bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONNEXIN43 IN NEONATAL EXCITATORY NEURONS IS IMPORTANT FOR MOTOR LEARNING
Authors: Yu *Yongchun 
Published: February 2025

Abstract

In the neocortex, gap junctions are expressed at very early developmental stages, and they are involved in many processes such as neurogenesis, neuronal migration and synapse formation. Connexin43 (Cx43), a gap junction protein, has been found to be abundantly expressed in radial glial cells, excitatory neurons and astrocytes. Although accumulating evidence suggests that Cx43-mediated gap-junctional coupling between astrocytes plays an important role in the central nervous system, the function of Cx43 in early excitatory neurons remains elusive. In this study, we knocked out Cx43 in the excitatory neurons with the Cre/loxP system to investigate the specific role(s) of early Cx43 expression in the regulation of behaviors. We crossed the Emx1-CreER mice with Cx43fl/fl mice to obtain Cx43 conditional knockout mice. Broad-spectrum behavioral tests, including assessments of emotionality (depression and anxiety), learning ability and motor capacity were applied to measure mouse behaviors. We performed tamoxifen injection around birth to remove Cx43 from excitatory neurons. Moreover, Western blot data suggest that Cx43 expression in neocortex were significantly reduced after deletion of Cx43 in neocortical excitatory neurons. Single-cell RT-PCR further confirmed the expression of Cx43 in neocortical excitatory neurons. The results from behavior tests showed that Cx43-cKO mice exhibited impaired short-term motor learning capacity. However, we did not detect a significant difference between Cx43- cKO and Cx43-WT mice in depression-related behaviors, anxiety-like behaviors, or memory capacity.
These results suggested that Cx43 expression in excitatory neurons at early postnatal stages contributes to short-term motor learning capacity.

References
1.Cotrina, M.L., Gao, Q., Lin, J.H.-C., Nedergaard, M. (2001) ‘Expression and function of astrocytic gap junctions in aging’ Brain Res, 901, 55–61.
2.Elias, L.A.B., Kriegstein, A.R. (2008) ‘Gap junctions: multifaceted regulators of embryonic cortical development’ Trends Neurosci, 31, 243–250.
3.Frisch, C., Theis, M., De Souza Silva, M.A., Dere, E., Sö hl, G., Teubner, B., Namestkova, K., Willecke, Ki., Huston, J.P. (2003) ‘Mice with astrocyte-directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels’ Eur J Neurosci, 18, 2313–2318.
4.Su, X., Chen, J.-J., Liu, L.-Y., Huang, Q., Zhang, L.-Z., Li, X.-Y., He, X.-N., Lu, W., Sun, S., Li, H., Yu, Y.-C. (2017) ‘Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety’ Proc Natl Acad Sci 114, 3228–3233.
LRTM2 AND ITS POTENTIAL BINDING PARTNERS: INSIGHTS INTO THEIR ROLES IN STRIATAL MEDIUM SPINY NEURONS
Authors: Ichise *Misato , Hatayama Minoru , Aruga Jun 
Published: February 2025

Abstract
Neural leucine-rich-repeat (LRR) transmembrane superfamily proteins have emerged as pivotal players in neural health and pathology. Notably, proteins characterized by LRR domains with no other discernible extracellular motifs have been established as crucial for synaptogenesis and synaptic maintenance.
Lrtm2, a member of this LRR-exclusive group, displays pronounced expression in the striatum, globus pallidus, and substantia nigra pars reticulata of mouse brains, with its protein levels rising during postnatal development. Past research indicated that Lrtm2-deficient mice presented with modified motor functions and fluctuations in dopamine metabolite levels within the striatum and associated regions. Our study aimed to elucidate Lrtm2's role in striatal medium spiny neurons. Our findings show alterations in the distribution of proteins pivotal for neurotransmitter regulation in the striatonigral GABAergic pathway of Lrtm2-deficient mice. These observations led us to hypothesize Lrtm2's involvement in macromolecular trafficking within striatal neurons. To further discern the molecular mechanisms by which Lrtm2 may regulate macromolecular transport, we verified the co-localization of Lrtm2 and its potential binding partners in vivo.
THE IN SILICO IDENTIFICATION OF AN HERB THAT CAN AMELIORATE COGNITIVE DECLINE IN MICE MODEL FOR ALZHEIMER’ S DISEASE
Authors: Lee Bomi , Yu Myeong-San , Song Jae Gwang , Na Dokyun , Kim *Hyung Wook 
Published: February 2025

Abstract

Background
Conventional drug discovery has focused on developing synthetic chemicals. However, a number of chemical drugs have been withdrawn during preclinical stages or from the market due to toxicity concerns. Natural herbs have been receiving more attention lately because of their relatively low toxicity levels and the abundance of historical medical documentation supporting their use.
Nevertheless, efforts to find those that might help treat diseases have frequently been ad hoc due to a need for more knowledge regarding these herbs and their compounds; consequently, there is a growing demand for an in silico method to identify beneficial herbs.

