Macrophage Activation Syndrome in Children: Update on Diagnosis and Treatment.

Macrophage activation syndrome (MAS) is potentially fatal; so, early diagnosis and timely treatment are essential. However, detecting MAS is sometimes challenging because its principal features can be observed in other pediatric diseases that cause severe inflammation. Cytokine storm due to immune dysregulation represents the clinical and laboratory features of MAS that are included in the diagnostic criteria. Most cases of MAS occur as an underlying condition worsens and progresses. Therefore, a patient with autoimmune or autoinflammatory disease who shows unexplained clinical deterioration despite appropriate management should be considered at high risk for MAS (i.e., occult MAS). The basic principles of treatment are control of triggering factors, supportive care, and relief of hyperinflammation. Systemic steroids and cyclosporine A are frequently used as a first-line treatment. For the treatment of refractory MAS, cytokine-specific biologic agents such as anakinra have recently become preferred over traditional immunosuppressive agents such as etoposide. MAS might be underrecognized in pediatric patients with infectious and inflammatory diseases due to its diverse clinical presentations. Clinical suspicion of MAS is of the utmost importance for early recognition of the disease.

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments.

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.

Clinical characteristics and otolith dysfunction in presbyvestibulopathy: A retrospective cross-sectional analysis.

Objective: The Bárány Society recently established diagnostic criteria for presbyvestibulopathy, an age-related bilateral vestibular impairments in older individuals. Drawing upon a cross-sectional database, this study delves into the demographic and clinical features of presbyvestibulopathy patients and investigates the implications of otolith dysfunction. Methods: The study retrospectively analyzed 1218 patients aged 60 years or older who visited the tertiary dizziness clinic in 2020, due to symptoms of dizziness or instability. By reviewing medical records, we gathered clinical information and laboratory vestibular test results, such as cervical and ocular vestibular evoked myogenic potentials, and subjective visual vertical. Results: Out of 1218 patients aged 60 and above who reported dizziness or unsteadiness, 33 patients (2.7 %, with an average age of 74.2 ± 9.2 years) were diagnosed with presbyvestibulopathy. Deficiencies in horizontal angular vestibulo-ocular reflex were found in caloric tests (75 %), video head impulse tests (51.7 %), and rotatory chair tests (47.8 %), respectively. Otolith dysfunction was also observed, as shown by abnormal ocular and cervical vestibular evoked myogenic potentials in 62.96 % and 51.85 % of patients, and abnormal subjective visual vertical in 45.8 % of the cases. Conclusions: Among elderly patients experiencing consistent dizziness or instability, the incidence of presbyvestibulopathy was approximately 2.7 % over one year. Alongside the abnormalities detected in the horizontal angular vestibulo-ocular reflex, significant changes were also noted in the ocular and cervical vestibular evoked myogenic potentials, as well as in the subjective visual vertical tests. As a result, it's vital to underscore the significance of both otolithic function and vestibulo-ocular reflex in the fundamental mechanisms of presbyvestibulopathy.

Vitis vinifera seed extract versus micronized purified flavonoid fraction for patients with chronic venous disease: a randomized, non-inferiority trial.

BACKGROUND: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was non-inferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease (CVD). METHODS: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire (AVVQ), visual analog scale (VAS), and Venous Clinical Severity Score (VCSS) at 4- and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant inter-group difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval [CI] -1.65 to 5.72). The lower limit of the 95% CI was within the predefined noninferiority margin of 6.9. Furthermore, the AVVQ, VAS, and VCSS scores significantly decreased at 4- and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS: Vitis vinifera seed extract was non-inferior to MPFF in relieving venous symptoms and improving the quality of life in patients with CVD.

Neuron-Specific Enolase as a Predictor of Neurologic Outcomes in Extracorporeal Cardiopulmonary Resuscitation Patients.

