bluuebunny/crossref_metadata_2025 huggingface dataset:
Buprenorphine‐naloxone, buprenorphine, and methadone throughout pregnancy in maternal opioid use disorder
Authors: Kanervo Minna M. , Tupola Sarimari J. , Nikkola Eeva M. , Rantakari Krista M. , Kahila Hanna K.
Published: December 2022

Introduction

Current WHO guidelines recommend using methadone or buprenorphine as maintenance treatments for maternal opioid use disorder. However, buprenorphine‐naloxone, with a lower abuse risk than buprenorphine monotherapy or methadone, offers a potentially beneficial alternative, but scientific evidence on its effects on pregnancies, fetuses, and newborns is scarce. This paper compares the outcomes of the pregnancies, deliveries, and newborns of women on buprenorphine‐naloxone, buprenorphine, or methadone maintenance treatments. According to the hypothesis, as a maintenance treatment, buprenorphine‐naloxone does not have more adverse effects than buprenorphine, whereas methadone is more complicated.

Material and methods

In this population‐based study, 172 pregnant women on medical‐assisted treatments were followed‐up at Helsinki University Women's Hospital (Finland). Women receiving the same opioid maintenance treatment from conception to delivery and their newborns were included. Consequently, 67 mother–child dyads met the final inclusion criteria. They were divided into three groups based on their opioid pharmacotherapy. The outcomes were compared among the groups and, where applicable, with the Finnish population.

Results

The buprenorphine‐naloxone and buprenorphine groups showed similar outcomes and did not significantly differ from each other in terms of maternal health during pregnancies, deliveries, or newborns. Illicit drug use during the pregnancy was common in all groups, but in the methadone group it was most common (p = 0.001). Most neonates (96%) were born full‐term with good Apgar scores. They were of relatively small birth size, with those in the methadone group tending to be the smallest. Of the neonates 63% needed pharmacological treatment for neonatal opioid withdrawal syndrome. The need was lower in the buprenorphine‐based groups than in the methadone group (p = 0.029).

Conclusions

Buprenorphine‐naloxone seems to be as safe for pharmacotherapy for maternal opioid use disorder as buprenorphine monotherapy for both mother and newborn. Hence it could be a choice for oral opioid maintenance treatment during pregnancy, but larger studies are needed before changing the official recommendations. Women on methadone treatment carry multifactorial risks and require particularly cautious follow up. Furthermore, illicit drug use is common in all treatment groups and needs to be considered for all patients with opioid use disorder.
Antibiotic prescriptions for child sinusitis varied between specialties after Finnish guidelines were updated in 2018
Authors: Korppi Matti , Palmu Sauli , Heikkilä Paula , Csonka Péter
Published: December 2022

Aim

We evaluated antibiotic prescriptions issued for Finnish children with acute sinusitis by a nationwide private outpatient clinic network from 2014–2020. Data were compared before and after updated guidelines in 2018.

Methods

The study comprised data on 45 296 children aged 2–17 years with acute sinusitis, namely diagnoses, ages, dates, the doctor's specialty and any antibiotics. We measured compliance with the updated 2018 Finnish guidelines, which recommended amoxicillin or amoxicillin‐clavulanic acid for children under 12 years old, with doxycycline as an alternative for 12 years plus.

Results

There were 6621–7585 visits per year for acute sinusitis in 2014–2019 and 2954 in 2020. Antibiotics were prescribed for 37.9%–41.6% of patients during the study years. Amoxicillin, including penicillin, accounted for 35.9% of prescriptions, followed by amoxicillin‐clavulanic acid (26.9%). Macrolides accounted for 20.6% and, encouragingly, decreased by 38% from 2014–2019. Doxycycline accounted for 5.3%. Paediatricians, general practitioners (GPs) and ear, nose and throat specialists followed the guidelines in 75.1%, 73.8% and 66.7% of cases, respectively. GPs prescribed antibiotics more often than other physicians.

Conclusion

Antibiotics were prescribed for about 40% of acute sinusitis visits by Finnish children from 2014–2019. Specialities differed with regard to prescribing rates and whether they followed the guidelines.
Diurnal variations of triglyceride accumulation in mouse and bovine adipocyte‐derived cell lines
Authors: Shiraishi Rena , Morita Satomi , Goto Yoshikuni , Mizoguchi Yasushi , Nakamura Wataru , Nakamura Takahiro J.
Published: December 2022

