bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathophysiological mechanisms of reduced physical activity: Insights from the human step reduction model and animal analogues
Authors: Sarto Fabio , Bottinelli Roberto , Franchi Martino V. , Porcelli Simone , Simunič Bostjan , Pišot Rado , Narici Marco V.
Published: May 2023

Physical inactivity represents a heavy burden for modern societies and is spreading worldwide, it is a recognised pandemic and is the fourth cause of global mortality. Not surprisingly, there is an increasing interest in longitudinal studies on the impact of reduced physical activity on different physiological systems. This narrative review focuses on the pathophysiological mechanisms of step reduction (SR), an experimental paradigm that involves a sudden decrease in participants' habitual daily steps to a lower level, mimicking the effects of a sedentary lifestyle. Analogous animal models of reduced physical activity, namely, the “wheel‐lock” and the “cage reduction” models, which can provide the foundation for human studies, are also discussed. The empirical evidence obtained thus far shows that even brief periods of reduced physical activity can lead to substantial alterations in skeletal muscle health and metabolic function. In particular, decrements in lean/muscle mass, muscle function, muscle protein synthesis, cardiorespiratory fitness, endothelial function and insulin sensitivity, together with an increased fat mass and inflammation, have been observed. Exercise interventions seem particularly effective for counteracting these pathophysiological alterations induced by periods of reduced physical activity. A direct comparison of SR with other human models of unloading, such as bed rest and lower limb suspension/immobilisation, is presented. In addition, we propose a conceptual framework aiming to unravel the mechanisms of muscle atrophy and insulin resistance in the specific context of reduced ambulatory activity. Finally, methodological considerations, knowledge gaps and future directions for both animal and human models are also discussed in the review.
Preclinical safety and biodistribution assessment of Ad‐KCNH2‐G628S administered via atrial painting in New Zealand white rabbits
Authors: Benson Janet M. , Wang Gensheng , Hutt Julie A. , Wu Guodong , Kaminsky Stephen M. , Cram Sara , Barur Rajeshkumar , Donahue J. Kevin
Published: May 2023

Post‐operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Despite implementation of several pharmacological strategies, incidence of POAF remains at approximately 30%. An adenovirus vector encoding KCNH2‐G628S has proven efficacious in a porcine model of AF. In this preclinical study, 1.5 × 1010 or 1.5 × 1012 Ad‐KCNH2‐G628S vector particles (vp) were applied to the atrial epicardium or 1.5 × 1012 vp were applied to the whole epicardial surface of New Zealand White rabbits. Saline and vector vehicle served as procedure controls. Animals were followed for up to 42 days. Vector genomes persisted in the atria up to 42 days, with no distribution to extra‐thoracic organs. There were no adverse effects attributable to test article on standard toxicological endpoints or on blood pressure, left atrial or ventricular ejection fractions, electrocardiographic parameters, or serum IL‐6 or troponin concentrations. Mononuclear infiltration of the myocardium of the atrial free walls of low‐dose, but not high‐dose animals was observed at 7 and 21 days, but these changes did not persist or affect cardiac function. After scaling for heart size, results indicate the test article is safe at doses up to 25 times the maximum proposed for the human clinical trial.
Deprescribing in a multimorbid older adult: A case vignette study among community pharmacists and primary care physicians
Authors: Bužančić Iva , Ortner Hadžiabdić Maja
Published: May 2023

Collaborative deprescribing can include pharmacists' medication review with identification and suggestion of potential deprescribing targets to physicians. Case vignettes can be a valuable method for researching variations in clinical decision making, especially in settings unaccustomed to newer clinical approaches such as deprescribing. This study aimed to explore if pharmacists can identify deprescribing targets and if physicians would accept pharmacist's deprescribing rationales. A cross‐sectional study was performed using an online case vignette based on a real‐life elderly patient. Pharmacists were asked to indicate which medicines they would recommend deprescribing, alongside a rationale. Physicians were asked to state their acceptance of the proposed pharmacist's deprescribing suggestion. Pharmacists gave 1275 deprescribing rationales, and most were given for deprescribing opioids, NSAID and diuretics. Physicians would accept rationales to deprescribe a median of 10 medicines, while pharmacist would recommend deprescribing a median of six medicines. Most difference lays in deprescribing of preventative medicines. Healthcare providers share agreement on deprescribing targets, but pharmacists show hesitancies in making recommendations that could hamper potential collaboration. Action is needed to improve pharmacists' skills in recognizing deprescribing targets and confidence in making suggestions, which could lead to opening of possibilities for joint patient care.
Depositional history of peatland pines (Pinus sylvestrisL.) in NW Enontekiö, Finnish Lapland: implications for Middle Holocene drought and temperature fluctuations
Authors: Helama Samuli , Herva Hannu , Uusitalo Joonas , Moir Andy , Mielikäinen Kari , Nöjd Pekka , Oinonen Markku , Sutinen Raimo
Published: May 2023

