bluuebunny/crossref_metadata_2025 huggingface dataset:
CHRONIC SLEEP FRAGMENTATION ACCELERATES THE DEVELOPMENT OF PRODROMAL SYMPTOMS AND PATHOLOGICAL CHANGES IN PARKINSON’ S DISEASE MODEL MICE
Authors: Miyazaki *Masayuki , Yagihara Hiroko , Fujita Hiromi , Yamakado Hodaka , Wada Keiji , Minakawa Eiko N
Published: February 2025

Background

Parkinson’ s disease (PD) is the second most common neurodegenerative disease after Alzheimer’ s disease. Patients with PD exhibit various non-motor symptoms, including constipation, hyposmia, and sleep disturbance, in addition to classical motor symptoms such as bradykinesia, muscular rigidity, and rest tremor. The pathological hallmarks of PD are phosphorylated alpha-synuclein (p-syn) accumulation and dopaminergic neuronal loss in substantia nigra pars compacta. Patients are generally diagnosed with PD after the onset of motor symptoms, but the onset of non-motor symptoms often precedes that of motor symptoms. This prodromal phase of PD, which lasts for more than a decade, is a critical time window for disease modification to prevent or delay the onset of motor symptoms. Insomnia is the most common sleep disorder in older adults and patients with PD. In patients with PD, chronic sleep fragmentation due to frequent nocturnal arousals is the most prevalent symptom of insomnia. While various PD-related etiologies induce chronic sleep fragmentation, recent epidemiological studies suggested that chronic sleep fragmentation itself may accelerate the clinical and pathological progression of PD. However, the precise causal relationship between progression of PD and chronic sleep fragmentation remains unknown.

Aims & Objectives

We aimed to test whether chronic sleep fragmentation accelerates the disease course of PD using model mice.

Method

Transgenic mouse model of PD (Tg) that recapitulates age-dependent onset and progression of premotor non-motor symptoms, or wild type (WT) mice were housed in either of the following cages from the age when Tg mice do not exhibit non-motor symptoms: (1) sleep disturbance (SD) cage, a running- wheel-based device that induces chronic sleep fragmentation similar to PD patients (SD group), (2) wheel cage (WC), a control cage with a running wheel but with no sleep disruption (WC group), or (3) normal cage (NC), another control cage without running wheel (NC group). After 5 or 6 weeks, multiple non- motor symptoms were evaluated. After 7 weeks, brains were collected, and p-syn accumulation in the brains of Tg mice was evaluated.

Results

Among Tg mice, only the SD group showed non-motor symptoms. Among WT mice, the SD group showed no or minimal non-motor symptoms which were milder than that of Tg mice in the SD group. Among Tg mice, the SD group showed significantly increased p-syn accumulation in multiple brain regions.

Discussion & Conclusion

These results suggest that chronic sleep fragmentation accelerates the onset of prodromal symptoms and p-syn accumulation in PD model mice. Our findings implicate that chronic sleep fragmentation would be a potential target for preventing or delaying the motor onset of PD.
A BRIEF SELF-COMPASSION AND SELF-ESTEEM INTERVENTION FOR SUICIDAL UNIVERSITY STUDENTS: A FEASIBILITY STUDY
Authors: Nguyen *Dat Tan , Mitsui Nobuyuki , Satoshi Asakura , Fujii Yutaka , Toyoshima Kuniyoshi , Kusumi Ichiro
Published: February 2025

Objectives

Suicide is a serious mental health problem among university students. The current study aimed to examine the effectiveness of a novel psychological education program targets suicidal ideation by enhancing self-esteem and self-compassion.

Methods

A single-arm study design was implemented to investigate the feasibility and acceptability of a novel four-session psychoeducation program for university students who experienced suicidal ideation. The study protocol was registered retrospectively in the national UMIN Clinical Trials Registry (Registration ID: UMIN000043702) and approved by Hokkaido University Ethical Committee (Approval ID: 20-031). Recruitment took place from Hokkaido university health care center. Suicidal behaviors, self- compassion, self-esteem, and other psychological variables were measured at baseline, post- intervention, and 1-month follow-up. Participants also completed an evaluation of the program’ s acceptability.

Results

Currently, twelve participants consented to take part in the intervention with nine participants completed post treatment assessments. The attrition rate was 25%. There was a significant reduction for depression (Cohen’ s d = 1.198) and suicidal behaviors (Cohen’ s d = 0.891) as well as a significant increase for self-compassion (Cohen’ s d =1.352) at post-intervention. Additionally, the psychoeducation program was highly appreciated and positively received by the participants.

