bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved setup and characterization of cadmium telluride detector for in-beam X-ray spectrometry up to 300 kV at Czech Metrology Institute
Authors: Šolc Jaroslav , Šmoldasová Jana , Štemberková Ludmila , Sochor Vladimír , Vykydal Zdenek
Published: February 2025

The paper describes the measurement geometry and summarizes
the improvement in the setup and methods used at Czech Metrology
Institute for the spectrometry of X-ray beams with cadmium telluride
X-123CdTe detector. The front, lateral, and rear shielding of the
detector was enlarged and sources of parasitic contribution to the
characteristic peaks in the measured spectrum were
supressed. Methodology for an accurate positioning of the detector
towards the focus point was improved with a tool allowing to
visualize projections of two pinholes using a pixel detector. The
estimated uncertainty of the alignment was 0.2∘. The tilt
of the aperture axis of tungsten collimation disks with 50 μm
and 100 μm aperture diameters, which caused distortion of
measured spectra, was determined allowing, together with the
improved methodology for the detector alignment, to use these disks
in the same way as the other collimation disks with larger aperture
diameters. As a result, the range of measurable photon flux was
increased roughly by a factor of 19. The instrumentation and methods
adopted and optimized at CMI allow to perform mobile in-beam X-ray
spectrometry up to 300 kV in laboratory and clinical conditions
with the range of collimation disks of nominal aperture diameters
starting from 50 μm.
A tannic acid coated silk fibroin sponge loaded with bioglass for noncompressible hemostasis
Authors: Chu Shanshan , Fang Xu , Xu Junfeng , Yuan Wenwen
Published: February 2025

A hemostatic sponge designed for hemostasis of noncompressible penetrating wounds should exhibit rapid shape recovery, strong coagulation activity, and effective antibacterial property. In this study, we prepared a tannic acid coated silk fibroin sponge loaded with bioglass. In vitro, the sponge had a three-dimensional porous structure, good liquid adsorption capacity, and a water-triggered shape recovery feature. The sponge possessed strong coagulation activity and antibacterial property, while exhibiting low cytotoxicity and minimal hemolytic effects. In vivo, the sponge showed a greater advantage in controlling bleeding from both rat liver injury and penetrating wounds compared to commercial gauze and gelatin sponge. In conclusion, the developed sponge can be promising for noncompressible hemostasis.
The modified Camassa–Holm equation with self-consistent sources
Authors: Li Xiaoyong , Qu Changzheng , Zhang Da-jun
Published: February 2025

The modified Camassa–Holm equation serves as the dual counterpart to the modified KdV equation. Notably, the modified KdV equation has been shown to possesses the corresponding equation with the self-consistent sources (SCSs). In this paper, we derive the modified Camassa–Holm equation with SCSs based on its bi-Hamiltonian structure. Subsequently, we obtain its Lax pair. Utilizing the Lax pair of the modified Camassa–Holm equation and its variant form with the SCSs, we also derive the Darboux transformations for both the modified Camassa–Holm equation and its counterpart with SCSs. Additionally, we propose a novel approach for constructing the Darboux transformation for these equations.
Zn/In dual doping enhances the thermoelectric performance of SnTe
Authors: Wang Lijun , Shi Xiao-Lei , Li Meng , Li Lvzhou , Dong Cuicui , Miao Pengcheng , Shen Ziyi , Yuan Ningyi , Ding Jianning , Zheng Shuqi , Chen Zhi-Gang
Published: February 2025

As a lead-free material, SnTe shows high thermoelectric potential. However, the larger energy separation of SnTe results in a substantially lower Seebeck coefficient, while the relatively lighter atomic mass of Sn contributes to high thermal conductivity, leading to relatively inferior thermoelectric performance. This study employs a simple and effective microwave synthesis method to tune band structures and introduce nano-defects into the SnTe matrix by dual doping with Zn/In. First-principles calculations indicate that Zn/In dual doping introduces energy levels, broadens the band gap to 0.53 eV, and reduces the energy difference between light and heavy hole valence bands to 0.11 eV, significantly increasing the power factor. Moreover, dual doping introduces many point defects and other nano-defects, which contribute to scattering phonons of different wavelengths and reduce the lattice thermal conductivity. As a result, the zT values of all doped samples are higher than those of pure SnTe. At 773 K, the Sn0.98Zn0.01In0.01Te achieves a maximum zT value of approximately 0.53, which is an increase of 60% compared to the zT for pure SnTe at the same temperature. This work demonstrates that effective dual doping using the solvothermal method is a viable strategy for improving the thermoelectric performance of SnTe.
Emerging trends in Hybrid ECM: a review of multi-assisted machining techniques
Authors: pawar Aniket Baburao , Chavan Sachin , Jadhav Pradeep V. , Jadhav Dattatray B.
Published: February 2025

