bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIGH-DEFINITION TRANSCRANIAL DIRECT CURRENT STIMULATION IN HOARDING DISORDER: A CASE REPORT
Authors: Mondino *Marine , Neige Cécilia , Bation Rémy , Brunelin Jérôme 
Published: February 2025

Abstract

Background
Hoarding disorder, characterized by excessive acquisition of possessions and difficulty in discarding them, is a major treatment challenge. At the brain level, hoarding disorder has been associated with increased activity in the right dorsolateral prefrontal cortex (DLPFC).

Aims & Objectives
In a case report, we explored a therapeutic strategy using high-definition transcranial direct current stimulation (HD-tDCS) to alleviate symptoms in a patient with hoarding disorder. HD-tDCS is an emerging neuromodulation technique for patients with treatment-resistant psychiatric symptoms.

Method
A 63-year-old patient with severe, treatment-resistant hoarding disorder received 15 sessions of 20-min HD-tDCS (3 sessions per day for 5 consecutive days), with the cathode placed over the right DLPFC using a 4x1 ring electrode montage. Hoarding symptoms were assessed before at baseline, after HD-tDCS, and at 1 and 3 months follow-up using the Saving Inventory-Revised (SI-R) scale. Mood was assessed using the Montgomery-Å sberg Depression Rating Scale (MADRS).

Results
The treatment was well tolerated with no adverse events. We observed a reduction in the SI-R total score from 80 to 66 at 1-month follow-up (-18.5 %). This improvement was mainly in the excessive acquisition subscale (-50%), while the difficulty discarding subscale showed a modest decrease (-22%), and there was no change in the clutter subscale. Depressive symptoms decreased by 27% (MADRS) at 1 month, but returned to baseline at 3 months. Nevertheless, a 38% decrease in the SI-R acquisition subscale persisted at 3-month follow-up (-12.5% for the SI-R total score).

Discussion & Conclusion
Cathodal HD-tDCS over the right DLPFC appears to be a safe and promising intervention for hoarding disorder. Further validation through randomized, sham-controlled trials is needed to confirm these encouraging findings.
DEEP TRANSCRANIAL MAGNETIC STIMULATION TREATMENT FOR TREATMENT-RESISTANT OBSESSIVE-COMPULSIVE DISORDER: A CASE SERIES FROM THAILAND
Authors: Wongsaisuwan *Waewwan , Virotjanakood Vasuthorn , Jarassaeng Nittaya , Chaiudomsom Kusalaporn , Piyavhatkul Nawanant , Paholpak Pongsatorn 
Published: February 2025

Abstract

Background
Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder. The first-line treatment of OCD is either pharmacological or psychotherapy. However, the rate of treatment resistant OCD after the treatment is still high (van Roessel et al., 2023). Deep Transcranial Magnetic Stimulation (dTMS) with H-7 coil has been recently approved for resistant OCD in the USA but has not been used widely in Asia.

Aims & Objectives
To report case series of the first 4 patients with resistant OCD who received dTMS in Thailand.

Cases
All 4 patients were males and they have received at least 2 antidepressants with inadequate improvement of symptoms. The mean dose of antidepressants was 85 mg/day of fluoxetine equivalent. Three of four were taking antipsychotics (2 risperidone & 1 aripiprazole)., and two of four were taking benzodiazepine. Duration of OCD varied from 1 – 6.5 years with psychiatric comorbidity ranging from insomnia disorder to post-autoimmune encephalitis. One patient underwent electroconvulsive therapy with unsatisfactory outcomes. All patients received at least 20 sessions of FDA-approved protocol of dTMS for OCD five days a week: Frequency = 20 Hz, Duration = 2 s, Wait time = 20 s, 50 trains per session, Intensity = 60% - 100% motor threshold. All patients continued taking the medications without changing the dosages. All patients reported an improvement of clinical outcomes after dTMS, reducing the overall subjective severity of the obsessive-compulsive symptoms. Minimal, transient, but tolerable adverse effects were reported without any serious events in this case series.

Discussion and Conclusion
This is the first report from Thailand on using dTMS as an add-on treatment with pharmacological treatments. Subjective clinical outcomes from all patients were favorable with good safety and tolerability.