Discussion

The study showed promising result for the psychoeducation program, especially in terms of reducing suicidal ideation and depression. However, the study suffers from a small sample size with a single-arm study design. Further study regarding the effectiveness of the program is highly warranted.
THE EFFICACY OF LACOSAMIDE AND PERAMPANEL IN THE ANIMAL MODEL OF AUTISM SPECTRUM DISORDER
Authors: Matsuoka *Satomi , Moriya Yuka , Ito Fuyuka , Miyachi Mai , Fuwa Takemi , Kurahashi Hitomi , Nabeshima Toshitaka , Mouri Akihiro , Hasegawa Yoichi
Published: February 2025

Background

Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by social deficits and restrictive patterns of behavior and interests. Epilepsy is comorbidity in ASD patients. The imbalance of excitation and inhibition in neural circuitry is hypothesized for the pathophysiology of ASD as well as epilepsy. It is epidemiologically reported that administration of valproic acid (VPA) during pregnancy increases the risk of ASD in the offspring. In this study, we investigated therapeutic potential of anti-epileptic drugs for ASD using prenatal VPA-induced ASD animal model.

Methods

Pregnant mice were injected with VPA (500 mg/kg, i.p.) on gestational day 12. The offspring were subjected social interaction test, novel object recognition and repetitive behavior test. The offspring were injected with anti-epileptic drugs (lacosamide, and perampanel) before each behavioral test.

Result

The offsprings from mice exposed to VPA during pregnancy showed decrease in social interaction time and exploratory preference for novel object, and increase in grooming numbers. The lacosamide, and perampanel increased exploratory preference for novel object and decreased grooming numbers in the offsprings from mice exposed to VPA during pregnancy.

Conclusion

Behavioral changes in offsprings from mice exposed to VPA during pregnancy are associated with the symptom of ASD (decrease in social interaction time: social disability, decrease in approach time for novel object: cognitive dysfunction). We suggest that lacosamide and perampanel improve visual recognition memory impairment and increased repetitive behavior in ASD model mice. These data suggested that anti-epileptic drugs attenuated could have therapeutic potential for ASD symptoms.
CONNEXIN43 IN NEONATAL EXCITATORY NEURONS IS IMPORTANT FOR MOTOR LEARNING
Authors: Yu *Yongchun
Published: February 2025

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

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

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

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

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

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<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

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

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

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

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.
Cabozantinib for brain metastases in renal cell carcinoma: a single-institution retrospective analysis
Authors: Tokura Yuumi , Kijima Toshiki , Kokubun Hidetoshi , Uematsu Toshitaka , Takei Kohei , Betsunoh Hironori , Yashi Masahiro , Kamai Takao
Published: February 2025

Objective

Brain metastases from renal cell carcinoma (RCC) present considerable treatment challenges and poor prognoses. In this study, we evaluated the efficacy of cabozantinib, a multi- tyrosine kinase inhibitors (TKIs), in improving the progression-free survival (PFS) and overall survival (OS) of patients with RCC with brain metastases.

Methods

This retrospective study included 30 patients with RCC and brain metastases treated at a single institution between 2010 and 2024. Patient demographics, treatment modalities, and survival outcomes were analyzed. Systemic therapies included cabozantinib, TKIs, and immune checkpoint inhibitors (ICIs). Local therapies included Gamma Knife surgery (GKS) and whole-brain radiation therapy (WBRT). Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models.

Results

Cabozantinib-treated patients (n = 12) exhibited significantly longer median PFS (21.6 vs. 4.1 months; P < .001) and OS (25.7 vs. 8.3 months; P = .019) compared to non-cabozantinib patients (n = 18). In patients treated with GKS, cabozantinib further improved PFS (29.6 vs. 3.9 months; P < .001) and OS (25.7 vs. 12.8 months; P < .001). Cox regression analysis identified cabozantinib as the sole independent predictor of improved PFS (hazard ratio [HR], 0.09; P = .004) and OS (HR, 0.17; P = .009).