Aims & Objectives
Using an in silico approach, we aimed to find a natural therapeutic herb that could help treat Alzheimer's disease (AD). We then tested the herb's effectiveness in treating AD in a mouse disease model.

Methods
This study offers a computational method for determining which natural herbs are particularly useful in treating AD patients' cognitive decline. Our in silico approach examined the parallels between herbal remedies and well-known medications that target proteins linked to AD. We were able to locate a possible medicinal herb for the treatment of AD via this method. Later, its effectiveness in treating cognitive decline in AD mouse models was evaluated experimentally.

Results
Our in silico approach allowed us to identify herb A, which dramatically reduced the cognitive decline brought on by neurodegeneration in an AD mouse model. According to behavioral analyses, herb A considerably enhanced memory and motor abilities. By using our approach, we determined that the compounds found in herb A were comparable to known inhibitors of multiple therapeutic target proteins of AD, which can regulate symptoms of AD.

Discussion & Conclusions
Our in silico method suggests that herb A may help AD patients' cognitive decline. Additionally, the trial findings demonstrated that herb A has the potential to be clinically helpful in preventing mild cognitive impairment in the early phases of Alzheimer's disease. These results demonstrate the potential value of our in silico approach and the potential therapeutic use of the identified natural herb in managing and preventing AD.
THE ROLE OF OPRM1 A118G POLYMORPHISMS IN NALTREXONE RESPONSE IN THE TREATMENT OF ALCOHOL USE DISORDER
Authors: Chen *Chun-Hsin , Huang Ming-Chyi 
Published: February 2025

Abstract

Background
The prevalence of alcohol use disorder (AUD) has been increased over the past decades in Taiwan. Naltrexone, an opiate antagonist, is currently approved for AUD treatment. However, relapse to heavy or uncontrolled drinking remains common. OPRM1 A118G (Asp40Asn, rs179997), a specific single nucleotide polymorphism (SNP) in the mu opioid receptor gene, moderates naltrexone efficacy.
Individuals who carried the A118G G (Asp) allele, approximately 25% in Caucasians and 40-45% in Asians. However, existing evidence largely had focused on Caucasians, leaving the genetic effect unresolved in our Asian people.

Aims and Objectives
We aimed to assess the clinical variables of patients with AUD, who were treated with naltrexone for 12 weeks, and followed the patients’ drinking outcomes at week 2, 4, 8, 12. In addition, we compared drinking outcomes and psychological assessments between patients with different OPRM1 A118G genotypes.

Methods
Patients with UAD were provided with naltrexone hydrochloride dosing was titrated from 25 mg per day for the first 3 days to 50 mg per day for the remainder of treatment for 12 weeks. Frequency and quantity of alcohol consumption in the previous 90 days before entering the detoxification treatment was determined using the Time-Line Follow-Back method. We examined average drinks per day, number of drinking days and heavy drinking days per week, and abstinence days during the 12-week study. Alcohol craving was measured by visual analog scale (VAS) and Penn Alcohol Craving Scale (PACS). The individual’ s attitude (self-efficacy or confidence) to abstain from drinking was assessed by Alcohol Abstinence Self-Efficacy scale (AASES). We genotyped OPRM1 A118G genotype (rs179997) for all individuals.

Results
A total of 94 patients with AUD, who were treated with naltrexone, were recruited into our study. The numbers of patients with OPRM1 A118G AA, AG and GG genotypes are 41, 45, and 8. We combined patients with AG and GG into one group (G-allele carriers) for further analyses. There were no differences in demographic characteristics and drinking history, including mean age, sex distribution, education, age of alcohol tolerance, and duration of drinking history, between G-allele carriers and non- carriers. Regarding drinking outcomes during 12-week naltrexone treatment, we did not find differences in average drinks per day, number of drinking days per week, heavy drinking days per week, and abstinence days between the two groups. Changes of psychological assessments including VAS, PACS, and AASES also did not differ between G-allele carriers and non-carriers.

