bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1
Authors: Liu Chenhao , Gao Xiaoxin , Lou Jinhui , Li Haiyin , Chen Yuxuan , Chen Molong , Zhang Yuyao , Hu Zhilei , Chang Xian , Luo Menglin , Zhai Yu , Li Changqing
Published: July 2023

Background

Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD.

Methods

Rats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats.

Results

Lumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery.

Conclusions

Aberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD.
Sex- and age-specific effects on the development of addiction and compulsive-like drinking in rats
Authors: Foo Jerome C. , Skorodumov Ivan , Spanagel Rainer , Meinhardt Marcus W.
Published: July 2023

Background

Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction and preclinical and clinical evidence suggests that sex is an important factor influencing disease dynamics in alcohol dependence. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans. Lifetime monitoring in rodents can be conducted under highly controlled conditions, during which one can systematically introduce multiple biological and environmental factors that impact behaviors of interest.

Methods

Here, we used the alcohol deprivation effect (ADE) rat model of alcohol addiction in a computerized drinkometer system, acquiring high-resolution data to study changes over the course of addictive behavior as well as compulsive-like drinking in cohorts of adolescent vs. adult as well as male vs. female rats.

Results

Female rats drank more alcohol than male rats during the whole experiment, drinking much more weak alcohol (5%) and similar amounts of stronger alcohol solutions (10%, 20%); female rats also consumed more alcohol than male rats during quinine taste adulteration. Increased consumption in females compared to males was driven by larger access sizes of alcohol. Differences in circadian patterns of movement were observed between groups. Early age of onset of drinking (postnatal day 40) in male rats had surprisingly little impact on the development of drinking behavior and compulsivity (quinine taste adulteration) when compared to rats that started drinking during early adulthood (postnatal day 72).

Conclusions

Our results suggest that there are sex-specific drinking patterns, not only in terms of total amount consumed, but specifically in terms of solution preference and access size. These findings provide a better understanding of sex and age factors involved in the development of drinking behavior, and can inform the preclinical development of models of addiction, drug development and exploration of options for new treatments.
RETRACTED ARTICLE: A novel energy-efficient scheduling method for three-dimensional heterogeneous wireless sensor networks based on improved memetic algorithm and node cooperation strategy
Authors: Gou Pingzhang , Guo Baoyong , Guo Miao
Published: July 2023

Nodes in performance heterogeneous wireless sensor networks (HWSNs) often have varying levels of available energy, storage space, and processing power due to the network’s limited resources. Additionally, coverage redundancy and channel conflicts may adversely influence the quality of service in a network when many nodes have been deployed at once. Energy as a major constrained resource requires an effective energy-efficient scheduling mechanism to balance node energy consumption to extend the network lifespan. Therefore, this research proposes an energy-efficient scheduling technique, IMA–NCS-3D for three-dimensional HWSNs on the basis of an improved memetic algorithm and node cooperation strategy. A multi-objective fitness function is created to encode the active and inactive states of nodes as genes, and the optimal scheduling set of the network is built via selection, crossover, variation, and local search. This phase of the process is known as node scheduling. Node-to-node cooperation solutions are offered during data transmission to deal with unforeseen traffic abnormalities and reduce congestion and channel conflicts when traffic volumes are high. Simulation results show that IMA–NCS-3D has superior scheduling capability, cross-network load balancing capability, and a longer network lifespan than other current coverage optimization approaches.
The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation
Authors: Wu Tingting , Wu Shuyi , Li Li , Xiang Jing , Wang Na , Chen Wenjun , Zhang Jinhua
Published: July 2023

Background

The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients.

Patients and methods

This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications.

Results

A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci.

Conclusion

This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.
Prevalence of probable eating disorders and associated risk factors in children and adolescents aged 5–16 years in Al Ain City, United Arab Emirates: observational case–control study
Authors: Al Mestaka Naji , Alneyadi Amna , AlAhbabi Ali , AlMatrushi Abdulla , AlSaadi Rehab , Alketbi Latifa Baynouna
Published: July 2023

Background

Eating disorders, including anorexia, bulimia, and binge eating, have become a significant health concern among young children and adolescents worldwide. The objective of this study is to examine the probable eating disorder prevalence and associated risk factors among obese and normal-weight children and adolescents aged (5–16 years) in Al Ain, United Arab Emirates (UAE).

Methods

This observational case–control study utilized data obtained from electronic medical records (age, gender, body measurements). SCOFF questionnaire and Patient Health Questionnaire-2 (PHQ-2) were used to estimate the probable prevalence of eating disorders and depression, respectively, in children and adolescents. The study was conducted in Al Ain Ambulatory health services clinics from 2018 to 2019. Descriptive statistics and linear regression analysis were employed for data analysis.

