bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a therapeutic drug‐monitoring algorithm for outpatients receiving voriconazole: A multicentre retrospective study
Authors: Kato Hideo , Umemura Takumi , Hagihara Mao , Shiota Arifumi , Asai Nobuhiro , Hamada Yukihiro , Mikamo Hiroshige , Iwamoto Takuya
Published: February 2024

Aims

Although therapeutic drug monitoring (TDM) of voriconazole is performed in outpatients to prevent treatment failure and toxicity, whether TDM should be performed in all or only selected patients remains controversial. This study evaluated the association between voriconazole trough concentrations and clinical events.

Methods

We investigated the aggravation of clinical symptoms, incidence of hepatotoxicity and visual disturbances, change in co‐medications and interaction between voriconazole and co‐medications in outpatients receiving voriconazole between 2017 and 2021 in three facilities. Abnormal trough concentrations were defined as <1.0 mg/L (low group) and >4.0 mg/L (high group).

Results

A total of 141 outpatients (578 concentration measurements) met the inclusion criteria (treatment, 37 patients, 131 values; prophylaxis, 104 patients, 447 values). The percentages of patients with abnormal concentrations were 29.0% and 31.5% in the treatment and prophylaxis groups, respectively. Abnormal concentrations showed 50% of the concentrations at the first measurement in both therapies. Aggravation of clinical symptoms was most frequently observed in the low treatment group (18.2%). Adverse events were most common in the high group for both therapies (treatment, hepatotoxicity 6.3%, visual disturbance 18.8%; prophylaxis, hepatotoxicity 27.9%). No differences were found in changes to co‐medications and drug interactions. In the prophylaxis group, prescription duration in the presence of clinical events tended to be longer than in their absence (47.4 ± 23.4 days vs 39.7 ± 21.9 days, P = .1132).

Conclusions

We developed an algorithm based on clinical events for appropriate implementation of TDM in outpatients. However, future interventions based on this algorithm should be validated.
Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards
Authors: De Vincentis Antonio , Soraci Luca , Arena Elena , Sciacqua Angela , Armentaro Giuseppe , Aucella Francesco , Corsonello Andrea , Aucella Filippo , Antonelli Incalzi Raffaele
Published: February 2024

Aims

Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards.

Methods

We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug–drug interactions (DDIs).

Results

At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin‐K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage—17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00–1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02–1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91–0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19–3.13 for missed prescription).

Conclusions

This study showed a suboptimal DOAC prescriptive practice in older in‐patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real‐life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.
Validating methods used to identify non‐adherence adverse drug events in Canadian administrative health data
Authors: Wickham Maeve E. , McGrail Kimberlyn M. , Law Michael R. , Cragg Amber , Hohl Corinne M.
Published: February 2024

Aims

Medication non‐adherence is a type of adverse drug event that can lead to untreated and exacerbated chronic illness, and that drives healthcare utilization. Research using medication claims data has attempted to identify instances of medication non‐adherence using the proportion of days covered or by examining gaps between medication refills. We sought to validate these measures compared to a gold standard diagnosis of non‐adherence made in hospital.

Methods

This was a retrospective analysis of adverse drug events diagnosed during three prospective cohorts in British Columbia between 2008 and 2015 (n = 976). We linked prospectively identified adverse drug events to medication claims data to examine the sensitivity and specificity of typical non‐adherence measures.

Results

The sensitivity of the non‐adherence measures ranged from 22.4% to 37.5%, with a proportion of days covered threshold of 95% performing the best; the non‐persistence measures had sensitivities ranging from 10.4% to 58.3%. While a 7‐day gap was most sensitive, it classified 61.2% of the sample as non‐adherent, whereas only 19.6% were diagnosed as such in hospital.

Conclusions

The methods used to identify non‐adherence in administrative databases are not accurate when compared to a gold standard diagnosis by healthcare providers. Research that has relied on administrative data to identify non‐adherent patients both underestimates the magnitude of the problem and may label patients as non‐adherent who were in fact adherent.
Patient preferences in the treatment of stage III/IV classic Hodgkin lymphoma: Results from the CONNECT cross‐sectional survey
Authors: Flora Darcy R. , Parsons Susan K. , Liu Nicholas , Yu Kristina S. , Holmes Katherine , Flores Carlos , Fanale Michelle A. , Surinach Andy , Byrd Rachel , Evens Andrew M.
Published: February 2024