Hybrid Electrochemical Machining (ECM) techniques have emerged as a promising solution for precision machining, particularly for hard-to-machine materials in industries like aerospace, biomedical, and micro-manufacturing. By integrating additional energy sources such as ultrasonic vibrations, magnetic fields, lasers, and plasma with conventional ECM, these hybrid processes overcome limitations such as low material removal rates, poor surface quality, and tool wear. This review provides a comprehensive overview of various hybrid ECM techniques, discussing their advantages, challenges, and current industrial applications. Key challenges highlighted include the high cost of equipment, complex process control, and difficulties in scaling up for large-scale industrial use. Recent advancements in smart monitoring systems and real-time feedback mechanisms offer potential solutions to these challenges by improving control over process parameters like electrolyte flow, voltage, and current density. The review also proposes hybrid-hybrid ECM—the integration of multiple assistive technologies—as a future research direction that could further enhance machining flexibility, precision, and surface quality. Additionally, the importance of sustainability in ECM processes, through the exploration of less hazardous electrolytes and energy-efficient techniques, is emphasized as a critical area for future research. Overall, this paper aims to guide future studies in advancing hybrid ECM technologies for broader industrial application and improved efficiency.
Milling cutter wear feature extraction based on complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and Lempel-Ziv complexity
Authors: Qiu Hui , Wei Junkang , Ji Yi , Zhang Shuai , Chen Leiqing , Pan Xiaoming
Published: February 2025

To accurately and quantitatively extract the wear characteristics of milling cutters during the milling process, the wear signal of the milling cutter is collected using a laser vibrometer. The characteristics of the tool wear signal during the milling process are analyzed in the time, frequency, and time-frequency domains. The Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) method is employed to extract the characteristic quantities from different wear signals of the milling cutter. Subsequently, the Lempel-Ziv complexity algorithm is applied to analyze the wear characteristics under various wear states, allowing for the quantitative evaluation of these states. Finally, the statistical principle is applied to establish the wear discrimination intervals for the milling cutter under different wear states: the normal working complexity interval is [0.139, 0.174], and the wear failure complexity interval is [0.202, 0.228]. The proposed CEEMDAN + Lempel-Ziv method achieves an accuracy of 93.33% in accurately identifying the normal operation of the milling cutter and an accuracy of 95% in identifying wear failure of the milling cutter.
Improvement of the reading algorithm for pointer instruments based on deep learning
Authors: Pang Junjie , Liu Bo , Han Zhiyin , Liu Xiaoqun , Hao Juan , Li Shaojie , Sun Xu , Liu Xiaolei , Wang Guoping , Gao Wei
Published: February 2025

Pointer instruments, widely used in complex environments, pose challenges for manual reading due to inefficiency and difficulty, and for intelligent devices, problems arise with instrument localization, low inference accuracy, and incorrect readings. To address these issues, this paper proposes a novel deep-learning algorithm that divides the reading problem of pointer instruments into three stages. First, the NV-YOLOv8 model is introduced to identify the instrument's location, and Spatial Transformer Networks are employed to correct spatial transformations of the instrument panel. Then, a U-Net-based improved algorithm is used to segment the instrument panel and pointer. Finally, an End-to-End text recognition method and a novel weighted angle approach are applied for reading. The mean relative error is introduced to evaluate the reading accuracy, and the algorithm is assessed on a collected dataset. Even on tilted, blurred, or damaged instrument panels, our algorithm demonstrates a certain advantage, with a mean relative error of only 2.76%, outperforming other mainstream methods. Experimental results verify the proposed reading method's promising performance.
Bark anatomy of Euphorbia tirucalli (Euphorbiaceae): A unique way of bark dilatation on a stem succulent tree
Authors: Shilaluke Kolwane Calphonia , Moteetee Annah , Oskolski Alexei
Published: February 2025

Background and aim

The covering tissue structure is important for leafless stem succulents, influencing their photosynthetic activity. Usually, the epidermis on succulent stems persists for a long time, making the stem photosynthesize as long as possible. Its persistence implies maintaining the continuity of covering tissues during bark dilatation. In most plants, dilatation is performed by developing periderm(s) to replace the epidermis. The ways of bark dilatation with delay of periderm formation remain poorly known. In the present study, we examine the structure of the juvenile and mature bark of succulent pencil tree Euphorbia tirucalli (Euphorbiaceae) to clarify the ways of dilatation of its protective tissues.

Methods

The bark structure of Euphorbia tirucalli at various developmental stages was examined using light and scanning electron microscopy.

Key results

The epidermis is found not only on young stems of E. tirucalli but also on the bark of its thick branches and trunk, which are up to about 6 cm in diameter. On the young stems, the stomata are sunken in long vertical grooves. On the older stems, these grooves are stretched out due to dilatation, bringing stomata to the surface. Expansion cracks, i.e. broad vertical epidermal ruptures underlaid by tightly arranged tangential strands of cortical parenchyma, appear between the stomatal zones on dilated bark. The phellogen is initiated in the depth of the cortex beneath the epidermal ruptures long after their formation.

