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The purpose of this study was to investigate the neural activity of electroacupuncture (EA) quantitatively. The responses of Sprague-Dawley rats' brain to EA on acupoints - Hegu (LI 4) and Neiguan (PC 6) - were detected by monocrystalline iron oxide nanoparticle (MION)-enhanced functional magnetic resonance imaging (MION-fMRI), which is a 1.5 T horizontal spectrometer equipped with a circular polarized extremity coil. During EA at LI 4, neural activities were analyzed by analysis of functional neural images (AFNI). Neural activation was detected at the structures of hypothalamus, thalamus, hippocampus, and the cortex, while neural deactivation existed at the areas adjacent to the activated sites. EA on PC 6 activated the structures of thalamus and the cortex but deactivated the structures of hypothalamus and hippocampus. The brain responses to EA existed in different areas of activation and deactivation despite stimulating the same acupoint. Additionally, distinct brain neuroimages were produced through stimulating different acupoints. This study suggests that fMRI with AFNI is a good approach to quantifying brain activities. This innovative method brings new perspective into the mechanisms of acupuncture. [ABSTRACT FROM AUTHOR]

Aims: Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design., Methods: Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity., Results: All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network., Conclusions: High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Competing Interests: The authors have no conflicts of interest to declare.

Background: Data describing the risk factors for the occurrence of severe infections in acute lymphoblastic leukemia (ALL) patients following induction chemotherapy and the role of prophylactic granulocyte-colony stimulating factor (G-CSF) in the era of antimicrobials prophylaxis are limited., Methods: This study enrolled 188 children aged ≤18 years with newly diagnosed ALL who received Taiwan Pediatric Oncology Group ALL-2002 and 2013 treatments between January 1, 2010 and June 30, 2021. Prophylactic G-CSF was administered when a patient continues neutropenia after achieving the first bone marrow remission since June 1, 2015. Clinical factors were assessed for their association with severe infections., Results: From January 2010 to May 2015, 80 children experienced a total of 11 (13.5%) episodes of severe infections; while 10 (9.2%) episodes were reported to occur in 108 patients who received prophylactic G-CSF. Reduction of severe infections occurrence did not achieve statistical significance during prophylactic G-CSF administration in ALL patients. Compared with ALL-high risk (HR) and very high risk patients with no G-CSF prophylaxis, the use of G-CSF prophylaxis significantly reduced episodes of febrile neutropenia. Occurrence of grade III-IV intestinal ileus, grade II-III oral mucositis, prolonged neutropenia, central venous catheter (CVC) placement, or the requirement insulin therapy for hyperglycemia were associated with higher risk of bloodstream infections., Conclusions: ALL-HR patients with G-CSF prophylaxis were associated with reduction of febrile neutropenia episodes. Occurrence of severe ileus, oral mucositis, hyperglycemia, CVC placement, or prolonged neutropenia were associated with severe infections in ALL patients receiving induction chemotherapy., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives : Genomic studies have identified several SNP loci associated with schizophrenia in East Asian populations. Environmental factors, particularly urbanization, play a significant role in schizophrenia development. This study aimed to identify schizophrenia susceptibility loci and characterize their biological functions and molecular pathways in Taiwanese urban Han individuals. Materials and Methods : Participants with schizophrenia were recruited from the Taiwan Precision Medicine Initiative at Tri-Service General Hospital. Genotype-phenotype association analysis was performed, with significant variants annotated and analyzed for functional relevance. Results : A total of 137 schizophrenia patients and 26,129 controls were enrolled. Ten significant variants ( p < 1 × 10 -5 ) and 15 expressed genes were identified, including rs1010840 ( SOWAHC and RGPD6 ), rs11083963 ( TRPM4 ), rs11619878 (LINC00355 and LINC01052), rs117010638 ( AGBL1 and MIR548AP), rs1170702 (LINC01680 and LINC01720), rs12028521 ( KAZN and PRDM2 ), rs12859097 ( DMD ), rs1556812 ( ATP11A ), rs78144262 (LINC00977), and rs9997349 ( ENPEP ). These variants and associated genes are involved in immune response, blood pressure regulation, muscle function, and the cytoskeleton. Conclusions : Identified variants and associated genes suggest a potential genetic predisposition to schizophrenia in the Taiwanese urban Han population, highlighting the importance of potential comorbidities, considering population-specific genetic and environmental interactions.