We explored patient front‐line treatment preferences in newly diagnosed stage III/IV classic Hodgkin lymphoma (cHL). The CONNECT patient survey, administered online from 30 December 2020 to 1 March 2021, examined preferences overall and by age at diagnosis in 182 adult patients diagnosed with stage III/IV cHL within the past 10 years in the United States. At diagnosis, patients' median age was 36 years; 66% of patients were younger (aged 16–41 years) and 34% older (aged 42–85 years). When asked about initial treatment goals, 74% of patients ranked cure as their first or second goal (86% younger vs. 52% older patients; p < 0.001). At diagnosis, 72% of patients preferred aggressive treatment, and 85% were willing to accept more short‐term risks in exchange for a better‐working therapy long term. For long‐term risks, younger versus older patients were significantly more concerned about second cancers (p < 0.001) and fertility issues (p = 0.007), whereas older patients were more concerned about lung damage (p = 0.028) and infections (p < 0.001). Most patients (94%) reported having a caregiver at some point, but 99% of these patients retained some control of treatment decisions. Collectively, these survey results highlight patient treatment preferences and differences in treatment goals and long‐term side effect concerns based on patient age.
Thrombotic and bleeding complications in patients with AL amyloidosis
Authors: Fotiou Despina , Theodorakakou Foteini , Spiliopoulou Sotiria , Gavriatopoulou Maria , Migkou Magdalini , Kanellias Nikolaos , Eleutherakis‐Papaiakovou Evangelos , Malandrakis Panagiotis , Dialoupi Ioanna , Roussou Maria , Ntanasis‐Stathopoulos Ioannis , Terpos Evangelos , Dimopoulos Meletios A. , Kastritis Efstathios
Published: February 2024

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were reported in 6% and arterial embolic events (AEEs) in 5% of patients, respectively, during a 55‐month median follow‐up. Lower albumin, lower eGFR, higher BM infiltration, soft tissue involvement, IMiD‐based therapy and prior thrombosis were associated with VTE risk. Prior thrombosis was the only independent prognostic variable (HR 9.3, p = 0.001). Coronary arterial disease, prior AEE, 24‐h proteinuria and higher platelet counts were associated with AEE risk. Significant bleeding events were reported in 9%, and associated mortality was 19%. Liver involvement, higher serum creatinine and higher baseline VWF:Ag levels were linked to bleeding risk. Using competing risk analysis, the cumulative probability of thrombosis/bleeding was higher during the first year following diagnosis, but a stable lower risk for both events remained for the duration of follow‐up. In AL amyloidosis patients, the risk of thrombotic/arterial embolic events is significant, but the bleeding risk is also high. A multiparametric assessment is required to initiate anti‐thrombotic or anti‐platelet therapy appropriately.
Ayahuasca‐enhanced extinction of fear behaviour: Role of infralimbic cortex 5‐HT2A and 5‐HT1A receptors
Authors: Werle Isabel , Nascimento Laura M. M. , dos Santos Aymee L. A. , Soares Luciane A. , dos Santos Rafael G. , Hallak Jaime E. C. , Bertoglio Leandro J.
Published: February 2024

Background and Purpose

Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N‐dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA‐treated rats.

Experimental Approach

We focused on the 5‐HT1A and 5‐HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis.

Key Results

A single oral treatment with AYA containing 0.3 mg·kg−1 of DMT increased the within‐session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1‐ and 21‐day‐old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA‐ and vehicle‐treated animals showed no differences when tested in the elevated plus‐maze. The 5‐HT2A receptor antagonist MDL‐11,939 and the 5‐HT1A receptor antagonist WAY‐100635 infused into the infralimbic cortex respectively blocked within‐ and between‐session fear extinction effects resulting from repeated oral administration of AYA.

Conclusion and Implications

Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress‐related disorders.
Disentangling the relations among help‐givers' instrumental helping ties, creativity, and creative idea implementation: A social network perspective
Authors: Liu Tao , Mao Yanhui , Lu Shaokai
Published: February 2024

How does the instrumental helping provided by individuals contribute to their creativity and subsequent implementation of creative ideas? This study aims to answer this question by investigating the relationship between help‐givers' helping strength and idea implementation, with a focus on disaggregating instrumental helping ties into helping strength and helping breadth from a social network perspective. In addition, the present work explores the mediating role of creativity and the moderating role of helping breadth in this relationship. The sample for this study consisted of 206 R&D employees from an engineering technology research centre. The results indicated that helping strength exhibited a direct inverted U‐shaped relationship with idea implementation and an indirect relationship through the mediating effect of creativity. Findings also demonstrated that helping breadth moderates the relationship between helping strength and idea implementation, with a shape‐flip effect. Specifically, when helping breadth was low, helping strength had an inverted U‐shaped relationship with idea implementation, whereas when helping breadth was high, the relationship shifted to a U‐shape. This study offers theoretical and practical insights into an intricate mechanism that underlies the contingent connections among help‐givers' instrumental helping ties, creativity, and idea implementation.
Antifascist praxis in developmental science: Possibilities for collective resistance to fascism
Authors: Arbeit Miriam R. , Negrete Andrea , Berger Natasha Panlilio , Dufault Anne E. , Onuoha Alexandria C. , Burnham Sarah L. F.
Published: February 2024