Discussion and Conclusion
We did not find any significant genetic effect of OPRM1 A118G on drinking outcomes during 12-week naltrexone treatment.
THE INTERPLAY OF CHILDHOOD TRAUMA, OXYTOCIN, AND IMPULSIVITY IN PREDICTING THE ONSET OF METHAMPHETAMINE USE
Authors: Goh *Kah Kheng , Chang Hu-Ming , Chen Chenyi , Lu Mong-Liang , Jou Susyan , Santos Vitor Hugo Jesus 
Published: February 2025

Abstract

Background
Childhood trauma is associated with substance use disorders, including methamphetamine use disorder (MUD). Oxytocin, involved in social bonding, stress regulation, and reward processing, may influence addiction vulnerability and impulsivity in individuals with a history of childhood trauma.

Aims & Objective
To investigate the relationships among childhood trauma, oxytocin levels, impulsivity, and the age of first methamphetamine use in individuals with MUD.

Method
The study included 298 male participants (148 individuals with MUD and 150 healthy controls) from both probation offices and psychiatric clinics. Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11), and plasma oxytocin levels were obtained.

Results
Individuals with MUD exhibited higher levels of childhood trauma, impulsivity, and lower plasma oxytocin levels compared to healthy controls. Childhood trauma was associated with a younger age of first methamphetamine use, higher impulsivity, and lower oxytocin levels among individuals with MUD. Plasma oxytocin levels partially mediated the relationship between childhood trauma and both the age of first methamphetamine use and impulsivity. Serial mediation analysis demonstrated that oxytocin levels and impulsivity sequentially mediated the relationship between childhood trauma and the age of first methamphetamine use.

Discussion & Conclusions
Findings indicate that lower oxytocin levels, consequent to early adversity, can lead to increased impulsivity and earlier initiation of methamphetamine use. Previous evidence indicates that oxytocin plays a crucial role in modulating stress response, emotion regulation, and social functioning, which could be affected by early life adversity on a more fundamental level, such as influencing neurocircuitry or methylation levels of the oxytocin receptor gene. These results emphasize oxytocin's influence on reward neurocircuitry and suggest that improving oxytocin levels could potentially ameliorate methamphetamine use-related risks, contributing to more effective prevention strategies for MUD. Future research should explore oxytocin and impulsivity-focused interventions to mitigate the effects of childhood trauma and reduce MUD development risk.
TNFR2 LEVEL CHANGES IN PATIENTS WITH ALCOHOL DEPENDENCE DURING EARLY WITHDRAWAL
Authors: Peng *Sheng-Hsun , Huang Ming-Chyi 
Published: February 2025

Abstract

Background
Alcohol Withdrawal Syndrome (AWS) is one of the defining characteristics of alcohol dependence (AD) and can manifest with various clinical features, including delirium tremens (DTs), which is recognized as a severe form of AWS. Cytokine receptors like tumor necrosis factor receptor 2 (TNFR2) can mediate anti-apoptotic signals. Knockout studies in mice suggest a role of TNFR2 in protecting neurons from apoptosis by stimulating antioxidative pathways. Previous studies found that TNFR2 levels were elevated in alcoholic patients. This research sought to explore differences in TNFR2 levels between individuals with AD experiencing early withdrawal and healthy controls (HC).

Methods
We recruited 224 patients diagnosed with AD based on DSM-IV criteria, along with 117 healthy control (HC) participants. Within the AD group, 25 participants exhibited DTs (DT group). Blood samples were obtained from the AD group on the first day of withdrawal, as well as from the HC group. Enzyme- linked immunosorbent assays were utilized to measure serum levels of TNFR2.

Results
Patients with AD at baseline exhibited significantly elevated TNFR2 levels compared to HC. We observed the highest TNFR2 levels in the DT group (4362 pg/ml), followed by non-DT group (3175 pg/ml), and then the HC group (2157 pg/ml) (p&lt;0.0001). The differences remain significant even after adjusting for education years and smoke package-years in the linear regression analysis. In addition, the multiple linear regression analysis demonstrated significant correlations between TNFR2 levels and age, smoking history, and alcohol consumption variables.