High altitude and latitude findings of subfossil peatland pine trees were unearthed from the region of NW Finnish Lapland and dated by14C and tree‐ring methods. The depositional history of the trees illustrated two distinct peatland pine phases dated to Middle Holocene intervals 4900–4400 and 4100–3400 cal. a BC. It seems evident that both thermal and hydroclimatic fluctuations have played roles of varying importance in the establishment of this pine population and its demise. The presence of these pines, from a site ~60 km north of the coniferous timberline and conditions ~1 °C and 100 degree‐days colder than those at the present‐day timberline, concurs with previous studies demonstrating the association between the high‐latitude summer‐temperature cooling and circumpolar timberline retreat since the Middle Holocene due to Milankovitch forcing. On the other hand, the peatland pine recruitment was made possible by drier than present surface conditions during the previously reconstructed Middle Holocene drought anomaly (Hyvärinen‐Alhonen event). Our data suggest this event was not continuous but reached its two‐phase climax during the peatland pine phases, with an interruption of several centuries with moister surface conditions between 4400 and 4100 cal. a BC. The findings highlight the sensitivity of well‐dated peatland tree assemblages in terms of recording past climatic evolution and events and the need for new collections from north and south Fennoscandia and the Baltic region, for more detailed analyses over extended time intervals and regions.
The therapeutic alliance in context: Institutional factors that impact social work with families
Authors: de‐Toro Consuagra Ximena , Sharim Kovalskys Dariela , Puig‐Cruells Carmina , Muñoz‐Guzmán Carolina
Published: May 2023

The therapeutic alliance is among the factors associated with positive results in therapy and has been extensively studied in psychotherapy. However, it has received less attention in social work and family intervention. Considering that such intervention occurs mainly within the framework of institutions and public policies, this article aims to identify the contextual factors that facilitate or hinder the therapeutic alliance between family members and social workers within the child protection system, taking the Chilean protection system as a case study. This longitudinal study followed six professional–caregiver dyads for 11 months using various qualitative techniques. The facilitating factors included the strengths approach of the child protection agency, family participation, a friendly work environment, and external supervision from a senior social worker. Among the obstacles were the high numbers of cases per professional, the undervaluing of their work, excessive workloads, stigma towards the system, and the mandatory nature of services. Facilitating factors were linked to the initiatives of the protection agency, while limitations were related to the type of welfare system. Similar obstacles and facilitators were found at the international level regardless of the kind of child protection system. The study concludes with recommendations for decision‐makers and social worker educators.
Characterization of novel CACNA1A splice variants by RNA‐sequencing in patients with episodic or congenital ataxia
Authors: Riant Florence , Burglen Lydie , Corpechot Michaelle , Robert Julien , Durr Alexandra , Solé Guilhem , Petit Florence , Freihuber Cécile , De Marco Olivier , Sarret Catherine , Castelnovo Giovanni , Devillard Françoise , Afenjar Alexandra , Héron Bénédicte , Lasserve Elisabeth Tournier
Published: May 2023

Loss of function variants in CACNA1A cause a broad spectrum of neurological disorders, including episodic ataxia, congenital or progressive ataxias, epileptic manifestations or developmental delay. Variants located on the AG/GT consensus splice sites are usually considered as responsible of splicing defects, but exonic or intronic variants located outside of the consensus splice site can also lead to abnormal splicing. We investigated the putative consequences on splicing of 11 CACNA1A variants of unknown significance (VUS) identified in patients with episodic ataxia or congenital ataxia. In silico splice predictions were performed and RNA obtained from fibroblasts was analyzed by Sanger sequencing. The presence of abnormal transcripts was confirmed in 10/11 patients, nine of them were considered as deleterious and one remained of unknown significance. Targeted next‐generation RNA sequencing was done in a second step to compare the two methods. This method was successful to obtain the full cDNA sequence of CACNA1A. Despite the presence of several isoforms in the fibroblastic cells, it detected most of the abnormally spliced transcripts. In conclusion, RNA sequencing was efficient to confirm the pathogenicity of nine novel CACNA1A variants. Sanger or Next generation methods can be used depending on the facilities and organization of the laboratories.
Adults with lower‐limb amputation: Reduced multifidi muscle activity and extensor muscle endurance is associated with worse physical performance
Authors: Sions Jaclyn M. , Seth Mayank , Beisheim‐Ryan Emma H. , Hicks Gregory E. , Pohlig Ryan T. , Horne John R.
Published: May 2023

