bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of chicken DA systems reveals that the avian personality gene, DRD4, is expressed in the mitral cells of the olfactory bulb
Authors: Fujita Toshiyuki , Aoki Naoya , Mori Chihiro , Homma Koichi J. , Yamaguchi Shinji
Published: January 2025

Animal personalities are stable, context-dependent behavioral differences. Associations between the personality of birds and polymorphisms in the dopamine receptor D4 (DRD4) gene have been repeatedly observed. In mammals, our understanding of the role of the dopamine (DA) system in higher cognitive functions and psychiatric disorders is improving, and we are beginning to understand the relationship between the neural circuits modulating the DA system and personality traits. However, to understand the phylogenetic continuity of the neural basis of personality, it is necessary to clarify the neural circuits that process personality in other animals and compare them with those in mammals. In birds, the DA system is anatomically and molecularly similar to that in mammals; however, the function of DRD4 remains largely unknown. In this study, we used chicks as model birds to reveal the expression regions of the DA neuron-related markers tyrosine hydroxylase (TH), dopa decarboxylase (DDC), dopamine β-hydroxylase (DBH), and DRD4, as well as other DRDs throughout the forebrain. We found that DRD4 was selectively expressed in the mitral cells of the olfactory bulb (OB). Furthermore, a detailed comparison of the expression regions of DA neurons and DRD4 in the OB revealed a cellular composition similar to that of mammals. Our findings suggest that the animal personality gene DRD4 is important for olfactory information processing in birds, providing a new basis for comparing candidate neural circuits for personality traits between birds and mammals.
Bibliometric insights into astrocytic roles in depression and treatment
Authors: Lin Linsun , Guo Ziyi , Ren Zhuoyu , Feng Yanchen , Fang Peigang , Wang Tao , Chen Min
Published: January 2025

Objective

Depression is a mental disorder that significantly impairs both physical and mental health. Recent studies have shown that reactive astrogliosis have gained significant attention for their involvement in the pathophysiology of depression. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots regarding the role of astrocytes in the mechanisms and treatment of depression through bibliometric analysis. The scope of the literature review encompasses both basic and clinical research.

Methods

Publications related to astrocytes in depression and treatment from 2014 to 2023 were searched in the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and the R package “bibliometrix” were used to conduct this bibliometric analysis.

Results

From 2014 to 2023, a total of 1,502 documents from 78 countries on astrocytes in depression and treatment were analyzed from 169 journals, with the most co-cited journals being the Journal of Neuroscience and PNAS. China Medical University was the most productive institution. The analysis identified key authors like Verkhratsky Alexei and Baoman Li, and major co-cited references by Rajkowska and Liddelow. Keywords such as “synaptic plasticity,” “astrocytes,” and “neuroinflammation” revealed research trends focusing on molecular mechanisms, gut microbiota, and inflammation.

Conclusion

This is the first bibliometric study to comprehensively summarize the research trends and advancements regarding astrocytes in depression and its treatment. Through this bibliometric analysis, we aim to enhance the understanding of the significance of astrocytes in depression research and provide new perspectives and insights for future investigations. We hope that this study will facilitate a broader integration of basic and clinical research, offering novel approaches for the treatment of depression.
Global remapping emerges as the mechanism for renewal of context-dependent behavior in a reinforcement learning model
Authors: Kappel David , Cheng Sen
Published: January 2025

Introduction

The hippocampal formation exhibits complex and context-dependent activity patterns and dynamics, e.g., place cell activity during spatial navigation in rodents or remapping of place fields when the animal switches between contexts. Furthermore, rodents show context-dependent renewal of extinguished behavior. However, the link between context-dependent neural codes and context-dependent renewal is not fully understood.

Methods

We use a deep neural network-based reinforcement learning agent to study the learning dynamics that occur during spatial learning and context switching in a simulated ABA extinction and renewal paradigm in a 3D virtual environment.

Results

Despite its simplicity, the network exhibits a number of features typically found in the CA1 and CA3 regions of the hippocampus. A significant proportion of neurons in deeper layers of the network are tuned to a specific spatial position of the agent in the environment—similar to place cells in the hippocampus. These complex spatial representations and dynamics occur spontaneously in the hidden layer of a deep network during learning. These spatial representations exhibit global remapping when the agent is exposed to a new context. The spatial maps are restored when the agent returns to the previous context, accompanied by renewal of the conditioned behavior. Remapping is facilitated by memory replay of experiences during training.

Discussion

Our results show that integrated codes that jointly represent spatial and task-relevant contextual variables are the mechanism underlying renewal in a simulated DQN agent.
A systematic review of cognitive telerehabilitation in patients with cognitive dysfunction
Authors: Jeon Hyeonwoo , Kim Doo Young , Park Si-Woon , Lee Bum-Suk , Han Hyeong-Wook , Jeon Namo , Kim Minsong , Kang Mingu , Kim Suebeen
Published: January 2025

Introduction

One of the possible treatment options for patient with cognitive dysfunction is cognitive telerehabilitation. Previous systematic reviews on cognitive telerehabilitation have focused on specific disease groups and the analysis of intervention methods did not differentiate between traditional face-to-face cognition treatment and usual care. In this systematic review, we aim to analyze randomized controlled trials (RCTs) that compare telerehabilitation with face-to-face treatment or usual care for improving cognitive function in elderly individuals with cognitive dysfunction or patients with acquired brain injury.