Background: Neuron-specific enolase (NSE) has traditionally been used as a biomarker to predict neurologic outcomes after cardiac arrest. This study aimed to evaluate the utility of NSE in predicting neurologic outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: This observational cohort study included 47 consecutive adult ECPR patients (median age, 59.0 years; 74.5% males) treated between January 2018 and December 2021 at a tertiary extracorporeal life support center. The primary outcome was a poor neurologic outcome, defined as a Cerebral Performance Category score of 3-5 at hospital discharge. Results: Twelve (25.5%) patients had abnormal findings on computed tomography of the brain. A poor neurologic outcome was demonstrated in 22 (46.8%) patients. The NSE level at 72 h after ECPR showed the best prediction power for a poor neurologic outcome compared with NSE at 24 and 48 h. A cutoff value exceeding 61.9 µg/L for NSE at 72 h yielded an area under the curve (AUC) of 0.791 for predicting poor neurologic outcomes and exceeding 62.1 µg/L with an AUC of 0.838 for 30-day mortality. Conclusions: NSE levels at 72 h after ECPR appear to be a reliable biomarker for predicting poor neurologic outcomes and 30-day mortality in ECPR patients.

Structural study for substrate recognition of human N-terminal glutamine amidohydrolase 1 in the arginine N-degron pathway.

The N-degron pathway determines the half-life of proteins by selectively destabilizing the proteins bearing N-degrons. N-terminal glutamine amidohydrolase 1 (NTAQ1) plays an essential role in the arginine N-degron (Arg/N-degron) pathway as an initializing enzyme via the deamidation of the N-terminal (Nt) glutamine (Gln). However, the Nt-serine-bound conformation of hNTAQ1 according to the previously identified crystal structure suggests the possibility of other factors influencing the recognition of Nt residues by hNTAQ1. Hence, in the current study, we aimed to further elucidate the substrate recognition of hNTAQ1; specifically, we explored 12 different substrate-binding conformations of hNTAQ1 depending on the subsequent residue of Nt-Gln. Results revealed that hNTAQ1 primarily interacts with the protein Nt backbone, instead of the side chain, for substrate recognition. Here, we report that the Nt backbone of proteins appears to be a key component of hNTAQ1 function and is the main determinant of substrate recognition. Moreover, not all second residues from Nt-Gln, but rather distinctive and charged residues, appeared to aid in detecting substrate recognition. These new findings define the substrate-recognition process of hNTAQ1 and emphasize the importance of the subsequent Gln residue in the Nt-Gln degradation system. Our extensive structural and biochemical analyses provide insights into the substrate specificity of the N-degron pathway and shed light on the mechanism underlying hNTAQ1 substrate recognition. An improved understanding of the protein degradation machinery could aid in developing therapies to promote overall health through enhanced protein regulation, such as targeted protein therapies.

Comparison between intermittent claudication versus chronic limb-threatening ischemia in peripheral arterial disease: a retrospective multicenter cohort study.

Purpose: The anatomical distribution, characteristics of lesions, and treatment modalities for peripheral artery disease (PAD) are diverse. Endovascular intervention is popular for symptomatic PAD, for both intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI). We aimed to investigate the endovascular devices used by comparing patients with PAD referred for endovascular revascularization with IC and CLTI. Methods: We identified 736 patients with PAD enrolled in the multicenter PAD registry in South Korea from 2019 to 2022. Of these patients, 636 received endovascular treatment at the time of this study. After excluding missing data, we analyzed 506 patients with IC or CLTI. Patients' characteristics, target lesions, and endovascular device data such as type, length, balloon diameter, and stent, were examined. Procedure outcomes of the aortoiliac, femoropopliteal, and below-the-knee lesions were analyzed. Results: Patients with CLTI were more likely to have diabetes mellitus, below-the-knee interventions, and multilevel PAD than the IC group. Patients with IC had more aortoiliac artery lesions and underwent atherectomies than the CLTI group (63.3% and 61.1% vs. 39.7% and 40.6%, respectively; P < 0.001). In patients with femoropopliteal lesions, those with CLTI were more revascularized with stents than the patients with IC, without significant differences (35.3% vs. 29.1%, P = 0.161). Compared to the IC group, the CLTI patients showed significantly worse rates of primary patency, amputation, and mortality (P = 0.029, P < 0.001, and P < 0.001, respectively). Conclusion: Among Korean patients with PAD, there is a significant difference in baseline and lesion characteristics, endovascular strategies, and short-term follow-up outcomes among those with IC and CLTI.

New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B.

Background: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC. Methods: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin. Conclusion: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Boosted Lithium-Ion Transport Kinetics in n-Type Siloxene Anodes Enabled by Selective Nucleophilic Substitution of Phosphorus.