Conclusions

The bark dilatation by forming epidermal ruptures with delayed initiation of periderm was found for the first time. Prolonged photosynthesis in the succulent stem is the main functional benefit of such a bark dilatation method. The initiation of periderm in the depth of the cortex has not been reported in stem succulents other than a few Euphorbia species.
The influence of dolphin group coordination on cooperative foraging with humans
Authors: McGarvey Kiera , Daura-Jorge Fábio G , Machado Alexandre M S , Farine Damien R , Rogan Emer , Cantor Mauricio
Published: February 2025

Social foraging is a collective solution to the challenge of catching prey. A remarkable example involving different predator species with complementary hunting skills is Lahille’s bottlenose dolphins (Tursiops truncatus gephyreus) foraging with net-casting human fishers to catch migratory mullet (Mugil liza). It remains unknown, however, to what extent dolphins coordinate their own actions when foraging with humans, and how intraspecific coordination impacts interspecific foraging success. Using drone-based tracking, we quantified dolphin group surfacing behaviours (diving synchrony, proximity, heading angles between individuals) and tested the repeatability of these behavioural metrics across independent human-dolphin cooperative foraging interactions. We then quantified how the variance and consistency in these behaviours influenced the likelihood of fishers catching mullet. We found repeatable patterns in dolphin group proximity and heading angles across cooperative foraging interactions with fishers, and that fishers were more successful at catching mullet when dolphins approached them along different trajectories with consistent diving synchrony. These findings suggest that groups of dolphins can be, to some extent, coordinated when fishing with humans, thereby influencing the collective outcome of this cooperative foraging tactic. We consider hypotheses for the underlying mechanisms of synchrony and coordination within groups of dolphins and highlight solutions for overcoming the inherent challenges associated with quantifying collective foraging dynamics in natural settings.
Resource utilisation associated with extracorporeal membrane oxygenation versus microaxial flow pump for infarct-related cardiogenic shock
Authors: Bogerd M , ten Hoorn L , ten Berg S , Peters E J , Engström A E , Malekzadeh A , Thiele H , Møller J E , Hassager C , Vlaar A P J , Henriques J P S
Published: February 2025

Background

Microaxial flow pump and venoarterial extracorporeal membrane oxygenation (VA-ECMO) are increasingly used in infarct-related cardiogenic shock (AMICS). This study provides a comparative overview of real-world resource utilisation associated with these devices (PROSPERO: CRD42024505174).

Methods

EMBASE, MEDLINE and Cochrane Library were sought from inception to 13-11-2024 for studies reporting at least one primary outcome, including intensive care unit (ICU) length of stay (LOS), hospital LOS, in-hospital costs and discharge destination. In-hospital mortality was included as secondary outcome. This study was guided by the PRISMA-2020 guideline. Study selection and data extraction were independently performed by two researchers. Risk-of-bias assessments were done using the Newcastle-Ottawa-Scale. Data were pooled using random-effect models.

Results

In total, 12 retrospective cohorts were identified encompassing 92,262 microaxial flow pump- and 16,474 VA-ECMO patients data. The meta-analysis of hospital LOS and in-hospital costs revealed favourable results for the microaxial flow pump, with mean differences (MD) of -5.3 days (95%CI: -6.6, -4.1) and -$113,983 (95%CI: -$143,153, -$84,812) respectively. Microaxial flow pump survivors were also 45% more likely to be discharged home (95%CI: 1.28 - 1.64). ICU-LOS was reported by one study, reporting a 10 days MD in favour of the microaxial flow pump. The averaged in-hospital mortality rates were 44% and 57% for the microaxial flow pump and VA-ECMO respectively. An inherent limitation of observational studies is confounding by indication.

Conclusions

Microaxial flow pump was associated with lower resource utilisation compared to VA-ECMO. Resource utilisation should be incorporated in prospective RCTs and taken into account when considering these devices.
Ways of implementing ELF in the classroom
Authors: Illés Éva
Published: February 2025

In response to ELF-aware language pedagogy expounded in the 2020 special issue of ELT Journal, this article intends to offer alternative ways of integrating ELF into the language classroom. In both cases, the intention is to challenge native-speaker norms of language use and prepare learners for the difficulties ELF communication presents. While ELF-aware pedagogy aims to raise learners’ awareness of the nature of ELF communication via exposure to samples of ELF interactions, the tasks proposed in this article engage learners on their own terms, acting not only as learners but also as users and researchers of ELF. The tasks outlined include exploiting the classroom as a venue of genuine communication, student presentations, translation, and linguistic landscape and other projects. To achieve active participation, teachers need to be familiar with their students’ individual differences, including their motivation, experiences, strengths and weaknesses, as well as their individual learning paths.
May Measurement Month 2022: an analysis of blood pressure screening results from Mexico
Authors: Alcocer Luis , Palomo Silvia , Lechuga Maria G Berumen , Cerda-Mancillar Megan C , Acosta-Mass Arlene G , Camarillo-Nava Victor M , Alvarez-Aguilar Cleto , Garcia-Cortes Luis R , Rincon-Leon Hector A , Avila-Jimenez Laura , Beaney Thomas , Kerr Gabriele , Poulter Neil R
Published: February 2025

The May Measurement Month (MMM) campaign was carried out in Mexico in 2022 with the aim of raising awareness of raised blood pressure (BP). Here, we report on the findings of the campaign. Adults aged ≥ 18 years were recruited opportunistically at first-contact health centers in several states of the Mexican Republic. Three seated BP readings were taken for each participant, along with completion of a questionnaire on demographics, lifestyle factors, and comorbidities. Hypertension was defined as a systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Controlled BP was defined as being on antihypertensive medication with a BP <140/90 mmHg. Multiple imputation was used to estimate any missing BP readings. In total, 41 953 adults were screened, with a mean age of 48.5 years and 58.2% were female. Of all participants, 16 888 (40.3%) had hypertension, of whom 14 465 (85.7%) were aware, and 14 265 (84.5%) were on antihypertensive medication. Of those on antihypertensive medication, 9712 (68.1%) had controlled BP, and of all participants with hypertension, 57.5% had controlled BP. In total, 7176 (17.1%) had either untreated or inadequately treated hypertension. In conclusion, the MMM campaign in Mexico in 2022 identified significant numbers of participants with either untreated or inadequately treated hypertension. Among those on antihypertensive medication, only two-thirds of them achieved controlled BP levels, despite receiving their medication at no direct cost to them, suggesting a significant problem of medical inertia.
Gay Men as Caregivers for Spouses with Dementia: Intersections of Gender and Sexual Orientation
Authors: Calasanti Toni , Snow Sadie , de Vries Brian , Geng Jing
Published: February 2025