The use of next-generation sequencing (NGS) for monitoring measurable residual disease (MRD) in acute lymphoblastic leukaemia (ALL) has been gaining traction. This study aimed to investigate the utility of NGS in MRD monitoring for the three major fusion transcript (FT) subtypes of B-precursor ALL (B-ALL). The MRD results for 104 bone marrow samples from 56 patients were analysed through NGS and real time quantitative reverse transcription PCR (RT-qPCR) for the three major FTs: BCR::ABL1, TCF3::PBX1, and ETV6::RUNX1. To validate the NGS approach, NGS-MRD was initially compared with allele-specific oligonucleotide-qPCR-MRD, and the coefficient of determination was good (R 2 =0.8158). A subsequent comparison of NGS-MRD with FT-MRD yielded a good coefficient of determination (R 2 =0.7690), but the coefficient varied by subtype. Specifically, the R 2 was excellent for TCF3::PBX1 ALL (R 2 =0.9157), good for ETV6::RUNX1 ALL (R 2 =0.8606), and subpar for BCR::ABL1 ALL (R 2 =0.5763). The overall concordance between the two methods was 83.7%, and an excellent concordance rate of 95.8% was achieved for TCF3::PBX1 ALL. Major discordance, which was defined as a >1 log difference between discordant NGS-MRD and FT-MRD, occurred in 6.7% of the samples, with all but one sample being BCR::ABL1 ALL. Among the four non-transplanted patients with BCR::ABL1-MRD (+)/NGS-MRD (-), three did not relapse after long-term follow-up. Our finding indicates that NGS-MRD has a better prognostic impact than RT-qPCR-MRD in ETV6::RUNX1 and BCR::ABL1 ALL, whereas in TCF3::PBX1 ALL, both methods exhibit comparable efficacy., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X 2 =17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE., Competing Interests: Declaration of competing interest All authors declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR 2 ) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10 Hz compared to those of 10 Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy., Competing Interests: Declaration of Competing Interest All authors declared no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole-exome sequencing revealed a de novo gain-of-function variant, p.Tyr715Cys, in the C-terminal domain of ClC-7 encoded by CLCN7., Methods: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents., Results: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC-7 antiporter activity in maintaining appropriate lysosomal pH., Conclusion: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype-phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC-7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes., Competing Interests: Competing interests statement:The authors declare no competing interest.