Trunk muscles may be an overlooked region of deficits following lower‐limb amputation (LLA). This study sought to determine the extent that trunk muscle deficits are associated with physical function following amputation. Sedentary adults with a unilateral transtibial‐ (n = 25) or transfemoral‐level (n = 14) amputation were recruited for this cross‐sectional research study. Participants underwent a clinical examination that included ultrasound imaging of the lumbar multifidi muscles, the modified Biering‐Sorensen Endurance Test (mBSET), and performance‐based measures, that is, the Timed Up and Go (TUG), Berg Balance Scale (BBS), and 10‐m Walk Test (10mWT). Associations between trunk muscle metrics and performance were explored with regression modeling, while considering covariates known to impact performance postamputation (p ≤ 0.100). Average ultrasound‐obtained, lumbar multifidi activity was 14% and 16% for transfemoral‐ and transtibial‐level amputations, respectively, while extensor endurance was 37.34 and 12.61 s, respectively. For TUG, nonamputated‐side multifidi activity and an interaction term (level x non‐amputated‐side multifidi activity) explained 9.4% and 6.2% of the total variance, respectively. For 10mWT, beyond covariates, non‐amputated‐side multifidi activity and the interaction term explained 6.1% and 5.8% of the total variance, respectively. For TUG, extensor endurance and an interaction term (level x mBSET) explained 11.9% and 8.3% of the total variance beyond covariates; for BBS and 10mWT, extensor endurance explained 11.2% and 17.2% of the total variance, respectively. Findings highlight deficits in lumbar multifidi activity and extensor muscle endurance among sedentary adults with a LLA; reduced muscle activity and endurance may be important factors to target during rehabilitation to enhance mobility‐related outcomes.
Adult progenitor rejuvenation with embryonic factors
Authors: Wang Peng , Liu Xupeng , Chen Yu , Jun‐Hao Elwin Tan , Yao Ziyue , Min‐Wen Jason Chua , Yan‐Jiang Benjamin Chua , Ma Shilin , Ma Wenwu , Luo Lanfang , Guo Luyao , Song Dan , Shyh‐Chang Ng
Published: May 2023

During ageing, adult stem cells' regenerative properties decline, as they undergo replicative senescence and lose both their proliferative and differentiation capacities. In contrast, embryonic and foetal progenitors typically possess heightened proliferative capacities and manifest a more robust regenerative response upon injury and transplantation, despite undergoing many rounds of mitosis. How embryonic and foetal progenitors delay senescence and maintain their proliferative and differentiation capacities after numerous rounds of mitosis, remains unknown. It is also unclear if defined embryonic factors can rejuvenate adult progenitors to confer extended proliferative and differentiation capacities, without reprogramming their lineage‐specific fates or inducing oncogenic transformation. Here, we report that a minimal combination of LIN28A, TERT, and sh‐p53 (LTS), all of which are tightly regulated and play important roles during embryonic development, can delay senescence in adult muscle progenitors. LTS muscle progenitors showed an extended proliferative capacity, maintained a normal karyotype, underwent myogenesis normally, and did not manifest tumorigenesis nor aberrations in lineage differentiation, even in late passages. LTS treatment promoted self‐renewal and rescued the pro‐senescence phenotype of aged cachexia patients' muscle progenitors, and promoted their engraftment for skeletal muscle regeneration in vivo. When we examined the mechanistic basis for LIN28A's role in the LTS minimum combo, let‐7 microRNA suppression could not fully explain how LIN28A promoted muscle progenitor self‐renewal. Instead, LIN28A was promoting the translation of oxidative phosphorylation mRNAs in adult muscle progenitors to optimize mitochondrial reactive oxygen species (mtROS) and mitohormetic signalling. Optimized mtROS induced a variety of mitohormetic stress responses, including the hypoxic response for metabolic damage, the unfolded protein response for protein damage, and the p53 response for DNA damage. Perturbation of mtROS levels specifically abrogated the LIN28A‐driven hypoxic response in Hypoxia Inducible Factor‐1α (HIF1α) and glycolysis, and thus LTS progenitor self‐renewal, without affecting normal or TS progenitors. Our findings connect embryonically regulated factors to mitohormesis and progenitor rejuvenation, with implications for ageing‐related muscle degeneration.
Prediction, prevention, and treatment of post reperfusion syndrome in adult orthotopic liver transplant patients
Authors: DeMaria Samuel , Nolasco Lyle , Igwe Divya , Jules Robert St. , Bekki Yuki , Smith Natalie K.
Published: May 2023

Importance

This review explores proposed predictors, preventative measures, and treatment options for post‐reperfusion syndrome (PRS) in liver transplantation and provides updated data for clinicians.

Objectives

The review aims to understand the status and progress made regarding PRS during orthotopic liver transplantation. Moreover, the predictors of PRS will be analyzed to highlight risk factors. Mediators of PRS and the modes of action of the currently available preventative and management agents that target particular PRS factors will be investigated.

Data Sources

Data is drawn from secondary sources from databases of peer‐reviewed journals. The bibliographies of select sources were also used to obtain additional data studies using the ‘snowball’ method.

Study Selection

The initial data search provided 1394 studies analyzed using PRISMA Extension for Scoping Reviews (PRISMA‐ScR) guidelines. After applying the eligibility criteria, 18 studies were fit for inclusion.

Results

The study identified that in addition to the severity of underlying medical conditions, other significant PRS predictors included patient age, sex, duration of cold ischemia, and the surgical technique. While the use of epinephrine and norepinephrine is well‐established, further preventative measures commonly involve specifically targeting known mediators of the syndrome, such as antioxidants, vasodilators, free radical scavengers, and anticoagulants. Current management strategies involve supportive therapy. Machine Perfusion may ultimately decrease the risk of PRS.

