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Objective: Preclinical data suggest that peroxisome proliferator-activated receptor γ (PPARγ) agonists have antineoplastic effects in colorectal cancer. We aimed to assess the association between the use of synthetic PPARγ agonists, represented by thiazolidinediones (TZDs), and the risk of developing colorectal cancer.Research Design and Methods: We conducted a nationwide, population-based, case-control study using the Taiwan National Health Insurance Research Database. Case subjects were defined as patients who were diagnosed with diabetes at least 365 days prior to a new diagnosis of colorectal cancer between 2000 and 2008. We randomly selected diabetic control subjects for each case subject, which were matched by sex, age, and the duration of diabetes. Among the 24,496 eligible case subjects and control subjects, we used conditional logistic regression to assess the risk of colorectal cancer in association with the use of TZDs. An additional analysis was conducted to assess the effects of concomitant use of TZDs and low-dose aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) on the risk of colorectal cancer.Results: A decreased risk of colorectal cancer was observed in patients who had used TZDs compared with those who had never used TZDs (adjusted odds ratio 0.86 [95% CI 0.79-0.94]). Furthermore, the benefit of a decreased colorectal cancer risk was also found with concomitant use of TZDs and low-dose aspirin or NSAIDs.Conclusions: The use of TZDs may be associated with a decreased risk of colorectal cancer in patients with diabetes. Further studies are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5 IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1 IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Whereas studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, here referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and support of left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underlie the simultaneous fulfillment of these functions. A brief overview of the tools used to investigate the AVA, such as medical imaging modalities, experimental methods, and computational modeling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this article support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso, and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.

Chronic pain is a complex condition that often poses diagnostic and management challenges due to its multifactorial etiology. This case report describes a 49-year-old pastor who presented with a three-year history of chronic pain affecting multiple sites, including the neck, bilateral shoulders, thoracic region, lower back, and bilateral knees. Additionally, he experienced shortness of breath on mild exertion, which adversely affected his ability to converse and speak publicly. The patient had a rapid resting heart rate of 100-120 beats per minute, occasional palpitations, and a 24-hour electrocardiogram that confirmed 15% premature ventricular complexes with bigeminy and trigeminy. He complained of limited appetite with early satiety, intermittent nausea, and regurgitation. Despite consultations with multiple specialists, no underlying causes were identified in the cardiac, respiratory, gastrointestinal, or psychological domains. Ultrasound-guided bilateral vagus nerve hydrodissection using 5% dextrose without local anesthetics was administered three times at monthly intervals, resulting in remarkable pain relief within three months and the effects persisted at the nine-month follow-up. Tachycardia was no longer perceived, resting heart rate slowed to 70-80 beats per minute, shortness of breath improved, and public speaking ability was restored. The patient's early satiety, nausea, and reflux complaints were resolved. This case report highlights the potential effectiveness of this novel intervention for chronic pain. Further research is warranted to validate these findings and explore the mechanism of action., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of the Chi Mei Medical Center issued approval 11208-014 dated September 14, 2023. The duration of this approval is one year (from September 15, 2023, until September 14, 2024). Investigators are responsible for keeping the subject information confidential. The principal investigator is required to submit an Annual Report two months before the expiry date for continuing review approval in order for the research to proceed. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lam et al.)

Background: Occipital neuralgia is a debilitating condition, and traditional treatments often provide limited or temporary relief. Recently, ultrasound-guided hydrodissection of the greater occipital nerve (GON) has emerged as a promising minimally invasive approach., Objectives: To describe two novel ultrasound-guided hydrodissections with 5% dextrose for GON and discuss their advantages, disadvantages, and considerations., Methods: Two cases are reported. Case 1 describes a lateral decubitus approach for hydrodissecting the GON between the semispinalis capitis (SSC) and obliquus capitis inferior (OCI) muscles. Case 2 details a cranial-to-caudal approach for hydrodissecting the GON within the SSC and upper trapezius (UT) muscles when the GON passes through these two muscles., Results: Both patients experienced significant and sustained pain relief with improvements in function., Conclusions: Ultrasound-guided GON hydrodissection using 5% dextrose is a promising treatment for occipital neuralgia. The lateral decubitus and cranial-caudal approaches provide additional options to address patient-specific anatomical considerations and preferences.

Background: The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN)., Methods: We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined. We stratified 55 of 95 patients as high or low subset group according to the median percentage of each lymphocyte subset and the association with changes in the eGFR (ΔeGFR) were analyzed. Peripheral blood bulk RNA-seq to identify differentially expressed genes (DEGs) in 9 active LN vs. 9 inactive LN patients and the DEG-derived network was constructed by Ingenuity Pathway Analysis (IPA)., Results: The mean ΔeGFR of low NK-low memory CD4 + T-high naive CD4 + T group (31.01 mL/min/1.73 m 2 ) was significantly greater than that of high NK-high memory CD4 + T-low naive CD4 + T group (11.83 mL/min/1.73 m 2 ; P  = 0.0175). Kaplan-Meier analysis showed that the median time for ΔeGFR decline to mean ΔeGFR is approximately 10 years for high NK-high memory CD4 + T-low naive CD4 + T group and approximately 5 years for low NK-low memory CD4 + T-high naive CD4 + T group (log-rank test P  = 0.0294)., Conclusions: Our study highlighted important connections between DEG-derived network, lymphocyte subset composition, and disease status of LN and GN. A novel scoring system based on lymphocyte subset proportions effectively stratified patients into groups with differential risks for declining renal function., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The purpose of this study is to develop a smart training and assessment system called SmartCPR , for teaching and training cardiopulmonary resuscitation (CPR), based on human posture estimation techniques. In this system, trainees can automatically recognize and evaluate whether chest compressions during CPR meet the standard of high-quality CPR by simply using a device such as a smart phone. Through the system, trainees are able to obtain real-time feedback on the quality of compressions so that they can adjust the cycle, depth, frequency, and posture of compressions to meet the standard of high-quality CPR. In addition, the SmartCPR system is convenient for CPR trainers. Trainers can instantly and accurately assess whether the trainee's compressions meet the standard of high-quality CPR, which reduces the risk of manual assessment errors and also reduces the trainer's teaching pressures. Therefore, the SmartCPR system developed in this study can be an important tool for CPR teaching and training for physicians, which can provide training and guidance for high-quality CPR maneuvers and enable trainees to become more proficient in CPR and self-training.