Aim: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well-studied., Method: In the first step, we compared the performance of ChatGPT GPT-4, Bard, and Llama-2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis., Result: Only GPT-4 passed the 2022 Taiwan Psychiatric Licensing Examination (scoring 69 and ≥ 60 being considered a passing grade), while Bard scored 36 and Llama-2 scored 25. GPT-4 outperformed Bard and Llama-2, especially in the areas of 'Pathophysiology & Epidemiology' (χ 2  = 22.4, P < 0.001) and 'Psychopharmacology & Other therapies' (χ 2  = 15.8, P < 0.001). In the differential diagnosis, the mean score of the 24 experienced psychiatrists (mean 6.1, standard deviation 1.9) was higher than that of GPT-4 (5), Bard (3), and Llama-2 (1)., Conclusion: Compared to Bard and Llama-2, GPT-4 demonstrated superior abilities in identifying psychiatric symptoms and making clinical judgments. Besides, GPT-4's ability for differential diagnosis closely approached that of the experienced psychiatrists. GPT-4 revealed a promising potential as a valuable tool in psychiatric practice among the three LLMs., (© 2024 The Authors. Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are rapidly gaining ground in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and acute myocardial infarction (AMI) by an unknown mechanism. Upregulation of Na + /H + exchanger 1 (NHE1), SGLT1, and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) in the diseased hearts was found to be attenuated by prolonged SGLT2i treatment. Unfortunately, dapagliflozin is not well understood as to how Na + /Ca 2+ homeostasis is affected in cardiomyocytes. In this study, we aimed to investigate whether mechanical stretch in cardiomyocytes upregulate SGLT2, resulted to loss of Na + /Ca 2+ homeostasis via ERK and eNOS signaling. AMI (+) and AMI (-) serum levels were estimated using ELISA assays of TGFβ-1 or endoglin (CD105). Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1 Hz for 24 h. Immunofluorescence assays were used to estimate troponin I, CD105, SGLT1/2, eNOS S633 , and ERK1/2 T202/Y204 levels was performed for 5% (mild), and 25% elongation for 24 h. AMI (+) serum showed increased TGFβ1 and CD105 compared to AMI (-) patients. In consistent, troponin I, CD105, SGLT1/2, eNOS S633 and ERK1/2 T202/Y204 were upregulated after 25% of 24 h cyclic stretch. Dapagliflozin addition caused SGLT2 inhibition, which significantly decreased troponin I, CD105, SGLT1/2, eNOS S633 , and ERK1/2 T202/Y204 under 25% cyclic stretching. In summary, SGLT2 may have sensed mechanical stretch in a way similar to cardiac overloading as in vivo. By blocking SGLT2 in stretched cardiomyocytes, the AMI biomarkers (CD105, troponin I and P-ERK) were decreased, potentially to rescue eNOS production to maintain normal cellular function. This discovery of CD105 and SGLT2 increase in mechanically stretched cardiomyocytes suggests that SGLT2 may conceive a novel role in direct or indirect sensing of mechanical stretch, prompting the possibility of an in vitro cardiac overloaded cell model, an alternative to animal heart model., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Parents must manage their own stress and help their child with cancer during the treatment process, both physically and emotionally. With the increased involvement of fathers in caring for the family, how fathers adjust to the stress and play a role in care responsibilities is unknown. This study aimed to explore the fathers' experiences of caring for their ill child during the cancer diagnosis and treatment process., Method: This study adopted a qualitative descriptive design and conducted in-depth interviews with 21 fathers with a diagnosed child recruited from a northern Taiwan medical center. Data were managed and analysed using content analysis., Results: Two main categories in the Taiwanese fathers' experiences of caring for their ill child during the cancer diagnosis and treatment process emerged: 1) the maintainer of family stability, and 2) thoughts and value adjustment. Each main category consists of 3-4 generic categories. They make the necessary adjustments between work and family, actively participate in caring for the entire family, and redefine family values. They convey information about the illness to their children, pay attention to the physical and psychological development of the child with cancer, and cherish the time spent together as a family., Conclusions: During the cancer treatment process, fathers play the roles of the protector and maintainer of family stability and adjust their attitudes and thoughts toward the family members and family life. Healthcare professionals can offer the fathers comprehensive support and improve the family's overall well-being during this demanding period., Competing Interests: Declaration of competing interest The authors do not have any conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1 plus . Both IKZF1 deletion (14.6%) and IKZF1 plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1 plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1 plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1 plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1 plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: This study aimed to report cases of bilateral corneal Bowman layer deposits in 4 patients with a history of keratorefractive surgery. To our knowledge, this condition has not previously been reported and should be distinguished from granular corneal dystrophy type 2 and other corneal dystrophies., Methods: We reviewed all available medical records that were collected between January 2010 and December 2021 at a tertiary referral center and performed whole-exome sequencing to provide diagnostic information., Results: Four patients exhibited similar bilateral corneal deposits that were observed more than 10 years after keratorefractive surgery. The patients' ages ranged from 36 to 53 years; 3 of the 4 patients were female. Three patients received laser in situ keratomileusis surgery, and 1 received radial keratotomy. All 4 patients denied having a family history of ocular diseases and reported an uneventful postoperative course. On examination, the best-corrected visual acuity ranged from 6/10 to 6/6 in all 4 patients. Slit-lamp examination revealed bilateral superficial corneal deposits involving the central cornea, and anterior segment optical coherence tomography revealed hyperreflective deposits located in the Bowman layer. Such unique manifestations suggested corneal dystrophy; thus, whole-exome sequencing was performed on all 4 patients. Only 1 patient exhibited a missense mutation in TGFBI . We further analyzed common de novo mutations to explore possible candidate genes associated with this presentation., Conclusions: We report a rare entity of presumed corneal dystrophy with deposits located in the Bowman layer in 4 patients who had received keratorefractive surgery. Clarifying the underlying pathophysiology and genetic predisposition of this disease may aid in diagnosing and preventing potential complications after keratorefractive surgery., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Dance education fosters embodied metacognition, enhancing student's creativity. This study examines the crucial role of functional connectivity (FC) between the neural correlates of metacognition (NCM) and dance (NCD) as the neurological foundation for dancers' embodied metacognition. The investigation also explores whether these consolidated FCs inform the general creativity in dancers., Methods: The research involved 29 dancers and 28 non-dancer controls. The study examined resting-state connections of the NCM through seed-based FC analysis. Correlation analyses were employed to investigate the connections between the targeted NCM-NCD FCs, initiated from the a priori NCM seed, and general creativity., Results: Dancers demonstrated heightened FC between NCM and NCD compared to non-dancer controls. The targeted regions included the putamen, globus pallidus, posterior cerebellum, and anterior insula of NCD. The dancers exhibited higher originality scores. In dancers, the enhanced FC showed a negative correlation with originality and a positive correlation with flexibility. Conversely, the controls exhibited no significant correlations., Discussion: Extended dance training enhances the NCM-NCD connection signifying embodied metacognition. This interconnectedness may serve as the neural predisposition for fostering general creativity performance in dancers. Dancers with heightened levels of originality could leverage the relatively weaker NCM-NCD FCs to facilitate better integration and coordination of creative cognitive processes. Our findings suggest that the consolidated functional connections as sculpted by domain-specific training may inform general creativity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Yu, Hong, Cheng, Li, Yeh, Chen and Hsieh.)