Several studies have suggested a strong interaction between the circadian clock and lipid metabolism in mammals. The circadian clock is driven by endogenous cyclic gene expression patterns, commonly referred to as clock genes, and transcription–translation negative feedback loops. Clock genes regulate the transcription of some lipid metabolism‐related genes; however, the relationship between the circadian clock and triglyceride (TG) accumulation at the cellular level remains unclear. Here, we evaluated rhythms of intracellular TG accumulation levels as well as the expression of clock genes and lipid metabolism‐related genes for 54 h in mouse and bovine adipose‐derived cell cultures. To the best of our knowledge, this study represents the first report demonstrating that TG accumulation exhibits diurnal variations, with the pattern differing among cell types. Furthermore, we found that expression of clock genes and corresponding lipid metabolism‐related genes exhibited circadian rhythms. Our results suggest that the cellular clock regulates lipid metabolism‐related genes to relate circadian rhythms of TG accumulation in each cell type. We anticipate that the amount of fat stored depends on the timing of the supply of glucose‐the precursor of fat. The findings of this study will contribute to the advancement of chrono‐nutrition.
Improving access to psychological therapies: Analysis of effects associated with remote provision during COVID‐19
Authors: Capobianco Lora , Verbist Irini , Heal Calvin , Huey Dale , Wells Adrian
Published: December 2022

Background

COVID‐19 had an immediate impact on the way Improving Access to Psychological Therapy (IAPT) services in the United Kingdom were delivered, requiring services to move to remote therapy. While remote therapy has been shown to be effective, little is known about the effects associated with moving to remote therapy delivered during COVID‐19 within IAPT services.

Objective

The objective of the study was to assess the characteristics of those undergoing remote therapy and test the effects associated with the effect of remote delivery on anxiety and depression symptoms compared with in‐person therapy before lockdown.

Methods

We conducted a retrospective, cross‐sectional benchmark comparison of remote therapy across four IAPT services in Greater Manchester. Routinely collected measures of anxiety (GAD‐7) and depression (PHQ‐9) were used to compare effects across the two time periods. A mixed‐effects model was conducted to assess within and between group changes in anxiety and depression, while controlling for pre‐specified confounders.

Findings

Remote therapy did not appear to impact on service provision, with the number of sessions offered and attended being similar to those prior to COVID‐19. Both face‐to‐face (pre‐COVID‐19) and remote therapy (during COVID‐19) were associated with variable improvements in anxiety and depression with no significant difference between them. However, remote therapy was associated with a more rapid decrease in symptoms in comparison with face‐to‐face treatment. Mean improvement in symptoms was small and increased as number of sessions/time increased and analysis of rates of improvement indicated that both face‐to‐face and remote therapy might need more time to reach target cut‐off points on measures.

Conclusions

Both face‐to‐face and remote therapies delivered under IAPT were associated with improvements in symptoms with no apparent difference apart from the finding that remote therapy was associated with more rapid change.

Clinical Implications

Remote therapy delivery in IAPT does not appear to confer a disadvantage over face‐to‐face contact, but at a group mean level the magnitude of improvement associated with both treatments was small. Remote therapy provision may widen patient access to and engagement with psychological services.
Lopsided inclusion: The impact of multi‐employer bargaining and class‐based unionism on non‐regular employment in South Korea
Authors: Park Dongwoo
Published: December 2022

This study examines the impact of multi‐employer bargaining on non‐regular workers across different unions and types of non‐regular employment. Using national representative survey data from South Korea, I find that multi‐employer bargaining increases the likelihood that a workplace union would address a pay increase for non‐regular workers when the union was affiliated with a confederation espousing class‐based as opposed to business‐unionism. However, such a relationship was weaker for temporary agency workers and subcontractors than for direct‐hire fixed‐term workers. This mechanism is further illustrated through a second round of data collection and analysis, namely in‐depth interviews. I identify two factors that characterize the class‐based confederation: (1) centralized pressure from the union and (2) activists and their identity work. Altogether, these results further an understanding of how the identities of national union confederations can influence local representatives’ approach to representing non‐regular workers and how those influences are manifested through workplace‐level collective bargaining.
Importance of receptor expression in the classification of novel ligands at the M2 muscarinic acetylcholine receptor
Authors: Jiang Ye , Yeasmin Mahmuda , Gondin Arisbel B. , Christopoulos Arthur , Valant Celine , Burger Wessel A. C. , Thal David M.
Published: December 2022

Background and Purpose

Affinity‐based, selective orthosteric ligands for the muscarinic acetylcholine receptors (mAChRs) are difficult to develop due to high sequence homology across the five subtypes. Selectivity can also be achieved via the selective activation of a particular subtype or signalling pathway. Promisingly, a prior study identified compounds 6A and 7A as functionally selective and Gi biased compounds at the M2 mAChR. Here, we have investigated the activation of individual G protein subfamilies and the downstream signalling profiles of 6A and 7A at the M2 mAChR.

Experimental Approach

G protein activation was measured with the TRUPATH assay in M2 mAChR FlpIn CHO cells. Activity in downstream signalling pathways was determined using the cAMP CAMYEL BRET sensor and assay of ERK 1/2 phosphorylation.

Key Results

M2 mAChRs coupled to Gɑi1, GɑoA and Gɑs, but not Gɑq, in response to canonical orthosteric agonists. Compounds 6A and 7A did not elicit any G protein activation, cAMP inhibition or stimulation, or ERK 1/2 phosphorylation. Instead, a Schild analysis indicates a competitive, antagonistic interaction of compounds 6A and 7A with ACh in the Gɑi1 activation assay. Overexpression of the M2 mAChR may suggest an expression‐dependent activation profile of compounds 6A and 7A.

