Published: October 2023

Few studies have examined racial/ethnic differences in rates and correlates of insomnia among veterans. This study compared rates of insomnia and interest in sleep treatment among veterans of diverse racial/ethnic backgrounds. Consistent with the 3P model, we tested racial discrimination as a predictor of insomnia, with post‐traumatic stress disorder symptoms and romantic partners as perpetuating and protective moderators of this association, respectively. A total of 325 veterans (N = 236 veterans of colour; 12% Asian, 36% Black, 14% Hispanic/Latine) completed questionnaires online from remote locations. Descriptive statistics were used to compare patterns across racial/ethnic groups. Linear regression was used to test moderators of the association between racial discrimination and insomnia severity. Overall, 68% of participants screened positive for insomnia: 90% of Asian; 79% of Hispanic/Latine; 65% of Black; and 58% of White participants. Of those, 74% reported interest in sleep treatment, and 76% of those with partners reported interest in including their partner in treatment. Racial discrimination and post‐traumatic stress disorder were correlated with more severe insomnia, while romantic partners were correlated with less severe insomnia. Only post‐traumatic stress disorder moderated the association between racial discrimination and insomnia severity. Rates of insomnia were highest among Asian and Hispanic/Latine participants, yet these groups were among the least likely to express interest in sleep treatment. Racial discrimination may exacerbate insomnia symptoms among veterans, but only among those who do not already have disturbed sleep in the context of post‐traumatic stress disorder. Romantic partners may serve as a protective factor in insomnia, but do not seem to mitigate the impact of racial discrimination.
Pluralism about introspection
Authors: Franco Kateryna Samoilova
Published: October 2023

If we can and do have some self‐knowledge, how do we acquire it? By examining the ways in which we acquire self‐knowledge—by introspection—we can try shedding some light onto the nature and the breadth of self‐knowledge, as others have tried to do with other forms of knowledge. My aim is to show that introspection involves multiple (that is, at least two) distinct processes, a view I call “pluralism about introspection”. One of the virtues of pluralism is that it explains how we can have such a wide variety of self‐knowledge despite our cognitive limitations.
Design and syntax in pictures
Authors: Hopkins Robert
Published: October 2023

Many attempts to define depiction appeal to viewers' perceptual responses. Such accounts are liable to give a central role in determining depictive content to picture features responsible for the response, design. A different project is to give a compositional semantics for depictive content. Such attempts identify syntax: picture features systematically responsible for the content of the whole. Design and syntax are competitors. But syntax requires system, in how picture features contribute to content, that design does not. By examining John Kulvicki's semantics for basic depictive content, I argue that the relevant systematicity is absent from the pictorial realm.
A case of a pilocytic astrocytoma with histological features of anaplasia and unprecedent genetic alterations
Authors: Moritsubo Mayuko , Furuta Takuya , Negoto Tetsuya , Nakamura Hideo , Uchiyama Yusuke , Morioka Motohiro , Oshima Koichi , Sugita Yasuo
Published: October 2023

We report a case of pediatric glioma with uncommon imaging, morphological, and genetic features. A one‐year‐old boy incidentally presented with a tumor in the fourth ventricle. The tumor was completely resected surgically and investigated pathologically. The mostly circumscribed tumor had piloid features but primitive and anaplastic histology, such as increasing cellularity and mitosis. The Ki‐67 staining index was 25% at the hotspot. KIAA1549::BRAF fusion and KIAA1549 partial deletions were detected by direct PCR, supported by Sanger sequencing. To the best of our knowledge, this is the first report of a glioma with both deletion of KIAA1549 p.P1771_P1899 and fusion of KIAA1549::BRAF. The tumor could not be classified using DNA methylome analysis. The present tumor fell into the category of pilocytic astrocytoma with histological features of anaplasia (aPA). Further studies are needed to establish pediatric aPA.
GlobalAMFungi: a global database of arbuscular mycorrhizal fungal occurrences from high‐throughput sequencing metabarcoding studies
Authors: Větrovský Tomáš , Kolaříková Zuzana , Lepinay Clémentine , Awokunle Hollá Sandra , Davison John , Fleyberková Anna , Gromyko Anastasiia , Jelínková Barbora , Kolařík Miroslav , Krüger Manuela , Lejsková Renata , Michalčíková Lenka , Michalová Tereza , Moora Mari , Moravcová Andrea , Moulíková Štěpánka , Odriozola Iñaki , Öpik Maarja , Pappová Monika , Piché‐Choquette Sarah , Skřivánek Jakub , Vlk Lukáš , Zobel Martin , Baldrian Petr , Kohout Petr
Published: October 2023

Arbuscular mycorrhizal (AM) fungi are crucial mutualistic symbionts of the majority of plant species, with essential roles in plant nutrient uptake and stress mitigation. The importance of AM fungi in ecosystems contrasts with our limited understanding of the patterns of AM fungal biogeography and the environmental factors that drive those patterns.

This article presents a release of a newly developed global AM fungal dataset (GlobalAMFungi database, https://globalamfungi.com) that aims to reduce this knowledge gap. It contains almost 50 million observations of Glomeromycotinian AM fungal amplicon DNA sequences across almost 8500 samples with geographical locations and additional metadata obtained from 100 original studies.

The GlobalAMFungi database is built on sequencing data originating from AM fungal taxon barcoding regions in: i) the small subunit rRNA (SSU) gene; ii) the internal transcribed spacer 2 (ITS2) region; and iii) the large subunit rRNA (LSU) gene.

The GlobalAMFungi database is an open source and open access initiative that compiles the most comprehensive atlas of AM fungal distribution. It is designed as a permanent effort that will be continuously updated by its creators and through the collaboration of the scientific community. This study also documented applicability of the dataset to better understand ecology of AM fungal taxa.