Conclusion

PRS still holds unknowns, including the underlying pathophysiology, controllable factors, and ideal management practices. There is a need for further study, particularly prospective trials since liver transplantation is the gold standard for treating end‐stage liver disease and the incidence of PRS remains high.
Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease
Authors: van Kraaij Sebastiaan J. W. , Pereira Diana R. , Smal Bastiaan , Summo Luciana , Konkel Anne , Lossie Janine , Busjahn Andreas , Grammatopoulos Tom N. , Klaassen Erica , Fischer Robert , Schunck Wolf‐Hagen , Gal Pim , Moerland Matthijs
Published: May 2023

The development of pharmacological therapies for mitochondrial diseases is hampered by the lack of tissue‐level and circulating biomarkers reflecting effects of compounds on endothelial and mitochondrial function. This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross‐sectional case–control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation. Plasma biomarkers GDF‐15, IL‐6, NT‐proBNP, and cTNI were significantly elevated in patients compared to HVs, as were several clinical chemistry and hematology markers. No differences between groups were found for mitochondrial membrane potential, mitochondrial reactive oxygen production, oxygen consumption rate, or extracellular acidification rate in PBMCs. Imaging revealed significantly higher nicotinamide‐adenine‐dinucleotide‐hydrogen (NADH) content in skin as well as reduced passive leg movement‐induced hyperemia in patients. This study confirmed results of earlier studies regarding plasma biomarkers in mitochondrial disease and identified several imaging techniques that could detect functional differences at the tissue level between participants with mitochondrial disease and HVs. However, assays of mitochondrial function in PBMCs did not show differences between participants with mitochondrial disease and HVs, possibly reflecting compensatory mechanisms and heterogeneity in mutational load. In future clinical trials, using a mix of imaging and blood‐based biomarkers may be advisable, as well as combining these with an in vivo challenge to disturb homeostasis.
Translatability of in vitro potency to clinical efficacious exposure: A retrospective analysis of FDA‐approved targeted small molecule oncology drugs
Authors: Kotani Naoki , Ito Kiyomi
Published: May 2023

In vitro potency is one of the important parameters representing efficacy potential of drugs and commonly used as benchmark of efficacious exposure at early clinical development. There are limited numbers of studies which systematically investigate on how predictive in vitro potency is to estimate therapeutic drug exposure, especially those focusing on targeted anticancer agents despite the recent increase in approvals. This study aims to fill in such knowledge gaps. A total of 87 small molecule targeted drugs approved for oncology indication between 2001 and 2020 by the US Food and Drug Administration (FDA) were identified; relevant preclinical and clinical data were extracted from the public domain. Relationships between the in vitro potency and the therapeutic dose or exposure (unbound average drug concentration [Cu,av] as the primary exposure metrics) were assessed by descriptive analyses. The Spearman's rank correlation test showed slightly better correlation of the Cu,av (ρ = 0.232, p = 0.041) rather than the daily dose (ρ = 0.186, p = 0.096) with the in vitro potency. Better correlation was observed for the drugs for hematologic malignancies compared with those for solid tumors (root mean square error: 140 [n = 28] versus 297 [n = 59]). The present study shows that in vitro potency is predictive to estimate the therapeutic drug exposure to some extent, whereas the general trend of overexposure was observed. The results suggested that in vitro potency alone is not sufficient and robust enough to estimate the clinically efficacious exposure of molecularly targeted small molecule oncology drugs. The totality of data, including both nonclinical and clinical, needs to be considered for dose optimization.
From clinical data management to clinical data science: Time for a new educational model
Authors: Ittenbach Richard F.
Published: May 2023

The purpose of this article is to propose and provide a blueprint for a graduate‐level curriculum in clinical data science, devoted to the measurement, acquisition, care, treatment, and inferencing of clinical research data. The curriculum presented here contains a series of five required core courses, five required research courses, and a list of potential electives. The coursework draws from but does not duplicate content from the foundational areas of biostatistics, clinical medicine, biomedical informatics, and regulatory affairs, and may be reproduced by any institution interested in and capable of offering such a program. This new curriculum in “clinical” data science will prepare students for work in academic, industry, and government research settings as well as offer a unifying knowledge base for the profession.
Gender‐based cytomorphometric analysis of buccal exfoliated cells in a South Indian population
Authors: Begum N. Fazulunnisa , Ramani Pratibha
Published: May 2023

Objective

To assess differences based on gender in nuclear area (NA), cytoplasmic area (CA), and nuclear‐cytoplasmic ratio (N:C ratio) values for clinically normal buccal smears in apparently healthy subjects of a South Indian population, thereby providing definitive baseline cytomorphometric measurements for the South Indian population.

Methods

Buccal smears were collected from 60 healthy subjects (30 males and 30 females) of a South Indian population above 18 years in age. Values of the NA and CA were measured, and the N:C ratio calculated, using ImageJ software. Statistical analysis of the data with independent t tests and 95% confidence intervals was done using SPSS version 21 (significance set at P < 0.05).

Results

The results showed that there were significant differences in the NA, CA, and N:C values between males and females irrespective of age (P = 0.01).