Antifascists have developed action‐oriented principles and practices for collective resistance to fascism. In this article, we discuss antifascism as praxis, which is the nexus of theory and practice through collective reflection and action. Antifascist praxis can inform developmental science at individual and contextual levels of analysis. For the study of individual developmental trajectories, we examine how antifascist praxis can inform research to stop fascist recruitment of youth and counter‐recruit youth into liberation movements. For the study of developmental contexts, we use the example of family separation to examine how antifascist praxis can inform research to identify fascist threats and support collective action against fascist violence. We also present next steps for developing a field of scholarship in which communities of developmental scientists engage in antifascist praxis. As developmental scientists, we must see ourselves as part of—not objectively disconnected from—broader mass movements building power against fascism and pursuing liberation for all.
Gene expression, micro‐CT and histomorphometrical analysis of sinus floor augmentation with biphasic calcium phosphate and deproteinized bovine bone mineral: A randomized controlled clinical trial
Authors: Arunjaroensuk Sirida , Nampuksa Katanchalee , Monmaturapoj Naruporn , Thunyakitpisal Pasutha , Porntaveetus Thantrira , Mattheos Nikos , Pimkhaokham Atiphan
Published: February 2024

Aims

The aim of this randomized controlled clinical trial was to compare the gene expression, micro‐CT, histomorphometrical analysis between biphasic calcium phosphate (BCP) of 70/30 ratio and deproteinized bovine bone mineral (DBBM) in sinus augmentation.

Materials and Methods

Twenty‐four patients in need for sinus floor augmentation through lateral approach were randomized into BCP 70/30 ratio or DBBM. After at least 6 months of healing, a total of 24 bone specimens were collected from the entire height of the augmented bone at the area of implant placement and underwent micro‐CT, histomorphometric and gene expression analysis. The 12 bone specimens of BCP 70/30 ratio were equally allocated to micro‐CT and histologic analysis (test group, n = 6) and gene expression analysis (test group, n = 6). Similarly, the 12 bone specimens of DBBM were also allocated to micro‐CT and histologic analysis (control group, n = 6) and gene expression analysis (control group, n = 6). The newly formed bone, remaining graft materials and relative change in gene expression of four target genes were assessed.

Results

The micro‐CT results showed no statistically significant difference in the ratio of bone volume to total volume (BV/TV ratio) for the two groups (BCP 41.51% vs. DBBM 40.97%) and the same was true for residual graft material to total volume (GV/TV ratio, BCP 9.97% vs. DBBM 14.41%). Similarly, no significant difference was shown in the histological analysis in terms of bone formation, (BCP 31.43% vs. DBBM was 30.09%) and residual graft area (DBBM 40.76% vs. BCP 45.06%). With regards to gene expression, the level of ALP was lower in both groups of bone grafted specimens compared with the native bone. On the contrary, the level of OSX, IL‐1B and TRAP was higher in augmented bone of both groups compared with the native bone. However, the relative difference in all gene expressions between BCP and DBBM group was not significant.

Conclusions

The BCP, HA/β‐TCP ratio of 70/30 presented similar histological and micro‐CT outcomes in terms of new bone formation and residual graft particles with DBBM. The gene expression analysis revealed different gene expression patterns between augmented and native bone, but showed no significant difference between the two biomaterials.
Bioenergy feedstock supply from wheat straw: A farm level model incorporating trade‐offs in crop choices, disease risk, and soil fertility
Authors: McKnight Curtis J. , Hauer Grant , Luckert Marty , Qiu Feng
Published: February 2024