Background: Spiritual care plays a significant role in holistic patient care, addressing not only physical ailments but also attending to patients' emotional and spiritual well-being. While the importance of spiritual care in nursing is widely recognized, there is often a gap in understanding nurses' willingness to provide such care. This cross-sectional study aimed to explore the association between self-efficacy, spiritual well-being, and willingness to provide spiritual care among nursing staff., Methods: The study conducted a cross-sectional survey of full-time registered nurses at a hospital in Taiwan from January 2019 to December 2019. A sample comprising 168 nurses was selected for participation in the study through a random sampling method. In addition to collecting demographic variables, the assessment tools used in the study include the General Self-Efficacy Scale (GSES) for measuring self-efficacy, the Spiritual Index of Well-Being Chinese Version (SIWB-C) for evaluating spiritual well-being, and the Spiritual Care Needs Inventory (SCNI) to gauge willingness to provide spiritual care., Results: Most participants in the study were female, accounting for 98.2% (n = 165). The mean age of all 168 nurses was 37.1 ± 9.3 years. Additionally, most participants held a Bachelor's degree (79.2%, n = 133) and possessed clinical experience was 10.5 ± 9.3 years. Through logistic regression analysis, it was found that regardless of whether participants have received sufficient spiritual care training, both GSES and SIWB-C remain influential factors in determining the provision of spiritual care., Conclusions: Collaboration between healthcare management and nursing staff is essential for fostering a healthcare environment that not only appreciates the physical and spiritual dimensions of patient care but also prioritizes the enhancement of nurses ' self-efficacy and well-being., (© 2024. The Author(s).)

Abstract: Patients with Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), are prone to Staphylococcus aureus infections and have a poor prognosis due to treatment resistance. Here, we report that S aureus and staphylococcal enterotoxins (SE) induce drug resistance in malignant T cells against therapeutics commonly used in CTCL. Supernatant from patient-derived, SE-producing S aureus and recombinant SE significantly inhibit cell death induced by histone deacetylase (HDAC) inhibitor romidepsin in primary malignant T cells from patients with SS. Bacterial killing by engineered, bacteriophage-derived, S aureus-specific endolysin (XZ.700) abrogates the effect of S aureus supernatant. Similarly, mutations in major histocompatibility complex (MHC) class II binding sites of SE type A (SEA) and anti-SEA antibody block induction of resistance. Importantly, SE also triggers resistance to other HDAC inhibitors (vorinostat and resminostat) and chemotherapeutic drugs (doxorubicin and etoposide). Multimodal single-cell sequencing indicates T-cell receptor (TCR), NF-κB, and JAK/STAT signaling pathways (previously associated with drug resistance) as putative mediators of SE-induced drug resistance. In support, inhibition of TCR-signaling and Protein kinase C (upstream of NF-κB) counteracts SE-induced rescue from drug-induced cell death. Inversely, SE cannot rescue from cell death induced by the proteasome/NF-κB inhibitor bortezomib. Inhibition of JAK/STAT only blocks rescue in patients whose malignant T-cell survival is dependent on SE-induced cytokines, suggesting 2 distinct ways SE can induce drug resistance. In conclusion, we show that S aureus enterotoxins induce drug resistance in primary malignant T cells. These findings suggest that S aureus enterotoxins cause clinical treatment resistance in patients with SS, and antibacterial measures may improve the outcome of cancer-directed therapy in patients harboring S aureus., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: We clarified the characteristics and risk factors of CVEs in young SLE patients., Method: We retrospectively reviewed the medical records of patients younger than 50 years of age diagnosed with SLE and first CVEs from 1995 to 2020 in a tertiary medical center in Taiwan. We collected data on the patient characteristics before the CVE and reviewed the laboratory data obtained during the period. At a ratio of 1:3, cases and controls were matched with sex, SLE diagnosis age, diagnosis year, and SLE duration., Results: We enrolled 43 CVE SLE patients and matched 129 non-CVE SLE controls. The median age at the time of the CVE was 39 years. Around 70% of young-aged CVE involved the cerebral lobes of frontal (∼30%), parietal (∼20%), occipital (∼10%), and temporal (∼10%). The peak incidence period for hemorrhagic CVE was within 1st year of SLE diagnosis (37%); in contrast, during the 2nd to 5th year of SLE diagnosis (25%) for ischemia CVEs. Hyperlipidemia (odds ratio [OR] = 19.36, p = 0.002), anti-phospholipid syndrome (APS) (OR = 41.9, p = 0.0068), a lower hemoglobin level (OR = 0.66, p = 0.0192), and a higher SLE Disease Activity Index (SLEDAI-2k) score (OR = 1.22, p = 0.0019) were independent risk factors for CVEs in young SLE patients., Conclusion: Hyperlipidemia, APS, low Hb level, and high SLEDAI-2k significantly increase the risk of young-aged SLE patients developing CVE., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Auto-immune bullous diseases (AIBD) are rare in children. Although their pathogenesis is similar to their adult counterpart, there are differences in the clinical presentation. Moreover certain AIBD prevail at certain ages. There are no guidelines for the treatment of AIBD specific for children. In this review the recent literature is summarised with attention to recent data including diagnostic criteria. We also propose a treatment algorithm., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

A novel defect control approach based on laminated HfO 2 /ZrO 2 with multifunctional TiN/Mo/TiO x N y electrode is proposed to significantly improve the endurance and data retention in HZO-based ferroelectric capacitor. The O-rich interface reduces leakage current and prolong the endurance up to 10 11 cycles while retaining a 2Pr value of 34 ( μ C cm -2 ) at 3.4 MV cm -1 . Using first-principles calculations and experiments, we demonstrate that the enhancement of endurance is ascribed to the higher migration barrier of oxygen vacancies within the laminated HZO film and higher work function of MoO x /TiO x N y between top electrode and the insulating oxide. This 2.5 nm thick TiO x N y barrier further increase the grain size of HZO, lowering the activation field and thus improving polarization reversal speed. This interfacial layer further decreases the overall capacitance, increases the depolarization field, thereby enhancing the data retention. By fitting the data using the Arrhenius equation, we demonstrate a 10 years data retention is achieved at 109.6 °C, surpassing traditional SS-HZO of 78.2 °C with a 450 °C rapid thermal annealing (required by backend-of-the-line). This work elucidates that interfacial engineering serves as a crucial technology capable of resolving the endurance, storage capability, and high-temperature data retention issues for ferroelectric memory., (Creative Commons Attribution license.)

Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements in the treatment of hematopoietic malignancies, particularly blood cancers. Yet their impact is constrained against tumors of hematopoietic origin manifesting in the skin. In this study, we employ a clonality-supervised deep learning methodology to dissect key pathological features implicated in mycosis fungoides, the most common cutaneous T-cell lymphoma. Our investigations unveil the prominence of the IL-32β-major histocompatibility complex (MHC)-I axis as a critical determinant in tumor T-cell immune evasion within the skin microenvironment. In patients' skin, we find MHC-I to detrimentally impact the functionality of natural killer (NK) cells, diminishing antibody-dependent cellular cytotoxicity and promoting resistance of tumor skin T-cells to cell-surface targeting therapies. Through murine experiments in female mice, we demonstrate that disruption of the MHC-I interaction with NK cell inhibitory Ly49 receptors restores NK cell anti-tumor activity and targeted T-cell lymphoma elimination in vivo. These findings underscore the significance of attenuating the MHC-I-dependent immunosuppressive networks within skin tumors. Overall, our study introduces a strategy to reinvigorate NK cell-mediated anti-tumor responses to overcome treatment resistance to existing cell-surface targeted therapies for skin lymphoma., (© 2024. The Author(s).)

Objectives: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can result in high morbidity if not treated. This retrospective study aimed to evaluate the outcomes of rituximab treatment in a paediatric SLE cohort in Taiwan., Methods: The medical records of paediatric patients diagnosed with SLE at the National Taiwan University Hospital between January 1992 and August 2022 who received rituximab as maintenance therapy between January 2015 and August 2022 were retrospectively reviewed. To enhance our analysis, we included a contemporary comparison group, matching in case number and demographic characteristics. This study aimed to describe the indications, efficacy and safety of rituximab in the treatment of paediatric SLE and to analyse the factors associated with disease outcomes., Results: The study included 40 rituximab-treated patients with a median age of 14.3 years at the time of disease diagnosis. In the rituximab-treated cohort, the median score on the Systemic Lupus Erythematosus Disease Activity Index 2000 decreased from 8 before rituximab administration to 4 after 2 years. The levels of C3 and C4 increased and anti-double stranded DNA (anti-dsDNA) levels decreased significantly within 6 months. The equivalent oral prednisolone dose halved after 6 months. Finally, 8 (20%) patients achieved disease control and 35 (87.5%) patients had no flare-ups during the follow-up period (median, 2 years). Those patients who achieved disease control had a significantly shorter interval between diagnosis and rituximab administration. In terms of adverse effects, only one patient developed hypogammaglobulinaemia that required intravenous immunoglobulin (IVIG) replacement. Compared with the comparison group (n=53), the rituximab-treated cohort exhibited superior disease outcomes and a reduced incidence of flare-ups., Conclusions: This study provides real-world data and illuminates rituximab's role in maintaining disease stability among patients with paediatric-onset SLE who are serologically active without major clinical deterioration. Most importantly, no mortality or development of end-stage renal disease was observed in the rituximab-treated cohort., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study compared ultrasound-guided nerve hydrodissection (HD) outcomes using two commonly used injectate volumes (10 and 5 mL) of normal saline to explore if there is a volume effect of HD for patients with moderate carpal tunnel syndrome (CTS)., Methods: Twenty-four participants were randomly assigned to treatment with HD using ultrasound-guidance and either 10 mL or 5 mL of normal saline (HD-10 and HD-5 groups respectively). Our primary outcome measures were the change scores of the two subscales of the Boston Carpal Tunnel Syndrome Questionnaire: The Symptom Severity Scale (SSS) and Functional Status Scale (FSS). We conducted a one-way repeated analysis of variance for 3 time points (4, 12, and 24 weeks) for both SSS and FSS, respectively, for change scores from time 0, and percentage change from time 0., Results: All participants (n = 12 per group) completed the study. From 0 to 24 weeks the HD-10 group outperformed the HD-5 group for improvement in SSS (median ± IQR; -0.8 ± 0.4 versus -0.5 ± 0.5; P = .024) and FSS scores (mean ± SD; -0.8 ± 0.2 versus -0.5 ± 0.5; P = .011). The HD-10 group improvement in FSS subtest significantly exceeded the MCID percentage-change-based threshold of 27% (34%; P = .039)., Conclusions: Despite the limitations of small study size, a largely inert injectate, and a single injection approach, these findings in favor of the 10 mL group suggest that the volume used for ultrasound-guided HD in moderate CTS matters, and a higher volume is more effective., (© 2023 American Institute of Ultrasound in Medicine.)

Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. DD patients often have skin involvement characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. The aim of this study was to characterize the cutaneous immune infiltrate in DD skin lesions in detail and to identify new therapeutic targets. Using gene and protein expression profiling assays including scRNA sequencing, we demonstrate enhanced expression of Th17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We provide evidence that targeting the IL-17/IL-23 axis in a case series of three DD patients with monoclonal antibodies is efficacious with significant clinical improvement. As DD is a chronic, relapsing disease, our findings might pave the way toward additional options for the long-term management of skin inflammation in patients with DD., (© 2023. The Author(s).)