References
1.van Roessel PJ, Grassi G, Aboujaoude EN, Menchó n JM, Van Ameringen M, Rodrí guez CI. Treatment- resistant OCD: Pharmacotherapies in adults. Compr Psychiatry. 2023 Jan;120:152352. doi: 10.1016/j.comppsych.2022.152352. Epub 2022 Oct 25. PMID: 36368186.
ELUCIDATION OF THE INVOLVEMENT OF ASTROCYTE FUNCTION IN THE PATHOGENESIS OF GLUT1 DEFICIENCY SYNDROME
Authors: Hirai *Shinobu , Tamura Shoko , Shimbo Hiroko , Park Jonghyuk , Okado Haruo 
Published: February 2025

Abstract

Background
Glucose is a main energy source to support healthy brain function. Glucose transporter-1 (GLUT1) is the most important transport protein that transports glucose from the blood to the brain parenchyma and is reported to be expressed mainly in vascular endothelial cells and astrocyte endfeet. GLUT1 deficiency syndrome (GLUT1-DS) is a metabolic encephalopathy caused by impaired glucose transport into the brain. GLUT1-DS is a congenital disorder and heterozygous de novo mutations in the GLUT1 gene (SLC2A1) have been found in the majority of patients with GLUT1-DS, hypoglycaemia within the central nervous system, resulting in a range of CNS dysfunctions, including cognitive and motor dysfunction. Several papers have reported that Glut1 expressed in vascular endothelial cells (ECs) is important in neurological symptoms, and Adeno-associated virus (AAV)-based GLUT1 replacement therapy targeting vascular ECs is under development.

Methods
Astrocyte- and vascular EC-specific and systemic Glut1 haploinsufficient mice were used to attempt to identify the cells involved in the development of GLUT1-DS symptoms. Specifically, Aldh1l1-cre; Glut1 fl/+ mice were selected to analyze the contribution of astrocytes to GLUT1-DS symptoms and Tie2-cre; Glut1 fl/+ mice to analyze the contribution of ECs. Each mouse strain was used to measure glucose concentrations in cerebrospinal fluid (CSF) and interstitial fluid (ISF). These mice were also used in behavioral tests to assess cognitive and motor function, followed by evaluation of inflammation in the brain.

Results
First, Glut1 was found to be expressed throughout the astrocytic branches, not only in the endfeet. Next, compared to wild-type mice, all Glut1-deficient mouse strains showed reduced glucose levels in both CSF and ISF in addition to reduced cognitive and motor function. (All Glut1-deficient mouse strains: Aldh1l1-cre; Glut1 fl/+ mice, Tie2-cre; Glut1 fl/+ mice, Glut1 haploinsafficient mice).

Conclusion
These results suggest that Glut1 in astrocytes plays an important role in glucose uptake into CSF and ISF and in cognitive and motor functions. The two facts that Glut1 is expressed throughout astrocytes and the glucose concentration in ISF as well as CSF was reduced in Aldh1l1-cre; Glut1 fl/+ mice suggests that astrocytes may play a role in actively transporting glucose from blood to ISF. From this study, in addition to vascular ECs, GLUT1 in astrocytes is implicated in the pathogenesis of GLUT1-DS, suggesting that astrocytes may be a promising therapeutic target for GLUT1-DS.
MINOCYCLINE PREVENTS PREMATURE COGNITIVE DECLINE IN A MOUSE MODEL OF INTELLECTUAL DISABILITY INDUCED BY ZBTB18/RP58 HAPLOINSUFFICIENCY
Authors: Tanaka *Tomoko , Hirai Shinobu , Manabe Hiroyuki , Shimbo Hiroko , Yoshitane Hikari , Okado Haruo 
Published: February 2025

Abstract
Transcriptional repressor ZBTB18/RP58 haploinsufficiency, consisting of heterozygous ZBTB18/RP58 missense and truncated variants, causes intellectual disability. However, the pathogenesis of intellectual disability and whether this disorder can be prevented or treated are unknown. Heterozygous Zbtb18/Rp58 knockout mice were used as a model of ZBTB18/RP58 haploinsufficiency. Multiple behaviors and local potentials were assessed, and histochemical analyses in the hippocampus was performed to assess microglial status and DNA fragmentation. Object location memory was similar in wild-type mice at 2 and 4-5-months-old mice, but it decreased at 12-18-months-old mice. In contrast, in Zbtb18/Rp58 heterozygous knockout mice, object location memory at 2-months-old was similar to that of age-matched wild-type mice but decreased at 4-5-months-old. In Zbtb18/Rp58 heterozygous knockout mice, DNA damage accumulation and activation of microglia in the dentate gyrus increased early, associated with defects in DNA repair. In particular, in Zbtb18/Rp58 heterozygous knockout mice, chronic administration of minocycline suppressed age-related phenotypes such as accumulation of DNA damage and impaired object location memory. In conclusion, Zbtb18/Rp58 heterozygous knockout mice exhibit early onset of cognitive decline related to defects in DNA repair, and minocycline suppressed this abnormality, suggesting that minocycline may be a potential therapeutic agent for cognitive dysfunction caused by ZBTB18/Rp58 haploinsufficiency.
IS THERE A DIFFERENCE IN VESTIBULAR SYSTEM REACTIVITY BETWEEN PATIENTS WITH SCHIZOPHRENIA AND HEALTHY CONTROL PARTICIPANTS?
Authors: Kambari *Yasaman , Song Jianmeng , Amaev Aron , Abdolizadeh Ali , Torres-Carmona Edgardo , Ueno Fumihiko , Koizumi Teruki , Rutka John , Leblanc Emma , Bailie Neil , Dillon Wanda , Harvey Kaitlin , Palmer Laurel , Graff-Guerrero Ariel , Gerretsen Philip 
Published: February 2025