Objectives

Despite the importance of spousal caregiving, and the increase in same-sex marriages concomitant to its legalization in 2015, few studies have examined the experiences of same-sex spousal caregivers. We use an intersectional approach to explore how gender and sexual orientation shape gay men’s particular caregiving approaches for their spouses living with dementia.

Methods

We focused on a subsample of gay (N=13) contrasted with straight husbands (N=15) from a national study of spousal dementia caregivers. Data were obtained through in-depth interviews and analyzed thematically by a team.

Results

We find that sexual minority status and gender interact to shape gay men’s caregiving approaches. Gay men’s broader division of labor in households combine with experiences of discrimination based on sexuality, and HIV/AIDS, as well as being a part of a same-sex couple to influence their caregiving approaches in unique ways. Specifically, they combine a task-oriented approach with concern for the personhood of the care receiver; bring strength and empathy borne of struggle; and what they feel is a deeper understanding of the care receiver given their shared status as gay men.

Discussion

Our findings indicate that gay men’s flexibility in divisions of labor results in variable sets of skills, resources, and identities they bring to and approach their caregiving. In addition, some of the many negative experiences borne of HIV/AIDS and discrimination are reframed as sources of strength and guide caregiving efforts. Together, these findings highlight the intersecting effects of gender and sexual orientation on spousal caregiving.
Frequency dependence of Rayleigh wave amplification by variation in Earth structure investigated using the constant energy flux approximation
Authors: Menke William , Dalton Colleen A , Lloyd Andrew , Lopes da Silva Danielle , Levin Vadim
Published: February 2025

The sensitivity of Rayleigh wave amplitude to Earth structure has applications to seismic tomography, both in cases where amplitude information is used to supplement phase velocity data to improve images of elastic parameters, and to correct amplitudes for local Earth structure in attenuation tomography. We review the theoretical basis of the ray theoretical approximation, in which the wave amplitudes are controlled by a combination of geometrical spreading and local changes in energy density due to Earth structure. We focus mainly on the latter effect, which we term the constant energy flux approximation. We investigate the ray theoretical basis for this approximation, test it against a full waveform simulation that verifies its accuracy and show how it can be used to compute the sensitivity of amplitude to elastic moduli and density. We investigate how perturbing these parameters in a set of simple Earth models affects Rayleigh wave amplitudes, and demonstrate that a slow velocity heterogeneity can cause either increased or reduced amplitudes, depending upon the depth of the heterogeneity and the observation frequency. Consequently, amplitude sensitivity can be either positive or negative, and its magnitude can vary significantly with frequency. Although an added complication, the very different behaviour of phase velocity and amplitudes to changes in Earth structure implies that the two types of data are complementary and suggest the effectiveness of using both in Rayleigh wave tomography.
MK2 Inhibition in CD4+ T Cells Protects Against IFNγ and IL-17A, Chronic Inflammation, and Fibrosis in Inflammatory Bowel Disease Models
Authors: Howe Cody S , Chulkina Marina , Syrcle Ryan , McAninch Christina , McAninch Steven , Pinchuk Irina V , Beswick Ellen J
Published: February 2025

Background

CD4+ T cells contribute to chronic inflammation and fibrosis in inflammatory bowel disease (IBD), but the cellular mechanisms remain elusive. We have found that the mitogen-activated protein kinase 2 (MK2) pathway plays a major role in inflammation and overall pathology in IBD. Thus, here, we examined the role of MK2 in regulating CD4+ T cell responses in IBD models.

Methods

Interleukin-10 (IL-10) knockout (KO) mice treated with MK2 inhibitors (MK2i) and CD4-specific MK2 knockdown mice treated with chronic dextran sodium sulfate (DSS) treatments were used to examine inflammation and fibrosis by multiplex array, gene expression, flow cytometry, and histology. Human tissues were treated with MK2i to examine Th1 and Th17 markers.

Results

IL-10 KO mice treated with MK2i therapeutically showed significantly reduced interferon gamma (IFNγ) and interleukin-17A (IL-17A) and a significantly reduced number of IFNγ+ and IL-17A+ producing CD4+ T cells by flow cytometry. To investigate the direct role of MK2 in CD4+ T cells during IBD, we utilized CD4-specific MK2 knockdown mice in chronic DSS colitis. A decrease in colonic inflammation, IFNγ and IL-17, 

pro-fibrotic genes, and extracellular matrix deposition was observed in mice with MK2 knockdown in CD4+ T cells compared to control mice. Additionally, IL-17A and IFNγ directly regulated the expression of fibrosis genes in colon tissues.