Methods

We conducted this systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In this systematic review, we searched 7 electronic databases (PubMed, Cochrane, EMbase, CINAHL, Web of Science, Scopus, KMbase) to identify relevant studies published through December 10, 2024. We conducted a meta-analysis to assess the quality of the studies and synthesize the evidence. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.

Results

Finally, 16 studies were included in the analysis. For comparing telerehabilitation with face-to-face cognition treatment, the meta-analysis included 2 RCTs for global cognition (immediate outcome), 2 RCTs for attention (immediate outcome), 2 RCTs for visuospatial function (immediate outcome). For comparing telerehabilitation with usual care, the meta-analysis included 7 RCTs for global cognition (immediate outcome), 3 RCTs for global cognition (persistence outcome), 4 RCTs for attention (immediate outcome), 3 RCTs for executive function (immediate outcome), 3 RCTs for working memory (immediate outcome), 3 RCTs for visuospatial function (immediate outcome).

Discussion

Telerehabilitation has been shown to be more effective than usual care in improving global cognitive function, and its effectiveness is not inferior to that of traditional face-to-face cognitive treatment. By overcoming the limitations of traditional cognition rehabilitation and providing continuous treatment, telerehabilitation can offer effective treatment in specific situations.
Effect of long-term transcutaneous auricular vagus nerve stimulation in multiple system atrophy-cerebellar subtype: a case report
Authors: Wang Zhao-Di , Cheng Xiao-Ping , Liu Zhen-Yi , Wu Di , Ni Jun , Chen Chuan-Juan , Chen Xin-Yuan
Published: January 2025

Background

Multiple system atrophy-cerebellar subtype (MSA-C) is a predominance of cerebellar ataxia and autonomic failure. MSA-C has a rapid progression, with average 9 years from symptom onset to death. Despite its prevalence, there is still a lack of effective treatments. In recent years, it has been established that taVNS has significant therapeutic effects on epilepsy, depression, migraine, insomnia, and other diseases. Hence, we performed taVNS treatment for one MSA-C patient to explore whether taVNS could alleviate patient’s motor and non-motor symptoms.

Case presentation

A 65-year-old woman diagnosed with MSA-C received taVNS treatment for the following duration and course: once a day, 40 min a time, 20 times a month continually for 12 months. Meanwhile, she received assessments of motor and non-motor symptoms at baseline, 4-weeks and 12-months after taVNS treatment. Motor symptoms assessments was made by Scale for the Assessment and Rating of Ataxia (SARA) and Unified Multiple System Atrophy Rating Scale (UMSARS), non-motor symptoms assessment by Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). After 4-weeks and 12-months of taVNS treatment, compared to baseline assessments, SARA scores decreased from 13 to 11 and then to 10.5, UMSARS scores from 28 to 24 and then to 23, PSQI scores from 19 to 13 and then to 6, HAMA scores from 13 to 3 and then remained unchanged, and HAMD scores from 7 to 4 and then remained unchanged.

Conclusion

In the case, we found that short-term taVNS treatment can alleviate ataxia, sleep problem, anxiety and depression of the MSA-C patient. The effects can be maintained and some symptoms may be further improved after receiving long-term treatment. Our case report supports the feasibility and effectiveness of taVNS treatment in MSA-C patients.
Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation
Authors: Gargus Makenna , Ben-Azu Benneth , Landwehr Antonia , Dunn Jaclyn , Errico Joseph P. , Tremblay Marie-Ève
Published: January 2025

The vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of microglia, the resident innate immune cells of the brain, is associated with various neurodevelopmental disorders, including schizophrenia, attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), and epilepsy. While the mechanistic understanding linking the VN, microglia, and neurodevelopmental disorders remains incomplete, vagus nerve stimulation (VNS) may provide a better understanding of the VN’s mechanisms and act as a possible treatment modality. In this review we examine the VN’s important role in modulating the immune system through the inflammatory reflex, which involves the cholinergic anti-inflammatory pathway, which releases acetylcholine. Within the central nervous system (CNS), the direct release of acetylcholine can also be triggered by VNS. Homeostatic balance in the CNS is notably maintained by microglia. Microglia facilitate neurogenesis, oligodendrogenesis, and astrogenesis, and promote neuronal survival via trophic factor release. These cells also monitor the CNS microenvironment through a complex sensome, including groups of receptors and proteins enabling microglia to modify neuroimmune health and CNS neurochemistry. Given the limitations of pharmacological interventions for the treatment of neurodevelopmental disorders, this review seeks to explore the application of VNS as an intervention for neurodevelopmental conditions. Accordingly, we review the established mechanisms of VNS action, e.g., modulation of microglia and various neurotransmitter pathways, as well as emerging preclinical and clinical evidence supporting VNS’s impact on symptoms associated with neurodevelopmental disorders, such as those related to CNS inflammation induced by infections. We also discuss the potential of adapting non-invasive VNS for the prevention and treatment of these conditions. Overall, this review is intended to increase the understanding of VN’s potential for alleviating microglial dysfunction involved in schizophrenia, ADHD, ASD, and epilepsy. Additionally, we aim to reveal new concepts in the field of CNS inflammation and microglia, which could serve to understand the mechanisms of VNS in the development of new therapies for neurodevelopmental disorders.
Experimental research on heat transfer characteristics of a two-layer corium pool based on a three-dimensional ellipsoidal lower plenum
Authors: Wu Shihao , Zhang Yapei , Yu Jian , Bai Jingyuan , Tian Wenxi , Qiu Suizheng , Su G. H.
Published: January 2025