Objectives: The aim of this network meta-analysis (NMA) was to assess whether participants assigned to a placebo and standard of care (SoC) group had different major coronavirus disease 2019 (COVID-19)-related outcomes than those assigned to SoC alone., Design: Frequentist model-based NMA., Setting: We searched for randomised controlled trials (RCTs) of Janus kinase/Bruton tyrosine kinase inhibitors for the management of COVID-19., Participants: Patients with COVID-19 infection., Main Outcome Measures: The primary outcome was the 28-day all-cause mortality, and secondary outcomes were: (1) use of mechanical ventilation; (2) secondary bacterial infection; (3) acceptability (i.e. drop-out rate); and (4) safety (i.e. serious adverse events). We conducted an NMA using the frequentist model. Effect sizes were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs)., Results: We identified 14 eligible RCTs enrolling a total of 13,568 participants with COVID-19. Participants assigned to placebo plus SoC had a significantly higher risk of 28-day all-cause mortality than those receiving SoC alone (OR = 1.39, 95% CI = 1.07-1.79). This finding did not change substantially by subgroup analysis stratified by epidemiology factor, pandemic history progression and statistical methodologic consideration. In addition, none of the treatments investigated were associated with a significantly different risk of secondary bacterial infection, acceptability or safety compared with the SoC group., Conclusions: This NMA suggested a higher all-cause mortality in patients treated with placebo plus SoC compared with those treated with SoC alone. However, caution is advised in interpreting these results due to the absence of a direct head-to-head comparison. Future research should critically evaluate the necessity of placebo administration in COVID-19 RCTs and consider alternative study designs to minimise potential biases. Trial registration: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022376217).

Aim: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19., Methods: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events., Results: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar., Conclusion: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials., (© 2023 The Authors. Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.)

Introduction: This study aimed to examine the white matter characteristics of visual artists (VAs) in terms of visual creativity and the structural connectivity within the cortical visual system., Methods: Diffusion spectrum imaging was utilized to examine the changes in white matter within the cortical visual system of a group of VAs ( n  = 25) in comparison to a group of healthy controls matched for age and education ( n  = 24). To assess the integrity of white matter and its relationship with visual creativity, we conducted a comprehensive analysis using region-based and track-specific tractographic examinations., Results: Our study uncovered that VAs demonstrated increased normalized quantitative anisotropy in specific brain regions, including the right inferior temporal gyrus and right lateral occipital gyrus, along with the corresponding white matter fiber tracts connecting these regions. These enhancements within the cortical visual system were also found to be correlated with measures of visual creativity obtained through psychological assessments., Discussion: The noted enhancement in the white matter within the cortical visual system of VAs, along with its association with visual creativity, is consistent with earlier research demonstrating heightened functional connectivity in the same system among VAs. Our study's findings suggest a link between the visual creativity of VAs and structural alterations within the brain's visual system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong, Yang, Cheng, Li, Tseng, Yeh, Yu, Chen and Hsieh.)

Background: Malposition may occur during peripherally inserted central catheter insertion. Accurately measuring the length of a peripherally inserted central catheter is crucial to preventing malposition, including "long peripherally inserted central catheter placement," in which the tip of a peripherally inserted central catheter is deeper than the target position. The traditional method of measuring peripherally inserted central catheter length involves measuring from the insertion site to the parasternal notch and down to the third or fourth intercostal space, which may result in overestimation because of the thickness of the pectoralis major and anterior chest wall. To avoid this overestimation, the authors developed and tested a modified method for reducing long peripherally inserted central catheter placement., Methods: This study employed a retrospective design. Chest X-rays were used to examine the peripherally inserted central catheter tip positions in 48 patients in the medical intensive care unit who had undergone peripherally inserted central catheter insertion. The traditional and modified measurement methods were used to measure the peripherally inserted central catheter length in 17 and 31 patients, respectively. Fisher's exact test was used to examine between-group differences in the incidence of different types of peripherally inserted central catheter malposition., Results: The peripherally inserted central catheter tip position was near the target position in five patients (29.41%) in the traditional measurement group and 17 patients (54.84%) in the modified measurement group ( p  = 0.132), whereas long peripherally inserted central catheter placement occurred in six patients (35.29%) in the traditional measurement group and one patient (3.23%) in the modified measurement group ( p  = 0.006). However, the incidence of other types of peripherally inserted central catheter malposition did not differ significantly between the groups., Conclusions: The results of this study that the proposed modified measurement method may be able to reduce the incidence of long peripherally inserted central catheter placement among medical intensive care unit patients. The method must be further evaluated in prospective studies and studies with larger sample sizes in the future., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Aims: Chronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects., Main Methods: SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6-12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats., Key Findings: In this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution., Significance: Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts., Competing Interests: Declaration of competing interest The authors declared no competing financial interest., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: The authors have no conflicts of interest to declare.