Conclusions

The MK2 pathway regulates inflammatory CD4+ T cells and fibrosis in IBD models and is a potential therapeutic target.
Long-term outcome after repair of interrupted aortic arch in a single center
Authors: Kreuzer Michaela , Sames-Dolzer Eva , Tulzer Andreas , Klapper Melanie , Mair Roland , Gierlinger Gregor , Seeber Fabian , Mair Rudolf
Published: February 2025

OBJECTIVES

Mortality in patients with interrupted aortic arch rates among the highest in congenital heart surgery. Various techniques for aortic arch repair are described, reintervention rates remain substantially. The aim of this retrospective single center study: To evaluate the long-term outcome in a biventricular series with a preferably performed direct anastomosis and one-stage repair.

METHODS

At the Children’s Heart Center Linz 58 biventricular patients with interrupted aortic arch were operated between 1999 and 2023. Median age at operation was 10 [7; 15] days, weight 3.3 [3; 3.7] kg. In the 24 children with VSDs only, the arch was repaired by a direct anastomosis. 34 had complex concomitant heart defects, the arch reconstruction was performed by direct anastomosis (20), direct anastomosis + patch (10), reverse subclavian flap + patch (3), aortic autograft + patch (1).

RESULTS

Median cardiopulmonary bypass time was 222 [159; 315] min, aortic cross-clamp time 94 [75; 143] min. 2 patients died during the hospital stay (4%), 2 patients after discharge (4%), 4 (7%) required an arch reintervention during a follow-up period of median 9.3 [6.2; 17.2] years. There was no death or arch reintervention in the VSD group.

CONCLUSIONS

All-cause mortality in biventricular patients with interrupted aortic arch was 7%, arch reintervention rate 8%. Direct aortic anastomosis in patients with VSD only can be performed with excellent outcomes, with no deaths or arch reinterventions being observed after a follow-up up to 24 years.
SLOWER CLOZAPINE TITRATION THAN THE OFFICIAL JAPANESE PROTOCOL LED TO FEWER INFLAMMATORY ADVERSE EFFECTS
Authors: Kikuchi *Yuki , Komatsu Hiroshi , Otsuka Yuji , Ito Fumiaki , Kanahara Nobuhisa , Tanifuji Hiroaki , Tomita Hiroaki
Published: February 2025

Background

Higher frequencies of inflammatory adverse effects of clozapine have been reported in Japan (Kishi et al., 2013; Tsukahara et al., 2021). Tsukahara et al. reported 38 % (57/152) clozapine- induced fever, 5 % (7/152) myocarditis, 13 % (20/152) pleuritis, and 1 % interstitial nephritis (2/152) in 152 patients first introduced to clozapine. The international titration protocol for Asians has set slower dose titration than the Japanese package insert to prevent clozapine-induced inflammatory adverse effects (de Leon et al., 2022).

Aims & Objectives

We hypothesized that a dose titration speed slower than the recommendation of the guideline would be associated with fewer inflammatory-related adverse events. We aimed to investigate the relationship between the rate of clozapine dose titration and inflammatory adverse events in Japanese individuals.

Method

The medical records of all 272 patients who were first started on clozapine at seven hospitals between 2009 and 2023 were studied retrospectively. Of those, 241 were included in the analysis. The patients were divided into two groups regarding whether the titration speed was faster or slower than the guideline for Asians. The incidence of inflammatory adverse events with clozapine was compared between the groups.

Results

The frequency of inflammatory adverse events was 34 % (37/110) in the faster titration group and 13 % (17/131) in the slower titration group, and a significant difference was observed by Fisher exact test (odds ratio 3.38; 95 % confidence interval 1.71–6.91; p <0.001). Serious adverse effects, fever for more than five days, and clozapine discontinuation were significantly more frequent in the faster titration group. Logistic regression analysis indicated significantly more inflammatory adverse events in the faster titration group (adjusted odds ratio 4.01; 95 % confidence interval 2.02–7.87; p < 0.001) considering age, sex, body mass index, concomitant valproic acid, and smoking as confounding factors.

Discussion & Conclusion

Clozapine-induced inflammatory adverse events were less frequent in Japanese individuals when a titration rate was more gradual than the protocol recommended in the Japanese package insert.

References

1. Kishi, T. et al. (2013) Efficacy and tolerability of clozapine in Japanese patients with treatment- resistant schizophrenia: results from a 12-week, flexible dose study using raters masked to antipsychotic choice. Asian J. Psychiatr. 6 (3), 200–207.

2. Tsukahara, M. et al. (2021) Clinical utility and safety of slower-than-recommended titration of clozapine for treatment-resistant schizophrenia: a retrospective cohort study. Psychiatr. Q. 92 (2), 703–713.

3. de Leon, J. et al. (2022) An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels. Pharmacopsychiatry 55 (2), 73–86.
CLINICALLY PREDICTIVE MODULATION OF COGNITIVE IMPAIRMENTS IN MOUSE TOUCHSCREEN TASKS
Authors: Spark *Daisy , Castelijn Juulke , Churilov Leonid , Pham Trang , Camerino Michelle , Langmead Christopher J , Stewart Gregory D , Nithianantharajah Jess
Published: February 2025

Background

Cognitive deficits in individuals with schizophrenia present a significant barrier to maintaining interpersonal relationships, employment, and independent living. Moderate to severe impairments have been found in cognitive domains including working memory, attention, learning and executive function. Despite the clear impact on functional outcomes, there are currently no approved treatments for cognitive impairments associated with schizophrenia (CIAS). Extensive efforts to develop pro-cognitive medicines, both for CIAS and other neuropsychiatric disorders, have repeatedly led to clinical trials that do not reflect the efficacy predicted in preclinical models.