Conclusion

Definitive gender‐specific baseline cytomorphometric data can be established using exfoliative cytology for the South Indian population, and this may be helpful in deciphering the occurrence of oral pre‐malignant diseases and oral squamous cell carcinoma in this population, as the incidence of these conditions varies with gender and different ethnic groups.
Hummingbird blood traits track oxygen availability across space and time
Authors: Williamson Jessie L. , Linck Ethan B. , Bautista Emil , Smiley Ashley , McGuire Jimmy A. , Dudley Robert , Witt Christopher C.
Published: May 2023

Predictable trait variation across environments suggests shared adaptive responses via repeated genetic evolution, phenotypic plasticity or both. Matching of trait–environment associations at phylogenetic and individual scales implies consistency between these processes. Alternatively, mismatch implies that evolutionary divergence has changed the rules of trait–environment covariation. Here we tested whether species adaptation alters elevational variation in blood traits. We measured blood for 1217 Andean hummingbirds of 77 species across a 4600‐m elevational gradient. Unexpectedly, elevational variation in haemoglobin concentration ([Hb]) was scale independent, suggesting that physics of gas exchange, rather than species differences, determines responses to changing oxygen pressure. However, mechanisms of [Hb] adjustment did show signals of species adaptation: Species at either low or high elevations adjusted cell size, whereas species at mid‐elevations adjusted cell number. This elevational variation in red blood cell number versus size suggests that genetic adaptation to high altitude has changed how these traits respond to shifts in oxygen availability.
Functional evaluation of epilepsy‐associated KCNT1 variants in multiple cellular systems reveals a predominant gain of function impact on channel properties
Authors: Hinckley Christopher A. , Zhu Zhonghua , Chu Jen‐hwa , Gubbels Cynthia , Danker Timm , Cherry Jonathan J. , Whelan Christopher D. , Engle Sandra J. , Nguyen Viet
Published: May 2023

Objective

Gain of function variants in the sodium‐activated potassium channel KCNT1 have been associated with pediatric epilepsy disorders. Here, we systematically examine a spectrum of KCNT1 variants and establish their impact on channel function in multiple cellular systems.

Methods

KCNT1 variants identified from published reports and genetic screening of pediatric epilepsy patients were expressed in Xenopus oocytes and HEK cell lines. Variant impact on current magnitude, current–voltage relationships, and sodium ion modulation were examined.

Results

We determined basic properties of KCNT1 in Xenopus oocyte and HEK systems, including the role of extra‐ and intracellular sodium in regulating KCNT1 activity. The most common six KCNT1 variants demonstrated strong gain of function (GOF) effects on one or more channel properties. Analysis of 36 total variants identified phenotypic heterogeneity but a strong tendency for pathogenic variants to exert GOF effects on channel properties. By controlling intracellular sodium, we demonstrate that multiple pathogenic KCNT1 variants modulate channel voltage dependence by altering the sensitivity to sodium ions.

Significance

This study represents the largest systematic functional examination of KCNT1 variants to date. We both confirm previously reported GOF channel phenotypes and expand the number of variants with in vitro GOF effects. Our data provide further evidence that novel KCNT1 variants identified in epilepsy patients lead to disease through generalizable GOF mechanisms including increases in current magnitude and/or current–voltage relationships.
Investor sentiment and the risk–return relation: A two‐in‐one approach
Authors: Duxbury Darren , Wang Wenzhao
Published: May 2023

Traditional finance theory posits a positive risk–return relation, but empirical evidence is inconclusive. Retail investor sentiment has long been viewed as a distorting factor, while more recently institutional investor sentiment is thought to play a role. We examine the separate and joint impacts of retail and institutional investor sentiments on the risk‐return relation. We find, at both market and firm levels, the risk‐return relation is more likely to be distorted by the two investor‐type sentiments jointly, rather than separately. We further find a cross‐sectional pattern, with the risk‐return relation being more sensitive to investor sentiment for stocks with specific characteristics.
Behavioral outcomes in children of adolescent and adult mothers: Linkages with coparenting and learning activities
Authors: Black Caroline F. D. , Barnett Melissa , Zambrano Priscilla L. , Noll Laura K. , Kortman Tianna
Published: May 2023

Objective

This study explored associations among supportive coparenting, maternal–child learning activities, and child behavioral outcomes in adult and adolescent mothers experiencing socioeconomic disadvantage.

Background

Supportive coparenting relationships are associated with positive parenting and child outcomes, yet research is limited for families experiencing socioeconomic adversities, particularly adolescent mothers, leading to an overemphasis of family risk and child negative outcomes.

Methods

Data were derived from the Fragile Families and Child Well‐being Study for a sample of 3‐year‐old children whose parents maintained functional relationships (N = 3, 421). Structural equation models tested whether supportive coparenting directly associated with child prosocial, externalizing, and internalizing behaviors and if indirect effects were transferred through maternal–child learning activities. Moderation analyses tested whether direct and indirect effects were conditional based on maternal age at childbirth (adolescent vs. adult).

Results

Maternal–child learning explained associations between supportive coparenting and child social outcomes. Higher levels of supportive coparenting directly associated with lower levels of child problem behaviors. Although findings varied between adult and adolescent mothers, no moderation effects were detected.

Conclusion

Supportive coparenting relationships are equally beneficial to children of adult and young mothers experiencing socioeconomic adversities, although pathways of influence differ.