Results

A total of 551 subjects participated in the study, with 288 (52%) categorized as normal-weight and 263 (48%) as obese. Among the obese participants, there was an equal distribution of males and females. Screening for eating disorders using the SCOFF questionnaire revealed that approximately 42% of the obese participants had a positive SCOFF result, indicating abnormal eating behaviors. In contrast, only 7% of the normal-weight participants had a positive SCOFF result. A significant positive correlation was observed between a positive SCOFF screening result, PHQ-2 score, and the participants' weight at the age of 6 years.

Conclusion

This study represents the first attempt to assess the probable prevalence of the risk of eating disorders in children and adolescents in the UAE. This young population have high risk of eating disorders and it was significantly higher in obese children than normal weight children. These results highlight the importance of addressing eating disorders in this population and the need for early detection and intervention strategies.
Genetic diversity and resilience in benthic marine populations
Authors: Vásquez Cynthia , Quiñones Renato A. , Brante Antonio , Hernández-Miranda Eduardo
Published: July 2023

Background

Understanding the mechanisms behind resilience has become more relevant in the last decades, due to the increasing and intensifying disturbances from natural and anthropogenic sources that threaten biodiversity. Evidence from terrestrial populations suggests that resilience increases with genetic diversity. Few studies, however, have evaluated the relationship between genetics and resilience in benthic marine populations.

Methods and results

For this review, we gathered studies where genetic diversity was the predictor variable, and resilience was the response variable. Twenty-five publications between 2001 and 2018 were included. Thirteen benthic marine species were identified, mainly sea-grass species, among which Zostera marina was the most frequently studied. The relationship between genetic diversity and resilience was variable-dependent. Considering all the analyses (N = 150) in the studies reviewed, 44% reported positive relationships between genetic diversity and resilience capacity. Negative relationships were found in 6%, and no relationship was found in 50%. Positive relationships indicated that genetic diversity increased resistance and recovery capacity after different types of disturbances. Dominance and complementarity were suggested as the underlying mechanism explaining these findings in the few studies that conducted this type of evaluation.

Conclusions

The results of this review suggest that the relationship between genetic diversity and resilience is mainly positive. However, this relationship relies on how genetic diversity and resiliency were measured, as well as on the biological characteristics of the species under study. This reinforces the importance of acknowledging and maintaining genetic diversity for the conservation of benthic populations in marine ecosystems.
Cardiovascular toxicities after anthracycline and VEGF-targeted therapies in adolescent and young adult cancer survivors
Authors: Wong-Siegel Jeannette R. , Hayashi Robert J. , Foraker Randi , Mitchell Joshua D.
Published: July 2023

Background

Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood.

Objective

This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following initiation of anthracycline and/or VEGF inhibitor therapy.

Methods

Data were extracted from electronic medical records over a fourteen-year period at a single institution. Cox proportional hazards regression modeling was used to examine risk factors for CT within each treatment group. Cumulative incidence was calculated with death as a competing risk.

Results

Of the 1,165 AYA cancer survivors examined, 32%, 22%, and 34% of patients treated with anthracycline, VEGF inhibitor, or both, developed CT. Hypertension was the most common outcome reported. Males were at increased risk for CT following anthracycline therapy (HR: 1.34, 95% CI 1.04–1.73). The cumulative incidence of CT was highest in patients who received both anthracycline and VEGF inhibitor (50% at ten years of follow up).

Conclusions

CT was common among AYA cancer survivors who received anthracycline and/or VEGF inhibitor therapy. Male sex was an independent risk factor for CT following anthracycline treatment. Further screening and surveillance are warranted to continue understanding the burden of CVD following VEGF inhibitor therapy.
DB-DCAFN: dual-branch deformable cross-attention fusion network for bacterial segmentation
Authors: Wang Jingkun , Ma Xinyu , Cao Long , Leng Yilin , Li Zeyi , Cheng Zihan , Cao Yuzhu , Huang Xiaoping , Zheng Jian
Published: July 2023

