bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge
Authors: Wan Shuangshuang , You Peijun , Shi Qikai , Hu Hui , Zhang Lu , Chen Leyang , Wu Ziyi , Lin Shan , Song Xiaojun , Luo Yongneng , Wang Yaxuan , Ju Feng , Jin Dazhi , Chen Yu
Published: April 2024

Introduction

Clostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.

Methods

In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.

Results

The results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge.

Conclusion

Based on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.
An IL-17A-centric response to Epstein-Barr virus DNA mediated by dendritic Cell-T cell interactions
Authors: Shehab Marwa , Hussein Hadi , Fadlallah Sukayna , Rahal Elias A.
Published: April 2024

Introduction: The Epstein-Barr virus has been associated with a considerable number of autoimmune diseases. We have previously demonstrated that EBV DNA enhances the production of IL-17A, a pro-inflammatory cytokine, via endosomal Toll-like receptor signalling.

Methods: We used RNA-seq to analyze the transcriptional profile of mouse immune cells treated with EBV DNA.

Results: We observed that EBV DNA upregulates an IL-17A-centric network of mediators. Ensemble Gene Set Enrichment Analysis (EGSEA) showed enriched expression of sets involved in inflammatory responses including IFNγ and TNF-α-associated pathways as well as proinflammatory diseases. On the other hand, while macrophages and B cells were somewhat able to induce an IL-17A response from T cells to EBV DNA, they were less potent than dendritic cells. EBV virions were also capable of eliciting the production of inflammatory mediators from dendritic cell-T cell cultures largely mirroring responses to the viral DNA.

Conclusions: Given the wide prevalence of EBV in the population, our analyses reveal a network of mediators and cell types that may serve as therapeutic targets in a large proportion of people affected by autoimmune diseases.
A novel speech analysis algorithm to detect cognitive impairment in a Spanish population
Authors: Kaser Alyssa N. , Lacritz Laura H. , Winiarski Holly R. , Gabirondo Peru , Schaffert Jeff , Coca Alberto J. , Jiménez-Raboso Javier , Rojo Tomas , Zaldua Carla , Honorato Iker , Gallego Dario , Nieves Emmanuel Rosario , Rosenstein Leslie D. , Cullum C. Munro
Published: April 2024

Objective

Early detection of cognitive impairment in the elderly is crucial for diagnosis and appropriate care. Brief, cost-effective cognitive screening instruments are needed to help identify individuals who require further evaluation. This study presents preliminary data on a new screening technology using automated voice recording analysis software in a Spanish population.

Method

Data were collected from 174 Spanish-speaking individuals clinically diagnosed as cognitively normal (CN, n = 87) or impaired (mild cognitive impairment [MCI], n = 63; all-cause dementia, n = 24). Participants were recorded performing four common language tasks (Animal fluency, alternating fluency [sports and fruits], phonemic “F” fluency, and Cookie Theft Description). Recordings were processed via text-transcription and digital-signal processing techniques to capture neuropsychological variables and audio characteristics. A training sample of 122 subjects with similar demographics across groups was used to develop an algorithm to detect cognitive impairment. Speech and task features were used to develop five independent machine learning (ML) models to compute scores between 0 and 1, and a final algorithm was constructed using repeated cross-validation. A socio-demographically balanced subset of 52 participants was used to test the algorithm. Analysis of covariance (ANCOVA), covarying for demographic characteristics, was used to predict logistically-transformed algorithm scores.

Results

Mean logit algorithm scores were significantly different across groups in the testing sample (p < 0.01). Comparisons of CN with impaired (MCI + dementia) and MCI groups using the final algorithm resulted in an AUC of 0.93/0.90, with overall accuracy of 88.4%/87.5%, sensitivity of 87.5/83.3, and specificity of 89.2/89.2, respectively.

Conclusion

Findings provide initial support for the utility of this automated speech analysis algorithm as a screening tool for cognitive impairment in Spanish speakers. Additional study is needed to validate this technology in larger and more diverse clinical populations.
Episodic memory assessment: effects of sex and age on performance and response time during a continuous recognition task
Authors: Clifford James O. , Anand Sulekha , Tarpin-Bernard Franck , Bergeron Michael F. , Ashford Curtis B. , Bayley Peter J. , Ashford John Wesson
Published: April 2024

Introduction

Continuous recognition tasks (CRTs) assess episodic memory (EM), the central functional disturbance in Alzheimer’s disease and several related disorders. The online MemTrax computerized CRT provides a platform for screening and assessment that is engaging and can be repeated frequently. MemTrax presents complex visual stimuli, which require complex involvement of the lateral and medial temporal lobes and can be completed in less than 2 min. Results include number of correct recognitions (HITs), recognition failures (MISSes = 1-HITs), correct rejections (CRs), false alarms (FAs = 1-CRs), total correct (TC = HITs + CRs), and response times (RTs) for each HIT and FA. Prior analyses of MemTrax CRT data show no effects of sex but an effect of age on performance. The number of HITs corresponds to faster RT-HITs more closely than TC, and CRs do not relate to RT-HITs. RT-HITs show a typical skewed distribution, and cumulative RT-HITs fit a negative survival curve (RevEx). Thus, this study aimed to define precisely the effects of sex and age on HITS, CRs, RT-HITs, and the dynamics of RTs in an engaged population.