Conclusion

Cabozantinib significantly improved survival outcomes in RCC patients with brain metastases, underscoring its role as an effective systemic therapy. However, potential risks such as brain hemorrhage highlight the importance of careful patient selection and close monitoring. Further prospective studies are warranted to explore optimal combination strategies.
Joint Trauma System: Behind the Scenes
Authors: Gurney Jennifer , Tadlock Matthew D , Van Gent Jan-Michael
Published: February 2025

The Joint Trauma System was created out of a crucial need for the integration of battlefield medicine. The Joint Trauma System supports the execution and advancement of combat casualty care throughout the continuum of care by medical and nonmedical providers, leaders, and commanders at all levels.
New Kids on the Block: Estimating Use of Next Generation Gram-negative Antibiotics Across Greater than 700 Hospitals in the United States
Authors: Harris Anthony D , Goodman Katherine E , Pineles Lisa , Walker Morgan , Bork Jacqueline T , Heil Emily L , Claeys Kimberly C , Brooks Justin , Kadri Sameer , Maron Bradley A , Baghdadi Jonathan D
Published: February 2025

Background

In recent years, new broad-spectrum antibiotics targeting Gram-negative organisms have been introduced, including cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, eravacycline, imipenem-relebactam, omadacycline and meropenem-vaborbactam. This study aimed to describe new antibiotic use across a large national cohort.

Methods

We performed a retrospective cohort study of hospital discharges from June 2022-May 2023 using the PINC-AI Database. Antibiotic utilization was ascertained from daily charges. Clinical indication(s) were inferred from ICD-10 diagnosis codes. Antibiotic therapy was considered definitive if continued >3 days. Piperacillin-tazobactam was used as a comparator.

Results

Across 832 hospitals, 3,890,557 admissions (61.9% of all admissions) included an antibiotic prescription. New antibiotics were prescribed in 9,768 admissions (0.25% of antibiotic-prescribing admissions) across 537 hospitals. Ceftolozane-tazobactam was prescribed in 4,157 admissions (42.6% of 9,768), ceftazidime-avibactam in 3,660 (37.5%), eravacycline in 1,213 (12.4%), cefiderocol in 1,060 (10.9%), meropenem-vaborbactam) in 456 (4.7%), omadacycline in 104 (1.1%), and imipenem-relebactam in 99 (1.0%). In contrast, piperacillin-tazobactam was prescribed in 731,719 (18.8%) and colistin in 570 (0.01%) admissions. 46% (n=4,647/9,768) of new antibiotics were started in the first 3 days of hospital admission, and 70% (n=6,799/9,768) were used as definitive therapy. Sepsis (76%), pneumonia (46%), and urinary tract infection (39%) were the most common clinical indications. On average, patients treated with new antibiotics had 8 more comorbid conditions than patients receiving piperacillin-tazobactam.

Conclusions

Ceftazidime-avibactam and ceftolozane-tazobactam remain the most frequently prescribed new antibiotics, with uptake of subsequently approved agents trailing. New antibiotics are most commonly used as treatment for sepsis among patients with multiple comorbidities.
Citizen preferences for online hate speech regulation
Authors: Munzert Simon , Traunmüller Richard , Barberá Pablo , Guess Andrew , Yang JungHwan
Published: February 2025

The shift of public discourse to online platforms has intensified the debate over content moderation by platforms and the regulation of online speech. Designing rules that are met with wide acceptance requires learning about public preferences. We present a visual vignette study using a sample (n=2,622) of German and US citizens that were exposed to 20,976 synthetic social media vignettes mimicking actual cases of hateful speech. We find people’s evaluations to be primarily shaped by message type and severity, and less by contextual factors. While focused measures like deleting hateful content are popular, more extreme sanctions like job loss find little support even in cases of extreme hate. Further evidence suggests in-group favoritism among political partisans. Experimental evidence shows that exposure to hateful speech reduces tolerance of unpopular opinions.
Comparative safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs for cardiovascular outcomes in rheumatoid arthritis
Authors: Sendaydiego Xavier , Gold Laura S , Dubreuil Maureen , Andrews James S , Reid Pankti , Liew David F L , Goulabchand Radjiv , Hughes Grant C , Sparks Jeffrey A , Jarvik Jeffrey G , Singh Siddharth , Liew Jean W , Singh Namrata
Published: February 2025

Objectives

To assess the comparative safety of tumor necrosis factor inhibitor (TNFi), non-TNFi, and Janus kinase inhibitor (JAKi) biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) for the risk of major adverse cardiovascular events (MACE) using US administrative claims data.

Methods

We performed a cohort study using MerativeTM Marketscan® Research Databases (2012–2021) of individuals aged 18–64 years with RA initiating b/tsDMARD treatment. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for developing MACE within 2 years of b/tsDMARD initiation, adjusting for potential confounders.