Background: We aim to characterise the ophthalmic findings and retinal vasculature changes in patients with WS, and to analyse the correlation between ophthalmic manifestations and the associated systemic diseases., Methods: This retrospective case-control study included 27 WS patients and 28 age-matched healthy participants. Stellate pattern of iris, central macular thickness (CMT), foveal width, retinal vessel diameter, superficial vascular density (SVD) of macula and foveal avascular zone (FAZ) were compared between WS patients and healthy participants., Results: Twenty-five patients (93%) had the classic stellate iris presentation. Compared with healthy controls, WS patients had decreased CMT, increased foveal width and a lower SVD of macula (all P < 0.001). Significantly decreased mean retinal arterial (117.9 ± 9.9 µm vs. 133.0 ± 6.7 µm in WS and controls, respectively; p < 0.001) and venous (158.9 ± 11.2 µm vs. 174.0 ± 8.0 µm in WS and controls, respectively; p < 0.001) outer diameters, as well as mean arterial wall thickness (11.2 ± 1.3 µm vs. 12.2 ± 0.8 µm in WS and controls, respectively; p < 0.01) were found in WS. Stellate iris grading was significantly associated with CMT, foveal width, retinal vessel diameter (all p < 0.05), and a significant increase in the odds of having hypertension (Odds ratio (OR), 5.63; P < 0.05). The severity of stellate iris in WS seemed to have the trend of increasing risk of having pulmonary stenosis, tricuspid regurgitation and mitral regurgitation., Conclusions: This study provides the first in vivo evidence reflecting current knowledge on vessel morphology in WS patients that deficient circumferential growth is the predominant pathophysiologic changes resulting from elastin deficiency. The ophthalmic characteristics may serve as a complementary tool to diagnose and follow-up patients suffering from WS., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Although O-mannosyltransferase TMTC1 is highly expressed by ovarian cancer, its pathophysiological role in ovarian cancer remains unclear. Here, immunohistochemistry showed that TMTC1 was overexpressed in ovarian cancer tissues compared with adjacent normal ovarian tissues, and high TMTC1 expression was associated with poor prognosis in patients with ovarian cancer. Silencing TMTC1 reduced ovarian cancer cell viability, migration, and invasion in vitro, as well as suppressed peritoneal tumor growth and metastasis in vivo. Moreover, TMTC1 knockdown reduced cell-laminin adhesion, which was associated with the decreased phosphorylation of FAK at pY397. Conversely, TMTC1 overexpression promoted these malignant properties in ovarian cancer cells. Glycoproteomic analysis and Concanavalin A (ConA) pull-down assays showed that integrins β1 and β4 were novel O-mannosylated protein substrates of TMTC1. Furthermore, TMTC1-mediated cell migration and invasion were significantly reversed by siRNA-mediated knockdown of integrin β1 or β4. Collectively, these results suggest that TMTC1-mediated invasive behaviors are primarily through integrins β1 and β4 and that TMTC1 is a potential therapeutic target for ovarian cancer., (© 2023. The Author(s).)

Introduction: Dance is an art form that integrates the body and mind through movement. Dancers develop exceptional physical and mental abilities that involve various neurocognitive processes linked to embodied cognition. We propose that dancers' primary trait representation is movement-actuated and relies on the extended mirror neuron system (eMNS)., Methods: A total of 29 dancers and 28 non-dancer controls were recruited. A hierarchical approach of intra-regional and inter-regional functional connectivity (FC) analysis was adopted to probe trait-like neurodynamics within and between regions in the eMNS during rest. Correlation analyses were employed to examine the associations between dance training, creativity, and the FC within and between different brain regions., Results: Within the eMNS, dancers exhibited increased intra-regional FC in various brain regions compared to non-dancers. These regions include the left inferior frontal gyrus, left ventral premotor cortex, left anterior insula, left posterior cerebellum (crus II), and bilateral basal ganglia (putamen and globus pallidus). Dancers also exhibited greater intrinsic inter-regional FC between the cerebellum and the core/limbic mirror areas within the eMNS. In dancers, there was a negative correlation observed between practice intensity and the intrinsic FC within the eMNS involving the cerebellum and basal ganglia. Additionally, FCs from the basal ganglia to the dorsolateral prefrontal cortex were found to be negatively correlated with originality in dancers., Discussion: Our results highlight the proficient communication within the cortical-subcortical hierarchy of the eMNS in dancers, linked to the automaticity and cognitive-motor interactions acquired through training. Altered functional couplings in the eMNS can be regarded as a unique neural signature specific to virtuoso dancers, which might predispose them for skilled dancing performance, perception, and creation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Yu, Hong, Shih, Yeh, Chen and Hsieh.)