Methods

MemTrax CRT online data on 18,255 individuals was analyzed for sex, age, and distributions of HITs, CRs, MISSes, FAs, TC, and relationships to both RT-HITs and RT-FAs.

Results

HITs corresponded more closely to RT-HITs than did TC because CRs did not relate to RT-HITs. RT-FAs had a broader distribution than RT-HITs and were faster than RT-HITs in about half of the sample, slower in the other half. Performance metrics for men and women were the same. HITs declined with age as RT-HITs increased. CRs also decreased with age and RT-FAs increased, but with no correlation. The group over aged 50 years had RT-HITs distributions slower than under 50 years. For both age ranges, the RevEx model explained more than 99% of the variance in RT-HITs.

Discussion

The dichotomy of HITs and CRs suggests opposing cognitive strategies: (1) less certainty about recognitions, in association with slower RT-HITs and lower HIT percentages suggests recognition difficulty, leading to more MISSes, and (2) decreased CRs (more FAs) but faster RTs to HITs and FAs, suggesting overly quick decisions leading to errors. MemTrax CRT performance provides an indication of EM (HITs and RT-HITs may relate to function of the temporal lobe), executive function (FAs may relate to function of the frontal lobe), processing speed (RTs), cognitive ability, and age-related changes. This CRT provides potential clinical screening utility for early Alzheimer’s disease and other conditions affecting EM, other cognitive functions, and more accurate impairment assessment to track changes over time.
Information-based rhythmic transcranial magnetic stimulation to accelerate learning during auditory working memory training: a proof-of-concept study
Authors: Whittaker Heather T. , Khayyat Lina , Fortier-Lavallée Jessica , Laverdière Megan , Bélanger Carole , Zatorre Robert J. , Albouy Philippe
Published: April 2024

Introduction

Rhythmic transcranial magnetic stimulation (rhTMS) has been shown to enhance auditory working memory manipulation, specifically by boosting theta oscillatory power in the dorsal auditory pathway during task performance. It remains unclear whether these enhancements (i) persist beyond the period of stimulation, (ii) if they can accelerate learning and (iii) if they would accumulate over several days of stimulation. In the present study, we investigated the lasting behavioral and electrophysiological effects of applying rhTMS over the left intraparietal sulcus (IPS) throughout the course of seven sessions of cognitive training on an auditory working memory task.

Methods

A limited sample of 14 neurologically healthy participants took part in the training protocol with an auditory working memory task while being stimulated with either theta (5 Hz) rhTMS or sham TMS. Electroencephalography (EEG) was recorded before, throughout five training sessions and after the end of training to assess to effects of rhTMS on behavioral performance and on oscillatory entrainment of the dorsal auditory network.

Results

We show that this combined approach enhances theta oscillatory activity within the fronto-parietal network and causes improvements in auditoryworking memory performance. We show that compared to individuals who received sham stimulation, cognitive training can be accelerated when combined with optimized rhTMS, and that task performance benefits can outlast the training period by ∼ 3 days. Furthermore, we show that there is increased theta oscillatory power within the recruited dorsal auditory network during training, and that sustained EEG changes can be observed ∼ 3 days following stimulation.

Discussion

The present study, while underpowered for definitive statistical analyses, serves to improve our understanding of the causal dynamic interactions supporting auditory working memory. Our results constitute an important proof of concept for the potential translational impact of non-invasive brain stimulation protocols and provide preliminary data for developing optimized rhTMS and training protocols that could be implemented in clinical populations.
High PD-L1 expression on immune cells along with increased density of tumor-infiltrating lymphocytes predicts a favorable survival outcome for patients with loco-regionally advanced head and neck cancer: early results from a prospective study
Authors: Blažek Tomáš , Petráš Marek , Hurník Pavel , Matoušek Petr , Knybel Lukáš , Čermáková Zuzana Zděblová , Štembírek Jan , Cvek Jakub , Soumarová Renata
Published: April 2024

Introduction

In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment.

Methods

To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression.

Results

Among a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates.

Discussion

The early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy.