Background: Extracorporeal photopheresis (ECP) has emerged as a systemic first-line immunomodulatory therapy in leukaemic cutaneous T-cell lymphoma (L-CTCL) and is now beginning to be utilized in other T-cell-mediated diseases. Although ECP has been used for nearly 30 years, its mechanisms of action are not sufficiently understood, and biomarkers for response are scarce., Objectives: We aimed to investigate the immunomodulatory effects of ECP on cytokine secretion patterns in patients with L-CTCL, to help elucidate its mechanism of action., Methods: A total of 25 patients with L-CTCL and 15 healthy donors (HDs) were enrolled in this retrospective cohort study. Concentrations of 22 cytokines were simultaneously quantified by using multiplex bead-based immunoassays. Neoplastic cells in patients' blood were evaluated by flow cytometry., Results: Firstly, we observed a distinct cytokine profile pattern difference between L-CTCLs and HDs. There was a significant loss of tumour necrosis factor (TNF)-α, and significant increase of interleukins (IL)-9, IL-12 and IL-13 in the sera of patients with L-CTCL compared with HDs. Secondly, patients with L-CTCL who received ECP were classified as treatment responders and nonresponders according to the quantitative reduction of malignant burden in their blood. We evaluated cytokine levels in culture supernatants from patients' peripheral blood mononuclear cells (PBMCs) at baseline and 27 weeks after ECP initiation. Strikingly, PBMCs purified from ECP responders released statistically higher concentrations of innate immune cytokines IL-1α, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-α in comparison with ECP nonresponders. In parallel, responders showed clearance of erythema, reduction of malignant clonal T cells in the blood, and a potent boost of relevant innate immune cytokines in individual patients with L-CTCL., Conclusions: Taken together, our results demonstrate that ECP stimulates the innate immune network, and facilitates redirection of the tumour-biased immunosuppressive microenvironment towards proactive antitumour immune responses. The alterations of IL-1α, IL-1β, GM-CSF and TNF-α can be used as biomarkers of response to ECP in patients with L-CTCL., Competing Interests: Conflicts of interest: F.D. has received honoraria and travel support from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre and Sun Pharma. E.G. has received consulting fees, payment or honoraria and/or research grant support from Helsinn, KIOWA Kirin, Mallinckrodt Pharmaceuticals, Novartis, Recordati Rare Diseases, Sanofi and Takeda outside the scope of the submitted work, has a patent on a diagnostic method for blood disease, has been involved in a leadership role for the European Academy of Dermatology and Venereology and European Organization for Research and Treatment of Cancer, and has stock/stock options for Scailyte AG., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism"., (© 2023. Springer Nature Limited.)

Objectives: The aim of this study was to develop a method to quantify the peel force in an in vitro model simulating repair of ascending aortic dissections with tissue glue (Bioglue)., Methods: This study adapted an adhesive T-Peel test for the determination of the peel strength of adhesives by measuring the peeling force of a T-shaped bonded tissue. Measurements were performed on iatrogenic dissected ascending porcine aorta, which has been repaired with Bioglue using different pressure levels. Four conditions were tested: zero sample pressure according to the manufacturer's recommendation (n = 10), low (504 Pa; n = 11), moderate pressure (1711 Pa; n = 24) and pressure applied by a round shaped vascular 'Borst clamp' (1764 Pa; n = 23). Non-parametric one-way analysis of variance was applied for statistical significance., Results: The median peel force (lower quartile, upper quartile) of aortic samples increased depending on the applied pressure: [no pressure 0.030 N/mm (0.016, 0.057), low pressure 0.040 N/mm (0.032, 0.070) and moderate pressure 0.214 N/mm (0.050, 0.304)]. Samples pressurized with the Borst clamp reached 0.078 N/mm (0.046, 0.152), which was comparable to the peel force of the unpeeled controls [0.107 N/mm (0.087, 0.124)]. Compared to samples without pressure, Bioglue with the application of the Borst clamp (P = 0.021) and with moderate pressure (P = 0.0007) performed significantly better., Conclusions: The novel T-Peel test offers an attractive method to test tissue glues in defined in vitro environments. Bioglue peel force increased with pressure on the aortic sample in contrast to low or no pressure as per the manufacturer's recommendation. Modifying current recommended use may aid in increasing effectiveness of this approach., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Fungal infections are the most frequent dermatoses. The gold standard treatment for dermatophytosis is the squalene epoxidase (SQLE) inhibitor terbinafine. Pathogenic dermatophytes resistant to terbinafine are an emerging global threat. Here, we determine the proportion of resistant fungal skin infections, analyse the molecular mechanisms of terbinafine resistance, and validate a method for its reliable rapid identification., Methods: Between 2013 and 2021, we screened 5634 consecutively isolated Trichophyton for antifungal resistance determined by hyphal growth on Sabouraud dextrose agar medium containing 0.2 μg/mL terbinafine. All Trichophyton isolates with preserved growth capacity in the presence of terbinafine underwent SQLE sequencing. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution method., Results: Over an 8-year period, the proportion of fungal skin infections resistant to terbinafine increased from 0.63% in 2013 to 1.3% in 2021. Our routine phenotypic in vitro screening analysis identified 0.83% (n = 47/5634) of Trichophyton strains with in vitro terbinafine resistance. Molecular screening detected a mutation in the SQLE in all cases. Mutations L393F, L393S, F397L, F397I, F397V, Q408K, F415I, F415S, F415V, H440Y, or A 398 A 399 G 400 deletion were detected in Trichophyton rubrum. Mutations L393F and F397L were the most frequent. In contrast, all mutations detected in T. mentagrophytes/T. interdigitale complex strains were F397L, except for one strain with L393S. All 47 strains featured significantly higher MICs than terbinafine-sensitive controls. The mutation-related range of MICs varied between 0.004 and 16.0 μg/mL, with MIC as low as 0.015 μg/mL conferring clinical resistance to standard terbinafine dosing., Conclusions: Based on our data, we propose MIC of 0.015 μg/mL as a minimum breakpoint for predicting clinically relevant terbinafine treatment failure to standard oral dosing for dermatophyte infections. We further propose growth on Sabouraud dextrose agar medium containing 0.2 μg/mL terbinafine and SQLE sequencing as fungal sporulation-independent methods for rapid and reliable detection of terbinafine resistance., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

This report presents the first case of painful anterior shoulder snapping due to a thickened, fibrotic bursa snapping between the subscapularis and the short head of the bicep during external and internal rotation of the humerus. A 46-year-old presented with a 10-month history of on-and-off anterolateral right shoulder pain and snapping. Direct treatment to the anterior suspected lesions partially and temporarily relieved the pain but did not reduce the snapping. Further musculoskeletal examination and dynamic ultrasound scanning showed dysfunction in the scapulothoracic movement and defects of the muscles that interact with the infraspinatus aponeurotic fascia. An ultrasound-guided diagnostic injection to the suspected lesions in the infraspinatus fascia and its muscles attachments improved the scapulothoracic movement, and the snapping and pain were eliminated immediately after the injection, which further shows that the defects in the infraspinatus fascia may be the root cause of the painful anterolateral snapping. The importance of the infraspinatus fascia and its related muscle in maintaining the harmony of the scapulothoracic movement and flexibility of the shoulder is considerable.