Sputum smear tests are critical for the diagnosis of respiratory diseases. Automatic segmentation of bacteria from sputum smear images is important for improving diagnostic efficiency. However, this remains a challenging task owing to the high interclass similarity among different categories of bacteria and the low contrast of the bacterial edges. To explore more levels of global pattern features to promote the distinguishing ability of bacterial categories and maintain sufficient local fine-grained features to ensure accurate localization of ambiguous bacteria simultaneously, we propose a novel dual-branch deformable cross-attention fusion network (DB-DCAFN) for accurate bacterial segmentation. Specifically, we first designed a dual-branch encoder consisting of multiple convolution and transformer blocks in parallel to simultaneously extract multilevel local and global features. We then designed a sparse and deformable cross-attention module to capture the semantic dependencies between local and global features, which can bridge the semantic gap and fuse features effectively. Furthermore, we designed a feature assignment fusion module to enhance meaningful features using an adaptive feature weighting strategy to obtain more accurate segmentation. We conducted extensive experiments to evaluate the effectiveness of DB-DCAFN on a clinical dataset comprising three bacterial categories: Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The experimental results demonstrate that the proposed DB-DCAFN outperforms other state-of-the-art methods and is effective at segmenting bacteria from sputum smear images.
Investigation of HER2 I655V and PHB 3′UTR C > T polymorphisms in azoospermic infertile males
Authors: Yildiz Irem , Karakus Nevin , Erdemir Fikret
Published: July 2023

Background

Male infertility is a complex, multifactorial pathological condition with a highly heterogeneous phenotypic variation, from complete absence of spermatozoa in the testicles (azoospermia) to marked changes in sperm quality. The Erb-B2 receptor tyrosine kinase 2 gene (ERBB2, also often called HER2) was hypothesized to be involved in spermatogenesis and Leydig cell steroidogenesis in males. Prohibitin (PHB) has been shown to regulate sperm motility in infertile men by changing mitochondrial membrane potential and increasing reactive oxygen species levels. In this study, we aimed to investigate the HER2 I655V and PHB 3′UTR C > T polymorphisms in azoospermic infertile males.

Methods

One hundred and thirty-three infertile males with idiopathic azoospermia and 100 healthy male controls were included in this study. Patient and control DNAs, which were extracted from peripheral blood, were analyzed using polymerase chain reaction and restriction fragment length polymorphism technics. For statistical evaluation, Chi-square and variance analyses were carried out using IBM SPSS (version 20.0) and Openepi (version 3.01) software programs.

Results

We did not observe any differences between azoospermic infertile males and healthy male controls in terms of allele and genotype distributions of both the HER2 I655V and PHB 3′UTR C > T polymorphisms (p > 0.05). Moreover, composite genotype analyses did not show any differences between two groups (p > 0.05).

Conclusions

No association was found between HER2 I655V and PHB 3′UTR C > T polymorphisms and azoospermic male infertility. The study can be expanded further by increasing the number of samples and studying in various populations.
A case report of Y-shaped bi-directional Fontan procedure: promising long-term outcomes for single ventricle physiology patients
Authors: Agarwal Abhimanyu , Cribbs Marc , Ahmed Asmaa Naguib , Abozeed Mostafa
Published: July 2023

Background

Achieving optimal hepatic factor distribution and total cavopulmonary resistance is crucial for long-term outcomes in single ventricle palliation patients. Y-shaped Gore-Tex Fontan procedure redirects hepatic drainage to both the right and left pulmonary arteries. The aim of this approach is to achieve bilateral pulmonary distribution of hepatic factors and reduce the risk of arteriovenous malformations that can develop in single-ventricle patients.

Case presentation

We present a unique case of a 20 years old female with symptoms of heart failure, who has a history of complex heterotaxy with polysplenia, interrupted Inferior vena-cava, and double outlet right ventricle with unbalanced atrio-ventricular septal defect, d-malposed great arteries, and pulmonary atresia. Fenestrated Y-shaped Gore-Tex Fontan procedure was successfully done which was confirmed by performing cardiac CT angiography.

Conclusions

Studies have shown that achieving balanced hepatic factor distribution and low resistance in the Fontan pathway can improve long-term outcomes. This procedure has demonstrated positive results in terms of oxygen saturation and reduced asymmetric blood flow distribution.

Level of Evidence

Level 4, Case Report.
Autistic Traits Among Adolescents and Young Adults Under Assessment for Psychiatric Conditions: An Experimental Analysis of Prevalence
Authors: İnci Sanem , Nisticò Veronica , Folatti Irene , Santangelo Giulia , Sanguineti Claudio , Faggioli Raffaella , Bertani Angelo , Gambini Orsola , Demartini Benedetta
Published: July 2023

Aims

Autism spectrum disorders have recently encountered a change in how they are perceived, since what used to be a narrowly defined rare disorder of childhood is now recognized as a fairly common heterogeneous disorder, which may receive a first-diagnosis during adolescence and adulthood, yet, a common scenario within this age group is that either the diagnosis is missed or misdiagnosed with other psychiatric disorders. Nevertheless, relatively little has been published about the prevalence of autistic traits in adolescent and young adults, and specifically in those investigated for psychiatric conditions.In the present study, we explore the prevalence of autistic traits among 170 adolescents and young adults who were referred to the outpatient psychiatry clinic “Centro Giovani Ponti” in Milan, Italy between September 2021 and March 2022.