Cardiac lymphoma is rare in children. Treatment typically includes chemotherapy, combination of radiotherapy, or surgery. We report a case of stage IV precursor B lymphoblastic lymphoma with secondary involvement of the heart in an 11-year-old girl who was treated with acute lymphoblastic leukemia-based chemotherapy. Also, we review the literature on this uncommon malignancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Quantitative analysis via bibliometric field analyses is a recent, gradually emerging method. We conducted a bibliometric study to investigate the authors' scientific influence and contributions and evaluate trends and research foci in good death-related literature using the Web of Science (WOS) Core Collection. A total of 1,157 publications were selected for the analysis. There was a significant increase in annual publications per year ( R 2 = 0.79). The publication (317, 27.4%) and average citation (29.2) numbers were highest in the USA. Controlling for population number and GDP, the Netherlands had the highest number of articles per million persons (5.89) and US$ 10 10 GDP (1.02). North American and Western European countries are leaders in the field, but some East Asian countries (Japan and Taiwan) perform well. Current research focuses on patient perspectives of good death and advance care planning among patients, families, and health care providers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The mental health of children and adolescents with autism spectrum disorder (ASD) is a concern of recent years. However, a large-scale longitudinal study investigating the risk and the time course of subsequent psychiatric comorbidities is still lacking., Methods: Using the Taiwan National Health Insurance Research Database, 13,382 children and adolescents with ASD, and 53,528 age- and sex-matched non-ASD controls were enrolled between 2001 and 2009, and followed to the end of 2011. The adjusted hazard ratio (HR) with a corresponding 95 % confidence interval for psychiatric comorbidities among children and adolescents with ASD vs matched controls was estimated. The subjects who developed schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and obsessive-compulsive disorder (OCD) were identified during the follow-up., Results: Children and adolescents with ASD compared with controls were more likely to be diagnosed with schizophrenia (19.21; 13.74, 26.88), bipolar disorder (17.59; 12.66, 24.44), depressive disorder (5.56; 4.72, 6.56), anxiety disorder (5.01; 4.49, 5.59), and OCD (16.12; 11.66, 22.30) later in life. The time course of subsequent psychiatric comorbidity showed that anxiety disorder occurred first, usually in late childhood, with psychotic and affective disorders proceeding in adolescence. Those with ASD and anxiety disorder had an additionally increased likelihood of developing subsequent psychiatric comorbidity compared with those with ASD only., Limitation: In claims data analysis, clinical parameters or possible confounders may not be fully captured., Conclusion: Patients with ASD are predisposed to the development of anxiety disorder in late childhood, as well as schizophrenia, bipolar disorder, depressive disorder, and OCD in adolescence., Competing Interests: Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Traditional Chinese herbal medicine has widespread use in Taiwan. This cross-sectional questionnaire survey investigates the preoperative use and discontinuation of Chinese herbal medicine and dietary supplements among Taiwanese patients. We obtained the types, frequency, and sources of Chinese herbal remedies and supplements used. Among 1428 presurgical patients, 727 (50.9%) and 977 (68.4%) reported the use of traditional Chinese herbal medicine and supplements in the past one month, respectively. Only 17.5% of the 727 patients stated discontinuation of herbal remedies 4.7 ± 5.1 (1-24) days before the surgery, and 36.2% took traditional Chinese herbal medicine with concomitant physician-prescribed Western medicine for their underlying diseases. The most commonly used Chinese herbs are goji berry ( Lycium barbarum ) (62.9%) and Si-Shen-Tang (48.1%) in single and compound forms, respectively. The presurgical use of traditional Chinese herbal medicine was common in patients undergoing gynecologic (68.6%) surgery or diagnosed with asthma (60.8%). Women and those with a high household income had a greater tendency to use herbal remedies. This study demonstrates the high proportion of the presurgical use of Chinese herbal remedies and supplements along with physician-prescribed Western medicine in Taiwan. Surgeons and anesthesiologists should be aware of the potential adverse effects of drug-herb interaction for Chinese patients.

Purpose: To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making., Methods: A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated., Results: The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane., Conclusion: The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.