Implications

Programs serving historically marginalized families, particularly adolescent mothers, may benefit by targeting coparenting and maternal–child learning activities as modifiable factors that promote positive child outcomes.
Reproductive collapse in European beech results from declining pollination efficiency in large trees
Authors: Bogdziewicz Michał , Kelly Dave , Tanentzap Andrew J. , Thomas Peter , Foest Jessie , Lageard Jonathan , Hacket‐Pain Andrew
Published: May 2023

Climate warming increases tree mortality which will require sufficient reproduction to ensure population viability. However, the response of tree reproduction to climate change remains poorly understood. Warming can reduce synchrony and interannual variability of seed production (“masting breakdown”) which can increase seed predation and decrease pollination efficiency in trees. Here, using 40 years of observations of individual seed production in European beech (Fagus sylvatica), we showed that masting breakdown results in declining viable seed production over time, in contrast to the positive trend apparent in raw seed count data. Furthermore, tree size modulates the consequences of masting breakdown on viable seed production. While seed predation increased over time mainly in small trees, pollination efficiency disproportionately decreased in larger individuals. Consequently, fecundity declined over time across all size classes, but the overall effect was greatest in large trees. Our study showed that a fundamental biological relationship—correlation between tree size and viable seed production—has been reversed as the climate has warmed. That reversal has diverse consequences for forest dynamics; including for stand‐ and biogeographical‐level dynamics of forest regeneration. The tree size effects suggest management options to increase forest resilience under changing climates.
Integrative population genetics and metagenomics reveals urbanization increases pathogen loads and decreases connectivity in a wild bee
Authors: Chau Katherine D. , Samad‐zada Farida , Kelemen Evan P. , Rehan Sandra M.
Published: May 2023

As urbanization continues to increase, it is expected that two‐thirds of the human population will reside in cities by 2050. Urbanization fragments and degrades natural landscapes, threatening wildlife including economically important species such as bees. In this study, we employ whole genome sequencing to characterize the population genetics, metagenome and microbiome, and environmental stressors of a common wild bee, Ceratina calcarata. Population genomic analyses revealed the presence of low genetic diversity and elevated levels of inbreeding. Through analyses of isolation by distance, resistance, and environment across urban landscapes, we found that green spaces including shrubs and scrub were the most optimal pathways for bee dispersal, and conservation efforts should focus on preserving these land traits to maintain high connectivity across sites for wild bees. Metagenomic analyses revealed landscape sites exhibiting urban heat island effects, such as high temperatures and development but low precipitation and green space, had the highest taxa alpha diversity across all domains even when isolating for potential pathogens. Notably, the integration of population and metagenomic data showed that reduced connectivity in urban areas is not only correlated with lower relatedness among individuals but is also associated with increased pathogen diversity, exposing vulnerable urban bees to more pathogens. Overall, our combined population and metagenomic approach found significant environmental variation in bee microbiomes and nutritional resources even in the absence of genetic differentiation, as well as enabled the potential early detection of stressors to bee health.
Structural factors affecting global trends towards isolationism and expansionism – A BERGM analysis
Authors: Jang Yeongkyun , Yang Jae‐Suk
Published: May 2023

The first purpose of this study is to define the network parameters that enable systemic analysis of international relations, identifying trends towards isolationism and expansionism. The second is to analyse the factors influencing global trends towards isolationism and expansionism from a structural point of view. The results of a network analysis, including a BERGM, indicate a trend towards isolationism in the economic arena since about 2010; in contrast, a trend towards expansionism has been continuously evident in the political and military sectors throughout the study period. These results also show that the international relations system is formed by reciprocal and triadic relations. In specific, the results reveal that the expansionism trends are influenced by relational substructures centred on importing states.
Episodic disability in the neoliberal university: Stories from the Canadian context
Authors: Rice Carla , Harrison Elisabeth , Giddings Carla , Chivers Sally , Meerai Sonia , Zitzelsberger Hilde
Published: May 2023

This article explores how episodic disability (ED) is created and intensified by, present within, and pushed out of the neoliberalized academy in Canada. ED is an umbrella term for a range of physical, mental, and neurological conditions characterized by fluctuation and unpredictability. Over two million working‐age Canadians are affected by ED, with women more likely to be impacted. To consider how ED interacts with post‐secondary education, we put feminist disability theories of embodied precarity, crip time, and disability justice into conversation with multimedia stories created by post‐secondary women workers with EDs, with story‐makers contextualizing and theorizing their creations, and revealing their complex embodied and embedded experiences. We chose these from stories generated in two research projects focused on transforming negative concepts of disability to serve as an “archivy” of embodied precarity that challenges ED's erasure in the academy. We think with the stories to analyze power and resistance in and on gendered and raced academic bodies along three overlapping themes: debility and vulnerability in the neoliberal university; fault‐lines of neoliberal time and embodied time; and EDs as produced in, and pushed out of, the neoliberal academy. Considering interrelations between ED and post‐secondary education under neoliberalism, we argue that feminist disability theory and justice praxis challenge debilitating and exclusionary expectations that harm people with EDs in and outside of the academy.
Improvement of the production process and the sensory and nutritional quality of m'bahou, a traditional plantain semolina, enriched with soy or cowpea
Authors: N'Goran Christelle Adjoua , Petit Jérémy , N'Guessan Arlette Akissi , Gonnety Jean Tia , Scher Joël
Published: May 2023