Aims & Objectives

The rodent touchscreen platform has begun to bridge the translational gap between preclinical and clinical assessments of cognitive function. However, to date there has been no pharmacological validation of whether these tests are stringent enough to be clinically predictive and can therefore improve translation of CIAS treatments.

Method

Here, we use an NMDA receptor antagonist mouse model (acute low-dose administration) that we have validated for cognitive deficits in working memory performance on the rodent trial-unique delayed nonmatch-to-location touchscreen task. We then measured the effect of 1) current standard of care (aripiprazole and olanzapine), 2) failed investigational new drugs (IND) for CIAS (atomoxetine and encenicline), and 3) a current IND for schizophrenia (xanomeline) on working memory and attentional impairments.

Results

For the first time, we demonstrate a translational method for cognitive assessment in mice that can distinguish drugs with clinical efficacy from those without.

Discussion & Conclusion

These results provide critical insight into the predictive validity of our preclinical assay and cognitive deficit model, and have significant implications for the development and translation of novel pro-cognitive medicines.
VOLUMETRIC ASSESSMENT OF INDIVIDUAL THALAMIC NUCLEI IN PATIENTS WITH DRUG-NAÏ VE, FIRST-EPISODE MAJOR DEPRESSIVE DISORDER
Authors: Chibaatar *Enkhmurun , Watanabe Keita , Okamoto Naomichi , Orkhonselenge Nasanbadrakh , Natsuyama Tomoya , Hayakawa Gaku , Ikenouchi Atsuko , Kakeda Shingo , Yoshimura Reiji
Published: February 2025

Introduction

Despite the previous inconsistent findings of structural and functional abnormalities of the thalamus in patients with major depressive disorder (MDD), the disruption of the thalamic nuclei in the pathophysiology of this disorder has not yet been adequately studied. Therefore, we investigated the volumetric changes of thalamic subregions and their nuclei in drug-naï ve, first-episode MDD patients. We also investigated the association between HAM-D scores, a clinical scale frequently used to evaluate the severity of depression and thalamic nuclei volumes in MDD patients.

Methods

This study included 76 drug-naï ve MDD patients and an equal number of healthy subjects. Magnetic resonance imaging (MRI) data were obtained using a 3T MR system and thalamic nuclei volumes were evaluated using FreeSurfer ver.7.11. The volumetric differences were compared by one-way analysis of covariance (ANCOVA) and to ensure that effects were not accounted for by other factors, age, sex, and ETICV variables were included as covariates.

Results

We observed significant volume reductions of the left whole thalamus (p <0.003) and several thalamic nuclei mostly on the left side in the MDD group compared with healthy controls (HCs). Furthermore, we have revealed weak negative correlations between several thalamic nuclei volumes and HAM-D total and subscale scores.

Discussion

This is the first research study to investigate alterations of the various thalamic nuclei volumes in MDD patients compared with HCs.

Moreover, we first analyzed the association between individual thalamic nuclei volumes and HAM-D subscale scores. Though our study may be restricted at certain levels, especially by the demographic difference between the two groups, they possibly contribute at a preliminary level to understanding the thalamic structural changes at its subregions in patients with drug-naï ve, first-episode MDD.
EFFICACY AND SAFETY OF DUAL-TARGET DEEP BRAIN STIMULATION FOR TREATMENT-RESISTANT ALCOHOL USE DISORDER: PROTOCOL FOR A MULTI-CENTER, SINGLE ARM, PROSPECTIVE STUDY
Authors: Jiang *Haifeng , Gan Hong , Zhao Min , Hao Wei
Published: February 2025

Background

Alcohol use disorder (AUD) is the most common, costly, and lethal substance use disorder worldwide, with a rising prevalence. Case reports and animal studies suggest deep brain stimulation (DBS) may be an effective harm-reduction treatment in AUD.

Aims & Objectives

The aim of this study is to explore whether deep stimulating the nucleus accumbens (NAc) and anterior limb of internal capsule (ALIC) simultaneously may have a synergistic effect against treatment-resistant AUD.

Method

Total of 12 subjects from two centers (Shanghai Mental Health Center and The Second Xiangya Hospital of Central South University) who fit inclusion and exclusion criteria are recruited to undergo neurosurgical implantation of dual-target DBS in bilateral NAc and ALIC on a certain date, the DBS system will be turned on for stimulation and parameters adjusted 10-14 days after implantation. Clinical observations will be follow-up during the 9-32 weeks after DBS system has been turned on. The primary outcome is the performance on alcohol use self-report which will be carried out regularly every three days during the study period. Safety assessments will include adverse event reporting, clinical laboratory tests, vital signs, and prior/concomitant medications.

Results

This study is recruiting subjects now, and all results will be reported after study completion.

Discussion & Conclusion

The study will provide evidence for the efficacy and safety of dual-target DBS for treatment-resistant AUD. This abstract describes the design and methodology of the study.