This Taiwan study examined the associations of parental age and mental disorders with the offspring risks of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), and bipolar disorder (BD). Children born between January 1991 and December 2004 in Taiwan were enrolled as the birth cohort (n = 4,138,151) and followed up until December 2011. A logistic regression analysis was performed to identify the odds ratio (OR). The advanced age effects were significant in ADHD (range of OR: 1.04 to 1.49) and ASD (range of OR: 1.35 to 2.27). Teenage mothers, teenage fathers, and fathers ≥ 50 years had higher offspring risks of MDD (range of OR: 1.24 to 1.46); and teenage mothers and fathers ≥ 50 years had increased offspring risks of BD (range of OR: 1.23 to 1.87). Both paternal and maternal mental disorders were associated with higher risks of within-disorder transmission for ADHD, ASD, MDD, and BD (range of OR: 2.64 to 30.41). Besides, parents with one of these four mental disorders (ADHD, ASD, MDD, and BD) might have higher risk of cross-disorder transmission to at least one of the other three mental disorders in the offspring (range of OR: 1.35 to 7.15). Parental age and mental disorders had complex and nuanced patterns in association with offspring mental disorders., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Propafenone is a class IC antiarrhythmic agent that is commonly used as the first-line therapy for patients with paroxysmal atrial fibrillation (AF) in Taiwan. This study compared the efficacy and safety of generic (Rhynorm) and brand name (Rytmonorm) propafenone for rhythm control of paroxysmal AF in Taiwan., Methods: This was an open-label randomized multicenter noninferior study conducted in Taiwan. We enrolled 76 patients with AF. To investigate the efficacy of propafenone, we used a wearable electrocardiogram (ECG) event recorder to evaluate the daily burden of AF episodes in patients for 24 weeks. The primary efficacy endpoint was the frequency of AF with clinical significance, which was indicated by AF duration ≥30 seconds. The safety endpoints included proarrhythmic or hemodynamic adverse events., Result: To analyze the efficacy and safety of these agents, 71 patients (five patients with screen failure) were randomized to two groups, specifically a Rhynorm group (n = 37) and a Rytmonorm group (n = 34), for 24 weeks of the treatment period. The baseline patient characteristics were comparable between the groups. However, the Rhynorm group was older (65.4 ± 8.40 vs 59.8 ± 10.8 years; p = 0.02). The primary efficacy endpoint at week 24 decreased by 4.76% ± 18.5% (from 24.3% ± 33.9% to 19.0% ± 28.7%; p = 0.13) in the Rhynorm group and by 3.27% ± 15.2% (from 16.9% ± 26.4% to 13.6% ± 19.2%; p = 0.22) in the Rytmonorm group, with an intergroup difference of 1.5% ± 17.0%; p = 0.71. This finding indicates that Rhynorm is not inferior to Rytmonorm ( p = 0.023 for noninferiority). The safety profile of the agents was comparable between the two groups., Conclusion: Our results verified that Rhynorm was noninferior to Rytmonorm in terms of efficacy and safety for treating paroxysmal AF in Taiwan ( ClinicalTrials.gov Identifier: NCT03674658)., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient's QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.

Background and Objectives : Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods : Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results : Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions : Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Pediatric extracranial germ cell tumors (GCTs) are rare, accounting for approximately 3.5% of childhood cancers. Since the introduction of platinum-based chemotherapy, the survival rate of patients has improved to more than 80%. However, poor-risk subtypes of pediatric extracranial GCTs do not respond well to chemotherapy, leading to refractory or relapsed (R/R) diseases. For example, long-term survival rates of mediastinal GCTs or choriocarcinoma are less than 50%. According to reports in recent years for adult patients with R/R GCTs, the use of high-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) has clinical advantages; however, HDCT combined with ASCT has rarely been reported in pediatric GCTs. The R/R and poor-risk groups of pediatric GCTs could benefit from HDCT and ASCT.

Primary intracranial ependymoma is a challenging tumor to treat despite the availability of multidisciplinary therapeutic modalities, including surgical resection, radiotherapy, and adjuvant chemotherapy. After the completion of initial treatment, when resistant tumor cells recur, salvage therapy needs to be carried out with a more precise strategy. Circulating tumor cells (CTCs) have specifically been detected and validated for patients with primary or recurrent diffused glioma. The CTC drug screening platform can be used to perform a mini-invasive liquid biopsy for potential drug selection. The validation of potential drugs in a patient-derived xenograft (PDX) mouse model based on the same patient can serve as a preclinical testing platform. Here, we present the application of a drug testing model in a six-year-old girl with primary ependymoma on the posterior fossa, type A (EPN-PFA). She suffered from tumor recurrence with intracranial and spinal seeding at 2 years after her first operation and extraneural metastases in the pleura, lung, mediastinum, and distant femoral bone at 4 years after initial treatment. The CTC screening platform results showed that everolimus and entrectinib could be used to decrease CTC viability. The therapeutic efficacy of these two therapeutic agents has also been validated in a PDX mouse model from the same patient, and the results showed that these two therapeutic agents significantly decreased tumor growth. After precise drug screening and the combination of focal radiation on the femoral bone with everolimus chemotherapy, the whole-body bone scan showed significant shrinkage of the metastatic tumor on the right femoral bone. This novel approach can combine liquid biopsy, CTC drug testing platforms, and PDX model validation to achieve precision medicine in rare and challenging tumors with extraneural metastases.