Second‐generation biofuel (e.g., ethanol, renewable diesel) can be made from crop residues. However, the availability of residues for biofuel production is uncertain, because farmers have the option to grow different crops and use the residues for alternative purposes, such as livestock bedding and feed, or leave them in the field to improve soil quality. Taking Canadian wheat straw supply as an example, we develop a dynamic programming model to investigate a farmer's wheat straw supply decision in response to different wheat straw and grain prices. Our model considers crop choices between wheat and canola in the context of disease risk, the trade‐off between the immediate payoffs a farmer may receive from bailing and selling wheat straw, and the long‐term adverse effects that removing wheat straw from the soil surface may have on wheat and canola yields. The results from this study provide insights into how farm‐level supply decisions, in response to wheat straw price changes, affect soil quality dynamics and scale up to regional wheat straw supply for biofuel production. This information also has implications for land use change and the sustainability of feedstock supply for biofuels.
A phase I trial assessing the safety, pharmacokinetics, cerebrospinal fluid penetrance, and food effect of BTK inhibitor tolebrutinib in healthy volunteers
Authors: Cabanis Marie‐José , Nicolas Olivier , Vitse Olivier , Jan Christelle , Brun Priscilla , Soubayrol Patrick , Smith William B. , Turner Timothy J. , Krupka Emmanuel
Published: February 2024

Tolebrutinib is an oral, brain‐penetrant, covalent Bruton's tyrosine kinase inhibitor in development to treat multiple sclerosis at 60 mg/day with food. A phase I trial was conducted in healthy volunteers to assess the safety and pharmacokinetics of tolebrutinib at oral doses higher than 60 mg with food and during fasting, and to determine cerebrospinal fluid (CSF) exposure after a single dose of 60 or 120 mg with food. The trial included double‐blind, placebo‐controlled single ascending dose (120, 240, and 300 mg; fed and fasted) and multiple ascending dose (120, 180, and 240 mg) arms. Additional open‐label cohorts received a single 60 mg dose with a high‐fat meal and during fasting using a crossover design or a single 60 or 120 mg dose with food and lumbar puncture to obtain CSF. Tolebrutinib was rapidly absorbed and converted to an active metabolite (designated “M2”), both of which had a terminal half‐life of ~5 h. Tolebrutinib and M2 exposures increased following administration with food versus fasting, and plasma levels were generally dose proportional. For up to 4 h (the last measurement timepoint) after a 60 mg dose, CSF concentrations of tolebrutinib exceeded its in vitro cellular potency (half‐maximal inhibitory concentration [IC50]) for microglia, and tolebrutinib and M2 surpassed their biochemical IC50. Tolebrutinib was well‐tolerated, and treatment‐emergent adverse events were generally mild. Concentration‐QTc modeling showed no effects on QT/QTc intervals for any tolebrutinib dose or fed status. In conclusion, tolebrutinib has an acceptable safety profile at supratherapeutic doses and achieved bioactive CSF exposures at the phase III dose.
Pigtail trap: Stent migration crisis following endoscopic ultrasound‐guided gallbladder drainage
Authors: Koga Takehiko , Ishida Yusuke , Hirai Fumihito
Published: February 2024

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Direct and indirect effects of mother's spatial ability on child's spatial ability: What role does the home environment play?
Authors: Garcia‐Sanchez Nelcida L. , Dick Anthony Steven , Hayes Timothy , Pruden Shannon M.
Published: February 2024

Individual differences in spatial thinking are predictive of children's math and science achievement and later entry into Science, Technology, Engineering, and Mathematics (STEM) disciplines. Little is known about whether parent characteristics predict individual differences in children's spatial thinking. This study aims to understand whether, and to what extent, mother's intrinsic (i.e., mental rotation) and extrinsic (i.e., spatial scaling) spatial ability directly and indirectly, via the variation in home spatial environment, predicts children's intrinsic and extrinsic spatial ability. A total of 165 mothers and their 4–6‐year‐old children were recruited to participate in a remote video session with an experimenter. Mothers were administered a forced‐choice Intrinsic Spatial Toy Preference Task gauging their preference for highly spatial versus less spatial toys and asked questions with the Home Intrinsic Spatial Environmental Questionnaire about the frequency with which they engage their child in spatial activities at home. Mothers completed a Mental Rotations Test and a Spatial Scaling Task adapted for adults. Children were administered the Picture Rotation Task, the Spatial Scaling Task, and the Peabody Picture Vocabulary Test. Structural equation modeling was used to examine direct and indirect, via home spatial environment and toy choices, influences of mother spatial ability on child spatial ability. Contrary to our predictions, we did not find direct, nor indirect, relations between mother and child spatial ability. These findings suggest that researchers should consider alternative conceptualizations of the early home spatial environment beyond the frequency of spatial play in the home.

Research Highlights

The identification of factors that predict individual differences in children's spatial ability is important in order to maximize STEM learning outcomes.