Conclusions and Implications

These data confirm that the M2 mAChR preferentially couples to Gɑi/o and to a lesser extent to Gɑs in response to canonical orthosteric ligands. However, this study was not able to detect Gɑi bias of compounds 6A and 7A, highlighting the importance of cellular background when classifying new ligands.

LINKED ARTICLES

This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc
Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome
Authors: Ying Qiao , Ye Zhinan , Zhang Wei , Pan Yingying , Dai Linxiong , Lin Kaisang , Feng Xiaocheng , Dong Xuehong , He Fei
Published: December 2022

Objective

Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide‐sensitive sodium‐chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees.

Design, Patients and Measurements

The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis.

Results

Both patients were middle‐aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin‐angiotensin‐aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves' disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs—Polyphen‐2, SIFT, Mutation Taster and LRT.

Conclusions

We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.
Fatal congenital copper transport defect caused by a homozygous likely pathogenic variant of SLC31A1
Authors: Dame Christof , Horn Denise , Schomburg Lutz , Grünhagen Johannes , Chillon Thilo Samson , Tietze Anna , Vogt Annika , Bührer Christoph
Published: December 2022

Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X‐linked spinal muscular atrophy type 3) and ATP7B (Wilson disease). Herein, we report a newborn infant of consanguineous parents with a homozygous pathogenic variant in a highly conserved sequence of SLC31A1, coding for the copper influx transporter 1, CTR1. This missense variant, c.236T > C, was detected by whole exome sequencing. The infant was born with pulmonary hypoplasia and suffered from severe respiratory distress immediately after birth, necessitating aggressive mechanical ventilation. At 2 weeks of age, multifocal brain hemorrhages were diagnosed by cerebral ultrasound and magnetic resonance imaging, together with increased tortuosity of cerebral arteries. Ensuing seizures were only partly controlled by antiepileptic drugs, and the infant became progressively comatose. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. No hair shaft abnormalities were detected by dermatoscopy or light microscopic analyses of embedded hair shafts obtained at 4 weeks of life. The infant died after redirection of care and elective cessation of invasive mechanical ventilation at 1 month of age. This case adds SLC31A1 to the genes implicated in severe hereditary disorders of copper transport in humans.
The role of the U.S. exchange‐rate equity market volatility on agricultural exports and forecasts
Authors: Addey Kwame Asiam , Nganje William
Published: December 2022

This article estimates the U.S. state‐level soybean export forecast until December 2024 using a seasonal autoregressive integrated moving average (SARIMA) model. We utilize the newly developed exchange‐rate equity market volatility (EMV‐EX) to improve model fit and the Dirichlet process mixture model (DPMM) to control for unobserved heterogeneity. Using monthly data from January 2004 to December 2020, the study shows that soybean exports for states without ports are underestimated at the expense of states with ports. The EMV‐EX has a positive effect on soybean exports. The forecasts reveal no expected changes in the trends for soybean exports until December 2024. This study's results are useful to make and to implement more informed policy decisions for risk‐mitigating strategies such as the market‐facilitation program.
LncRNA LINC01018/miR‐942‐5p/KNG1 axis regulates the malignant development of glioma in vitro and in vivo
Authors: Xu Jinfang , Wang Jianli , Zhao Mingfei , Li Chenguang , Hong Shen , Zhang Jianmin
Published: December 2022

Aims

Since the inhibitory effect of KNG1 on glioma has been proved, this study further explores the regulation of the lncRNA/miRNA axis on KNG1 in glioma.

Methods

The miRNAs that target KNG1 and the lncRNA that targets miR‐942‐5p were predicted by bioinformatics analysis and verified by experiments. The correlations between miR‐942‐5p and the survival of patients and between KNG1 and miR‐942‐5p were analyzed. After transfection, cell migration, invasion, proliferation, and cell cycle were detected through wound healing, Transwell, colony formation, and flow cytometry assays. A mouse subcutaneous xenotransplanted tumor model was established. The expressions of miR‐942‐5p, KNG1, LINC01018, and related genes were evaluated by quantitative real‐time reverse transcription polymerase chain reaction (RT‐qPCR), Western blot, or immunohistochemistry.

Results

MiR‐942‐5p targeted KNG1, and LINC01018 sponged miR‐942‐5p. The high survival rate of patients was related to low miR‐942‐5p level. MiR‐942‐5p was highly expressed, whereas KNG1 was lowly expressed in glioma. MiR‐942‐5p was negatively correlated with KNG1. Silent LINC01018 or KNG1 and miR‐942‐5p mimic enhanced the migration, invasion, and proliferation of glioma cells, and regulated the expressions of metastasis‐related and proliferation‐related genes. LINC01018 knockdown and miR‐942‐5p mimic promoted glioma tumor growth in mice. The levels of miR‐942‐5p and KNG1 were decreased by LINC01018 knockdown, and LINC01018 expression was suppressed by miR‐942‐5p mimic. MiR‐942‐5p inhibitor, KNG1, and LINC01018 had the opposite effect to miR‐942‐5p mimic.