Methods

Socio-demographic information was collected and all participants completed the following questionnaires; (1) The Autism Quotient (AQ), (2) The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R), (3) The Sensory Perception Quotient (SPQ) and (4) The Empathy Quotient (EQ).

Results

Out of 170 participants, a striking 103 (60.6%) of the subjects scored above the cut-off in RAADS-R, and 31 (18.2%) of the subjects scored above the cut-off in AQ. Furthermore, 99 (58.2%) participants were in the medium range and 47 (27.6%) were in the low empathy category according to EQ results. A significant sensory sensitivity was measured with an SPQ total score of 55.25 (SD = 17.76). Finally, gender difference was of significance in the RAADS-R, EQ and SPQ, but not in the AQ. In the RAADS-R, non-binary subjects (128.60) scored higher than females (78.68). Whereas, in the SPQ female (57.39) participants scored higher than non-binary subjects (40.30). Furthermore, females scored significantly higher compared to males in the EQ total score with values of 42.56 and 35.89, respectively.

Conclusion

To conclude, we report that a significant proportion of adolescents and young adults seeking psychiatric care have unrecognized autistic traits and that an impact of gender is observed. This so called ‘lost generation’ is attributed to be created by the complex phenotypic presentations, changes in diagnostic criteria and associated diagnostic difficulties. It is of utmost importance to clarify the prevalence of autistic traits within this age range and to increase awareness among clinicians, since establishing the true diagnosis, which is commonly complicated by the high rates of psychiatric comorbidity or overlapping mental health symptoms, will reduce the burden on patients, their families, clinicians, and the society.
Factors Affecting Compliance for Patients Post First Episode Psychosis
Authors: Mehta Meet , Hocaoglu Mevhibe
Published: July 2023

Aims

Psychosis is a symptom of various health disorders characterised by hallucinations and delusions. Medication and appointment compliance amongst sufferers of psychosis remains a major issue. The aim of this study is to explore factors affecting compliance to inform interventions for improving service quality.

Methods

A rapid systematic review was conducted on PubMed. Following screening, these papers were extracted and assessed using the hawker tool. 161 papers were identified with a search criterion and 33 were screened after removing non- English records, paid articles and pre-2015 papers. Abstracts of 33 papers were screened and 9 studies were looked at in detail.

Results

33 papers were identified after establishing a search criterion, from this 9 progressed to the inclusion stage. After using the Hawker tool, the quality of the papers averaged 32.8/36 and several significant factors were identified. The most significant factors that affect compliance are: insight, type of treatment, early signs of psychosis, ethnicity, income and qualitative factors.

Conclusion

Various measures can be suggested to help improve medication and appointment adherence for service users. Improving insight through targeted-informative leaflets on medication available at first contact with the Psychiatrist or GP. More frequent medication reviews for select patient groups identified with a higher risk of non-adherence. Greater income assistance through food and travel vouchers or information on how funding can be accessed. Lastly, staff training on increasing insight for psychosis patients delivered through a 1-day course/e-learning module.
Probiotics as Adjunctive Treatment in Major Depressive Disorder: Estimates of Treatment Effect and Underlying Mechanisms From a Double-Blind Placebo-Controlled Randomised Pilot Trial
Authors: Nikolova Viktoriya , Cleare Anthony , Young Allan , Stone James
Published: July 2023

Aims

Despite considerable preclinical evidence, clinical trials assessing the effects of probiotics on individuals with major depressive disorder (MDD) are scarce. This study aimed to provide further evidence of the acceptability, tolerability and putative efficacy of probiotics in this patient group and to improve our understanding of the underlying mechanisms of action.

Methods

This double-blind randomised placebo-controlled pilot and mechanistic trial investigated the effects of an 8-week adjunctive multi-strain probiotic intervention in adults with MDD taking antidepressants. Psychiatric data and stool and blood samples were collected at baseline, week 4 and week 8. A computer-based emotion recognition task was also administered. Stool samples from 25 matched healthy controls were also obtained.