Trial registration

The study is registered with Clinicaltrials.gov. – NCT05941676
Diverse and reprogrammable mechanisms of malignant cell transformation in lymphocytes: pathogenetic insights and translational implications
Authors: Wasik Mariusz A. , Kim Patricia M. , Nejati Reza
Published: April 2024

While normal B- and T-lymphocytes require antigenic ligands to become activated via their B- and T-cell receptors (BCR and TCR, respectively), B- and T-cell lymphomas show the broad spectrum of cell activation mechanisms regarding their dependence on BCR or TCR signaling, including loss of such dependence. These mechanisms are generally better understood and characterized for B-cell than for T-cell lymphomas. While some lymphomas, particularly the indolent, low-grade ones remain antigen-driven, other retain dependence on activation of their antigen receptors seemingly in an antigen-independent manner with activating mutations of the receptors playing a role. A large group of lymphomas, however, displays complete antigen receptor independence, which can develop gradually, in a stepwise manner or abruptly, through involvement of powerful oncogenes. Whereas some of the lymphomas undergo activating mutations of genes encoding proteins involved in signaling cascades downstream of the antigen-receptors, others employ activation mechanisms capable of substituting for these BCR- or TCR-dependent signaling pathways, including reliance on signaling pathways physiologically activated by cytokines. Finally, lymphomas can develop cell-lineage infidelity and in the extreme cases drastically rewire their cell activation mechanisms and engage receptors and signaling pathways physiologically active in hematopoietic stem cells or non-lymphoid cells. Such profound reprograming may involve partial cell dedifferentiation or transdifferentiation towards histocytes, dendritic, or mesodermal cells with various degree of cell maturation along these lineages. In this review, we elaborate on these diverse pathogenic mechanisms underlying cell plasticity and signaling reprogramming as well as discuss the related diagnostic and therapeutic implications and challenges.
Virtual reality–guided mindfulness for chronic pain in cancer survivors: protocol for the virtual mind study—a single-group feasibility trial
Authors: Baydoun Mohamad , Gajtani Zen , Patton Michaela , McLennan Andrew , Cartwright Stephen , Carlson Linda E.
Published: April 2024

Background

Chronic cancer-related pain (CRP) can have a significant negative impact on quality of life. Mindfulness is hypothesized to mitigate chronic CRP by regulating both physical and emotional resistance to pain. In recent years, there has been interest in the use of virtual reality (VR) to deliver mindfulness meditation. VR provides an immersive and engaging environment, which may enhance one's focused attention to present-moment experiences, potentially making mindfulness less effortful and more efficacious for individuals with chronic pain. There has been little research in this area for people with a history of cancer.

Objective

The aim of this mixed methods study is to evaluate the feasibility of a VR-guided mindfulness (VRGM) intervention offered to adult cancer survivors with chronic CRP.

Methods

This mixed methods feasibility study will employ a single-arm, pretest-posttest design with semistructured interviews. In total, 15 cancer survivors will be enrolled in a 6-week home-based intervention that consists of 10–15 min of daily VRGM practice. The primary outcome is feasibility as assessed by accrual rates, retention in the study, intervention adherence, questionnaire completion, and side effect rates. Participants will be assessed on psychosocial outcome measures (i.e., pain, sleep, depressive and anxiety symptoms, fatigue, quality of life, and mindfulness) before and after the intervention, and 6 weeks post intervention (follow-up). Changes in pain will be described in relation to levels of immersion and presence in the virtual environment, trait mindfulness, and amount of VRGM practice. Qualitative information will provide subjective detail on participants’ experience with VRGM to complement quantitative data. This study has been approved by the Health Research Ethics Board of Alberta Cancer Committee (HREBA.CC-20-0411).

Conclusions

This novel intervention provides a potential alternative treatment to pharmacological pain management. Results from this study may inform future larger VGRM trials for chronic CRP to help reduce suffering in people with cancer. Study findings will be disseminated through open access publications, traditional conference presentations, professional cancer organizations, and social media platforms.
Spatial distribution of zero-dose children in Ethiopia: evidence for a targeted intervention from a large-scale cross-sectional evaluation survey
Authors: Shiferie Fisseha , Gebremedhin Samson , Andargie Gashaw , DelPizzo Frank , Belete Kidist , Fenta Teferi Gedif
Published: April 2024

Background

Ethiopia is the fourth leading contributor to the global total of zero-dose children (those who lack the first dose of diphtheria-tetanus-pertussis containing vaccine) and has substantial regional variations in zero-dose children. This study explored the spatial pattern of zero-dose children aged 12–35 months in Ethiopia.