To better understand the application of IVR (In-Vessel Retention), extensive experiments have been conducted on the heat transfer characteristics of molten pool. However, most research mainly focuses on hemispherical lower heads, and the research on ellipsoidal lower head suitable for small pressurized water reactors is relatively lacking. In order to provide some reference for the implementation of IVR with ellipsoidal lower head, this paper conducted the experimental study on the heat transfer characteristics of a three-dimensional double-layer molten pool based on the design of a small pressurized water reactor. The test section consists of two parts: ellipsoidal and cylindrical, with a span of 1150 mm and a total height of 700 mm. The molten material is simulated by nitrate mixture (20mol%NaNO3-80mol%KNO3), and electric heating wire is chosen to simulate the oxide layer decay heat. The effects of heating power, oxide layer height and layered partition thickness on heat transfer characteristics of two-layer molten pool under static conditions were studied. The results show that the thermal stratification phenomenon mainly occurs in the lower and middle regions of the oxide layer, with a smaller dimensionless temperature gradient in the upper region; with the similar volumetric power densities, the height of the oxide layer has little effect on the wall heat flux density; the layered partition increases the thermal resistance between the two layers and reduces the upward heat transfer to the ceramic pool. In addition, the heat transfer relationships in the oxide layer, both downward and upward, are fitted for the internal Rayleigh number range of 3.43 × 1012 to 1.54 × 1013.
The association between blood selenium and metabolic syndrome in adults: a systematic review and dose–response meta-analysis of epidemiologic studies
Authors: Hajhashemy Zahra , Foshati Sahar , Bagherniya Mohammad , Askari Gholamreza
Published: January 2025

Background and aim

Although the relationship between selenium and metabolic syndrome (MetS) was previously investigated, the findings were inconsistent. Therefore, we performed a systematic review and dose–response meta-analysis to summarize the association between blood selenium and MetS in adults.

Methods

A comprehensive search was conducted in Medline (PubMed), ISI Web of Science, Scopus, and motor engineering of Google Scholar up to October 1st, 2024. Observational studies which reported the risk of MetS in relation to blood selenium in adults were included. The protocol of the current analysis was registered at PROSPERO as CRD42024486035.

Results

Overall, 16,779 participants and 6,471 cases with MetS from 5 cross-sectional and 7 case–control studies were included in the current systematic review and meta-analysis. The findings showed that participants with the highest blood values of selenium (mean: 268.5 μg/L) in comparison to those with the lowest values (mean: 75.27 μg/L) had 40% higher risk of MetS. Nevertheless, this association was not significant (95%CI: 0.99–1.97). Due to a significant between-study heterogeneity (I2 = 90.4%, p < 0.001), subgroup analysis was conducted based on potential confounders. However, this association was only significant in a few subgroups with low number effect sizes. Linear dose–response analysis illustrated each 50 μg/L increment in circulating selenium was related to 7% higher risk of MetS (RR: 1.07, 95%CI: 0.99, 1.15) However, this association was not statistically significant. Additionally, non-linear dose–response analysis indicated a U-shaped association between blood selenium and risk of MetS with the lowest risk at 160 ug/L of blood selenium (p < 0.001).

Conclusion

There is a U-shaped relationship between blood selenium levels risk of MetS. However, more longitudinal studies are needed to verify the causality of findings and clarify the underlying mechanisms.
Serum NLR combined with CA125 and HE4 improves the diagnostic and prognostic efficiency in patients with ovarian cancer
Authors: Tian Yun , Li Xiabing , Zhang Hongjian , Wang Yaping , Li Hongyu , Qin Qiaohong
Published: January 2025

Background

Ovarian cancer (OC) represents a common neoplasm within the female reproductive tract. The prognosis for patients diagnosed at advanced stages is unfavorable, primarily attributable to the absence of reliable screening markers for early detection. An elevated neutrophil-to-lymphocyte ratio (NLR) serves as an indicator of host inflammatory response and has been linked to poorer overall survival (OS) across various cancer types; however, its examination in OC remains limited. This study seeks to identify combination diagnostic and prognostic markers for OC, aiming to improve diagnostic and prognostic efficacy, especially in the early stages.