Results

49 participants, randomised to probiotic (n = 24) or placebo (n = 25), were included in intent-to-treat analyses. Standardised effect sizes (SES) from linear mixed models demonstrated that the probiotic group attained greater improvements in depressive (HAMD week 4: SES [95%CI] = 0.70[0.01, 0.98]; IDS week 8: SES [95%CI] = 0.64 [0.03, 0.87]) and anxiety symptoms (HAMA week 4: SES [95%CI] = 0.67 [0.00, 0.95]; week 8: SES [95%CI] = 0.79 [0.06, 1.05]), compared to the placebo group. Attrition was 8% (n = 3 placebo, n = 1 probiotic), adherence was 97.2% and there were no serious adverse reactions. The probiotic modified the composition of the faecal microbiota by normalising richness and diversity towards healthy control levels. The probiotic also increased levels of specific taxa, including Bacillaceae (FDR p < 0.05), which correlated with reductions in anxiety scores (FDR p < 0.05). There was no impact of treatment on levels of inflammatory cytokines (CRP, TNFα, IL-1β, IL-6, IL-17) or BDNF. However, probiotics showed a tendency to increase positive affective bias and improved the accuracy of recognition of all emotions, except sadness.

Conclusion

Compared to placebo, the probiotic group had greater improvement in depressive and anxiety scores, from as early as 4 weeks. The acceptability, tolerability and estimated effect sizes on key clinical outcomes are promising and encourage further investigation of this probiotic as add-on treatment in MDD. The beneficial effects of probiotics in this patient group may be partially mediated by modification of the composition of the gut microbiota and improvement of affective biases, inherent to depressive disorders.
The Advancing Mental Health Equality Collaborative: Using Quality Improvement to Advance Equality in Mental Health Care
Authors: de Bono Adele , Milarski Matt , Souza Renata , Akhtar Saiqa , Bevan Rosana , Cannon Emily , Ayers Tom , Aya Viviana , Arundell Laura-Louise , Farmer Mark , Burgess Meera , Smith Lade , Mohan Rajesh , Shah Amar
Published: July 2023

Aims

The Advancing Mental Health Equality Collaborative is an innovative 3-year quality improvement programme led by the Royal College of Psychiatrists’ National Collaborating Centre for Mental Health (NCCMH). The collaborative was launched in July 2021 and involves 18 organisations across the UK who, with quality improvement support from the NCCMH, are working to understand the needs of their population and identify communities at risk of experiencing inequality to improve access, experience and outcomes of mental health care, support, and treatment for those populations.

Methods

An overarching driver diagram for the Collaborative was developed in collaboration with a wide range of stakeholders through steering group meetings, design workshops and remote consultation. This overarching driver diagram informs the development of population-specific driver diagrams, based on the population segments organisations selected to focus on. Each organisation was allocated an experienced quality improvement coach who supports them to apply a quality improvement approach to plan and deliver their projects, including support to generate insights based on data, staff and community engagement, carry out assets mapping, develop the project's aim and key drivers organisations need to work towards, identify measures, generate change ideas to be tested, and sustain successful changes.

Members of organisations taking part also attend quarterly learning sets where they come together to network, share challenges and ideas, and learn from each other.

Results

Populations identified by organisations include children and young people; Black, Asian and Ethnic minority men aged 18+ years; carer population; neurodivergent individuals with comorbid mental health diagnoses; Muslim women/Black women; refugees and forced migrants; women military veterans in Greater Manchester and Lancashire; Bangladeshi and Pakistani men and women in Oldham; Traveller community in Somerset. A number of initiatives are being tested by teams to improve access, experience and outcomes of mental health care, support, and treatment for these populations, such as offering mental health awareness sessions for refugees in a range of languages.

Conclusion

Addressing inequality in mental health care is a long and complex process. The AMHE collaborative is supporting teams to take an innovative approach to tackle this issue, by ensuring their projects are fully co-produced with those affected by inequality. This includes engaging representatives from the communities they are trying to improve access, experience and outcomes for in all aspects of their quality improvement projects; from design to generating ideas to test, and ensuring they measure what is important to these communities to determine whether improvements have been made.
International Tuberculum Sellae Meningioma Study: Preoperative Grading Scale to Predict Outcomes and Propensity-Matched Outcomes by Endonasal Versus Transcranial Approach
Authors: Magill Stephen T. , Schwartz Theodore H. , Couldwell William T. , Gardner Paul A. , Heilman Carl B. , Sen Chandranath , Akagami Ryojo , Cappabianca Paolo , Prevedello Daniel M. , McDermott Michael W.
Published: July 2023

BACKGROUND AND OBJECTIVES:

Tuberculum sellae meningiomas are resected via an expanded endonasal (EEA) or transcranial approach (TCA). Which approach provides superior outcomes is debated. The Magill–McDermott (M-M) grading scale evaluating tumor size, optic canal invasion, and arterial involvement remains to be validated for outcome prediction. The objective of this study was to validate the M-M scale for predicting visual outcome, extent of resection (EOR), and recurrence, and to use propensity matching by M-M scale to determine whether visual outcome, EOR, or recurrence differ between EEA and TCA.

METHODS:

Forty-site retrospective study of 947 patients undergoing tuberculum sellae meningiomas resection. Standard statistical methods and propensity matching were used.