Background: Predicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan., Methods: Data was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression., Results: In total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission., Conclusion: The results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs., 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 Chu, Tsan, Chen, Chen, Hao, Chan, Chen, Hsu, Lin and Yang.)

A new dissipation function Wv is devised and presented to capture the rate-dependent mechanical behavior of the semilunar heart valves. Following the experimentally-guided framework introduced in our previous work (Anssari-Benam et al., 2022 "Modelling the Rate-Dependency of the Mechanical Behaviour of the Aortic Heart Valve: An Experimentally Guided Theoretical Framework," J. Mech. Behav. Biomed. Mater., 134, p. 105341), we derive our proposed Wv function from the experimental data pertaining to the biaxial deformation of the aortic and pulmonary valve specimens across a 10,000-fold range of deformation rate, exhibiting two distinct rate-dependent features: (i) the stiffening effect in σ-λ curves with increase in rate; and (ii) the asymptotic effect of rate on stress levels at higher rates. The devised Wv function is then used in conjunction with a hyperelastic strain energy function We to model the rate-dependent behavior of the valves, incorporating the rate of deformation as an explicit variable. It is shown that the devised function favorably captures the observed rate-dependent features, and the model provides excellent fits to the experimentally obtained σ-λ curves. The proposed function is thereby recommended for application to the rate-dependent mechanical behavior of heart valves, as well as other soft tissues that exhibit a similar rate-dependent behavior., (Copyright © 2023 by ASME.)

Neuroinflammation is a key feature in the pathogenesis of entrapment neuropathies. Clinical trial evidence suggests that perineural injection of glucose in water at entrapment sites has therapeutic benefits beyond a mere mechanical effect. We previously demonstrated that 12.5-25 mM glucose restored normal metabolism in human SH-SYFY neuronal cells rendered metabolically inactive from TNF-α exposure, a common initiator of neuroinflammation, and reduced secondary elevation of inflammatory cytokines. In the present study, we measured the effects of glucose treatment on cell survival, ROS activity, gene-related inflammation, and cell cycle regulation in the presence of neurogenic inflammation. We exposed SH-SY5Y cells to 10 ng/mL of TNF-α for 24 h to generate an inflammatory environment, followed by 24 h of exposure to 3.125, 6.25, 12.5, and 25 mM glucose. Glucose exposure, particularly at 12.5 mM, preserved apoptotic SH-SY5Y cell survival following a neuroinflammatory insult. ROS production was substantially reduced, suggesting a ROS scavenging effect. Glucose treatment significantly increased levels of CREB, JNK, and p70S6K ( p < 0.01), pointing to antioxidative and anti-inflammatory actions through components of the MAPK family and Akt pathways but appeared underpowered (n = 6) to reach significance for NF-κB, p38, ERK1/2, Akt, and STAT5 ( p < 0.05). Cell regulation analysis indicated that glucose treatment recovered/restored function in cells arrested in the S or G2/M-phases. In summary, glucose exposure in vitro restores function in apoptotic nerves after TNF-α exposure via several mechanisms, including ROS scavenging and enhancement of MAPK family and Akt pathways. These findings suggest that glucose injection about entrapped peripheral nerves may have several favorable biochemical actions that enhance neuronal cell function.

Background: Air pollution is a key public health factor with the capacity to induce diseases. The risk of ischemia heart disease (IHD) in those suffering from systemic lupus erythematosus (SLE) from air pollution exposure is ambiguous. This study aimed to: (1) determine the hazard ratio (HR) of IHD after the first-diagnosed SLE and (2) examine the effects of air pollution exposure on IHD in SLE for 12 years., Methods: This is a retrospective cohort study. Taiwan's National Health Insurance Research Database and Taiwan Air Quality Monitoring data were used in the study. Cases first diagnosed with SLE in 2006 cases without IHD were recruited as the SLE group. We randomly selected an additional sex-matched non-SLE cohort, four times the size of the SLE cohort, as the control group. Air pollution indices by residence city per period were calculated as the exposure. Life tables and Cox proportional risk models of time-dependent covariance were used in the research., Results: This study identified patients for the SLE group (n = 4,842) and the control group (n = 19,368) in 2006. By the end of 2018, the risk of IHD was significantly higher in the SLE group than in the control group, and risks peaked between the 6th and 9th year. The HR of incidence IHD in the SLE group was 2.42 times that of the control group. Significant correlations with risk of developing IHD were noted for sex, age, CO, NO 2 , PM 10 , and PM 2.5 , of which PM 10 exposure had the highest risk of IHD incidence., Conclusions: Subjects with SLE were at a higher risk of IHD, especially those in the 6th to 9th year after SLE diagnosis. The advanced cardiac health examinations and health education plan should be recommended for SLE patients before the 6th year after SLE diagnosed., (© 2023. The Author(s).)