Conclusion
Our findings indicate that the dysregulation of immunocytokines could be linked to the underlying mechanisms of AD. In addition, the differential TNFR2 levels between DT and non-DT groups underscores a possible role of TNFR2 in DTs subtypes among AD patients undergoing withdrawal. The increase in TNFR2 levels following chronic and heavy alcohol consumption could be a compensatory response to prolonged inflammation and physiological imbalance. Further investigations are necessary to understand the mechanisms of TNFR2 in alcohol addiction more comprehensively.
EXAMINING THE EFFECTS OF PHARMACOLOGICAL AND NUTRITIONAL INTERVENTIONS ON METABOLIC SYNDROME ASSOCIATED WITH ANTIPSYCHOTIC TREATMENT IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Liu *Chun-I , Tsai Yuan-Jen , Goh Kah Kheng 
Published: February 2025

Abstract

Background
Currently, anticholinergic medications are commonly administered to mitigate antipsychotic-related extrapyramidal symptoms. However, there is a need for further research into medications that can effectively reduce metabolic side effects.

Aims & Objective
This research aims to quantitatively compare the effects of nutritional and pharmacological augmentation on metabolic and anthropometric profiles in the individuals with schizophrenia who are undergoing antipsychotic treatment.

Method
We performed a comprehensive search of PubMed, EMBASE, Web of Science, and Cochrane Controlled Register of Trials up to June 1, 2023. The Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias. A total of 90 studies involving 5,125 participants were included. Bayesian network meta-analysis (NMA) was conducted using Rstudio 4.3.0. The effect sizes were reported as mean differences (MDs). The primary outcome was body weight and fasting glucose, and secondary outcomes included waist circumference, HbA1c, Homeostasis Model Assessment-Insulin Resistance index and PANSS total score. A random-effects model was utilized to combine the data. The surface under the cumulative ranking curve was used to rank the various pharmacological and nutritional interventions.

Results
Analysis showed several agents could significantly reduce the fasting glucose (Figure 1). In terms of body weight, several interventions showed significant effects in attenuating antipsychotic-induced weight gain. Metformin (MD = -3.74, 95% CI [-4.93, -2.54]), exenatide (MD = -4.50, 95% CI [-8.47, - 0.53]), topiramate (MD = -4.40, 95% CI [-7.19, -1.61]), liraglutide (MD = -4.23, 95% CI [-6.87, -1.58]), nizatidine (MD = -3.05, 95% CI [-6.09, -0.11]), probiotic combined with dietary fiber (MD = -5.15, 95% CI [-8.65, -1.65]), ramelteon (MD = -9.15, 95% CI [-18.38, -0.04]) and sibutramine (MD = -5.05, 95% CI [-8.94, -1.16]) all demonstrated significant effects in reducing weight gain. For the secondary outcome, metformin and naltrexone showed significant improvements in insulin resistance. Melatonin was associated with improvements in psychopathology. However, no intervention, either pharmacological or nutritional, showed significant effects in reducing waist circumference or HbA1c.

Conclusion
Several pharmacological and nutritional interventions showed significant improvements in antipsychotic- related metabolic disturbances. Prescribing augmented medication at an earlier stage to mitigate the side effects of antipsychotics could be a viable strategy.
A NATURALISTIC RETROSPECTIVE STUDY OF ARIPIPRAZOLE ONCE- MONTHLY 400 MG USED FOR SCHIZOPHRENIA
Authors: Chiu *Nan-Ying , Kung Pei-Shan 
Published: February 2025

Abstract

Background
Schizophrenia requires lifetime management with medication to prevent worsening of clinical features. Poor and non-adherence with antipsychotics is associated with an overall poor prognosis. Long-acting injectable antipsychotics seen as an intervention to improve adherence. Aripiprazole is considered atypical. Aripiprazole has a unique receptor profile as a partial agonist at the D2 receptor, resulting in fewer extrapyramidal symptoms and other side effects while still controlling psychotic symptoms. Aripiprazole is available as an oral daily medication, as well as a depot formulation – aripiprazole once-monthly. Real-world data on the efficacy and adverse effects of aripiprazole depot are needed.

Aim & Objectives
The aims of this study were to review the efficacy and safety/tolerability of aripiprazole once-monthly 400mg (AOM 400).

Methods
A naturalistic, retrospective study was conducted to examine the electronic records of schizophrenics who were receiving or had received aripiprazole once-monthly 400 mg before May 2022. The patients received aripiprazole depot for over 12 months were enrolled. Hospitalization issue, psychiatric symptoms/signs and adverse effects were compared between pre- and post-aripiprazole depot treatment of 12 months.