RESULTS:

The M-M scale predicted visual worsening (odds ratio [OR]/point: 1.22, 95% CI: 1.02-1.46, P = .0271) and gross total resection (GTR) (OR/point: 0.71, 95% CI: 0.62-0.81, P < .0001), but not recurrence (P = .4695). The scale was simplified and validated in an independent cohort for predicting visual worsening (OR/point: 2.34, 95% CI: 1.33-4.14, P = .0032) and GTR (OR/point: 0.73, 95% CI: 0.57-0.93, P = .0127), but not recurrence (P = .2572). In propensity-matched samples, there was no difference in visual worsening (P = .8757) or recurrence (P = .5678) between TCA and EEA, but GTR was more likely with TCA (OR: 1.49, 95% CI: 1.02-2.18, P = .0409). Matched patients with preoperative visual deficits who had an EEA were more likely to have visual improvement than those undergoing TCA (72.9% vs 58.4%, P = .0010) with equal rates of visual worsening (EEA 8.0% vs TCA 8.6%, P = .8018).

CONCLUSION:

The refined M-M scale predicts visual worsening and EOR preoperatively. Preoperative visual deficits are more likely to improve after EEA; however, individual tumor features must be considered during nuanced approach selection by experienced neurosurgeons.
Attenuated cerebellar phenotypes in Inpp4a truncation mutants with preserved phosphatase activity
Authors: Tran Dang Minh , Yoshioka Nozomu , Bizen Norihisa , Mori-Ochiai Yukiko , Yano Masato , Yanai Shogo , Hasegawa Junya , Miyashita Satoshi , Hoshino Mikio , Sasaki Junko , Sasaki Takehiko , Takebayashi Hirohide
Published: July 2023

Phosphoinositides (PIPs) act as intracellular signaling molecules that regulate various cellular processes. Abnormalities in PIP metabolism cause various pathological conditions, including neurodegenerative diseases, cancer and immune disorders. Several neurological diseases with diverse phenotypes, such as ataxia with cerebellar atrophy or intellectual disability without brain malformation, are caused by mutations in INPP4A, which encodes a phosphoinositide phosphatase. We examined two strains of Inpp4a mutant mice with distinct cerebellar phenotypes: the Inpp4aΔEx1,2 mutant exhibited striatal degeneration without cerebellar atrophy, and the Inpp4aΔEx23 mutant exhibited a severe striatal phenotype with cerebellar atrophy. Both strains exhibited reduced expression of Inpp4a mutant proteins in the cerebellum. N-terminal-truncated Inpp4a proteins were expressed from the Inpp4aΔEx1,2 allele by alternative translation initiation and had phosphatase activity for PI(3,4)P2, whereas the Inpp4a mutant protein encoded by Inpp4aΔEx23 completely lacked phosphatase activity. Our results indicate that the diverse phenotypes observed in Inpp4a-related neurological diseases could be due to the varying protein expression levels and retained phosphatase activity in different Inpp4a variants. These findings provide insights into the role of INPP4A mutations in disease pathogenesis and may help to develop personalized therapy.
Membrane insertases at a glance
Authors: Kizmaz Büsra , Herrmann Johannes M.
Published: July 2023

Protein translocases, such as the bacterial SecY complex, the Sec61 complex of the endoplasmic reticulum (ER) and the mitochondrial translocases, facilitate the transport of proteins across membranes. In addition, they catalyze the insertion of integral membrane proteins into the lipid bilayer. Several membrane insertases cooperate with these translocases, thereby promoting the topogenesis, folding and assembly of membrane proteins. Oxa1 and BamA family members serve as core components in the two major classes of membrane insertases. They facilitate the integration of proteins with α-helical transmembrane domains and of β-barrel proteins into lipid bilayers, respectively. Members of the Oxa1 family were initially found in the internal membranes of bacteria, mitochondria and chloroplasts. Recent studies, however, also identified several Oxa1-type insertases in the ER, where they serve as catalytically active core subunits in the ER membrane protein complex (EMC), the guided entry of tail-anchored (GET) and the GET- and EMC-like (GEL) complex. The outer membrane of bacteria, mitochondria and chloroplasts contain β-barrel proteins, which are inserted by members of the BamA family. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of these different types of membrane insertases and discuss their function.
Spectral sensitivity of retinal photoreceptors of tortricid moths is not tuned to diel activity period
Authors: Martín-Gabarrella Alejandro , Gemeno César , Belušič Gregor
Published: July 2023