Childhood asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to a broad range of clinical presentations. Nonallergic asthma is asthma without allergic sensitization. Both clinical manifestations and immunopathological mechanisms of nonallergic childhood asthma were rarely investigated. We aimed to compare the clinical features between nonallergic and allergic childhood asthma and apply microRNA to explore the underlying mechanism of nonallergic childhood asthma. We enrolled 405 asthmatic children (76 nonallergic, 52 allergic with total IgE < 150 IU/mL and 277 allergic with total IgE > 150 IU/mL). Clinical characteristics were compared between groups. Comprehensive miRNA sequencing (RNA-seq) was performed using peripheral blood from 11 nonallergic and 11 allergic patients with elevated IgE, respectively. Differentially expressed miRNA (DEmiRNA) were determined with DESeq2. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed to determine functional pathways involved. Publicly available mRNA expression data was applied to investigate the predicted target mRNA networks via Ingenuity Pathway Analysis (IPA). The average age of nonallergic asthma was significantly younger (5.614 ± 2.743 vs 6.676 ± 3.118 years-old). Higher severity and worse control were more common in nonallergic asthma (two-way ANOVA, P < 0.0001). Long-term severity was higher, and intermittent attacks persisted in nonallergic patients. We identified 140 top DEmiRNAs based on false discovery rate (FDR) q-value < 0.001. Forty predicted target mRNA gene were associated with nonallergic asthma. The enriched pathway based on GO included Wnt signaling pathway. IgE expression was predicted to be downregulated by a network involving simultaneous interaction with IL-4, activation of IL-10 and inhibition of FCER2. Nonallergic childhood asthma were distinct in their younger age, higher long-term severity and more persistent course. Differentially expressed miRNA signatures associate with downregulation of total IgE expression and predicted target mRNA genes related molecular networks contribute to canonical pathways of nonallergic childhood asthma. We demonstrated the negative role of miRNAs involved in regulating IgE expression indicating differences between asthma phenotypes. Identification of biomarkers of miRNAs could contribute to understand the molecular mechanism of endotypes in nonallergic childhood asthma, which can potentially allow delivery of precision medicine to pediatric asthma., (© 2023. The Author(s).)

Background: Lupus nephritis (LN) is a crucial organ involvement in systemic lupus erythematosus (SLE). Patients with LN have higher morbidity and mortality rates than those without. Among all patients with LN, 20-40% had delayed onset, but the data for patients with juvenile-onset SLE (jSLE), who have a higher percentage of LN than patients with adult-onset SLE (aSLE), were limited. This study aimed to determine the risk factors for subsequent LN in patients with jSLE., Methods: A retrospective cohort study was conducted between 2008 and 2018 in a single tertiary medical centre. Patients with diagnosed jSLE were reviewed. We investigated those without LN at diagnosis and whether they developed LN afterward. The primary outcome was the development of subsequent LN. Clinical manifestations at diagnosis, serial laboratory data, and treatments were reviewed during follow-up periods., Results: Among the 48 patients with jSLE without initial LN, 20 developed subsequent LN later (Group 1), whereas 28 remained free of LN (Group 2). There was no difference in the percentage of initial manifestations except for more discoid rashes in Group 2 patients. In the Cox regression model, elevated average anti-double-stranded DNA (dsDNA) antibody, low average serum complements, and high average erythrocyte sedimentation rate (ESR) levels during follow-up were predictors of subsequent LN. After adjusting for these factors in multivariable analyses, only high average anti-dsDNA antibody and high average ESR levels remained predictive of subsequent LN. For every 100 IU/ml increase in anti-dsDNA antibody, the risk for subsequent LN in jSLE increases by 1.29 times (hazard ratio = 1.29, 95% confidence interval 1.055-1.573)., Conclusion: Persistently high anti-dsDNA antibody and ESR levels during the follow-up period were risk factors for subsequent LN in patients with jSLE., (© 2023. The Author(s).)

Carpal tunnel syndrome (CTS) is the most common peripheral entrapment, and recently, ultrasound-guided perineural injection (UPIT) and percutaneous flexor retinaculum release (UPCTR) have been utilized to treat CTS. However, no systematic review or meta-analysis has included both intervention types of ultrasound-guided interventions for CTS. Therefore, we performed this review using four databases (i.e., PubMed, EMBASE, Scopus, and Cochrane) to evaluate the quality of evidence, effectiveness, and safety of the published studies on ultrasound-guided interventions in CTS. Among sixty studies selected for systemic review, 20 randomized treatment comparison or controlled studies were included in six meta-analyses. Steroid UPIT with ultrasound guidance outperformed that with landmark guidance. UPIT with higher-dose steroids outperformed that with lower-dose steroids. UPIT with 5% dextrose in water (D5W) outperformed control injection and hydrodissection with high-volume D5W was superior to that with low-volume D5W. UPIT with platelet-rich plasma outperformed various control treatments. UPCTR outperformed open surgery in terms of symptom improvement but not functional improvement. No serious adverse events were reported in the studies reviewed. The findings suggest that both UPIT and UPCTR may provide clinically important benefits and appear safe. Further treatment comparison studies are required to determine comparative therapeutic efficacy.

Introduction and Objectives: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy., Materials and Methods: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured., Results: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0., Conclusion: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy., (© 2022 John Wiley & Sons Ltd.)