Trial Registration

ClinicalTrials.gov ID NCT05786872

References

None.
ALCOHOL INTAKE IS ASSOCIATED WITH EATING HABITS DURING DEVELOPMENT
Authors: Yamaguchi *Yasuharu , Kasai Shinya , Hasegawa Junko , Ikeda Kazutaka
Published: February 2025

Background & Objectives

There are individual differences in susceptibility to alcohol use disorders, and multiple factors including genetic and lifestyle factors would be involved in the susceptibility. The genetic contribution of alcohol use disorders is estimated from twin studies to be around 0.5. Many genetic factors, including single nucleotide variations, have been reported to be involved in alcohol use disorders, but most have low effect sizes and have not been reproducible in subsequent studies. Few analyses have been conducted on life and environmental factors related to alcohol use disorders. The present study focused on eating habits during the developmental period to identify lifestyle factors related to drinking and alcohol use disorders.

Method

This study included 628 patients who were treated at White Dental Clinic (Saitama, Japan). All of the patients provided written informed consent before participating in the study. Twenty patients were excluded because of incomplete data. The participants completed a questionnaire that consisted of various questions about drinking behaviors and eating habits. The associations between drinking-related traits and eating habits were statistically evaluated using the chi-square test. The study protocol was approved by the Institutional Review Board of the Tokyo Metropolitan Institute of Medical Science.

Result

Patients who ate more sweet and sour foods during their developmental years had lower rates of drinking (χ2 = 14.828; p <0.001, χ2 = 6.499; p = 0.015, respectively). Conversely, patients who ate more salty foods had higher rates of drinking (χ2 = 7.150; p = 0.009).

Discussion & Conclusion

Sweet, sour, and salty tastes are sensations elicited via their unique receptors. Alcohol intake by drinking would act on the central nervous system via the taste buds in the mouth before being taken up into the bloodstream. The formation of neural circuits via taste receptors during the developmental period may influence the rewarding effects of alcohol in adulthood. This study suggests the possibility of developing a new drug for alcohol abstinence.
FUNCTIONAL NEAR-INFRARED SPECTROSCOPY: A POTENTIAL TOOL IN ASSISTING DIAGNOSTIC APPLICATIONS FOR PSYCHIATRIC DISORDERS
Authors: Kim *Yuna , Park Yun Seong , Kim Jaehyun , Jang Yoonjeong , Myung Woojae
Published: February 2025

Background

Psychiatric disorders such as mood disorders are increasingly common in modern society, carrying social and economic burdens, including the risk of suicide. Timely identification of these disorders and intervention is crucial, and ongoing research explores adjunctive diagnostic tools and biomarkers, alongside patient history, to aid early detection.

Aims & Objectives

The study seeks to utilize functional near-infrared spectroscopy (fNIRS) for its cost-effectiveness and ease of use, aiming to improve the diagnosis and differentiation of Major Depressive Disorder (MDD) and Bipolar Disorder (BP) from the healthy control (HC) group.

Method

Thirty participants each from MDD, BP, and HC groups, were diagnosed using DSM-IV criteria, Hamilton Depression Rating Scale, and Clinical Global Impression scores, and performed a verbal fluency task. They recited Korean vowels and produced words starting with specific consonants within the allotted times. The fNIRS system, NIRSIT, included 24 lasers, 32 photodetectors, and oxyhemoglobin waveforms were analyzed for integral and centroid values. One-way ANOVA and ANCOVA assessed differences and the impact of age, education, and task performance. Results

Figure 1 displays the average oxyhemoglobin waveforms in the frontal region (R1) and bilateral temporal regions (R2) for each group. The MDD participants were older than the BP and HC groups (F = 14.664, p<0.005). Task performance was similar for MDD and HC, and better than BP (F = 5.622, p <0.005). One- way ANOVA indicated significant differences in integral values across the groups and post-hoc analyses highlighted substantial distinctions between the healthy control (HC) and the psychiatric disorder groups (HC vs BP, HC vs MDD; P <0.05). Although no significant differences were observed in centroid values between patient groups, each group exhibited unique patterns.

Discussion & Conclusion

Using fNIRS, the findings suggest that IV and CV, derived from changes in hemoglobin waveforms, hold promise in distinguishing individuals with mood disorders from healthy controls. While further research is needed to explore their applicability to other psychiatric conditions such as psychosis, there is potential for them to serve as auxiliary diagnostic tools in the future for personalized psychiatric treatment.
NEUROPHYSIOLOGICAL CHARACTERISTICS OF BIPOLAR DISORDER BY RESTING EEG MICROSTATE ANALYSIS
Authors: Taniguchi *Keita , Nakajima Shinichiro Luke , Moriyama Sotaro , Wada Masataka , Kaneko Naotsugu , Takano Mayuko , Honda Shiori , Mimura Masaru , Uchida Hiroyuki , Noda Yoshihiro
Published: February 2025

Background

Behind the difficulty in diagnosing bipolar disorder (BD) is the reality that it takes several years after the initial consultation before the diagnosis is confirmed. In this context, it is essential to establish biomarkers that contribute to the diagnosis of BD. In recent years, electroencephalography (EEG) microstates (MS) have garnered great attention as a useful tool to elucidate whole-brain neural network activity due to their high reproducibility. Therefore, EEG-MS is expected to be an aid in the diagnosis of psychiatric disorders, including BD. Specifically, MS-E is associated with the processing of internal and emotional information as well as cognitive functions.