Abstract

Background
Conventional caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve and eliciting the vestibulo-ocular reflex. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function. In schizophrenia, there is no conclusive link between psychopathology and vestibular dysfunction. Initial data from another CVS study by our group suggests that individuals with schizophrenia may have greater reactivity to body temperature (37° C) CVS, as measured by the peak slow phase velocity of the resulting nystagmus (PSPV), than would be expected for healthy participants1. However, we are unaware of any studies that have investigated the differential effects of CVS temperature gradients on individuals with schizophrenia versus healthy control participants.

Aim & Objective
In the current study we aimed to examine if individuals with schizophrenia have greater reactivity to caloric vestibular stimulation than healthy control (HC) participants.

Methods
Patients with schizophrenia and HC participants received three conditions bilaterally: (1) body temperature (37° C) CVS; (2) warm CVS (44° C), and (3) cold CVS (30° C). All conditions were performed by an audiologist. The physiological response of vestibular stimulation was assessed with videonystagmography, which provides a measure of the intensity of the nystagmus via PSPV. Independent sample t-tests were conducted to compare vestibular reactivity (i.e., nystagmus) between patients and HC participants for each CVS condition.

Results
A total of 20 patients (mean age 39.2, SD=12.6, 25% female) and 20 HC participants (mean age 37.9, SD=13.1; 25% female) completed the study. There was no statistically significant difference between patients and HC participants in body temperature, warm or cold CVS (p&gt;0.05).

Discussion & Conclusion
In schizophrenia, there is no conclusive link between psychopathology and vestibular dysfunction, and we are not aware of any data that exists on the range of responses to CVS in persons with schizophrenia. We did not find any differences in vestibular reactivity between patients with schizophrenia and HC participants in response to CVS.

References
Gerretsen, P.et al.(2017) ‘Vestibular stimulation improves insight into illness in schizophrenia spectrum disorders’, Psychiatry Research, 251, pp. 333–341. doi:10.1016/j.psychres.2017.02.020.
THE EFFECT OF FOOD ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF ICLEPERTIN (BI 425809), A GLYCINE TRANSPORTER 1 INHIBITOR, IN HEALTHY VOLUNTEERS: A PHASE I OPEN-LABEL, RANDOMIZED, CROSSOVER TRIAL
Authors: Harada *Akiko , Madari Shilpa , Jungnik Arvid , Breithaupt-Groegler Kerstin , Hohl Kathrin 
Published: February 2025

Abstract

Background
Iclepertin (BI 425809) is a glycine transporter 1 inhibitor being developed for the treatment of cognitive impairment associated with schizophrenia (CIAS).

Aims and Objectives
To investigate the effect of food on the pharmacokinetics (PK) of iclepertin in healthy volunteers (HV).

Methods
This Phase I, open-label, two-period, two-sequence crossover trial included Caucasian HV (18–55 years of age). HV were randomized (1:1) to a single oral dose of iclepertin 10 mg (film-coated tablet) when fasted (reference, R) and following a standard high-fat, high-calorie meal (test, T), or received T then R. Iclepertin administrations were separated by a wash-out period of at least 14 days. The primary endpoints were area under the concentration– time curve over the time interval from 0 to the last quantifiable data point (AUC0-tz) and maximum measured concentration (Cmax) of iclepertin in plasma. The secondary endpoint was area under the concentration– time curve over the time interval from 0 extrapolated to infinity (AUC0-∞) of iclepertin in plasma. Relative bioavailability was estimated by calculating a geometric mean (gMean) T/R ratio using an analysis of variance. Safety and tolerability assessments included adverse event (AE) reporting; HVs with AEs were analysed descriptively.