Background: The direct comparison of molecular responses of front-line imatinib (IM) monitored at the same laboratory between children and adults with chronic phase (CP) of chronic myeloid leukaemia (CML) had not been reported. In this multicenter study, we compared the landmark molecular responses and outcomes of paediatric and adult CML-CP cohorts treated with front-line IM in whom the BCR::ABL1 transcript levels were monitored at the same accredited laboratory in Taiwan., Methods: Between June 2004 and July 2020, 55 newly diagnosed paediatric and 782 adult CML-CP patients, with molecular diagnosis and monitoring at the same reference laboratory in Taiwan, were enrolled. The criteria of 2020 European LeukemiaNet were applied to evaluate the molecular responses., Results: By year 5, the cumulative incidences of IS <1%, MMR, MR 4.0 and MR 4.5 of paediatric patients were all significantly lower than those of adult patients (58 vs 75%, 48 vs 66%, 25 vs 44%, 16 vs 34%, respectively). The 10-year progression-free survival (PFS) (90%) and overall survival (OS) (94%) of paediatric patients did not differ from those (92%) of adult patients., Conclusions: We demonstrated the paediatric cohort had slower molecular responses to front-line IM and similar outcomes in 10-year PFS and OS in real-world practice., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59-1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56-1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.

Introduction: This study sought to elucidate the cognitive traits of visual artists (VAs) from the perspective of visual creativity and the visual system (i.e., the most fundamental neural correlate)., Methods: We examined the local and long-distance intrinsic functional connectivity (FC) of the visual system to unravel changes in brain traits among VAs. Twenty-seven university students majoring in visual arts and 27 non-artist controls were enrolled., Results: VAs presented enhanced local FC in the right superior parietal lobule, right precuneus, left inferior temporal gyrus (ITG), left superior parietal lobule, left angular gyrus, and left middle occipital gyrus. VAs also presented enhanced FC with the ITG that targeted the visual area (occipital gyrus and cuneus), which appears to be associated with visual creativity., Discussion: The visual creativity of VAs was correlated with strength of intrinsic functional connectivity in the visual system. Learning-induced neuroplasticity as a trait change observed in VAs can be attributed to the macroscopic consolidation of consociated neural circuits that are engaged over long-term training in the visual arts and aesthetic experience. The consolidated network can be regarded as virtuoso-specific neural fingerprint., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong, Yang, Shih, Fan, Yeh, Yu, Chen and Hsieh.)

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5-7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham ( p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.

Purpose: Individuals with bipolar disorder (BD) may have an increased risk of exposure to prescription opioids. However, it is still unknown whether such risk also occurs in their offspring. This study aimed to investigate the risk of exposure to prescription opioid use and related medical conditions in the offspring of parents with BD., Methods: This study used the Taiwan National Health Research Database and included offspring who had any parent with a diagnosis of BD. The matched-control cohort was randomly identified from the offspring of parents without any major psychiatric disorders (MPD). We identified data pertaining to opioid prescription and related medical conditions, namely pain disorder, malignancy, autoimmune disease, and arthropathy. The Poisson regression was used to estimate odds ratios and 95% confidence intervals., Results: In total, 11,935 offspring of parents with BD and 119,350 offspring of parents without any MPD were included. After controlling for demographics and mental disorders, offspring of parents with BD demonstrated higher rates of prescription opioid use than those of parents without MPD, especially the intravenous/intramuscular form of opioids and prescription in hospital settings. In addition, offspring of parents with BD had a higher odds of pain disorders than those of parents without MPD., Conclusion: Our study identifies a higher odd for developing pain disorders and exposure to prescription opioids among children of parents with BD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Competing Interests: Declaration of interests We declare no competing interests.

Background: The public health strategy of increasing access to comprehensive home or community-based healthcare services and emergency home visits is intent on reducing the overcrowding of emergency departments. However, scientific evidence regarding the association between home-based healthcare services and emergency department uses is surprisingly insufficient and controversial so far. The present retrospective study identified the risk factors for emergency department visits among patients receiving publicly-funded homecare services., Methods: The personal demographic and medical information, caregiver characteristics, and behaviours related to homecare services and emergency department visits from the medical records and structured questionnaires of 108 patients who were recipients of integrated homecare services in a regional hospital in southern Taiwan between January 1, 2020, and December 31, 2020, were collected. After screening the potential predictor variables using the preliminary univariate analyses, the multivariate logistic regression with best subset selection approach was conducted to identify best combination of determinants to predict unplanned emergency department utilizations., Results: Best subset selection regression analysis showed Charlson Comorbidity Index (odds ratio (OR)=1.33, 95% CI=1.05 to 1.70), male caregiver (OR=0.18, 95% CI=0.05 to 0.66), duration of introducing homecare services (OR=0.97, 95% CI=0.95 to 1.00), working experience of dedicated nurses (OR=0.89, 95% CI=0.79 to 0.99) and number of emergency department utilizations within previous past year before enrollment (OR=1.54, 95% CI=1.14 to 2.10) as significant determinants for unplanned emergency department visits., Conclusions: The present evidence may help government agencies propose supportive policies to improve access to integrated homecare resources and promote appropriate care recommendations to reduce unplanned or nonurgent emergency department visits among patients receiving homecare services., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)