Methods

A survey was conducted in pastoralist regions, developing regions, newly-established regions, conflict-affected areas, underserved urban populations, hard-to-reach areas, internally displaced populations, and refugees. Spatial autocorrelation was measured using the Global Moran'sIstatistic. Getis-Ord Gi* statistics was applied to calculate the spatial variability of the high and low prevalence rates of zero-dose children. The spatial interpolation technique was also applied to estimate unknown values that fall between known values. Inverse distance weighting interpolation method was used to predict the risk of zero-dose children. ArcGIS version 10.8 was used for the spatial analysis.

Results

A total of 3,646 children aged 12–35 months were included in the study. The spatial distribution of zero-dose children in Ethiopia was non-random (Global Moran'sI = 0.178971, p < 0.001). According to the hotspot analysis, western, eastern and northern parts of Somali and western and central parts of Afar regions had the highest load of zero-dose children (hotspot areas) followed by the Northeastern part of Amhara and southeastern part of Oromia regions. On the other hand, Southern Nations, Nationalities, and Peoples, Sidama, and the Eastern part of the Southwest Ethiopia peoples regions were identified as cold spot areas. The spatial interpolation analysis corresponded with the hotspot analysis results where western and central parts of Afar and western, eastern and northern parts of Somali regions were identified as high-risk areas for zero-dose children. However, Addis Ababa, Dire Dawa, Harari, Southern Nations, Nationalities, and Peoples, Sidama, Southwest Ethiopia Peoples, and parts of Oromia were found to be low-risk areas for zero-dose children.

Conclusion

The spatial analysis identified that zero-dose children had a significant spatial variation across the study areas. High clusters of zero-dose children were detected in Afar and Somali regions. Implementing routine and mop-up vaccination campaigns in the identified hotspot areas will help Ethiopia to improve coverage and reduce immunization inequalities.
Pole balancing on the fingertip: model-motivated machine learning forecasting of falls
Authors: Debnath Minakshi , Chang Joshua , Bhandari Keshav , Nagy Dalma J. , Insperger Tamas , Milton John G. , Ngu Anne H. H.
Published: April 2024

Introduction: There is increasing interest in developing mathematical and computational models to forecast adverse events in physiological systems. Examples include falls, the onset of fatal cardiac arrhythmias, and adverse surgical outcomes. However, the dynamics of physiological systems are known to be exceedingly complex and perhaps even chaotic. Since no model can be perfect, it becomes important to understand how forecasting can be improved, especially when training data is limited. An adverse event that can be readily studied in the laboratory is the occurrence of stick falls when humans attempt to balance a stick on their fingertips. Over the last 20 years, this task has been extensively investigated experimentally, and presently detailed mathematical models are available.

Methods: Here we use a long short-term memory (LTSM) deep learning network to forecast stick falls. We train this model to forecast stick falls in three ways: 1) using only data generated by the mathematical model (synthetic data), 2) using only stick balancing recordings of stick falls measured using high-speed motion capture measurements (human data), and 3) using transfer learning which combines a model trained using synthetic data plus a small amount of human balancing data.

Results: We observe that the LTSM model is much more successful in forecasting a fall using synthetic data than it is in forecasting falls for models trained with limited available human data. However, with transfer learning, i.e., the LTSM model pre-trained with synthetic data and re-trained with a small amount of real human balancing data, the ability to forecast impending falls in human data is vastly improved. Indeed, it becomes possible to correctly forecast 60%–70% of real human stick falls up to 2.35 s in advance.

Conclusion: These observations support the use of model-generated data and transfer learning techniques to improve the ability of computational models to forecast adverse physiological events.
Morphological and molecular response mechanisms of the root system of different Hemarthria compressa species to submergence stress
Authors: Shen Bingna , Li Wenwen , Zheng Yuqian , Zhou Xiaoli , Zhang Yinuo , Qu Minghao , Wang Yinchen , Yuan Yang , Pang Kaiyue , Feng Yanlong , Wu Jiahai , Zeng Bing
Published: April 2024

Introduction

The severity of flood disasters is increasing due to climate change, resulting in a significant reduction in the yield and quality of forage crops worldwide. This poses a serious threat to the development of agriculture and livestock. Hemarthria compressa is an important high-quality forage grass in southern China. In recent years, frequent flooding has caused varying degrees of impacts on H. compressa and their ecological environment.

Methods

In this study, we evaluated differences in flooding tolerance between the root systems of the experimental materials GY (Guang Yi, flood-tolerant) and N1291 (N201801291, flood-sensitive). We measured their morphological indexes after 7 d, 14 d, and 21 d of submergence stress and sequenced their transcriptomes at 8 h and 24 h, with 0 h as the control.