Results
The 16 enrolled HV (9 women, 7 men) had a mean (standard deviation) age of 37.1 (10.1) years. The treatment adjusted gMean AUC0-tz, Cmax and AUC0-∞ and the adjusted gMean T/R ratios for the PK endpoints were higher following iclepertin 10 mg administration in the fed versus the fasted state (Table). Overall, 8/16 HV (50.0%) reported at least 1 AE; 6/16 HV (37.5%) reported drug-related AEs (fasted: 4/16 HV [25%]; fed: 3/15 HV [20.0%]) and headache was reported most frequently.

Discussion and Conclusion
Although the exposure (AUC0-tz, Cmax and AUC0-∞) and relative bioavailability of a single oral dose of iclepertin 10 mg was higher in the fed versus the fasted state, increases were deemed minor and not clinically meaningful. Further, iclepertin was generally well tolerated by Caucasian HV participating in this trial and no new safety signals were identified. These findings may be relevant to the Asian population (Rosenbrock et al., 2023).

Funding
Boehringer Ingelheim (1346-0053; NCT05347004).

References
Rosenbrock, H., Desch, M. and Wunderlich, G. (2023). Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia. Eur Arch Psychiatry Clin Neurosci, 273(7), pp.1557–1566.
SYSTEMATIC REVIEW OF INDUCED PLURIPOTENT STEM CELL THERAPY IN TRAUMATIC BRAIN INJURY
Authors: Amalakanti *Sridhar , Avula Vijaya Chandra Reddy , Singh Sachin 
Published: February 2025

Abstract

Background
Traumatic brain injury (TBI) is a major global health problem with limited treatment options. Induced pluripotent stem cells (iPSCs) have emerged as a promising therapy for neural regeneration and repair after TBI.

Aims & Objectives
This systematic review aimed to evaluate preclinical studies on the efficacy of iPSC- based therapies for functional recovery after TBI.

Method
From, PubMed, Ovid Medline, Cochrane Library, SCOPUS, and Web of Science 102 studies were found for studies on iPSCs in TBI animal models. Included studies (n=9) used neural stem cells derived from iPSCs transplanted into rodent models of TBI. Outcome measures were brain injury volume, functional recovery, and tissue repair biomarkers. Study quality was assessed using a 10-point scale.

Results
The majority of studies showed significant improvement in motor function, cognition, and social behavior with iPSC therapy. Transplanted iPSC-neural stem cells migrated to injury sites, differentiated into neurons and glia, reduced lesion size, and increased neural repair markers. Higher quality scores were noted for studies reporting randomization, blinded assessment, and temperature control.

Discussion & Conclusions
Preclinical evidence demonstrates the potential of iPSC-derived neural stem cell transplantation to improve functional outcomes after TBI through neuroregenerative effects. Further research is warranted to evaluate safety, optimize protocols, and translate findings to clinical trials for TBI patients. iPSC-based therapies may offer new hope for recovery after this devastating injury.
DEVELOPMENT OF AN AUTOMATION SYSTEM OF CULTURE AND LONGITUDINAL EVALUATION OF PATIENT IPS CELL-DERIVED ORGANOIDS (ASCLEPIOS)
Authors: Shiraishi *Atsushi , Inoue Takahito , Takaba Junji , Futamura Takashi 
Published: February 2025

Abstract

Background
Misfolding and aggregation of neurodegenerative disease proteins induce synaptic loss and neuronal cell death in specific regions of central nervous system (CNS). Although discoveries in rodent models have led to a better understanding of the mechanisms leading to neurodegeneration, differences between the rodent and human genomes may have profound effects for developing rodent models. For example, binding sites of RNA binding proteins and single nucleotide variants (SNV) associated with neurodegeneration are less conserved in rodent models.

Method
Human induced pluripotent stem cells (iPSCs) contain donor genetic background and have the potential to generate any type of cells or tissues. Therefore, the iPSC-derived neurons and tissues, called brain organoids, are expected to be useful for establishing CNS disease models and drug discovery. We have generated several brain region-specific organoids from various patient iPS cell lines.

Aims & Objectives
There are three challenges in drug discovery using iPSCs; (i) reproducibility of experiments, (ii) coordination of differentiation status among different iPSC lines and (iii) adequate cell supply.

Results
To overcome these challenges, we are developing an automation system of culture and longitudinal evaluation of patient iPS cell-derived organoids named ASCLEPiOs. ASCLEPiOs includes two robotic arms, a liquid handling system, two automated CO2 incubators and a confocal image cytometer.