Methods

We analyzed the targeted biomarkers in a cohort of 104 OC patients and 100 controls, which comprised 50 patients with benign ovarian tumors and 50 healthy women, using enzyme-linked immunosorbent assay (ELISA) and complete blood counting (CBC). After validating the biomarker panel, we compared the expression levels of the biomarkers in OC patients with various clinical features to assess their relevance. A biomarker panel was developed and validated with an independent cohort of 70 OC patients and 60 controls, including 30 with benign ovarian tumors and 30 healthy women. We evaluated the diagnostic accuracy using the area under the receiver-operating characteristic (ROC) curve and overall survival analysis was used for prognosis.

Results

The results from ELISA and CBC analyses indicated that the NLR was significantly higher in patients with OC. This elevation was especially notable in those with advanced stages of the disease, lymph node metastasis, and ascites. The diagnostic performance of the NLR, when combined with CA125 and HE4, outperformed each marker used individually, especially when compared to the traditional combination of CA125 and HE4. Importantly, we observed similar results in patients with early-stage ovarian cancer and those with low levels of CA125 and HE4. In addition, these results suggest that NLR combined with CA125 and HE4 levels in OC patients have significant prognostic value.

Conclusions

The effective combination of serum NLR, CA125, and HE4 significantly enhances diagnostic efficiency in patients with OC. Serum NLR, CA125, and HE4 levels were identified as independent prognostic markers for OC.
Case report: Selpercatinib in the treatment of RET fusion-positive advanced lung adenocarcinoma: a challenging clinical case
Authors: Pagliaro Raffaella , Medusa Paola Maria , Vitiello Fabiana , Aronne Luigi , Campbell Susan F. M. , Perrotta Fabio , Bianco Andrea
Published: January 2025

Background

Rearranged during transfection (RET) fusions represent a distinct molecular subset of non-small cell lung cancer (NSCLC) with targeted therapeutic potential. Selpercatinib, a highly selective RET inhibitor, has demonstrated efficacy in various solid tumors harboring RET alterations. Here, we present a case highlighting the use and clinical outcomes of selpercatinib in a patient diagnosed with advanced lung adenocarcinoma harboring a RET fusion.

Case presentation

A 59-year-old woman with a history of stage IV lung adenocarcinoma harboring a KIF5B-RET fusion presented with disease progression following first-line chemo-immunotherapy. Selpercatinib was initiated as a targeted therapy, leading to a notable radiographic response and clinical improvement. The patient experienced a significant reduction in tumor burden and reported improved symptom control, with no significant adverse effects during the 21-month follow-up period.

Conclusions

This case highlights the efficacy and tolerability of selpercatinib in treating advanced lung adenocarcinoma with a RET fusion. The observed clinical response supports the early use of selpercatinib as a targeted therapy for RET fusion-positive NSCLC, including in patients with compromised general and respiratory conditions, especially in cases refractory to conventional treatments. Long-term follow-up studies are warranted to validate these findings and assess the durability of responses.
Responsiveness and clinical utility of PROMIS instruments in pediatric Crohn's disease: insights from a longitudinal study
Authors: Azevedo Sara , Oliveira Maria Miguel , Nogueira Paulo , Lopes Ana Isabel
Published: January 2025

Background

Inflammatory bowel disease (IBD) may adversely affect physical, psychological, and social well-being. Integrating patient-reported outcomes (PROs) into clinical practice is crucial for comprehensive disease management.

Objective

To evaluate the responsiveness and clinical utility of Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, compared with standard clinical assessment tools in pediatric CD patients.

Methods

A longitudinal, prospective study with 31 pediatric Crohn's disease (CD) patients aged 8–17 years recruited from a Pediatric Gastroenterology Unit. Data were collected at baseline and every 6 months over 18 months. PROMIS pediatric measures assessed PROs. Disease activity was evaluated using the pediatric Crohn's disease activity index (PCDAI) and clinical markers. IMPACT-III was also applied. Linear mixed-effects models (LMMs) and bivariate analyses were used to assess changes over time.

Results

PROMIS Global Health scores showed significant improvement over time, indicating enhanced overall health perceptions among patients. Notable reductions were observed in PROMIS Pain Interference and Fatigue scores, indicating better physical health. PROMIS depression scores generally decreased, suggesting improved mental health. PCDAI scores, hemoglobin, and platelet count significantly changed and correlated with PROMIS measures. Globally, the study demonstrated significant and clinically relevant changes in multiple PROMIS measures, confirming their responsiveness to changes in disease activity.