Data collection was conducted remotely rather than in traditional preschool or laboratory settings.

Contrary to our pre‐registered hypotheses, no significant relations between mother spatial ability, the early home spatial environment, and children's development of spatial skills were found.

Future research should consider examining the amount of spatial language used in the home or the quality of parent–child interactions during spatial play as potential explanations for individual differences in children's spatial ability.
Global Health Impact: Human rights, access to medicines, and measurement
Authors: Hassoun Nicole
Published: February 2024

Should people have a legal human right to health? And, if so, what exactly does protecting this right require? This essay defends some answers to these questions recently articulated in Global Health Impact. It explains how these answers depend on a particular way of thinking about health and the minimally good life, how quality of life matters at and over time, what various agents should do to help people who are unable to live well enough, and many other things. Moreover, it suggests some ways of improving common metrics for measuring and advancing our collective global health impact.
Use of primary health care services among children and adolescents with cerebral palsy
Authors: Johansen Stine , Andersen Guro L. , Lydersen Stian , Kalleson Runa , Hollung Sandra Julsen
Published: February 2024

Aim

To investigate the use of general practitioners and urgent care centres (UCC) among children and adolescents with cerebral palsy (CP) compared to a control group, and per gross motor function level.

Method

Data on children with CP born 1996 to 2014 were collected from the Norwegian Quality and Surveillance Registry for Cerebral Palsy. A control group was extracted from Statistics Norway. The date and diagnosis codes for general practitioner and UCC contacts from 2006 to 2015 were collected from the Norwegian Control and Payment of Health Reimbursement Database. Incidence rate ratios (IRR) for the number of contacts per person‐year with 95% confidence intervals (CI) were calculated using Poisson regression. Risk differences with 95% CI were used to compare cumulative diagnosis incidences between children with CP and the control group.

Results

The study included 2510 children (1457 males; 58.1%) with CP and 12 041 (7003 males; 58.2%) without CP (mean age in both groups 7 years 2 months, SD 4 years 8 months, range 0–19 years), with 336 250 contacts. Children with CP had more general practitioner (IRR 1.47; 95% CI 1.29–1.67) and UCC (IRR 1.30; 95% CI 1.13–1.50) contacts than children without CP, for all ages. IRRs remained unchanged when comparing children with CP in Gross Motor Function Classification System (GMFCS) levels I and II to children without CP. Among children with CP, contact increased as GMFCS levels increased, and they were in contact most often for respiratory and general and unspecified diagnoses. The risk for epilepsy was highest for those in contact with general practitioners.

Interpretation

Children with CP, including those with less severe motor impairments, contacted general practitioners and UCCs more than children without CP. However, contact increased as gross motor impairment increased. They had contact for many diagnoses, mostly respiratory.
Prevention of internalizing difficulties in the middle years: Protocol for a noninferiority randomized trial of Mindfulness‐Based Cognitive Therapy for Children and Cognitive Behavioural Therapy
Authors: Taylor Amanda , Wright Kathleen , Roberts Rachel M. , Proeve Michael , Turner Jasmine , Miller Caroline
Published: February 2024

Aim

Mindfulness‐based interventions have been tested as preventive programs for childhood internalizing difficulties, but most research has been at a ‘universal’ level with small to null effects. Mindfulness‐Based Cognitive Therapy for Children (MBCT‐C) has similar effects to Cognitive Behaviour Therapy (CBT) when used as a small‐group, targeted preventive program. Knowledge gaps include the longer‐term effectiveness of MBCT‐C relative to CBT and the benefits of adding a parent module. This trial aims to compare MCBT‐C to traditional CBT, including a parent module, to 15‐months post‐intervention and to test the feasibility and acceptability of adding a parent module.

Methods

Participants will be recruited from primary schools in areas of socio‐economic disadvantage in South Australia (n = 194). Children (aged 9–12) years with signs of internalizing difficulties (e.g., shy, withdrawn, worried), and their parents, will be eligible for this two‐armed randomized controlled non‐inferiority trial (RCT). Children will participate in 10 group sessions of MBCT‐C or CBT, facilitated by psychologists, and parents from both conditions will participate in two parent‐only group sessions. Child self‐report measures include depression and anxiety, as well as attention, mindfulness and self‐compassion. Parent measures include symptoms of depression and anxiety, mindfulness, and parent–child relationship strength. The primary outcome will be child anxiety and depression (Revised Child Anxiety and Depression Scale‐25). Measures will be collected pre and post intervention, and at 3, 6, 12 and 15‐month follow up.