M'bahou is a traditional Ivorian food dish prepared from senescent plantain and cassava powder which has a low protein content and a weak technological aptitude because of its stickiness. The present study aims at investigating the possibility to lower m'bahou stickiness by using fermented cassava powders and evaluating the impact of partial substitution of cassava by soy and cowpea on its sensory, nutritional and textural properties. A descriptive test was performed to deduce the impact of cassava fermentation time. Formulating m'bahou with 4‐h fermented cassava permitted to reach the best compromise between stickiness, taste, and smell. A hedonic test was performed to choose the adequate proportion of soybean or cowpea powders to substitute for 4‐h fermented cassava powder in the formulation of m'bahou, leading to 10% soy or 15% cowpea in final formulations. Moreover, it was highlighted that substitution permitted to improve nutritional quality and energy value. Texture analysis showed that semolina containing fermented cassava powder prepared as compacts after reconstitution slightly differed from the reference m'bahou formulated with unfermented cassava: although their hardness was higher and their elasticity and masticability lower, they appeared to be less adhesive and cohesive, showing their better technological aptitude.
Insights into the non‐targeted metabolomic profile, rheological, functional and structural characteristics of rice bran and pulse protein isolates
Authors: Kumar Ajay , Joshi Robin , Awasthi Tamanna , Singh Narpinder
Published: May 2023

Rice bran protein isolates and seven legume protein isolates (moong bean, green pea, white pea, black chickpea and white chickpea, soya bean and lentil) were evaluated for functional, structural and metabolomic properties. Rice bran protein isolates (RBI) had higher solubility, foaming, oil absorption capacity and water absorption capacity but lower denaturing temperature compared to legume proteins. The functionality of proteins isolates impacted significantly with structural characteristics. The β‐sheet, α‐helix, β‐turn and anti‐parallel β‐sheets proportions were evaluated by FTIR. RBI revealed lower molecular weight, less rigid conformational structure and lower proportion of β‐sheet. The evaluation of untargeted metabolomics compounds was determined by ultraperformance liquid chromatography quadruple time‐of‐flight ion mobility mass spectrometry (UHPLC‐QTOF‐IMS), evaluated using PCA and presented as a heatmap. Analysis revealed 46 metabolites including sugars, amino acids, lipids, terpenoid, phenolics, saponins and their derivatives. Significant differences in selected compounds from 126 identified metabolites among protein isolates were observed. This work provides new insights into metabolite distribution among protein isolates and also presents future implementations for applications in food and nutraceuticals.
Immediate flap increases patient safety for deep sternal wound infection: A meta‐analysis
Authors: Qiu Xiaotong , Sun Xingwang , Huang Guobao
Published: May 2023

Deep sternal wound infection is a severe complication after cardiac surgery. We performed a meta‐analysis evaluating the impact of immediate flap and NPWT on mortality and length of hospital stay. The meta‐analysis was registered (CRD42022351755). A systematic literature search was conducted from inception to January, 2023, including PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov and EU Clinical Trials Register. The main outcome were in‐hospital mortality and late mortality. And additional outcomes were length of stay and ICU stay time. A total of 438 patients (Immediate flap: 229; NPWT: 209) from four studies were included in this study. Immediate flap was associated with lower in‐hospital mortality (OR 0.33, 95% CI 0.13‐0.81, P = .02) and length of stay (SMD −13.24, 95% CI −20.53 to −5.94, P = .0004). Moreover, pooled analysis demonstrated no significant difference was found in two groups in terms of late mortality (OR 0.64, 95% CI 0.35‐1.16, P = .14) and ICU stay time (SMD −1.65, 95% CI −4.13 to 0.83, P = .19). Immediate flap could reduce in‐hospital mortality and length of stay for patients with deep sternal wound infection. Flap transplantation as soon as possible may be advised.
Correlations between motor competencies, physical activity and self‐concept in children with intellectual disabilities in inclusive education
Authors: Schluchter Thierry , Nagel Siegfried , Valkanover Stefan , Eckhart Michael
Published: May 2023

Background

Reciprocal relationships exist between motor competencies, physical activity and self‐concept.

Aims

Using a structural equation model, this study examined whether these relationships also appear in children with intellectual disabilities, how they can be validly measured, and if there are differences between children with and without intellectual disabilities.

Materials & Methods

Data from a cross‐sectional research project involving 121 children with intellectual disabilities and 1721 without intellectual disabilities were analysed.

Results

The results demonstrate that reciprocal relationships also apply to children with intellectual disabilities and can be elucidated if inverse items are omitted.

Discussion

Children with intellectual disabilities have less developed motor competencies and are less physically active but have a higher general self‐concept compared to children without intellectual disabilities. The sport‐related ability self‐concept of both groups is comparable.