Aims & Objectives

In this study, we aimed to identify EEG-MS biomarker of BD by comparison with that of healthy controls (HC).

Method

We included 36 individuals with BD (age: 47.7±15.7, %female: 38.9%) and 72 HC (age: 47.5±15.4, %female: 38.9%). Using a 64-channel high-density EEG system, we recorded resting-state EEG for 5 minutes with participants eyes closed. EEG-MS were classified into five states from A to E using the k- means clustering method. Then, three temporal indices were calculated for each MS: duration, occurrence, and coverage. Two-way repeated-measures analysis of variance (ANOVA) was conducted for the three temporal indices of each MS. MS classes and three indices served as within-subject factors while participant groups were treated as a between-subject factor. For MS indices for which the interaction was significant, an independent t-test was performed as a post-hoc analysis to test for differences between the BD and HC groups.

Results

The ANOVA showed significant interactions between the groups, MS classes, and temporal indices (F(1,8)=3.91, p<0.001). Subsequent ANOVAs indicated significant interactions across the two groups in duration (F(1,4)=2.412, p=0.049), occurrence (F(1,4)=3.861, p=0.004), and coverage (F(1,4)=2.924, p=0.021), as well as in MS-D (F(1,2)=3.304, p=0.039) and MS-E (F(1,2)=6.759, p=0.001). Finally, post-hoc independent t-tests for MS-D and MS-E revealed that in MS-D, the BD group showed longer values in duration (t(106)=3.967, p<0.001) and coverage (t(106)=2.904, p=0.004) compared to the HC group. In contrast, in MS-E, the BD group showed lower values in occurrence (t(106)=-2.600, p=0.011) and coverage (t(106)=-2.382, p=0.019) compared to the HC group.

Discussion & Conclusion

This study demonstrated that the BD group exhibited a higher occurrence and longer duration for MS-D compared to the HC group. Conversely, regarding MS-E, the BD group showed a lower occurrence and decreased coverage than the HC group. Based on the physiological significance of MS-E, there may be a potential decline in cognitive function in the BD group compared to the HC group.
APPETITE HORMONE DYSREGULATION AND EXECUTIVE DYSFUNCTION AMONG ADOLESCENTS WITH BIPOLAR DISORDER AND DISRUPTIVE MOOD DYSREGULATION DISORDER
Authors: Da Huang Guan- , Chen *Mu-Hong , Hsu Ju-Wei
Published: February 2025

Background

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear.

Methods

We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test.

Results

Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p =.023) compared with the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p =.035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p =.035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (β = 1.847, p = 032).

Discussion

Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared with healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation.

References

1.Hsu et al. Eur Child Adolesc Psychiatry. 2023 May 26

2.Chen et al. World J Biol Psychiatry. 2021 Jul;22(6):428-434
IMPACT OF COVID-19 INFECTION AND RELATED SOCIAL CONCERNS ON DEPRESSIVE SYMPTOMS: MEDIATING EFFECTS OF DAILY LIFE RESTRICTION
Authors: Ho *Dham , Park Min-A , Lim Weon-Jeong
Published: February 2025

Background

As the COVID-19 outbreak persisted, the accompanying increase in depression had emerged as a significant issues.

Aims & Objectives

This study examined the mediating effect of daily life restriction after COVID-19 pandemic on depressive symptoms, considering COVID-19 infection or social concerns about COVID-19 infection. Additionally, comparisons of path coefficients between groups were conducted based on gender and age.

Method

Data derived from the 2020 Korean Community Health Survey (KCHS) consisted of 229,269 individuals aged 19 to 110. This study used self-reported questionnaire including Patient Health Questionnaire-9 (PHQ-9), three items addressing social concerns related to COVID-19 infection (concerns about blame from the surroundings, economic impact, and infection of vulnerable family members), a self-questionnaire to confirm whether individuals had experienced quarantine or hospitalization due to COVID-19 infection within last 3 months, and scores of daily life restriction due to the COVID-19 pandemic. Structural equation model analysis was conducted to identify whether daily life restriction serves as a mediating factor in the association between COVID-19 infection and related social concerns and depressive symptoms. In addition, chi-square tests for comparing path coefficients based on age (below 65 years old, 65 and older) and gender were conducted.

Results

Structural equation models revealed significant direct effects of COVID-19 infection and related social concerns on depressive symptoms (COVID-19 infection to PHQ-9: β = 0.011, p <0.01; social concerns about COVID-19 infection to PHQ-9: β = 0.049, p <0.01), along with indirect effects through daily life restrictions after the COVID-19 pandemic on PHQ-9 symptoms (COVID-19 infection to PHQ-9: β = 0.014, p <0.01; social concerns about COVID-19 infection to PHQ-9: β = 0.001, p <0.01). When comparing path coefficients between subgroups based on age and gender, path coefficients associated with depression were higher in the groups under 65 years of age and females.

Discussion & Conclusions

Considering the impact of daily life restrictions on depression related to COVID-19 infection and related social concerns is essential, and more attention is needed for women and individuals under age of 65.