Results

Schools will be recruited from October 2022. Nomination of children will commence from February 2023. Program implementation will begin May 2023.

Conclusions

This trial will have implications for the feasibility of involving parents in preventative programs, as well as whether mindfulness‐based interventions prevent internalizing difficulties over time.
The potential predictors for treatment‐resistance depression after selective serotonin reuptake inhibitors therapy in Han Chinese: A resting‐state functional magnetic resonance imaging study
Authors: Li Yi , Yin Yan , Yu Yingyi , Hu Xiwen , Liu XiaoYan , Wu Sha
Published: February 2024

Aim

Selective serotonin reuptake inhibitors (SSRIs) are among the most important antidepressants. However, there is limited research on predicting the occurrence of treatment‐resistant depression (TRD) after 5 years. Examining the predictive effect of TRD occurrence using resting‐state fMRI in patients initiating SSRIs treatment at the onset of major depressive disorder (MDD) could potentially enhance TRD management.

Methods

A total of 60 first‐episode drug‐naive MDD patients who met the criteria, along with 41 healthy controls of Han Chinese ethnicity, were recruited. All MDD patients received SSRIs as the initial treatment for relieving depressive symptoms. Resting‐state fMRI scans were conducted for all subjects. Follow‐up assessments were conducted over a period of five years, during which MDD patients were categorized into treatment‐resistant depression (TRD) and non‐treatment‐resistant depression (NRD) groups based on disease progression. Amplitude of low‐frequency fluctuations (ALFF), fractional amplitude of low‐frequency fluctuations (fALFF), and Regional Homogeneity (ReHo) values were calculated and compared among the three groups. Additionally, receiver operating characteristic (ROC) curves were employed to identify potential predictors.

Results

After 5 years of follow‐up, it was found that 43 MDD patients were classified as NRD, while 17 were classified as TRD. In comparison to TRD, NRD exhibited decreased ALFF in the left middle cingulum gyrus (MCG.L) and in the right middle frontal gyrus (MFG.R), as well as decreased ReHo in MCG.L. Furthermore, NRD showed increased fALFF in the left precuneus (PCUN.L). The area under the curve (AUC) values were as follows: 0.724 (MCG.L by ALFF), 0.732 (MFG.R), 0.767 (PCUN.L), 0.774 (MCG.L by ReHo), 0.878 (combined), 0.547 (HAMD), and 0.408 (HAMA) respectively.

Conclusion

The findings suggest that PCUN.L, MFG.R, MCG.L, and the combined measures may indicate the possibility of developing TRD after 5 years when SSRIs are used as the initial therapy for relieving depressive symptoms in MDD patients.
Development and validation of a self‐regulated learning teaching scale for preschool teachers
Authors: Bai Barry , Li Jing
Published: February 2024

The present study developed and validated a self‐regulated learning (SRL) teaching scale with a total sample of 966 preschool teachers. A pool of items was generated from literature reviews, teacher interviews, and expert reviews using Zimmerman's cyclical model of SRL. An exploratory factor analysis (N = 333) in study 1, and a confirmatory factor analysis (N = 334), discriminant, and convergent validity (N = 667) in study 2 were performed to support a six‐factor construct, including task analysis, self‐motivation beliefs, self‐control, self‐observation, self‐judgement, and self‐reaction, with a satisfactory fit. In study 3, the T‐SRL was found significantly correlated with teacher self‐efficacy, validating the scale's concurrent validity with another sample of 299 teachers. Overall, the findings collectively support the further development of the T‐SRL to assess teaching practice while emphasizing the need for more empirical research on promoting children's SRL.
Integration, negotiation, interrogation: Gendered‐racialised barriers to the socialisation of doctoral students in Belgian higher education
Authors: Bourabain Dounia
Published: February 2024