Leafrollers (Lepidoptera: Tortricidae) are a large family of small moths containing over 10,000 species, many of which are crop pests. Grapholita molesta, Lobesia botrana and Cydia pomonella adults are sexually active before, during and after sunset, respectively. We wanted to determine whether being active at different times of the day and night is associated with differences in their visual system. Spectral sensitivity (SS) was measured with electroretinograms and selective adaptation with green, blue and ultraviolet light. SS curves could be fitted with a triple nomogram template which indicated the existence of three photoreceptor classes peaking at 355, 440 and 525 nm. The retinae showed clear regionalization, with fewer blue receptors dorsally. No differences among species or between sexes were found. Intracellular recordings in C. pomonella also revealed three photoreceptor classes with sensitivities peaking at 355, 440 and 525 nm. The blue photoreceptors showed inhibitory responses in the green part of the spectrum, indicating the presence of a colour-opponent system. Flicker fusion frequency experiments showed that the response speed was similar between sexes and species and fused at around 100 Hz. Our results indicate that the three species have the ancestral insect retinal substrate for a trichromatic colour vision, based upon the UV, blue and green-sensitive photoreceptors, and lack any prominent adaptations related to being active under different light conditions.
Vitamin C Supplementation and Athletic Performance: A Review
Authors: Rogers Dylan R. , Lawlor Denis J. , Moeller James L.
Published: July 2023

Many athletes utilize high-dose vitamin C supplementation to optimize athletic performance. A review of research over the past 10 years on the use of vitamin C and athletic performance show mixed results. Fourteen randomized control trials were reviewed. In most studies, vitamin C was used with at least one additional supplement, usually vitamin E. Three studies showed positive outcomes associated with decreased markers of muscle damage after intense exercise with some form of vitamin C supplementation. The remaining 11 articles showed either neutral or negative effects of high dose vitamin C supplementation on muscle damage, physical performance, perceived muscle soreness, and/or adaptations to training. Based on a lack of consistent data and potential for blunted physiologic adaptations to training, long-term high-dosage supplementation with vitamin C is not recommended. Athletes should obtain antioxidants through a nutrient-rich diet instead of through supplement use.
MTaxi: A comparative tool for taxon identification of ultra low coverage ancient genomes
Authors: Atağ Gözde , Vural Kıvılcım Başak , Kaptan Damla , Özkan Mustafa , Koptekin Dilek , Sağlıcan Ekin , Doğramacı Sevcan , Köz Mevlüt , Yılmaz Ardan , Söylev Arda , Togan İnci , Somel Mehmet , Özer Füsun
Published: July 2023

A major challenge in zooarchaeology is to morphologically distinguish closely related species’ remains, especially using small bone fragments. Shotgun sequencing aDNA from archeological remains and comparative alignment to the candidate species’ reference genomes will only apply when reference nuclear genomes of comparable quality are available, and may still fail when coverages are low. Here, we propose an alternative method, MTaxi, that uses highly accessible mitochondrial DNA (mtDNA) to distinguish between pairs of closely related species from ancient DNA sequences. MTaxi utilises mtDNA transversion-type substitutions between pairs of candidate species, assigns reads to either species, and performs a binomial test to determine the sample taxon. We tested MTaxi on sheep/goat and horse/donkey data, between which zooarchaeological classification can be challenging in ways that epitomise our case. The method performed efficiently on simulated ancient genomes down to 0.3x mitochondrial coverage for both sheep/goat and horse/donkey, with no false positives. Trials on n=18 ancient sheep/goat samples and n=10 horse/donkey samples of known species identity also yielded 100% accuracy. Overall, MTaxi provides a straightforward approach to classify closely related species that are difficult to distinguish through zooarchaeological methods using low coverage aDNA data, especially when similar quality reference genomes are unavailable. MTaxi is freely available at https://github.com/goztag/MTaxi.
Association between living with children, vaccination, and outcomes from COVID-19: an OpenSAFELY cohort study of 12 million adults in England during 2021–22
Authors: Cowling Thomas E , Forbes Harriet , Wing Kevin , Tazare John , Schultze Anna , Morton Caroline E , Bacon Sebastian , MacKenna Brian , Walker Alex J. , Hulme Will , Bates Chris , Mehrkar Amir , Curtis Helen J. , Evans David , Inglesby Peter , Davy Simon , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , Douglas Ian J , Evans Stephen J W , Bhaskaran Krishnan , Williamson Elizabeth J , Eggo Rosalind M , Goldacre Ben , Tomlinson Laurie A
Published: July 2023

Background: Living with children has been associated with greater risks of SARS-CoV-2 infection, COVID-19 hospitalisation, and COVID-19 death. We examined how these associations varied during 2021–22 and according to the COVID-19 vaccination status of adults.