Conclusion

LINC01018/miR‐942‐5p/KNG1 pathway regulates the development of glioma cells in vitro and in vivo.
A review of remote ischemic conditioning as a potential strategy for neural repair poststroke
Authors: Yu Wantong , Ren Changhong , Ji Xunming
Published: December 2022

Ischemic stroke is one of the major disabling health‐care problem and multiple different approaches are needed to enhance rehabilitation, in which neural repair is the structural basement. Remote ischemic conditioning (RIC) is a strategy to trigger endogenous protect. RIC has been reported to play neuroprotective role in acute stage of stroke, but the effect of RIC on repair process remaining unclear. Several studies have discovered some overlapped mechanisms RIC and neural repair performs. This review provides a hypothesis that RIC is a potential therapeutic strategy on stroke rehabilitation by evaluating the existing evidence and puts forward some remaining questions to clarify and future researches to be performed in the field.
Leukopenia is an independent risk factor for early postoperative complications following incision and drainage of anorectal abscess
Authors: Khan Mustafa Tamim Alam , Patnaik Ronit , Huang Jian Yu , Campi Haisar Dao , Montorfano Lisandro , De Stefano Felice , Rosenthal Raul J. , Wexner Steven D.
Published: December 2022

Aim

Few data are available regarding the management of anorectal abscess in patients with leukopenia. The aim of this study was to investigate the impact of leukopenia among patients undergoing incision and drainage for anorectal abscess.

Method

A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP) database identified patients from 2015 to 2020. Perianal fistulas and supralevator abscesses were excluded. Patients were grouped based on white blood cell (WBC) count: WBC < 4.5 cells/μl, WBC = 4.5–11.0 cells/μl and WBC > 11.0 cells/μl. The 30‐day overall complications and outcomes were compared using regression models, accounting for demographics and comorbidities.

Results

Ten thousand two hundred and forty (70.3% male) patients were identified. Univariate analysis showed that, compared with patients with leukocytosis (WBC > 11.0 cells/μl) and normal WBC count (WBC = 4.5–11.0 cells/μl), patients with leukopenia (WBC <4.5 cells/μl) had higher rates of overall (p < 0.001), pulmonary (p < 0.001) and haematological complications (p < 0.001). They also had higher rates of readmission (p < 0.001), reoperation (p = 0.005), discharge to a care facility (p = 0.003), increased length of hospital stay (p = 0.004) and death (p < 0.001). Multivariable analysis identified leukopenia as an independent risk factor for overall complications [odds ratio (OR) 2.31, 95% CI 1.65–3.24; p < 0.001], pulmonary complications (OR 5.65, 95% CI 1.88–16.97; p = 0.002), haematological complications (OR 4.30, 95% CI 2.94–6.28; p < 0.001), unplanned readmission (OR 2.20, 95% CI 1.43–3.40; p < 0.001), reoperation (OR 1.80, 95% CI 1.10–2.93; p = 0.019) and death (OR 2.77, 95% CI 1.02–7.52; p = 0.046). Discharge to a care facility and length of stay were not significant on multivariable analysis.

Conclusion

Leukopenia is associated with increased risk for pulmonary and haematological complications, readmissions, reoperations, discharge to a care facility and death after incision and drainage for anorectal abscess.
1044. SORBUS PORRIGENTIFORMIS: Rosaceae
Authors: Rich Tim C. G. , Barlow Gillian , Brown Andrew P. , Fay Michael F.
Published: December 2022

Sorbus porrigentiformis, GREY‐LEAVED WHITEBEAM, is described and illustrated. It is a neoendemic with obovate leaves and fruits wider than long, and it is widespread in south‐west England and South Wales. It was originally broadly circumscribed, but it has now been split into at least 11 constituent parts. It is a cornerstone species for Sorbus speciation in Britain. It may have originated from S. aria × S. rupicola or from an ancestral taxon in Central Europe.
1047. SORBUS RUPICOLA: Rosaceae
Authors: Rich Tim C. G. , King Christabel , Fay Michael F.
Published: December 2022

Sorbus rupicola, ROCK WHITEBEAM, is described and illustrated. It is one of the most widespread apomictic polyploids in the genus. Its origin within Sorbus subgenus Aria is still not clear, but it is an important parent of hybridogenic taxa throughout its range. Notes on propagation and cultivation are also included.
1048. SORBUS SUBCUNEATA: Rosaceae
Authors: Fay Michael F. , Hamston Tracey , Barlow Gillian , Brown Andrew P. , Rich Tim C. G.
Published: December 2022