In this paper, I discuss the gendered‐racialised interactional and contextual dynamics hindering the socialisation of ethnic minoritised women (EMW) within Belgian higher education. Based on in‐depth interviews, I develop the concept of ‘socialisation climates’ to explain the key aspects that determine EMW's socialisation process. Three socialisation climates are identified: integration, negotiation and interrogation. Findings show that insiders play a crucial role in hindering or facilitating EMW's socialisation. Developmental relationships are gendered‐racialised relations in which EMW's identity impacts supervisor and peer support. The departmental context in terms of hierarchy, an Equality, Diversity, and Inclusion culture, and team composition is relevant to their socialisation process. EMW are able to socialise rapidly only in a context that is (radically) inclusive which is still rare in academia. This paper informs higher education institutions to be aware of the gendered‐racialised climate and interactions that influence EMW's socialisation and increase the risk of pushing them out.
Neuro‐immune interactions in health and disease: Insights from FENS‐Hertie 2022 Winter School
Authors: Binder Luisa B. , Rosa Priscila B. , de Sousa Bárbara M. , Chagas Luana S. , Dubljević Olga , Martineau Fanny Sandrine , Mottarlini Francesca , Castany Sílvia , Morton Lorena , Krstanović Fran , Tassinari Isadora D. , Choconta Jeiny L. , Pereira‐Santos Ana Raquel , Weinhard Laetitia , Pallegar Praveen N. , Vahsen Björn F. , Lepiarz‐Raba Izabela , Compagnion Anne‐Claire , Lorente‐Picón Marina
Published: February 2024

In a great partnership, the Federation of European Neuroscience Societies (FENS) and the Hertie Foundation organized the FENS‐Hertie 2022 Winter School on ‘Neuro‐immune interactions in health and disease’. The school selected 27 PhD students and 13 postdoctoral fellows from 20 countries and involved 14 faculty members experts in the field. The Winter School focused on a rising field of research, the interactions between the nervous and both innate and adaptive immune systems under pathological and physiological conditions. A fine‐tuned neuro‐immune crosstalk is fundamental for healthy development, while disrupted neuro‐immune communication might play a role in neurodegeneration, neuroinflammation and aging. However, much is yet to be understood about the underlying mechanisms of these neuro‐immune interactions in the healthy brain and under pathological scenarios. In addition to new findings in this emerging field, novel methodologies and animal models were presented to foment research on neuro‐immunology. The FENS‐Hertie 2022 Winter School provided an insightful knowledge exchange between students and faculty focusing on the latest discoveries in the biology of neuro‐immune interactions while fostering great academic and professional opportunities for early‐career neuroscientists from around the world.
Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate
Authors: Li Yu‐Ting , Huang Yi‐Ling , Chen Jia‐Jin Jason , Hyland Brian Ian , Wickens Jeffery R.
Published: February 2024

The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention‐deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast‐scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward‐predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low‐dose methylphenidate in ADHD.
A quantitative framework for identifying the role of individual species in Nature's Contributions to People
Authors: Bianco Giovanni , Manning Peter , Schleuning Matthias
Published: February 2024

It is widely acknowledged that biodiversity change is affecting human well‐being by altering the supply of Nature's Contributions to People (NCP). Nevertheless, the role of individual species in this relationship remains obscure. In this article, we present a framework that combines the cascade model from ecosystem services research with network theory from community ecology. This allows us to quantitatively link NCP demanded by people to the networks of interacting species that underpin them. We show that this “network cascade” framework can reveal the number, identity and importance of the individual species that drive NCP and of the environmental conditions that support them. This information is highly valuable in demonstrating the importance of biodiversity in supporting human well‐being and can help inform the management of biodiversity in social‐ecological systems.
Plant interaction networks reveal the limits of our understanding of diversity maintenance
Authors: Bimler Malyon D. , Stouffer Daniel B. , Martyn Trace E. , Mayfield Margaret M.
Published: February 2024

Species interactions are key drivers of biodiversity and ecosystem stability. Current theoretical frameworks for understanding the role of interactions make many assumptions which unfortunately, do not always hold in natural, diverse communities. This mismatch extends to annual plants, a common model system for studying coexistence, where interactions are typically averaged across environmental conditions and transitive competitive hierarchies are assumed to dominate. We quantify interaction networks for a community of annual wildflowers in Western Australia across a natural shade gradient at local scales. Whilst competition dominated, intraspecific and interspecific facilitation were widespread in all shade categories. Interaction strengths and directions varied substantially despite close spatial proximity and similar levels of local species richness, with most species interacting in different ways under different environmental conditions. Contrary to expectations, all networks were predominantly intransitive. These findings encourage us to rethink how we conceive of and categorize the mechanisms driving biodiversity in plant systems.
Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study
Authors: Deng Xia , Hou Shuai , Wang Yanqiang , Yang Haiyan , Wang Chunping
Published: February 2024

Background and purpose

Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk.

Methods

By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk.

Results

Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T‐cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87–0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90–0.97; p < 0.001), show notable neuroprotection against ischemic stroke.