Results

During submergence stress, the number of adventitious roots and root length of both GY and N1291 tended to increase, but the overall growth of GY was significantly higher than that of N1291. RNA-seq analysis revealed that 6046 and 7493 DEGs were identified in GY-8h and GY-24h, respectively, and 9198 and 4236 DEGs in N1291-8h and N1291-24h, respectively, compared with the control. The GO and KEGG enrichment analysis results indicated the GO terms mainly enriched among the DEGs were oxidation-reduction process, obsolete peroxidase reaction, and other antioxidant-related terms. The KEGG pathways that were most significantly enriched were phenylpropanoid biosynthesis, plant hormone signal transduction etc. The genes of transcription factor families, such as C2H2, bHLH and bZIP, were highly expressed in the H. compressa after submergence, which might be closely related to the submergence adaptive response mechanisms of H. compressa.

Discussion

This study provides basic data for analyzing the molecular and morphological mechanisms of H. compressa in response to submergence stress, and also provides theoretical support for the subsequent improvement of submergence tolerance traits of H. compressa.
Pooled DNA sequencing in hairy vetch (Vicia villosa Roth) reveals QTL for seed dormancy but not pod dehiscence
Authors: Tilhou Neal , Kissing Kucek Lisa , Carr Brandon , Douglas Joel , Englert John , Ali Shahjahan , Raasch John , Bhamidimarri Suresh , Mirsky Steven , Monteros Maria J. , Hayes Ryan , Riday Heathcliffe
Published: April 2024

Introduction

Hairy vetch (Vicia villosa Roth) is a promising legume cover crop, but its use is limited by high rates of pod dehiscence and seed dormancy.

Methods

We used phenotypically contrasting pooled DNA samples (n=24 with 29-74 individuals per sample) from an ongoing cover crop breeding program across four environments (site-year combinations: Maryland 2020, Maryland 2022, Wisconsin 2021, Wisconsin 2022) to find genetic associations and genomic prediction accuracies for pod dehiscence and seed dormancy. We also combined pooled DNA sample genetic association results with the results of a prior genome-wide association study.

Results and discussion

Genomic prediction resulted in positive predictive abilities for both traits between environments and with an independent dataset (0.34-0.50), but reduced predictive ability for DNA pools with divergent seed dormancy in the Maryland environments (0.07-0.15). The pooled DNA samples found six significant (false discovery rate q-value<0.01) quantitative trait loci (QTL) for seed dormancy and four significant QTL for pod dehiscence. Unfortunately, the minor alleles of the pod dehiscence QTL increased the rate of pod dehiscence and are not useful for marker-assisted selection. When combined with a prior association study, sixteen seed dormancy QTL and zero pod dehiscence QTL were significant. Combining the association studies did not increase the detection of useful QTL.
Effects of systemic pretreatment with the NAALADase inhibitor 2-PMPA on oral methamphetamine reinforcement in C57BL/6J mice
Authors: Fultz Elissa K. , Nei Andrea Y. T. , Chi Joyce C. , Lichter Jacqueline N. , Szumlinski Karen K.
Published: April 2024

Introduction

Repeated exposure to methamphetamine (MA) in laboratory rodents induces a sensitization of glutamate release within the corticoaccumbens pathway that drives both the rewarding and reinforcing properties of this highly addictive drug. Such findings argue the potential for pharmaceutical agents inhibiting glutamate release or its postsynaptic actions at glutamate receptors as treatment strategies for MA use disorder. One compound that may accomplish both of these pharmacological actions is the N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA). 2-PMPA elevates brain levels of the endogenous agonist of glutamate mGluR3 autoreceptors, N-acetyl-aspartatylglutamate (NAAG), while potentially acting as an NMDA glutamate receptor antagonist. Of relevance to treating psychomotor stimulant use disorders, 2-PMPA is reported to reduce indices of both cocaine and synthetic cathinone reward, as well as cocaine reinforcement in preclinical rodent studies.

Method

Herein, we conducted three experiments to pilot the effects of systemic pretreatment with 2-PMPA (0-100 mg/kg, IP) on oral MA self-administration in C57BL/6J mice. The first experiment employed female mice with a prolonged history of MA exposure, while the mice in the second (females) and third (males and females) experiment were MA-naïve prior to study. In all experiments, mice were trained daily to nose-poke for delivery of unadulterated MA solutions until responding stabilized. Then, mice were pretreated with 2-PMPA prior to operant-conditioning sessions in which nose-poking behavior was reinforced by delivery of 120 mg/L or 200 mg/L MA (respectively, in Experiments 1 and 2/3).

Results

Contrary to our expectations, 30 mg/kg 2-PMPA pretreatment altered neither appetitive nor consummatory measures related to MA self-administration. In Experiment 3, 100 mg/kg 2-PMPA reduced responding in the MA-reinforced hole, as well as the number of reinforcers earned, but did not significantly lower drug intake.