Sorbus subcuneata, SOMERSET WHITEBEAM, is described and illustrated. This narrow endemic species from coastal Devon and Somerset is endangered. Details of its discovery, historical taxonomic treatment and reproductive biology are provided.
Prenatal daily musical exposure is associated with enhanced neural representation of speech fundamental frequency: Evidence from neonatal frequency‐following responses
Authors: Arenillas‐Alcón Sonia , Ribas‐Prats Teresa , Puertollano Marta , Mondéjar‐Segovia Alejandro , Gómez‐Roig María Dolores , Costa‐Faidella Jordi , Escera Carles
Published: December 2022

Fetal hearing experiences shape the linguistic and musical preferences of neonates. From the very first moment after birth, newborns prefer their native language, recognize their mother's voice, and show a greater responsiveness to lullabies presented during pregnancy. Yet, the neural underpinnings of this experience inducing plasticity have remained elusive. Here we recorded the frequency‐following response (FFR), an auditory evoked potential elicited to periodic complex sounds, to show that prenatal music exposure is associated to enhanced neural encoding of speech stimuli periodicity, which relates to the perceptual experience of pitch. FFRs were recorded in a sample of 60 healthy neonates born at term and aged 12–72 hours. The sample was divided into two groups according to their prenatal musical exposure (29 daily musically exposed; 31 not‐daily musically exposed). Prenatal exposure was assessed retrospectively by a questionnaire in which mothers reported how often they sang or listened to music through loudspeakers during the last trimester of pregnancy. The FFR was recorded to either a /da/ or an /oa/ speech‐syllable stimulus. Analyses were centered on stimuli sections of identical duration (113 ms) and fundamental frequency (F0 = 113 Hz). Neural encoding of stimuli periodicity was quantified as the FFR spectral amplitude at the stimulus F0. Data revealed that newborns exposed daily to music exhibit larger spectral amplitudes at F0 as compared to not‐daily musically‐exposed newborns, regardless of the eliciting stimulus. Our results suggest that prenatal music exposure facilitates the tuning to human speech fundamental frequency, which may support early language processing and acquisition.

Research Highlights

Frequency‐following responses to speech were collected from a sample of neonates prenatally exposed to music daily and compared to neonates not‐daily exposed to music.

Neonates who experienced daily prenatal music exposure exhibit enhanced frequency‐following responses to the periodicity of speech sounds.

Prenatal music exposure is associated with a fine‐tuned encoding of human speech fundamental frequency, which may facilitate early language processing and acquisition.
Teachers' beliefs about standardised testing and test‐based accountability: Comparing the perceptions and experiences of teachers in Chile and Norway
Authors: Camphuijsen Marjolein K. , Parcerisa Lluís
Published: December 2022

The global popularity of test‐based accountability appears to signal political trust in standardised assessments as valid and relevant measures of education quality. Nonetheless, research shows that educators' perceptions of standardised testing and test‐based accountability can vary significantly, as do their responses to accountability demands. Considering the key influence of teachers' beliefs on the way in which they respond to education reforms, in this article we examine teachers' beliefs and opinions about standardised tests and test‐based accountability. We analyse a comparative study on interpretations and experiences of standardised testing and test‐based accountability demands of compulsory education teachers in Chile and Norway. These cases were selected following a most‐different‐systems design approach. The data was derived from an electronic survey (n = 2,531) and in‐depth interviews (n = 41). The analysis shows how in both contexts, teachers are relatively critical about the validity, usefulness and fairness of standardised tests. This indicates lacking teacher trust in standardised testing and test‐based accountability. Still, despite similar trends, some key differences in the beliefs of Chilean and Norwegian teachers are found, which highlight the influence of the sociocultural context in shaping teachers' beliefs. By illuminating how teachers in different contexts make sense of test‐based accountability, our analysis contributes to the understanding of why the often‐reported mismatch between policy expectations and policy outcomes might occur.
Prefrontal transcranial magnetic stimulation boosts response vigour during reinforcement learning in healthy adults
Authors: Biernacki Kathryn , Myers Catherine E. , Cole Sally , Cavanagh James F. , Baker Travis E.
Published: December 2022

A 10‐Hz repetitive transcranial magnetic stimulation to the left dorsal lateral prefrontal cortex has been shown to increase dopaminergic activity in the dorsal striatum, a region strongly implicated in reinforcement learning. However, the behavioural influence of this effect remains largely unknown. We tested the causal effects of 10‐Hz stimulation on behavioural and computational characteristics of reinforcement learning. A total of 40 healthy individuals were randomized into active and sham (placebo) stimulation groups. Each participant underwent one stimulation session (1500 pulses) in which stimulation was applied over the left dorsal lateral prefrontal cortex using a robotic arm. Participants then completed a reinforcement learning task sensitive to striatal dopamine functioning. Participants' choices were modelled using a reinforcement learning model (Q‐learning) that calculates separate learning rates associated with positive and negative reward prediction errors. Subjects receiving active stimulation exhibited increased reward rate (number of correct responses per second of task activity) compared with those in sham. Computationally, although no group differences were observed, the active group displayed a higher learning rate for correct trials (αG) compared with incorrect trials (αL). Finally, when tested with novel pairs of stimuli, the active group displayed extremely fast reaction times, and a trend towards a higher reward rate. This study provided specific behavioural and computational accounts of altered striatal‐mediated behaviour, particularly response vigour, induced by a proposed increase of dopamine activity by 10‐Hz stimulation to the left dorsal lateral prefrontal cortex. Together, these findings bolster the use of repetitive transcranial magnetic stimulation to target neurocognitive disturbances attributed to the dysregulation of dopaminergic‐striatal circuits.
GPR4 in the pH‐dependent migration of melanoma cells in the tumor microenvironment
Authors: Stolwijk Judith Anthea , Wallner Susanne , Heider Judith , Kurz Bernadett , Pütz Lisa , Michaelis Stefanie , Goricnik Barbara , Erl Julia , Frank Linda , Berneburg Mark , Haubner Frank , Wegener Joachim , Schreml Stephan
Published: December 2022