Conclusion

This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune‐targeted therapies for stroke prevention and management.
Generalized myasthenia gravis with acetylcholine receptor antibodies: A guidance for treatment
Authors: Gilhus Nils Erik , Andersen Henning , Andersen Linda Kahr , Boldingh Marion , Laakso Sini , Leopoldsdottir Margret Oddny , Madsen Sidsel , Piehl Fredrik , Popperud Trine Haug , Punga Anna Rostedt , Schirakow Liselotte , Vissing John
Published: February 2024

Background

Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research.

Methods

MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings.

Results

Pyridostigmine represents the first‐line symptomatic treatment, while ambenonium and beta adrenergic agonists are second‐line options. Early thymectomy should be undertaken if a thymoma, and in non‐thymoma patients up to the age of 50–65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first‐line option. Mycophenolate, methotrexate, and tacrolimus represent second‐line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast‐acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost–benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended.

Conclusions

Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long‐term specialized follow‐up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.
Genetic parameters and genomic prediction of growth and breast morphological traits in a crossbreed duck population
Authors: Cai Wentao , Hu Jian , Fan Wenlei , Xu Yaxi , Tang Jing , Xie Ming , Zhang Yunsheng , Guo Zhanbao , Zhou Zhengkui , Hou Shuisheng
Published: February 2024

Genomic selection (GS) has great potential to increase genetic gain in poultry breeding. However, the performance of genomic prediction in duck growth and breast morphological (BM) traits remains largely unknown. The objective of this study was to evaluate the benefits of genomic prediction for duck growth and BM traits using methods such as GBLUP, single‐step GBLUP, Bayesian models, and different marker densities. This study collected phenotypic data for 14 growth and BM traits in a crossbreed population of 1893 Pekin duck × mallard, which included 941 genotyped ducks. The estimation of genetic parameters indicated high heritabilities for body weight (0.54–0.72), whereas moderate‐to‐high heritabilities for average daily gain (0.21–0.57) traits. The heritabilities of BM traits ranged from low to moderate (0.18–0.39). The prediction ability of GS on growth and BM traits increased by 7.6% on average compared to the pedigree‐based BLUP method. The single‐step GBLUP outperformed GBLUP in most traits with an average of 0.3% higher reliability in our study. Most of the Bayesian models had better performance on predictive reliability, except for BayesR. BayesN emerged as the top‐performing model for genomic prediction of both growth and BM traits, exhibiting an average increase in reliability of 3.0% compared to GBLUP. The permutation studies revealed that 50 K markers had achieved ideal prediction reliability, while 3 K markers still achieved 90.8% predictive capability would further reduce the cost for duck growth and BM traits. This study provides promising evidence for the application of GS in improving duck growth and BM traits. Our findings offer some useful strategies for optimizing the predictive ability of GS in growth and BM traits and provide theoretical foundations for designing a low‐density panel in ducks.
Reliability of trans‐generational genetic mark–recapture (tGMR) for enumerating Pacific salmon
Authors: Rosenbaum Samuel W. , May Samuel A. , Shedd Kyle R. , Cunningham Curry J. , Peterson Randy L. , Elliot Brian W. , McPhee Megan V.
Published: February 2024

As Pacific salmon (Oncorhynchus spp.) decline across much of their range, it is imperative to further develop minimally invasive tools to quantify population abundance. One such advancement, trans‐generational genetic mark–recapture (tGMR), uses parentage analysis to estimate the size of wild populations. Our study examined the precision and accuracy of tGMR through a comparison to a traditional mark–recapture estimate for Chilkat River Chinook salmon (O. tshawytscha) in Southeast Alaska. We examined how adult sampling location and timing impact tGMR by comparing estimates derived using samples collected in the lower river mainstem to those using samples obtained in upriver spawning tributaries. Results indicated that tGMR estimates using a representative sample of mainstem adults were most concordant with, and 3% more precise than, the traditional mark–recapture estimate for this stock. Importantly, the timing and location of adult sampling were found to impact abundance estimates, depending on what proportion of the population dies or moves to unsampled areas between downriver and upriver sampling events. Additionally, we identified potential sources of bias in tGMR arising from violations of key assumptions using a novel individual‐based modeling framework, parameterized with empirical values from the Chilkat River. Simulations demonstrated that increased reproductive success and sampling selectivity of older, larger individuals, introduced negative bias into tGMR estimates. Our individual‐based model offers a customizable and accessible method to identify and quantify these biases in tGMR applications (https://github.com/swrosenbaum/tGMR_simulations). We underscore the critical role of system‐specific sampling design considerations in ensuring the precision and accuracy of tGMR projects. This study validates tGMR as a potentially useful tool for improved population enumeration in semelparous species.