Discussion

These results provide mixed evidenced related to the efficacy of this NAALADase inhibitor for reducing oral MA reinforcement in female mice.
Optimal site selection strategies for urban parks green spaces under the joint perspective of spatial equity and social equity
Authors: Zhao Youqiang , Gong Peng
Published: April 2024

Urban park green spaces (UPGS) are a crucial element of social public resources closely related to the health and well-being of urban residents, and issues of equity have always been a focal point of concern. This study takes the downtown area of Nanchang as an example and uses more accurate point of interest (POI) and area of interest (AOI) data as analysis sources. The improved Gaussian two-step floating catchment area (G2SFCA) and spatial autocorrelation models are then used to assess the spatial and social equity in the study area, and the results of the two assessments were coupled to determine the optimization objective using the community as the smallest unit. Finally, the assessment results are combined with the k-means algorithm and particle swarm algorithm (PSO) to propose practical optimization strategies with the objectives of minimum walking distance and maximum fairness. The results indicate (1) There are significant differences in UPGS accessibility among residents with different walking distances, with the more densely populated Old Town and Honggu Tan areas having lower average accessibility and being the main areas of hidden blindness, while the fringe areas in the northern and south-western parts of the city are the main areas of visible blindness. (2) Overall, the UPGS accessibility in Nanchang City exhibits a spatial pattern of decreasing from the east, south, and west to the center. Nanchang City is in transition towards improving spatial and social equity while achieving basic regional equity. (3) There is a spatial positive correlation between socioeconomic level and UPGS accessibility, reflecting certain social inequity. (4) Based on the above research results, the UPGS layout optimization scheme was proposed, 29 new UPGS locations and regions were identified, and the overall accessibility was improved by 2.76. The research methodology and framework can be used as a tool to identify the underserved areas of UPGS and optimize the spatial and social equity of UPGS, which is in line with the current trend of urban development in the world and provides a scientific basis for urban infrastructure planning and spatial resource allocation.
Moderated moderation modelling of subjective social status, pocket money and depressive symptoms of university students in Ghana
Authors: Quansah Frank , Srem-Sai Medina , Agormedah Edmond Kwesi , Ankomah Francis , Hagan John Elvis , Schack Thomas
Published: April 2024

Introduction

Although the relationship between subjective social status and depression in university students has been well-established, this association could be seen as a spurious one. Previous studies have shown that key variables like financial resources and age could play key roles in explaining the variances in social status and mental health outcomes. In this research, we assessed the complex interrelationships between subjective social status, financial resources at their disposal and depressive symptoms among university students within their young and middle adulthood stages.

Methods

A cross-sectional survey was conducted in a university in Ghana to sample 1134 university students through accidental sampling. The McArthur Scale and WHO-5 Well-being measure were used for the data collection.

Results

The results revealed that higher levels of subjective social status were associated with lower levels of depression. It was further found that the interaction between students’ pocket money and age played unique roles in the relationship between subjective social status and depression.

Conclusion

The study findings call on stakeholders in education to explore funding opportunities and to examine ways of empowering parents (financially) to adequately support the students. Health educationists and promoters, including psychologists, school counsellors and parents could compliment these efforts by helping to train and empower students through self-regulation or management skills to help improve their well-being. Continuous efforts are required to improve the financial status and mental health of students.
We-Care-Well: exploring the personal recovery of mental health caregivers through Participatory Action Research
Authors: Redublo Tyler , Paul Sayani , Joshi Anahita , Arbour Simone , Murray Ross , Chiu Mary
Published: April 2024

Family caregivers play a critical role in supporting the recovery journeys of their loved ones, yet the recovery journeys of family caregivers have not been well-explored. Using a Participatory Action Research approach, we explore the personal recovery journeys of family caregivers for individuals with mental illness. This case study involved piloting and exploring the impact of a novel online workshop series offered to mental health caregivers at Ontario Shores Center for Mental Health Sciences. Recovery courses and workshops conventionally engage patients living with mental health conditions. In the current case, the recovery model is adapted to the needs and experiences of their family caregivers, resulting in a pilot workshop series called “We Care Well”. Through participant-led discussions, interactive and take-home activities, and experiential learning, caregivers co-created workshop content and engaged in peer-learning on seven personal recovery-oriented topics. This included: self-care, resilience-building, non-violent communication, storytelling, and mental health advocacy. Throughout the sessions, participants implemented their learnings into their caregiving roles, and shared their experiences with the group to progress through their own recovery journeys. The We Care Well series was found to be an effective intervention to adapt and apply the personal recovery framework to mental health caregivers. PAR, and co-design are viable approaches to engage caregivers in mental health research, and can facilitate knowledge exchange, as well as relationship building with peers and program facilitators.
What can we learn about stress and sleep from COVID-19 pandemic—perspective from the theory of preventive stress management
Authors: Liu Fang , Liang Weijie , Li Hanqi , Li Yuyang , Zhang Yue , Ding Lei , Zhang Qianqian , Chen Liang
Published: April 2024