Due to its high metastatic potential, malignant melanoma is one of the deadliest skin cancers. In melanoma as well as in other cancers, acidification of the tumor microenvironment (=TME, inverse pH‐gradient) is a well‐known driver of tumor progression and metastasis. Membrane‐bound receptors, such as the proton‐sensitive GPCR (pH‐GPCR) GPR4, are considered as potential initiators of the signalling cascades relevant to malignant transformation. In this study, we investigated the pH‐dependent migration of GPR4 wildtype/overexpressing SK‐Mel‐28 cells using an impedance‐based electrical wounding and migration assay and classical Boyden chamber experiments. Migration of GPR4 overexpressing SK‐Mel‐28 cells was enhanced in a range of pH 6.5–7.5 as compared to controls in the impedance‐based electrical wounding and migration assay. In Boyden chamber experiments, GPR4 overexpression only increased migration at pH 7.5 in a Matrigel‐free setup, but not at pH 6.5. Results indicate that GPR4 is involved in the migration of melanoma cells, especially in the tumor periphery, and that this process is affected by pH in the TME.
In‐session gaming as a tool in treating adolescent problematic gaming
Authors: Nielsen Philip , Rigter Henk , Weber Niels , Favez Nicolas , Liddle Howard A.
Published: December 2022

For some adolescent gamers, playing online games may become problematic, impairing functioning in personal, family, and other life domains. Parental and family factors are known to influence the odds that adolescents may develop problematic gaming (PG), negative parenting and conflictual family dynamics increasing the risk, whereas positive parenting and developmentally supportive family dynamics protecting against PG. This suggests that a treatment for adolescent PG should not only address the gaming behaviors and personal characteristics of the youth, but also the parental and family domains. An established research‐supported treatment meeting these requirements is multidimensional family therapy (MDFT), which we adapted for use as adolescent PG treatment. We report here on one adaptation, applying in‐session gaming.

In‐session demonstration of the “problem behavior” is feasible and informative in PG. In the opening stage of therapy, we use in‐session gaming to establish an alliance between the therapist and the youth. By inviting them to play games, the therapist demonstrates that they are taken seriously, thus boosting treatment motivation.

Later in treatment, gaming is introduced in family sessions, offering useful opportunities to intervene in family members' perspectives and interactional patterns revealed in vivo as the youth plays the game. These sessions can trigger strong emotions and reactions from the parents and youth and give rise to maladaptive transactions between the family members, thus offering ways to facilitate new discussions and experiences of each other. The insights gained from the game demonstration sessions aid the therapeutic process, more so than mere discussion about gaming.
Global net biome CO2exchange predicted comparably well using parameter–environment relationships and plant functional types
Authors: Famiglietti Caroline A. , Worden Matthew , Quetin Gregory R. , Smallman T. Luke , Dayal Uma , Bloom A. Anthony , Williams Mathew , Konings Alexandra G.
Published: December 2022

Accurate estimation and forecasts of net biome CO2exchange (NBE) are vital for understanding the role of terrestrial ecosystems in a changing climate. Prior efforts to improve NBE predictions have predominantly focused on increasing models' structural realism (and thus complexity), but parametric error and uncertainty are also key determinants of model skill. Here, we investigate how different parameterization assumptions propagate into NBE prediction errors across the globe, pitting the traditional plant functional type (PFT)‐based approach against a novel top‐down, machine learning‐based “environmental filtering” (EF) approach. To do so, we simulate these contrasting methods for parameter assignment within a flexible model–data fusion framework of the terrestrial carbon cycle (CARDAMOM) at a global scale. In the PFT‐based approach, model parameters from a small number of select locations are applied uniformly within regions sharing similar land cover characteristics. In the EF‐based approach, a pixel's parameters are predicted based on underlying relationships with climate, soil, and canopy properties. To isolate the role of parametric from structural uncertainty in our analysis, we benchmark the resulting PFT‐based and EF‐based NBE predictions with estimates from CARDAMOM's Bayesian optimization approach (whereby “true” parameters consistent with a suite of data constraints are retrieved on a pixel‐by‐pixel basis). When considering the mean absolute error of NBE predictions across time, we find that the EF‐based approach matches or outperforms the PFT‐based approach at 55% of pixels—a narrow majority. However, NBE estimates from the EF‐based approach are susceptible to compensation between errors in component flux predictions and predicted parameters can align poorly with the assumed “true” values. Overall, though, the EF‐based approach is comparable to conventional approaches and merits further investigation to better understand and resolve these limitations. This work provides insight into the relationship between terrestrial biosphere model performance and parametric uncertainty, informing efforts to improve model parameterization via PFT‐free and trait‐based approaches.
E‐cadherin‐dependent coordinated epithelial rotation on a two‐dimensional discoidal pattern
Authors: Luo Shuangyu , Furuya Kanji , Matsuda Kimiya , Tsukasa Yuma , Usui Tadao , Uemura Tadashi
Published: December 2022