Results
Sixty-one schizophrenic patients enrolled. Some patients had comorbid other mental disorders. Oral antipsychotic was effective in improving hallucinations, delusions and mood symptoms; these benefits were maintained or enhanced further with depot. We found score of Clinical Global Impression- Severity (CGI-S) decreased, also reduced concomitant medications. Twenty-one patients admitted in psychiatric ward prior using aripiprazole depot in one year, 9 patients hospitalized after using aripiprazole depot for 1 year, the admission rate reduced, days of hospitalization decreased too. By study end, only one patient (1.6%) discontinued aripiprazole depot. Only few side effects were noted, such as akathisia, anxiety, insomnia, weight gain, most of the severity of adverse effects were mild.

Discussion & Conclusion
Our data showed AOM 400 was effective and well tolerated. It reduced hospitalization rate and days of admission, also improved clinical manifestations of schizophrenia, no overt adverse effects were noted, but side effects should prompt full evaluations and management should be considered. Further close observation for a longer period is essential.

References
Dawood, J.G. Smith, N. Nadeem, C. Abbasian. Safety and effectiveness of long-acting injectable Aripiprazole in daily practice: A naturalistic retrospective study. European J Psychiatry. 2020; 34(2):82- 89.
THE ROLE OF PSYCHOPHARMACOLOGY AS CONTRIBUTION TO THE PREVENTION OF FURTHER CRIMES INTEGRATIVE FORENSIC TREATMENT IN SWITZERLAND
Authors: Schlemper *Manola , Saceleanu Vicentiu 
Published: February 2025

Abstract

Background
In forensic treatment, the legal prognosis is of central importance. The reduction of the risk of recidivism with criminal offenders who suffer from mental illnesses can only be achieved if the patient’ s mental health is improved and stabilized (1).

Aims & Method
The complex integrative course of treatment of patients suffering from paranoid schizophrenia will be demonstrated by a case study in a specific forensic context. In addition, an example of the inpatient therapeutic measure that a court in Switzerland can order if a perpetrator is classified as mentally ill, the crime or offense is related to it and the perpetrator is considered dangerous, will be presented.

Results & Conclusion
Treating schizophrenia, psychopharmacology has the most important role (2). An effective dose and the compliance of the patient are also very important factors to achieve the primary goal in the offense - oriented treatment of the schizophrenia. This is to prevent further decompensation and thus avoid possible further crimes.

References
Schlemper, M., Saceleanu, V. (2021).The Integrative Treatment of Schizophrenia in a Forensic Context, Acta Medica Transilvanica, 26(4), p. 27-29.
Fleischhacker, W. (1995). Die pharmakologische Behandlung schizophrener Stö rungen. In: Hinterhuber H, et al, editors. Die Behandlung der Schizophrenien. State oft he Art, Innsbruck: Verlag Integrative Psychiatrie, p. 9-116.
Automatic Interpretation of Seismic Horizon Based on Multi-Attribute and Attention-UNet
Authors: Ren Junjie , Wu Hao , Zheng Di , Wang Shaoxiang 
Published: February 2025

Abstract
Horizontal tracking constitutes a foundational and critical aspect of seismic data processing and interpretation. The traditional manual horizon tracking work is time-consuming and subjectively interferes with huge factors. In response, automated horizon tracking methods have been developed, albeit with the drawback of requiring extensive parameterization. Intelligent horizon tracking methods combined with deep learning are also a popular development direction in the future. Nonetheless, the efficacy of conventional convolutional neural network (CNN) approaches, reliant solely on seismic amplitude data, is markedly limited in scenarios characterized by poor data quality, complex geological structures, and the prohibitive cost of acquiring extensive high-quality training labels. In addressing these challenges, this work based on the current mainstream intelligent horizon tracking method, we further optimize and propose a method based on seismic multi-attribute constraints and Attention mechanism of U-Net neural network. Through the multi-attribute combined analysis, the two attributes with the most obvious features for horizon interpretation (instantaneous phase, principal component filtering) are selected to be combined with the amplitude data for seismic attribute constraints. Multi-attribute analysis furnishes extensive feature information crucial for interpreting subterranean structures and horizons. It enables the capture of multi-scale feature details throughout network training, facilitating enhanced visualization and identification of horizons. Moreover, a curve reconstruction method using waveform similarity is added to augment the training data and training labelled data to improve the generalization of the training model. The Attention-UNet network model designed in this work captures the target horizon feature information more accurately. The prediction results of multi-channel seismic attribute data with 1D input at the network end show that the horizon tracking results of this work are significantly better than those predicted by the traditional U-Net network using a single seismic amplitude data.