Background

The COVID-19 pandemic has presented unique challenges to individuals worldwide, with a significant focus on the impact on sleep. However, the precise mechanisms through which emotional and cognitive variables mediate this relationship remain unclear. To expand our comprehensive understanding of variables, the present study utilizes the Preventive Stress Management theory, to test the relationship between perceived social support and sleep quality, as well as the effect of perceived COVID-19 stress, hope, negative emotions and coping styles.

Methods

Data were collected in March 2022 from 1,034 college students in two universities located in Liaoning Province, China, using an online survey platform regarding perceived social support, perceived COVID-19 stress, sleep quality, hope, negative emotions and coping styles. The moderated mediation model were conducted using Process macro program (Model 6) and the syntax in SPSS.

Results

The results revealed perceived COVID-19 stress and negative emotions sequentially mediated the negative relationship between perceived social support and sleep quality. Furthermore, hope and coping styles were found to moderate the sequential mediating effect.

Conclusion

The present study sheds light on the pathways that affect sleep quality among college students during the COVID-19 pandemic. Findings highlight the protective roles played by positive social and personal resources, such as perceived social support, hope, and effective coping styles, against sleep problems. These insights have important implications for the development of targeted interventions to improve sleep outcomes during this challenging time.
Sagittal and transverse ankle angle coupling can influence prosthetic socket transverse plane moments
Authors: Klute Glenn K. , Mulcahy Connor W.
Published: April 2024

Introduction

The intact foot and ankle comprise a complex set of joints that allow rotation in multiple planes of motion. Some of these motions are coupled, meaning rotation in one plane induces motion in another. One such coupling is between the sagittal and transverse planes. For every step, plantar- and dorsi-flexion motion is coupled with external and internal rotation of the shank relative to the foot, respectively. There is no prosthetic foot available for prescription that mimics this natural coupling. The purpose of this study was to determine if a sagittal:transverse ankle angle coupling ratio exists that minimizes the peak transverse plane moment during prosthetic limb stance.

Methods

A novel, torsionally active prosthesis (TAP) was used to couple sagittal and transverse plane motions using a 60-watt motor. An embedded controller generated transverse plane rotation trajectories proportional to sagittal plane ankle angles corresponding to sagittal:transverse coupling ratios of 1:0 (rigid coupling analogous to the standard-of-care), 6:1, 4:1, 3:1, and 2:1. Individuals with unilateral transtibial amputation were block randomized to walk in a straight line and in both directions around a 2 m circle at their self-selected speed with the TAP set at randomized coupling ratios. The primary outcome was the peak transverse plane moment, normalized to body mass, during prosthetic limb stance. Secondary outcomes included gait biomechanic metrics and a measure of satisfaction.

Results

Eleven individuals with unilateral transtibial amputations participated in the study. The 6:1 coupling ratio resulted in reduced peak transverse plane moments in pairwise comparisons with 3:1 and 2:1 coupling ratios while walking in a straight line and with the prosthesis on the outside of the circle (p < .05). Coupling ratio had no effect on gait biomechanic metrics or satisfaction.

Discussion

The general pattern of results suggests a quadratic relationship between the peak transverse plane moment and coupling ratio with a minimum at the 6:1 coupling ratio. The coupling ratio did not appear to adversely affect propulsion or body support. Subjects indicated they found all coupling ratios to be comfortable. While a mechatronic prosthesis like the TAP may have limited commercial potential, our future work includes testing a robust, passive prosthetic foot with a fixed coupling ratio.
Constructing a novel clinical indicator model to predict the occurrence of thalassemia in pregnancy through machine learning algorithm
Authors: Long Yaoshui , Bai Wenxue
Published: April 2024