In vivo, cells collectively migrate in a variety of developmental and pathological contexts. Coordinated epithelial rotation represents a unique type of collective cell migrations, which has been modeled in vitro under spatially confined conditions. Although it is known that the coordinated rotation depends on intercellular interactions, the contribution of E‐cadherin, a major cell–cell adhesion molecule, has not been directly addressed on two‐dimensional (2D) confined substrates. Here, using well‐controlled fibronectin‐coated surfaces, we tracked and compared the migratory behaviors of MDCK cells expressing or lacking E‐cadherin. We observed that wild‐type MDCK II cells exhibited persistent and coordinated rotations on discoidal patterns, while E‐cadherin knockout cells migrated in a less coordinated manner without large‐scale rotation. Our comparison of the collective dynamics between these two cell types revealed a series of changes in migratory behavior caused by the loss of E‐cadherin, including a decreased global migration speed, less regularity in quantified coordination, and increased average density of topological defects. Taken together, these data demonstrate that spontaneous initiation of collective epithelial rotations depends on E‐cadherin under 2D discoidal confinements.
Women in public cultural organizations and their professional paths strategies: A rhizomatic approach
Authors: Góral Anna
Published: December 2022

The aim of this article is to explore the rhizomatic nature of the professional development strategies used by the female workforce of public cultural organizations. The research problem of this study are (1) the challenges of women who work in public cultural organizations and (2) ways of dealing with them by women. The empirical material was collected between January 2021 and January 2022 through 20 in‐depth interviews with female managers of public cultural organizations in Poland. The findings are presented in three sections: (1) specificity of work in culture, (2) twists and configurations on the way to grow, and (3) communities. In this way, it was possible to capture the specific strategies used by the female workforce for the development of their professional paths. To illustrate the complexity of these strategies, the concept of Rhizome—a root structure that grows in unpredictable and manifold directions—developed by Deleuze and Guattari was used. It also highlighted the fact that the professional development strategies used by women develop in a strong relationship with their environment and constantly evolve according to the needs of the women who decide to undertake them. The results of the research illustrate the impact of the far‐reaching gendered nature of work in cultural organizations on the professional development of women in this sector. Moreover, this reveals that to achieve their professional ambitions, women in cultural organizations co‐create complex informal organizational constructs, rhizome‐like in structure, which help women cope with the challenges that arise along their professional paths. These findings contribute to the theory of gendered organizations and the knowledge of gender inequality in cultural organizations.
Supporting the parent‐to‐child transfer of self‐management responsibility for chronic kidney disease: A qualitative study
Authors: Nightingale Ruth , Kirk Sue , Swallow Veronica , McHugh Gretl A.
Published: December 2022

Introduction

As children with long‐term conditions (LTCs) mature, they are usually expected to assume responsibility from their parents for self‐management of their condition. Little is known about what supports families with this handover of responsibility, including the role of healthcare professionals (HCPs). This study aimed to explore what supports young people with chronic kidney disease (CKD) to assume self‐management responsibility and parents to relinquish control.

Methods

A qualitative study, using a grounded theory approach was conducted. Individual and dyadic interviews and focus groups were carried out with 16 young people aged 13–17 years old with CKD, 13 parents, and 20 HCPs. Participants were recruited from two UK children's renal units.

Findings

Building and maintaining trust, fostering positivity, learning from mistakes, forming partnerships and individualized support, facilitated the transfer of self‐management responsibility. However, HCPs' focus on developing partnerships with young people meant some parents felt excluded, highlighting uncertainty around whether support should be child‐ or family‐centred. Although tailored support was identified as critical, aspects of local service provision appeared to impact on HCPs' capacity to implement individualized approaches.

Conclusion

This study has identified what supports the handover of responsibility, and, importantly, HCPs' current, and potential role in helping young people to assume responsibility for managing their LTC. Further research is needed to explore how HCPs' involvement balances child‐ and family‐centred care, and how HCPs can adopt personalized, strengths‐based approaches to help ensure the support that families receive is tailored to their individual needs.