Methods: We carried out a population-based cohort study, with the approval of NHS England. Primary care data and pseudonymously-linked hospital and death records from England, between 20th December 2020 and 21st February 2022, were used for adults (≥18 years) registered at a general practice on 20th December 2020. Adjusted hazard ratios (HRs) for SARS-CoV-2 infection, COVID-19 hospitalisation, or COVID-19 death, by presence of children in the household were calculated.

Results: The cohort included 9,417,278 adults aged ≤65 years and 2,866,602 adults aged >65 years. Adults aged ≤65 years living with children of any age (versus no children) had greater risks of SARS-CoV-2 infection and COVID-19 hospitalisation (but not COVID-19 death), both when schools were open and closed (e.g. HR=1.50, 95% CI:1.49-1.51, for SARS-CoV-2 infection in the ‘Omicron dominant’ period, when schools were open, in adults living with children aged 0–11 years only). These associations also existed for adults aged >65 years, and there was some evidence that adults living with children also had greater risks of COVID-19 death. Vaccinated adults living with children had greater risks of SARS-CoV-2 infection, but lower risks of COVID-19 hospitalisation and death, than unvaccinated adults not living with children.

Conclusions: In an era of widespread adult vaccination, adults living with children remained at increased risk of SARS-CoV-2 infection and COVID-19 hospitalisation.
The Avon Longitudinal Study of Parents and Children - a resource for COVID-19 research: questionnaire data capture July 2021 to December 2021, with a focus on long COVID
Authors: Northstone Kate , Suarez-Perez Almudena , Matthews Sarah , Crawford Michael , Timpson Nicholas
Published: July 2023

ALSPAC, the Avon Longitudinal Study of Parents and Children is a prospective population-based cohort study. Pregnant women were recruited in 1990-1992 and the study has followed them, their partners (Generation 0; G0) and their offspring (Generation 1; G1) for over 30 years. During the coronavirus 2019 (COVID-19) pandemic, ALSPAC deployed a series of online questionnaires to capture participant experiences during this unprecedented time. In July 2021, a fifth questionnaire was deployed which primarily focussed on the symptoms of long COVID, also known as post-COVID syndrome.

G0 and G1 participants were offered both online and paper questionnaires between 21st July 2021 and 11th December 2021. Of 21,138 invitations, 11,148 (52.8%) participants returned the questionnaire (4,763 original mothers [mean age 59.1 years], 2,074 original fathers/partners [mean age 62.0 years] and 4,311 offspring [mean age 29.0 years]). Of these 11,148 participants, 2835 (25.4%) had not completed any of the previous COVID-19 questionnaires, while 3480 (31.2%) had returned all four previous questionnaires.

In this questionnaire, 1077 participants (9.8%) reported a previous positive COVID-19 test over the course of the pandemic. Of these, 109 (1.0%) had received medical advice that they likely had COVID-19, and 838 (7.6%) suspected that they had had COVID-19. Almost a third of participants (n=796, 31.1%) reported possible long COVID (experiencing symptoms for at least 4 weeks), whilst 351 (13.7%) reported symptom duration of 12 weeks or more (post-COVID syndrome). G0 mothers were more likely to report a longer duration of symptoms compared to their partners and their children.

The fifth COVID-19 questionnaire deployed by ALSPAC and the data obtained from are described in this data note.
The Influence of Modern Trends in the Development of the Creative Economy on the Education System
Authors: Vakhorina Marina
Published: July 2023

The aim of the study is an integration approach in the implementation of current business risk management problems through a new management technology that is becoming increasingly in demand in Russian practice. Research objectives: the theoretical provisions of the unit economy composition are substantiated; the indicators for assessing the business at the stage of creation are determined; the influence of the unit economy as an integral part of the business model is disclosed in order to ensure the viability of client–oriented entrepreneurship.

Results and practical significance. The presented research reveals the theoretical foundations and reveals the specific features inherent in the unit-economy system. Determines the economic content of the indicators of the new management model and the relationship between them. Practical approaches to the use of unit economics in the conditions of economic crisis are illustrated and the connection of unit economics with the management accounting system is substantiated. The work uses general scientific methods, in particular, the method of systematization and critical evaluation, practical methods of generalization and system reasoning. The historical prerequisites for the emergence of the unit economy are determined. The methodological features of the unit-economy, which formalized it into an independent management technology, are revealed.

The results obtained reflect the scientific novelty: the provisions that explain the use of unit economics as an integral part of the business model in a crisis economy are substantiated and the procedures for further development of new management technology for the purpose of efficiency and stimulation of entrepreneurial activity are predicted.

The results of the study can be used as recommendations on business risk management in practical activities by entrepreneurs, as well as a theoretical basis for further research on this topic.