Discussion & Conclusion
ASCLEPiOs will enable us to execute cell culture experiments and image processing analyses to an accurate schedule. We expect that cell-based assays using vulnerable human neuronal cells and organoids produced by ASCLEPiOs will accelerate the discovery of drug candidates including small-molecules and new modalities for neurodegenerative diseases.
BARRIERS IN ACCESS TO MENTAL HEALTH CARE SERVICES BY KEY POPULATIONS IN POLAND
Authors: Kowalczyk *Katarzyna Kinga 
Published: February 2025

Abstract
The mental health of Poles has been deteriorating for many years, with a particularly critical situation concerning children and teenagers. Recent events, such as the COVID pandemic and war in Ukraine, have further exacerbated this issue. According to the Comprehensive survey of the mental health status of the population and its determinants (EZOP II), almost 25% of adults, have experienced at least one mental health disorder in their lifetime within the 2016-2020 period. One of the key groups that are facing mental health problems are people who use drugs, however, the existing mental health services are incapable of addressing their needs, particularly those with dual diagnosis. The presented study is part of a Eurasian Harm Reduction Association project run in 2022 aimed at assessing the Barriers in Access To Mental Health Care Services by Key Populations in four countries: Czech Republic, Estonia, Moldova and Poland. The poster presentation will focus on Poland and Polish opioid users. To assess the barriers desk research and semi-structured interviews with 12 Polish experts (professionals working in drug treatment facilities and people who use drugs) were conducted. Some of the key findings include lack of a holistic, client-centered approach to drug dependence and mental health treatment, lack of mental health professional personnel, low accessibility of mental health services, dominance of medical treatment methods in comparison to psychotherapy options, insufficient funding for mental health care services, language barriers, stigmatization, self-stigma and discrimination based on drug and psychiatry registry. The study provides several crucial recommendations, including improving the primary health care system to ensure optimal access to mental health care, integrating harm reduction and mental health services, moving the professional community to client-centered evidence-based approaches, preparing information campaigns aimed at raising awareness of the availability of mental health services for people who use drugs, and combating stigma.
DP427 DEFICIENCY AND ITS IMPACT ON THUNDER SOUND-INDUCED FREEZING RESPONSES IN DUCHENNE MUSCULAR DYSTROPHY DOGS
Authors: Takeuchi *Eri , Imamura Michihiro , Kikusui Takefumi , Sekiguchi Masayuki , Aoki Yoshitsugu 
Published: February 2025

Abstract

Background
Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease characterized by progressive muscle wasting caused by a mutation in the DMD gene which encodes dystrophin protein. Approximately 30% of DMD patients show cognitive deficits and psychiatric symptoms. In the brain, Dp427 dystrophin isoform is localized to a subset of GABAergic synapses in the amygdala and hippocampus. We previously reported that the number of GABAA receptor α2 clusters was reduced in the basolateral amygdala (BLA) of dystrophic mdx mice. This resulted in impaired GABAergic transmission in the BLA and a freezing response to threat. However, the characterization of brain Dp427 deficiency and its impact on brain phenotypes still need to be better understood. Canine X-linked muscular dystrophy in Japan (CXMDJ), a middle-sized and emotionally expressive model of DMD, is suitable for examining the neurobehavior associated with brain Dp427 deficiency.

Aims & Objectives
We aim to elucidate the molecular mechanism of brain Dp427 and the impact of its absence on brain phenotypes in CXMDJ.

Method
CXMDJ and wild-type littermates were observed in the thunder sound-induced fear response behavior. In this study, we used the open field apparatus consisting of an aluminum canine circle (W240 × L240 × H120 cm). Dogs were placed in a carrier cage, and the test was started when the door was opened. A reward was placed on the diagonal, and a thunder sound (110-140 dB) was presented when the dog approached the reward. A video camera was mounted on the ceiling to record each dog's behavior. Images were analyzed using image analysis software (Move-tr/2D). An electrocardiogram (ECG) measurement was recorded during the sound-induced fear response behavior to evaluate the emotional state.

Results
CXMDJ exhibited enhanced anxiety-like behavior in the open field test. The measurement of heart rate variability revealed decreased parasympathetic nerve activity in CXMDJ during the open field test. Moreover, CXMDJ showed an increased freezing behavior and decreased total distance traveled in the sound-induced fear response compared to wild-type littermates. This result suggests that CXMDJ exhibits enhanced fear behavior associated with brain Dp427 deficiency.

Discussion & Conclusion
We showed that CXMDJ exhibited highly anxiety-like behavior and freezing response. It is postulated that the absence of Dp427 in the amygdala may contribute to heightened anxiety and fear levels in CXMDJ.