Conclusion

PROMIS instruments are clinically useful in managing pediatric CD, providing valuable insights into global health and quality of life. Integrating PROMIS measures into routine clinical practice may enhance disease management and treatment strategies for pediatric IBD patients.
External negative pressure improves lung aeration in near-term rabbit kittens at risk of developing respiratory distress
Authors: Diedericks C. , Crossley K. J. , Jurkschat D. , Wallace M. J. , Davies I. M. , Riddington P. J. , te Pas A. B. , Kitchen M. J. , Hooper S. B.
Published: January 2025

Introduction

As airway liquid is cleared into lung interstitial tissue after birth, the chest wall must expand to accommodate this liquid and the incoming air. We examined the effect of applying external positive and negative pressures to the chest wall on lung aeration in near-term rabbit kittens at risk of developing respiratory distress.

Methods

Rabbit kittens (30 days; term ∼31 days) were randomised into Control and Elevated Liquid (EL) groups. Lung liquid was drained in Control kittens to simulate expected volumes following vaginal delivery. EL kittens had lung liquid drained before 30 ml/kg was returned to simulate expected volumes after caesarean section. Kittens were delivered, placed in a water-filled plethysmograph and the external pressure was adjusted to −6 (negative), 0 (atmospheric), or +6 (positive) cmH2O. Kittens were ventilated with an 8 ml/kg tidal volume and PEEP of 0 cmH2O and lungs imaged using phase contrast x-ray imaging.

Results

Compared to external atmospheric pressures, external negative pressures expanded the chest (by 2100 ± 43 vs. 1805 ± 59 mm2; Control kittens; P = 0.028), directed tidal ventilation into lower, larger lung regions and increased functional residual capacity (FRC) levels in both Control (26.7 ± 2.0 vs. 12.6 ± 2.2 ml/kg; P < 0.001) and EL (19.6 ± 1.6 vs. 10.0 ± 2.9 ml/kg; P < 0.01) kittens. External positive pressures reduced FRC levels in Control (6.3 ± 0.8 vs. 12.6 ± 2.2 ml/kg; P < 0.05), but not in EL kittens, and directed tidal ventilation into upper lung regions.

Discussion

External negative pressures increased lung aeration and resulted in a more evenly distributed tidal ventilation immediately after birth in near-term rabbit kittens, whereas external positive pressures reduced lung aeration and compliance.
A review of the Bovis Calculus’s intervention mechanism and clinical application in ischemic stroke
Authors: Xu Ke , Deng Bowen , Jia Tongtong , Ren Mihong , Chen Hai , Zhang Jing , Guo Jinlin , Li Yong , Wang Jian
Published: January 2025

Background

Bovis Calculus (BC), also named Niuhuang in Chinese, is utilized as a resuscitation drug in Traditional Chinese Medicine (TCM) for the treatment of neurological disorders. Ischemic stroke (IS) is a significant global public health issue that currently lacks safe and effective therapeutic drugs. Ongoing efforts are focused on identifying effective treatment strategies from Traditional, Complementary, and Integrative Medicine. Noticeably, BC has been used in TCM for thousands of years to prevent or treat IS-related diseases.

Methods

The historical origins of BC in the treatment of IS were investigated through the examination of ancient Chinese medical texts. Furthermore, the chemical components of BC were analyzed, and its mechanisms of action against IS were summarized using literature sourced from databases such as Web of Science, PubMed, and China National Knowledge Infrastructure. Information on Chinese medicine preparations and clinical reports was also integrated to provide an overview of modern applications and safety considerations.

Results

BC mainly includes chemical components such as bile pigments, bile acids, cholesterol, proteins amino acids, and trace elements. Additionally, the efficacy of BC in treating cerebral ischemia/reperfusion injury (CI/RI) is certain, particularly due to the components of bile pigments, bile acids, and amino acids that can interfere with the enzymatic cascade reaction of CI/RI through multiple components, targets, and pathways. The active components of BC exert neuroprotective effects by reducing microcirculation disturbance, excitatory amino acid toxicity, and oxidative stress injury in the acute stage; inhibiting inflammatory injury, apoptosis, and blood-brain barrier (BBB) disruption in the subacute stage; and promoting angiogenesis and neurogenesis in the restoration stage. Furthermore, as a crude drug, BC appears in many Chinese patent medicine (CPM) preparations for the treatment of IS, and clinical and preclinical studies have proved its safety.

Conclusion

The use of BC in the treatment of IS has a long history, proven efficacy, and widespread application. Future efforts should focus on elucidating its mechanisms of action and exploring its applications.
Large variability in the alkaloid content of Corydalis yanhusuo dietary supplements
Authors: Luis Paula B. , Schneider Claus
Published: January 2025

Introduction

Extracts from the rhizome of the traditional Chinese medicinal plant Corydalis yanhusuo (CY) mediate a number of biologic effects that are associated with its content of isoquinoline alkaloids. CY alkaloids have shown analgesic, cardioprotective, and anti-addictive effects in animal models of disease. Since CY alkaloids are available to consumers as dietary supplements we analyzed the content of alkaloids in 14 products including open powders, capsules, and liquid formulations, capturing a majority of the products available online in the US.

Methods

Nineteen alkaloids were quantified using HPLC analyses with diode array detection after extraction using a weak cation exchange column.