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by defective neutrophil killing of microbial pathogens and recurrent infections. We aimed to investigate the clinical, genetic features, treatment, and outcomes in patients with CGD., Methods: Pediatric patients diagnosed with CGD from a medical center in Taiwan were enrolled from January 1999 to Oct 2021., Results: Nine pediatric patients with CGD were enrolled: six X-linked (XL) CGD with CYBB gene mutations, three autosomal recessive (AR) CGD with two NCF1 and one CYBA gene mutations. The median age of onset and age of diagnosis was 0.92 and 2.64 years, respectively. Patients with XL-CGD had a younger age of onset (4.6 months vs. 1.83 years, P = 0.06) and age of diagnosis (1.71 vs. 8.86 years, P = 0.024) than AR-CGD patients. The most common sites of infections were skin and soft tissue abscesses. The most common pathogens were Staphylococcus, Serratia, and Salmonella spp. Prophylactic antibiotics, anti-fungal agents, and interferon-gamma (IFN-γ) were given in 9 (100%), 7 (77.8%), and 8 (88.9%) patients, respectively. The mean duration of IFN-γ usage was 5.15 years. One male patient with XL-CGD was successfully treated with hematopoietic stem cell transplantation at 2.2 years. The mortality rate was 11.1%, and the estimated overall survival at 20 years was 66.7%., Conclusion: Staphylococcus aureus, Serratia marcescens, and Salmonella infections are important in Taiwanese CGD patients. Patients with XL-CGD have early disease onset. IFN-γ prophylaxis and prophylactic anti-microbial agents might have an effect on alleviating the infection episodes in CGD patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: This study aimed to investigate the risk factors surrounding an increase in both burnout levels and depression among health care professionals in Taiwan through use of a longitudinal study design., Design: This is a 2-year observational study that took place from January 2019 to December 2020., Setting and Participants: Data among health care professionals were extracted from the Overload Health Control System of a tertiary medical center in central Taiwan., Methods: Burnout was measured through use of the Chinese version of the Copenhagen Burnout Inventory (C-CBI), whereas depression was ascertained by the Taiwanese Depression Questionnaire. Each participant provided both burnout and depression measurements during a nonpandemic period (2019) as well as during the COVID pandemic era (2020). Risk factors surrounding an increase in burnout levels and depression were analyzed through a multivariate logistic regression model with adjusting confounding factors., Results: Two thousand nineteen participants completed the questionnaire over 2 consecutive years, including 132 visiting doctors, 105 resident doctors, 1371 nurses, and 411 medical technicians. After adjustments, sleeplessness, daily working hours >8, and stress due to one's workload were all found to be risk factors for an increase in depression levels, whereas sleeplessness, lack of exercise, and stress due to one's workload were all found to be risk factors for an increase in personal burnout level. Being a member of the nursing staff, a younger age, sleeplessness, and lack of exercise were all risk factors for an increase in work-related burnout levels., Conclusions and Implications: Poor sleep, lack of exercise, long working hours, and being a member of the nursing staff were risk factors regarding an increase in personal burnout, work-related burnout levels and depression among health care professionals. Leaders within the hospital should investigate the working conditions and personal habits of all medical staff regularly and systematically during the COVID-19 pandemic and take any necessary preventive measures, such as improving resilience for nursing staff, in order to best care for their employees., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

The growth of financial literacy is significant nowadays. Because of this, more people are becoming increasingly responsible in their financial planning, investments, and living expenses. In developing new technology, it is necessary to know the technological acceptance of the prospective users of the technology itself. This study aims to identify the primary factors influencing the technology acceptance levels of lower-middle socio-economic users for a digital financial literacy application. The proposed model in this research was developed based on UTAUT, TAM, and Usability model, and it consists of six primary constructs: (1) Performance Expectancy; (2) Effort Expectancy; (3) Social Influence; (4) Resources and Cost; (5) Satisfaction; (6) Behavior Intention. All the hypotheses used in this study were statistically measured using SmartPLS tools. This study found that because many lower-middle socio-economic users lack sufficient understanding of technology to properly utilize it, that a digital platform is not the right tool to teach them financial literacy., Competing Interests: The authors declare no conflicts of interest.

Objective: This study investigated the efficacy of extracorporeal shock wave therapy as well as the optimal intervention timing for extracorporeal shock wave therapy for patients with spasticity after stroke., Design: A search of randomized controlled trials was conducted in different electronic databases. We performed a meta-analysis to measure the effect of extracorporeal shock wave therapy versus sham interventions on spasticity and limb functionality. The meta-regression analysis was performed to determine the adequate intervention timing of extracorporeal shock wave therapy. The follow-up period of the outcomes was divided into the short (<2 wks), mid (>2 wks and ≤4 wks), and long (>4 wks and ≤3 mos) terms., Results: Thirteen studies with 677 participants were evaluated. Spasticity significantly improved throughout the follow-up duration. Limb functionality significantly improved in the short-term follow-up period. The meta-regression analysis showed that patients with stroke duration less than 45 mos may be benefited from extracorporeal shock wave therapy in improving limb function in all follow-up periods., Conclusions: Extracorporeal shock wave therapy is an effective method for reducing spasticity in patients with stroke, and the effect could be maintained for up to 3 mos. Its effects on limb functionality could persist for at least 2 wks. Patients who had stroke for less than 45 mos may have significant benefit from extracorporeal shock wave therapy in all follow-up periods., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: Students with learning disabilities have difficulties in reading abilities; however, their IQ is no less than that of ordinary students of the same age. This study investigated and developed three articles as the author and schoolteachers developed reading materials. Article A is with a standard layout; Article B is with keywords of various font sizes, and Article C is with a related illustration., Methods: Data of eye movements and reading tests from thirty students wherein 15 participants have dyslexia were collected. An eye-tracking methodology was employed to assess the dyslexics' students reading patterns and behavior., Results: ANOVA analysis shows differences in reading test performance among students for Article A with usual layout [F (1, 28) = 133.16, p = 0.000], but no significant differences for the other two articles. Based on the gaze map analysis, Article C (with illustration) can improve the reading completeness of the dyslexic students (eight out of fifteen dyslexic students had completed the reading during our experiment) than Article A and Article B., Conclusion: The results affirm that special layouts and narrative writing styles can improve the reading attention of students with dyslexia. This study's results and conclusions can reference future teaching materials or lesson preparation using lateral layouts for people with dyslexia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The world is aging, and hemophilia patients are as well. The association between patients with hemophilia (PWH) and low bone mineral density is clear. However, the incidence of fractures in patients with hemophilia is inconclusive, and no research has yet explored repeated fractures among PWH. In this study, we investigated the incidence of all-site fractures, repeated fractures and osteoporotic fractures amongst PWH. The study compared the incidence of all-site fractures, repeated fractures and osteoporotic fractures occurring in all PWH who were enrolled in Taiwan's National Health Insurance Research Database between 1997 and 2013 with an age- and gender-matched group from the general population. Eight-hundred thirty-two PWH, along with 8320 members of the general population, were included in the final analysis. After multivariate COX regression analysis with an adjustment for confounding factors, it was found that PWH experienced a higher risk of osteoporotic fracture (HR: 1.25 with 95% CI of 1.03-2.52) but only saw a neutral effect with regards to both all-sites of fracture (HR: 1.00 with 95% CI of 0.92-1.09) and repeated fractures (HR: 1.01 with 95% CI of 0.92-1.10), when compared with the general population. This 14-year population-based cohort study showed that PWH had a higher risk of osteoporotic fracture, but that hemophilia only had a neutral effect in all-sites of fracture and repeated fractures. Screening, prevention and treatment for osteoporosis and further osteoporotic fractures among PWH, in order to improve quality of life and achieve healthy aging in this particular population, remain essential.

Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans and can present with highly variable clinical manifestations. Immune deficiencies occur because of thymic hypoplasia or aplasia., Methods: This retrospective study included patients diagnosed with 22q11.2DS at a medical center between 2000 and 2021. We analyzed the association between clinical phenotypes, immunological abnormalities, age, and outcomes., Results: Eighty-seven patients with 22q11.2DS had a median diagnostic age of 1.78 months. Patients presented with congenital heart disease (CHD; 86.2%), major infections (75.9%), and failure to thrive (FTT; 58.6%). Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Neonatal seizures were associated with early diagnosis before 2 months (OR 8.56, 95% CI 1.21-60.58, P = 0.032). Immunological abnormalities included lymphopenia (93.1%), T lymphopenia (71.9%), CD4 + T lymphopenia (64.1%), a lack of hepatitis B vaccine antibodies (46.2%), and complete DiGeorge syndrome (cDGS) (2.3%). Severe lymphopenia and T lymphopenia improved at 3 years of age. Two patients with cDGS were treated with hematopoietic stem cell transplantation, and one survived. The mortality rate was 12.8% and the estimated 35-year survival probability was 77.5%. Major infections experienced > four times were significantly associated with a decreased survival rate of 60%. Patients with CHD without FTT or recurrent infections had a better 20-year survival rate (96.2%)., Conclusions: CHD, major infection, and FTT were common manifestations and poor prognostic factors. Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Although T lymphopenia may improve with age, patients with 22q11.2DS require lifelong monitoring for immune dysregulation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Childhood asthma is an inflammatory disease with heterogeneous outcomes. We sought to determine the impact of total IgE, blood eosinophil, allergen sensitization, and inhaled corticosteroid (ICS) on longitudinal outcomes and to identify characteristics for discriminating different outcomes., Methods: We conducted a retrospective study in 383 childhood asthma patients and another 313 patients with blood eosinophil data only receiving regular program-based visits from September 1, 2004, to December 31, 2018. Peak expiratory flow (PEF) variability, PEF predicted %, asthma severity, and asthma control at each visit were assessed as clinical outcomes., Results: Our data show that the percentage of blood eosinophils was significantly associated with increased asthma severity (OR: 1.043, 95% CI: 1.002-1.086, P = 0.0392). Mold sensitization was significantly associated with asthma severity (OR: 2.2485, 95% CI: 1.3253-3.8150, P = 0.0027). Characteristics including sensitization status plus ICS dosage had the best area under the receiver operating characteristic curve (AUC) value for predicting longitudinal PEF predicted % (0.6609), PEF variability (0.6885), asthma severity (0.5918), and asthma control (0.6441), respectively., Conclusions: We showed that the risk for adverse clinical outcomes at follow-up differed between serum IgE, blood eosinophil, and allergen sensitization identified at baseline. Sensitization and ICS dosage were predictive characteristics of long-term clinical outcomes., Impact: The unique aspects of the study are its longitudinal assessment of patients receiving guideline-based asthma management program to help characterize the stability of the clinical outcomes over time. Characteristics including allergen sensitization and ICS dosage demonstrated an improved capability for distinguishing between better and worse clinical outcomes. Through longitudinal serial assessment, this study indicates the risk for adverse clinical outcomes differed between children with serum IgE/blood eosinophil/allergen sensitization characterized at baseline., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

A theoretical framework, based on extant experimental findings, is presented to devise a novel viscous dissipation function W v in order to model the rate-dependent mechanical behaviour of the aortic heart valve. The experimental data encompasses Cauchy stress-stretch (σ-λ) curves obtained across a 10,000-fold range of stretch rates (λ˙), from quasi-static (λ˙= 0.001 s -1 ) to upper-range of physiological (λ˙= 12.4 s -1 ) deformation rates. The analysis of the data elicits two important trends: (i) the mechanical behaviour of the aortic valve across the tested rates is rate-dependent, with specimens becoming stiffer by increasing rate; and (ii) there appears to be a plateau in the rate-effects on the σ-λ curves; i.e. the rate-effects approach an asymptote with increase in the stretch rate λ˙. Guided by these empirical observations, we devise our new W v function and demonstrate that the well-known form of the dissipation function commonly used in the literature is a special case of our proposed W v . The ensuing model is then compared against the experimental σ-λ curves and is shown to provide favourable predictions. An important advantage of the employed modelling framework is that it allows the incorporation of the rate of deformation, which is a direct experimental control parameter, as an explicit modelling variable. The application of the proposed model is thereby recommended for heart valves and other soft tissues that exhibit similar rate-dependent features., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rapid and reliable fungal identification is crucial to delineate infectious diseases, and to establish appropriate treatment for onychomycosis. Compared to conventional diagnostic methods, molecular techniques are faster and feature higher accuracy in fungal identification. However, in current clinical practice, molecular mycology is not widely available, and its practical applicability is still under discussion. This study summarizes the results of 16,094 consecutive nail specimens with clinical suspicion of onychomycosis. We performed PCR/sequencing on all primary nail specimens for which conventional mycological diagnostics remained inconclusive. In specimens with a positive direct microscopy but negative or contaminated culture, molecular mycology proved superior and specified a fungal agent in 65% (587/898). In 75% (443/587), the identified pathogen was a dermatophyte. Positive cultures for dermatophytes, yeasts and non-dermatophyte molds (NDMs) were concordant with primary-specimen-DNA PCR/sequencing in 83% (10/12), 34% (22/65) and 45% (76/169), respectively. Among NDMs, agreement was high for Fusarium spp. (32/40; 80%), but low for Penicillium spp. (5/25; 20%) and Alternaria spp. (1/20; 5%). This study underlines the improvement in diagnostic yield by fungal primary-specimen-DNA PCR/sequencing in the event of a negative or contaminated culture, as well as its significance for the diagnosis of dermatophyte and non-dermatophyte onychomycosis. Molecular mycology methods like PCR and DNA sequencing should complement conventional diagnostics in cases of equivocal findings, suspected NDM onychomycosis or treatment-resistant nail pathologies.