Conclusions

The results are broadly consistent with extant research and illustrate that the development of motor competencies, physical activity and self‐concept in children with intellectual disabilities must be encouraged.
Behavioural sleep problems in children and adults with intellectual disabilities: An integrative literature review
Authors: Harper Lynette , McAnelly Su , Walshe Ian , Ooms Ann , Tuffrey‐Wijne Irene M.
Published: May 2023

Background

People with intellectual disabilities are more likely to experience sleep problems, which can affect quality of life, physical health, mental health and well‐being.

Methods

An integrative literature review was conducted to investigate what is known about behavioural sleep disturbances in people with an intellectual disability. The search used the following databases: Scopus, PsycInfo and Cinahl, to find papers published since 2015.

Results

Within intellectual disability research, sleep appears as a common issue due to its high prevalence, negative relationships with an individual's physical and mental health, their quality of life, and impact of sleep problems on family or carers. The growing evidence base appears to support the use of behavioural, lifestyle and pharmacological interventions to improve sleep in people with an intellectual disability.

Conclusion

A wide array of literature provides evidence that people with intellectual disabilities are affected by and need support with their sleep.
Inactivation of EGFR/ERK/NF‐κB signalling associates with radiosensitizing effect of 18β‐glycyrrhetinic acid on progression of hepatocellular carcinoma
Authors: Liu Yu‐Chang , Lin Cheng Hsun , Chen Kuan‐Tin , Lai De‐Wei , Hsu Fei‐Ting
Published: May 2023

Hepatocellular carcinoma (HCC) is recognized as the fifth most common cancer and the third most common cause of death in Asian population. Studies reported that HCC is relatively insensitive to radiotherapy (RT); thus, considering how to sensitize HCC to RT is worth to be elucidated. Epidermal growth factor receptor (EGFR)‐mediated signalling transduction plays the important role in regulating treatment efficacy of HCC. An active compound, 18beta‐glycyrrhetinic acid (18β‐GA), has been reported to own anti‐tumour effect. However, whether 18β‐GA possess RT sensitization ability in HCC remains unclear. Here, we used RNA data from TCGA‐LIHC (Liver hepatocellular carcinoma) to identify the role between EGFR/ERK/nuclear factor kappa B (NF‐κB) signalling and RT by radiosensitivity index (RSI) analysis. We suggested that patients with activated NF‐κB signalling may show resistance to RT treatment, whereas combining 18β‐GA may reinforce RT efficacy in a Hep3B‐bearing animal model. 18β‐GA combined with RT showed superior tumour inhibition capacity as compared to monotherapy and even reached similar efficacy as erlotinib combined with RT. Treatment promotion of RT by 18β‐GA in HCC is not only through diminishing RT‐induced EGFR/ERK/NF‐κB signalling but also promoting RT‐induced apoptosis pathways. 18β‐GA may act as radiosensitizer through inactivating EGFR‐mediated HCC progression and inducing caspase‐dependent apoptosis signalling.
The role of sexual isolation during rapid ecological divergence: Evidence for a new dimension of isolation in Rhagoletis pomonella
Authors: Lackey Alycia C. R. , Murray Alyssa C. , Mirza Nadia A. , Powell Thomas H. Q.
Published: May 2023

The pace of divergence and likelihood of speciation often depends on how and when different types of reproductive barriers evolve. Questions remain about how reproductive isolation evolves after initial divergence. We tested for the presence of sexual isolation (reduced mating between populations due to divergent mating preferences and traits) in Rhagoletis pomonella flies, a model system for incipient ecological speciation. We measured the strength of sexual isolation between two very recently diverged (~170 generations) sympatric populations, adapted to different host fruits (hawthorn and apple). We found that flies from both populations were more likely to mate within than between populations. Thus, sexual isolation may play an important role in reducing gene flow allowed by early-acting ecological barriers. We also tested how warmer temperatures predicted under climate change could alter sexual isolation and found that sexual isolation was markedly asymmetric under warmer temperatures – apple males and hawthorn females mated randomly while apple females and hawthorn males mated more within populations than between. Our findings provide a window into the early speciation process and the role of sexual isolation after initial ecological divergence, in addition to examining how environmental conditions could shape the likelihood of further divergence.

Abstract

New evidence for sexual isolation between two recently diverged (~170 generations) sympatric populations of Rhagoletis pomonella flies adapted to different host fruits (hawthorn and apple). Our findings provide a window into the early speciation process and the role of sexual isolation after initial ecological divergence as well as the temperature sensitivity of sexual isolation.
Knodus borari, a new species from the lower Rio Tapajós basin (Characiformes: Characidae)
Authors: Silva‐Oliveira Cárlison , Colares Canto André L. , Ribeiro Frank Raynner V.
Published: May 2023

A new species of Knodus from the Rio Cupari, a right‐bank tributary of the lower Rio Tapajós, is described. Among its congeners, the new species shares exclusively with K. figueiredoi the presence of only uni‐tricuspid teeth in the premaxilla, maxilla and dentary. Knodus borari differs from K. figueiredoi by the colour pattern and morphological characteristics. The new species is the fifth species of the genus described from the Rio Tapajós basin, and the second restricted to the lower portion of the basin. This is additional evidence that the lower Rio Tapajós basin is a region of ichthyofaunal endemism.