Results

Total alkaloid content was highly variable among the products, ranging from below quantifiable in some to ≈11 mg/g in others. Five of the products had comparable content of alkaloids (9.5 ± 1.6 mg/g), equaling about the amount of alkaloids of an extract prepared from CY rhizome (12.7 mg/g). The other samples had much lower content (1.8 ± 0.9 mg/g), or alkaloids were below quantifiable. One of the products was highly enriched in tetrahydropalmatine (≈5 mg/g), suggesting adulteration from the natural product, and raising concerns about possible toxicologic liability.

Discussion

Considering alkaloid content as a key quality criterium for CY supplements, the large variability among the products seems unacceptable and makes it difficult for consumers to select products with an appropriate content of alkaloids.
Case Report: Targeted treatment by fluoxetine/norfluoxetine of a KCNC2 variant causing developmental and epileptic encephalopathy
Authors: Li Ping , Butler Alice , Zhou Yu , Magleby Karl L. , Gurnett Christina A. , Salkoff Lawrence
Published: January 2025

The Kv3.2 subfamily of voltage activated potassium channels encoded by the KCNC2 gene is abundantly expressed in neurons that fire trains of fast action potentials that are a major source of cortical inhibition. Gain-of-function (GOF) de novo pathogenic variants in KCNC1 and KCNC2, encoding Kv3.1 and Kv3.2 respectively, cause several types of epilepsy including developmental and epileptic encephalopathy (DEE). Fluoxetine (Prozac) is a known inhibitor of the Kv3.1 current and was reported to improve seizure control in a single patient with a KCNC1 GOF variant. Here, we describe fluoxetine treatment of two siblings with a de novo KCNC2 V473A variant associated with DEE, which resulted in improved seizure control, ability to wean antiepileptic medications, and improved development. The KCNC2 V437A variant showed GOF activity as demonstrated by HEK293 cells expressing variant subunits activating at more hyperpolarized potentials than WT channels. Fluoxetine reduced currents equally for both Kv3.2 WT and Kv3.2-V473A variant channels, with an IC50 of ∼12 µM. Further analysis of this repurposed drug showed that norfluoxetine, a long-lasting metabolite of fluoxetine which is produced in the liver and accumulates in the brain, was more effective than fluoxetine itself in selectively inhibiting the dominant pathogenic channel activity of the pathogenic allele. Norfluoxetine showed 7-fold greater selectivity in inhibiting Kv3.2 variant currents (IC50 of ∼0.4 µM) compared to WT currents (IC50 of ∼2.9 µM). Combined with a previous report of improved outcomes for a KCNC1 variant, our results suggest that fluoxetine or its metabolite, norfluoxetine, may be beneficial for patients with GOF variants in KCNC2 and other neuronal potassium channels.
History and prospects of flax genetic markers
Authors: Zhernova Daiana A. , Pushkova Elena N. , Rozhmina Tatiana A. , Borkhert Elena V. , Arkhipov Alexander A. , Sigova Elizaveta A. , Dvorianinova Ekaterina M. , Dmitriev Alexey A. , Melnikova Nataliya V.
Published: January 2025

Flax (Linum usitatissimum L.) is known as a dual-purpose crop, producing both fiber and oil, which have a wide range of uses. Successful flax breeding requires knowledge on the genetic determinants of flax traits. The former identification of molecular markers for valuable traits used labor-intensive and sometimes poorly reproducible approaches. However, they allowed an assessment of the genetic diversity of flax and its relatives, the construction of linkage maps, and the identification of some markers for important characteristics. The sequencing of flax whole genome triggered the development of genome-wide association studies (GWAS) and quantitative trait locus (QTL) mapping. QTLs and quantitative trait nucleotides (QTNs) were identified for valuable seed- and fiber-related features and for resistance to biotic and abiotic stressors. Cost-effective and accurate analysis of large number of genotypes for multiple markers simultaneously using microarrays or targeted deep sequencing became available, as well as HRM, TaqMan, KASP, and other fluorescence-based high-throughput methods for detecting DNA polymorphisms. However, most DNA markers identified in flax are ambiguously linked to trait expression and are not universally applicable. A major challenge remains the lack of knowledge on functional polymorphisms. To date, only a few are known, mainly mutations in the FAD3 genes responsible for reduced linolenic acid content in linseed oil. For the further development of marker-assisted and genomic selection of flax, it is necessary to analyze exhaustively phenotyped sample sets, to identify DNA polymorphisms that determine valuable traits, and to develop efficient DNA test systems.
Opportune moments for task interruptions: examining the cognitive mechanisms underlying interruption-timing effects
Authors: Hirsch Patricia , Moretti Luca , Leichtmann Benedikt , Koch Iring , Nitsch Verena
Published: January 2025

Introduction

Several studies showed that task interruptions at high mental workload moments are more harmful than task interruptions at low mental workload moments. In the present study, we used a theory-driven approach to define the mental workload during primary-task execution and to examine the effects of the interruption timing on primary-task performance.