Results

We included a total of 34 375 treatment exposures: 71% TNFi, 10% JAKi, 8% abatacept, 5% rituximab, and 5% IL-6i. Most individuals were female (77–84%) with a median (interquartile range) of 50 (42, 56) years. Rituximab had the highest incidence rate of MACE (196/10 000 person-years; 95% CI 126, 291), followed by IL-6i (111/10 000 person-years; 95% CI 57, 193). Multivariable analyses showed non-statistically significantly higher MACE risk with rituximab (HR 1.5; 95% CI 0.9, 2.4) and IL-6i (HR 1.3; 95% CI 0.7, 2.4) exposures but no increased risk with JAKi relative to TNFi use.

Conclusion

In this large nationwide study, rituximab and IL-6i users had numerically higher, but not statistically significant, MACE risk. Our data support the safety of b/tsDMARD use for RA treatment. This study was limited by short follow-up time and confounding by indication; further studies that can overcome these limitations are needed.
Heart rate variability responses of horses and veterans with post-traumatic stress disorder to ground-based adaptive horsemanship lessons: a pilot study
Authors: Rankins Ellen M , Faremi Boluwatife E , Hartmann Kyle , Quinn Andrea , Posada-Quintero Hugo F , McKeever Kenneth H , Malinowski Karyn
Published: February 2025

Heart rate variability (HRV) can be measured as an indicator of autonomic nervous system (ANS) balance and thus, stress and affective arousal. Mixed results have been reported in the limited literature addressing the effects of equine-assisted services (EAS) on HRV in the human and horse participants. The aims of the present study were to determine the effects of ground-based adaptive horsemanship (AH) lessons on veterans’ and horses’ HRV during weekly lessons as well as veterans’ resting HRV outside of lessons. Veterans with post-traumatic stress disorder (PTSD) were randomly assigned to 8 weeks of AH or control (CON, no changes in treatments or activities) conditions. Horses were assigned to AH or control (CON, stall in arena) conditions based on previous experience (EAS or recreational riding). Electrocardiogram traces from the veteran and AH and CON horses were recorded during the 30-min lessons. Traces were recorded during resting conditions before (PRE) and after (POST) the 8-week period from AH and CON veterans and healthy, non-veterans. Heart rate (HR), root mean square of successive differences (RMSSD) and low frequency to high frequency ratios (LF/HF) were calculated after identification of peaks with the Pan-Tompkins algorithm and manual correction during 5-min epochs. Data were analyzed with repeated measures, mixed model ANOVAs (SAS v9.4). HR was lowest (p ≤ 0.0323) in the horses and veterans during the first 10 min of the lessons. Veterans’ RMSSD was higher (p ≤ 0.0496) in weeks 4 and 6 than week 2. LF/HF was greater in veterans with PTSD than healthy, non-veterans across PRE and POST time points. Increased HR later in the lessons is likely a result of increased movement in the horses and veterans. An interval of decreased stress and increased resiliency might be present in veterans participating in multi-day AH sessions. Increased sympathetic arousal measured via LF/HF was not mitigated by 8 weeks of AH. Horses appeared unstressed by the interactions as no changes in HRV were observed
Adapalene potentiates the cytotoxicity of anti-cancer drugs by enhancing cell cycle dysregulation and apoptosis in MKN-45 cells
Authors: Yuan Tein-Ming , Liu Bang-Hung , Huang Yi-Ching , Chuang Show-Mei
Published: February 2025

Adapalene is a third-generation synthetic retinoid that has been approved by the FDA as a dermatological drug was recently repurposed for its potential anti-cancer effects. Here, its anti-cancer potential was determined in human gastric adenocarcinoma cell lines. Adapalene did not show significant cytotoxicity toward AGS and MKN-45 cells, but displayed synergistic or additive effects in inhibiting cell growth and increasing apoptosis in MKN-45 cells, but not AGS cells, when combined with 5-FU, cisplatin, docetaxel, or doxorubicin. Co-treatment with adapalene plus docetaxel or doxorubicin increased DNA damage and S-phase arrest without affecting the expression levels of HR23A/B, XPC, or Rad51. In MKN-45 cells exposed to docetaxel or doxorubicin, adapalene co-treatment downregulated Aurora A and upregulated p21, potentially contributing to its ability to enhance DNA damage and cell cycle dysregulation, and increased reactive oxygen species (ROS) accumulation, which may potentiate the cytotoxicity of the anti-cancer agents. Our present results reveal that adapalene is not cytotoxic towards MKN-45 gastric cancer cells when applied alone, but can synergistically enhance the sensitivity of these cells to conventional chemotherapeutic drugs. Further investigations are warranted to fully elucidate the mechanisms underlying the synergistic effects of adapalene and identify markers that could, given the heterogeneity of gastric cancers, identify patients who are likely to benefit from adapalene co-treatment.
PTPN9 promotes melanoma progression by regulating the ferroptosis pathway
Authors: Wang Hongmei , Qiao Sen , Huang Lingyan , Zhang Zhengping , Wang Jiao , Tian Wenxiu
Published: February 2025