Patient or Public Contribution

Patient and public involvement was integrated throughout the study, with young adults with CKD and parents who had a child with CKD actively involved in the study's design and delivery.
Investigating confounding in network‐based test‐negative design influenza vaccine effectiveness studies—Experience from the DRIVE project
Authors: Stuurman Anke L. , Levi Miriam , Beutels Philippe , Bricout Hélène , Descamps Alexandre , Dos Santos Gaël , McGovern Ian , Mira‐Iglesias Ainara , Nauta Jos , Torcel‐Pagnon Laurence , Biccler Jorne ,   DRIVE consortium
Published: December 2022

Background: Establishing a large study network to conduct influenza vaccine effectiveness (IVE) studies while collecting appropriate variables to account for potential bias is important; the most relevant variables should be prioritized. We explored the impact of potential confounders on IVE in the DRIVE multi‐country network of sites conducting test‐negative design (TND) studies.

Methods: We constructed a directed acyclic graph (DAG) to map the relationship between influenza vaccination, medically attended influenza infection, confounders, and other variables. Additionally, we used the Development of Robust and Innovative Vaccines Effectiveness (DRIVE) data from the 2018/2019 and 2019/2020 seasons to explore the effect of covariate adjustment on IVE estimates. The reference model was adjusted for age, sex, calendar time, and season. The covariates studied were presence of at least one, two, or three chronic diseases; presence of six specific chronic diseases; and prior healthcare use. Analyses were conducted by site and subsequently pooled.

Results: The following variables were included in the DAG: age, sex, time within influenza season and year, health status and comorbidities, study site, health‐care‐seeking behavior, contact patterns and social precautionary behavior, socioeconomic status, and pre‐existing immunity. Across all age groups and settings, only adjustment for lung disease in older adults in the primary care setting resulted in a relative change of the IVE point estimate >10%.

Conclusion: Our study supports a parsimonious approach to confounder adjustment in TND studies, limited to adjusting for age, sex, and calendar time. Practical implications are that necessitating fewer variables lowers the threshold for enrollment of sites in IVE studies and simplifies the pooling of data from different IVE studies or study networks.
Mechanistic modeling of lifetime distribution of SiC/SiC composite claddings
Authors: Hu Chen , Labuz Joseph F. , Koyanagi Takaaki , Le Jia‐Liang
Published: December 2022

Silicon carbide (SiC) fiber‐reinforced SiC matrix (SiC/SiC) composites have emerged as a new material candidate for fuel claddings in light water reactors. Recent studies showed that the load capacity of SiC/SiC materials exhibits a considerable statistical variation. Therefore, reliability analysis plays a critical role in design of SiC/SiC composite claddings. This paper presents a probabilistic model for the lifetime distribution of SiC/SiC composites. The model is anchored by a multiaxial stress‐based failure criterion and subcritical damage accumulation mechanism. Based on the kinetics of subcritical damage growth, the lifetime distribution of a laboratory test specimen for any given loading history can be calculated. A finite weakest‐link model is used to extrapolate the lifetime distribution of test specimens to full‐length claddings. It is shown that the damage accumulation mechanism has a strong influence on the lifetime distribution of the cladding. This finding highlights the importance of understanding the static fatigue behavior of SiC/SiC composites. The present analysis also demonstrates an intricate length effect on the failure probability of the cladding, which is expected to play a crucial role in design extrapolation.
Experimental diabetes exacerbates autophagic flux impairment during myocardial I/R injury through calpain‐mediated cleavage of Atg5/LAMP2
Authors: Guan Lichun , Yu Ziqin , Che Zhimei , Zhang Hang , Yu Yong , Yang Dicheng , Qian Dewei , Chen Ruizhen , Yu Min
Published: December 2022

To explore the role of autophagic flux in the increased susceptibility of the experimental diabetic heart to ischaemia‐reperfusion (I/R) injury, we established STZ‐induced diabetic mice and performed I/R. In vitro, neonatal mouse cardiomyocytes were subjected to high glucose and hypoxia/reoxygenation challenge to mimic diabetic I/R injury. We found that experimental diabetes aggravated I/R‐induced injury than compared with nondiabetic mice. Autophagic flux was impaired in I/R hearts, and the impairment was exacerbated in diabetic mice subjected to I/R with defective autophagosome formation and clearance. Calpains, calcium‐dependent thiol proteases, were upregulated and highly activated after I/R of diabetes, while calpain inhibition attenuated cardiac function and cell death and partially restored autophagic flux. The expression levels of Atg5 and LAMP2, two crucial autophagy‐related proteins, were significantly degraded in diabetic I/R hearts, alterations that were associated with calpain activation and could be reversed by calpain inhibition. Co‐overexpression of Atg5 and LAMP2 reduced myocardial injury and normalized autophagic flux. In conclusion, experimental diabetes exacerbates autophagic flux impairment of cardiomyocytes under I/R stress, resulting in worse I/R‐induced injury. Calpain activation and cleavage of Atg5 and LAMP2 at least partially account for the deterioration of autophagic flux impairment.