Methods

Participants performed a primary task comprising a pre-defined sequence of six subtasks, with task interruptions occasionally occurring before the second, third, or fourth subtasks. Critically, the subtasks were organized either in two lag-2 repetition triplets or in two lag-2 switch triplets (e.g., ABA-CBC vs. CBA-CAB). This set-up allowed us to test two predictions about the effects of interruption timing on the resumption costs (i.e., the performance in subtasks following an interruption compared to the performance in the same subtask in non-interrupted primary tasks). First, we expected task interruptions before the fourth subtask being the less detrimental due to the presumed chunking of the six subtasks into two triplets. Second, in lag-2 switch triplets, task interruptions before the second and third subtasks were predicted to result in comparable resumption costs. In contrast, in lag-2 repetition triplets, task interruptions before the third subtask were hypothesized to be more disruptive than those before the second subtask. This is because the mental workload should be higher due to the need to overcome subtask inhibition.

Results

We found an interruption-timing effect with higher resumption costs for task interruptions occurring before the third subtask compared to interruptions before the second and the fourth subtasks. However, this effect did not differ across lag-2 repetition sequences and lag-2 switch sequences.

Discussion

These findings are discussed from a memory perspective and a context reconstruction perspective.
Co-creating a person-centered creative engagement intervention for Parkinson's care
Authors: Spee Blanca T. M. , Stap Thieme B. , Plijnaer Marjoke , Pasman Gert , Zeggio Sara , Duits Annelien , Crone Julia S. , Haeyen Suzanne , Pelowski Matthew , Bloem Bastiaan R. , Koksma Jan-Jurjen
Published: January 2025

Background

Recent research in the field of “Arts and Health” has demonstrated the beneficial impact of arts-based interventions on health and well-being across diverse populations. Recognizing their potential, especially in cases where conventional healthcare cannot address the multifaceted impact of conditions such as in Parkinson's disease (PD), our study advocates for an integrative approach in medical practice and neuroscience. We recommend incorporating learning environments from the design phase through long-term care. The arts offer a unique opportunity to create such environments. In this study, we specifically focus on individuals with PD, co-designing an intervention as a creative engagement learning environment and a PD-specific creative arts therapy. In this study, the narratives of those affected contribute as scientific knowledge, shaping care and increasing the intervention's relevance to participants' lives.

Methods

We used a participatory design-based research approach. Fourteen individuals with PD, along with three creative therapists and three researchers, collaborated through iterative design cycles to co-develop a creative arts therapy intervention. Qualitative data were collected through interviews, group reflections, and ethnographic observations. Data were analyzed using reflexive thematic analysis.

Results

The co-creation process resulted in a 10-week creative engagement intervention delivered in a “creative playground” setting. Participants chose from multiple media and autonomously decided their creative activities. Guidance from the creative therapists was provided as needed to support individual engagement and guide reflection and learning processes. Narratives offered insights into the relevance of autonomy in care, the role of the arts, and the individuality of disease experience, resulting in seven key features of our intervention framework, which include (i) intervention structure (e.g., duration of the intervention and sessions), (ii) freedom in selection of creative media, (iii) environment as a creative playground, (iv) skills of creative therapists, (v) PD-specific considerations, (vi) financial considerations and logistics, and we list (vii) responsibilities of the Design Team.

Discussion

This study establishes an initial framework for a PD-specific creative arts therapy intervention designed as a creative engagement learning environment. Future research will focus on rigorously evaluating its effectiveness and exploring its scalability in diverse settings.
Transforming students’ green behavior through environmental education: the impact of institutional practices and policies
Authors: Chen Cai , Shahbaz Pomi , Haq Shamsheer ul
Published: January 2025

Environmental education is crucial for achieving ecological sustainability goals and transforming human behavior to promote responsible consumption. Higher education institutions play a fundamental role in transforming societies aimed at a more sustainable future through the dissemination of environmental education to millions of young people worldwide. Therefore, this study aimed to measure the role of environmental education in transforming students’ green behavior (SGB), along with other higher education institutional factors such as green campus initiatives (GCI), institutional ecosystem (IEC), institutional sustainability system (ISS), and institutional support system (ISP) through students’ green intentions (SGI). The study data were collected from 480 Chinese students enrolled in the four cities with highest number of higher education institutions through face-to-face cross-sectional survey. The collected data were analyzed through partial least squares structural equation modeling. The findings indicate a significant and positive impact of GCI, IEC, ISS, and ISP on SGI, which further positively affects the SGB. This implies that green initiatives at campus, green ecosystems, sustainable and environmentally oriented policies, and support systems of educational institutions greatly contribute to the development of students’ green intentions (SGI), which further turn into green habits fostering their green behavior. Moreover, environmental education also played a significant moderating role between SGI and SGB. The provision of support systems, organizing hands-on workshops and seminars, providing sustainable food items at cafeterias, and short campus visits focusing on campus green practices may inspire students to adopt green practices in their daily routines.
Imprint of ancestral and modern threats in human mind – experience of fear, disgust, and anger
Authors: Landová Eva , Polák Jakub , Janovcová Markéta , Štolhoferová Iveta , Peterková Šárka , Chomik Aleksandra , Frynta Daniel
Published: January 2025

Introduction

Threats to our survival are often posed by the environment in which humans have evolved or live today. Animal and human ancestors developed complex physiological and behavioral response systems to cope with two types of threats: immediate physical harm from predators or conspecifics, triggering fear, and the risk of infections from parasites and pathogens leading to the evolution of the behavioral immune system (BIS) with disgust as the key emotion. Here we ask whether the BIS has adapted to protect us from pandemic risks or poisoning by modern toxic substances.