In recent years, there has been a gradual increase in the incidence and mortality rates of melanoma, posing a significant threat to human health and life. Protein tyrosine phosphatases (PTPNs) have been implicated in the progression of various human cancers, including breast, lung, and cervical cancer. To investigate PTPN9 expression in melanoma, impacting the disease's survival and prognosis. Our study, which involved an analysis of The Cancer Genome Atlas database and immunohistochemical staining of pathological sections, identified an upregulation of PTPN9 expression in melanoma, impacting the disease's survival and prognosis. At the cellular level, we investigated the effects of PTPN9 on the proliferation, invasion, and metastasis of A375 and SK‐MEL‐28 cells. Through various experimental techniques such as Western blot protein detection, electron microscopy, and oil red O staining, we observed that PTPN9 potentially contributes to the development of skin cutaneous melanoma (SKCM) by regulating ferroptosis‐related proteins ACSL4, FTH1, and P53, thereby influencing lipid metabolism. The results of this study highlight the unique role of PTPN9 in SKCM and suggest its potential as a biomarker for the disease.
REBOA for remote damage control resuscitation and the race against time
Authors: Marsden Max , Lendrum Robert , Perkins Zane , Davenport Ross A.
Published: February 2025

Purpose of review

The management of noncompressible haemorrhage (NCH) remains a critical challenge in trauma care, with early mortality rates persistently high despite advances in trauma systems. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as a potential intervention to address severe haemorrhage in prehospital and hospital settings. This review examines the role of REBOA in remote damage control resuscitation, focusing on the ‘golden hour’ and the ‘platinum 5 minutes’ concepts that underscore the urgency of timely interventions.

Recent findings

Evidence from the UK-REBOA trial and related studies highlights the complexity of implementing REBOA in prehospital settings, emphasising the importance of early deployment, appropriate patient selection, and minimisation of delays. Technological innovations, including AI-assisted decision-making and automated partial REBOA systems, offer promising avenues for optimising REBOA’s application. Furthermore, the concept of damage control prehospital care prioritises essential interventions tailored to individual patient needs, advocating for a streamlined approach to reduce on-scene time.

The integration of REBOA with advanced prehospital strategies holds the potential for reducing preventable deaths from traumatic haemorrhage, but further research is needed to refine protocols and enhance outcomes in this high-stakes domain.
Is the heart rate dipping pattern associated with sleep quality during an ambulatory blood pressure monitoring? A cross-sectional study
Authors: Leiva Sisnieguez Carlos E. , Olano Ricardo D. , Stavile Rodolfo N. , Minetto Julián , Cerri Gustavo , Espeche Walter G. , Carbajal Horacio A. , Salazar Martín R.
Published: February 2025

Objective:

The aim of this study was to characterize individuals with nondipping heart rate (HR) and to assess the association between that pattern and sleep quality during the night of an ambulatory blood pressure monitoring (ABPM).

Methods:

Individuals who attended our Unit to perform an ABPM, from February 2022 to May 2024, were asked about clinical and epidemiological antecedents and responded two validated surveys, about sleep quality during the night of the ABPM and in the prior 30 days. Then, they were categorized according to the presence of a dipping in nocturnal HR (defined as a decline in average HR at night equal or higher than 10% compared with daytime values) as HR dippers or HR nondippers (drop in mean nighttime HR lower than 10% of diurnal mean) in order to compare the mentioned variables.

Results:

One thousand two hundred and nine individuals were included. They were predominantly female (61.8%), middle-aged (median 50 years, IQR 36–60), overweight (median BMI 29, IQR 25.3–33.5) and had median ABPM estimates within normal ranges. In individuals without beta-blockers (n = 1107), HR nondippers had an adverse cardiovascular disease (CVD) risk profile, and no differences were found between HR dippers and HR nondippers concerning perceived good rest during the ABPM night (63.5 vs. 59.7%, P = 0.211) and usual sleep quality. The sensitivity analysis including beta-blockers’ users (n = 102) was consistent.

Conclusion:

A blunted dipping in mean nighttime HR identifies individuals with a high CVD risk profile and is not associated with bad sleep quality during the night of an ABPM.