Thalassemia is one of the inherited hemoglobin disorders worldwide, resulting in ineffective erythropoiesis, chronic hemolytic anemia, compensatory hemopoietic expansion, hypercoagulability, etc., and when a mother carries the thalassemia gene, the child is more likely to have severe thalassemia. Furthermore, the economic and time costs of genetic testing for thalassemia prevent many thalassemia patients from being diagnosed in time. To solve this problem, we performed least absolute shrinkage and selection operator (LASSO) regression to analyze the correlation between thalassemia and blood routine indicators containing mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell (RBC). We then built a nomogram to predict the occurrence of thalassemia, and receiver operating characteristic (ROC) curve was used to verify the prediction efficiency of this model. In total, we obtained 7,621 cases, including 847 thalassemia patients and 6,774 non-thalassemia. Among the 847 thalassemia patients, with a positivity rate of 67.2%, 569 cases were positive for α-thalassemia, and with a rate of 31.5%, 267 cases were positive for β-thalassemia. The remaining 11 cases were positive for both α- and β-thalassemia. Based on machine learning algorithm, we screened four optimal indicators, namely, MCV, MCH, RBC, and MCHC. The AUC value of MCV, MCH, RBC, and MCHC were 0.907, 0.906, 0.796, and 0.795, respectively. Moreover, the AUC value of the prediction model was 0.911. In summary, a novel and effective machine learning model was built to predict thalassemia, which functioned accurately, and may provide new insights for the early screening of thalassemia in the future.
Gender systems in the Putin autocracy
Authors: Wood Elizabeth A.
Published: April 2024

Over the last 23 years, Russian President Vladimir Putin’s autocracy has revealed a set of interlocking gender systems that have come to the fore particularly vividly since the full-scale invasion of Ukraine on February 24, 2022. How, this article asks, have the masculinist cultural and political practices of the Putin regime undermined democratic practices and engagement broadly speaking? How have they organized Russian state and society in ways that have led to today’s war in Ukraine with its massive destruction, violence, and brutality? And have there been earlier signals that should have warned observers that this regime might undertake such a war of aggression? Drawing on public, mass media data, this article analyzes the gendered structures of power in Russia that have contributed to the degeneration of democracy in three main areas: (1) male-on-male domination in discourse and practice that supports Putin’s personal rule and emasculates his enemies; (2) the elevation of male power clans, including the President’s personal praetorian guard and the Russian private military companies; and (3) the overall taming and emasculation of the Russian Parliament combined with the elevation of tough women deputies, whom I call the Baba Commissars. These female MPs support the President’s domination by creating an appearance of a threatening outside world that needs to be kept at bay. At the same time, they support a neo-traditional gender order with women managing the house under the direction of the patriarchal male leader.
Farming practices, varietal preferences, and land suitability analyses for yam production in Eastern D.R. Congo: implications for breeding initiatives and food sovereignty
Authors: Mondo Jean M. , Chuma Géant B. , Matiti Henri M. , Balezi Alphonse Z. , Kihye Jacques B. , Ayagirwe Rodrigue B. , Agre Paterne A. , Banda Vishnuvardhan B. , Adebola Patrick , Asfaw Asrat
Published: April 2024

Yam (Dioscorea spp.) is a key tuber crop in sub-Saharan Africa (SSA) with huge potential for poverty alleviation, food sovereignty, and nutrition security. Exploiting its full potential requires that factors holding it down are understood and mitigated. This study, conducted between May and July 2022 and 2023, assessed yam farming practices, varietal preferences, and land suitability in the Eastern Democratic Republic of Congo (DRC). We interviewed 765 smallholder farmers within four agro-ecological zones (AEZ) to assess the sociocultural, agronomic, varietal, and biophysical factors affecting yam production. Land suitability analyses were conducted using the Analytic Hierarchy Process (AHP) to identify areas suitable to extensive yam production and to cluster environments that could optimize yam varietal selection and testing. Results showed that yam is mainly cultivated by women in eastern DRC (70%). The seed delivery system is informal, relying primarily on farmer-saved seeds and farmer-seed exchanges (74.9%). Soil depletion (68.3%), limited access to high-quality seeds (54.5%), youth disengagement in yam value chain (50.3%), insect pests (17.9%), and short tuber shelf-life (65.8%) were, respectively, the main ecological, agronomic, sociocultural, biological, and tuber quality factors hindering yam production in eastern DRC. However, the perceived importance of most factors significantly varied with farmer gender and age categories. A multitude of varietal traits was used to assess yam varieties in eastern DRC, of which the tuber taste (59%) was the most valued trait regardless of gender and age categories, though it had highest scores among middle-aged adult women. Land suitability analyses discriminated five clusters; the most significant part of the region falling under suitable (27%), highly suitable (24%), and very highly suitable classes (37%). We further discussed how breeding initiatives for delivering yam varieties, suiting local producers’ and end-users’ needs, could unlock the crop’s potential for enhancing food security and wealth creation in eastern DRC. The land suitability map from this study is a valuable decision-making tool in defining priority areas for extensive yam production and varietal selection and testing. This study provided valuable insights on factors affecting yam production and suggested yam breeding as a backbone of a holistic approach seeking to address challenges faced in unlocking the potential for yam production in eastern DRC.