Methods

We have developed a survey comprised of 60 vignettes describing threats evoking fear and disgust belonging to one of the three main categories of threats: (1) ancestral, (2) modern, and (3) pandemic of airborne disease. Each vignette was evaluated on a 7-point Likert scale based on fear, disgust, and anger. Respondents also completed an assessment battery.

Results

The results show that the strongest fear is triggered by modern threats (electricity, car accidents), while the highest disgust is evoked by ancient threats (body waste products, worms). Disgust does not respond to modern threat stimuli such as toxic substances or radioactivity as these evoke mainly fear and anger. A discriminant factor analysis classified nine out of 10 pandemic disgust vignettes into the ancestral disgust category, convincingly assigning the pandemic disgust threats to the ancestral type. Gender, age, and type of education were significant moderators of emotional responses across all threat categories.

Discussion

Our study reveals that while fear is more context-dependent, particularly triggered by modern threats, disgust operates on an evolutionarily hardwired basis, making it less effective against contemporary risks. Furthermore, disgust experienced during a pandemic outbreak is more closely aligned with ancestral disgust-related threats tapping into evolutionary ancient survival circuits of the BIS. However, as disgust declines with age, the brain must adaptatively shift the emotional processing from disgust to fear to protect older adults from contamination risks. Finally, our study reveals that pandemic fear is better predicted by specific behaviors rather than general anxiety, suggesting a need for new assessments.
Attribution theory of poverty and beliefs about charity in Malaysia: an inter-ethnic comparison
Authors: Khan Abidullah , Shafiai Muhammad Hakimi Mohd , Abbas Ghulam , Zaidi Syeda Beena , Hassan Mehboob Ul
Published: January 2025

Introduction

Malaysia as an ethnically diverse country has a history of interethnic inequality and poverty which led to the development of different views about the existence of poverty. Among these ethnic groups, some sympathize with the poor and help them through different charity organizations. However, these charity organizations are mostly unaware of the target donors that can aid their charity funds. Therefore, this study explores the attitudinal differences regarding poverty among Malays, Chinese, and Indians and the demographic groups that can be targeted for donation and social policy development purposes.

Methodology

A survey is conducted in Selangor, where the data through a questionnaire is extracted from the three ethnic groups. Through the quota sampling technique, a sample of 700 is derived. The results are analyzed through ANOVA, regression, and mediation analysis.

Results

The results show that attitudinal differences between Malays and Chinese regarding structuralist beliefs could be observed. Moreover, among Malays, it is found that the relationship between gender, income, education, wealth, and structuralist beliefs is significantly mediated by beliefs about charity. On the other hand, mediation analysis for Chinese identifies gender, education, and income while among Indians gender, education, and wealth are identified as key demographic groups.

Discussion

This study highlights the role of attribution theory to identify the charity donors among the different ethnic groups which was overshadowed by the previous research in Malaysia. The results also hold significance for charity institutions to target the specified groups through their marketing campaigns. Also, based on these results government can reduce the misconception about the existence of poverty and to develop policies that encourage high income groups to support the poor.
My Bad, You Got This: witnessing, therapist attitude and the synergy between psychedelics and inner healing intelligence in the treatment of trauma
Authors: Fischman Lawrence
Published: January 2025

The MAPS (Multidisciplinary Association for Psychedelic Studies) sponsored MDMA-assisted therapy protocol has had greater success in treating trauma in preliminary clinical trials than any prior psychotherapeutic, pharmacologic, or combined approach. It is predicated on a synergy between drug action and the participant’s inner healing intelligence. The latter is described mainly by analogy with the body’s capacity to heal itself, and the treatment is characterized as a means of activating or accessing this capacity. How is this rather mysterious-sounding process so effective? I suggest that the therapist’s full commitment to, and trust in this treatment framework, along with the medication’s subjective enhancement of trust, encourages individuals who have suffered trauma and have difficulty trusting others to engage the therapist as a kind of witness. I discuss parallels between the therapeutic attitude implied in the inner healing intelligence model and the way a therapist can act as witness in the resolution of dissociative enactment in relational psychoanalysis. Trusting the healing capacity of one’s inner healing intelligence is dynamically equivalent to trusting the relational process. This makes trusting one’s inner healing intelligence a process of feeling witnessed. In both settings, the therapist’s willingness to acknowledge her technical limitations or failings, coupled with a conviction that the participant/patient’s primary need in processing trauma is to feel witnessed, facilitates the integration of dissociated experience.