Doped two-dimensional (2D) materials hold significant promise for advancing many technologies, such as microelectronics, optoelectronics, and energy storage. Herein, n-type 2D oxidized Si nanosheets, namely n-type siloxene (n-SX), are employed as Li-ion battery anodes. Via thermal evaporation of sodium hypophosphite at 275 °C, P atoms are effectively incorporated into siloxene (SX) without compromising its 2D layered morphology and unique Kautsky-type crystal structure. Further, selective nucleophilic substitution occurs, with only Si atoms being replaced by P atoms in the O3≡Si-H tetrahedra. The resulting n-SX possesses two delocalized electrons arising from the presence of two electron donor types: (i) P atoms residing in Si sites and (ii) H vacancies. The doping concentrations are varied by controlling the amount of precursors or their mean free paths. Even at 2000 mA g-1, the n-SX electrode with the optimized doping concentration (6.7 × 1019 atoms cm-3) delivers a capacity of 594 mAh g-1 with a 73% capacity retention after 500 cycles. These improvements originate from the enhanced kinetics of charge transport processes, including electronic conduction, charge transfer, and solid-state diffusion. The approach proposed herein offers an unprecedented route for engineering SX anodes to boost Li-ion storage.

Design and Evaluation of an Eye Mountable AutoDALK Robot for Deep Anterior Lamellar Keratoplasty.

Partial-thickness corneal transplants using a deep anterior lamellar keratoplasty (DALK) approach has demonstrated better patient outcomes than a full-thickness cornea transplant. However, despite better clinical outcomes from the DALK procedure, adoption of the technique has been limited because the accurate insertion of the needle into the deep stroma remains technically challenging. In this work, we present a novel hands-free eye mountable robot for automatic needle placement in the cornea, AutoDALK, that has the potential to simplify this critical step in the DALK procedure. The system integrates dual light-weight linear piezo motors, an OCT A-scan distance sensor, and a vacuum trephine-inspired design to enable the safe, consistent, and controllable insertion of a needle into the cornea for the pneumodissection of the anterior cornea from the deep posterior cornea and Descemet's membrane. AutoDALK was designed with feedback from expert corneal surgeons and performance was evaluated by finite element analysis simulation, benchtop testing, and ex vivo experiments to demonstrate the feasibility of the system for clinical applications. The mean open-loop positional deviation was 9.39 µm, while the system repeatability and accuracy were 39.48 µm and 43.18 µm, respectively. The maximum combined thrust of the system was found to be 1.72 N, which exceeds the clinical penetration force of the cornea. In a head-to-head ex vivo comparison against an expert surgeon using a freehand approach, AutoDALK achieved more consistent needle depth, which resulted in fewer perforations of Descemet's membrane and significantly deeper pneumodissection of the stromal tissue. The results of this study indicate that robotic needle insertion has the potential to simplify the most challenging task of the DALK procedure, enable more consistent surgical outcomes for patients, and standardize partial-thickness corneal transplants as the gold standard of care if demonstrated to be more safe and more effective than penetrating keratoplasty.

Targeting IGF2-IGF1R Signaling to Reprogram the Tumor Microenvironment for Enhanced Viro-Immunotherapy.

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME). METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance. RESULTS: Transcriptome analysis identified IGF2 as one of the top secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%) (p=0.0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8+cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice. CONCLUSION: This is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.

C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer.

Although Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved in multiple diseases, including BRCA1/2 mutant breast cancer, responses are usually transient requiring the deployment of combination therapies for optimal efficacy. Here we thus explore mechanisms underlying sensitivity and resistance to PARPi using two intrinsically PARPi sensitive (T22) and resistant (T127) syngeneic murine breast cancer models in female mice. We demonstrate that tumor associated macrophages (TAM) potentially contribute to the differential sensitivity to PARPi. By single-cell RNA-sequencing, we identify a TAM_C3 cluster, expressing genes implicated in anti-inflammatory activity, that is enriched in PARPi resistant T127 tumors and markedly decreased by PARPi in T22 tumors. Rps19/C5aR1 signaling is selectively elevated in TAM_C3. C5aR1 inhibition or transferring C5aR1hi cells increases and decreases PARPi sensitivity, respectively. High C5aR1 levels in human breast cancers are associated with poor responses to immune checkpoint blockade. Thus, targeting C5aR1 may selectively deplete pro-tumoral macrophages and engender sensitivity to PARPi and potentially other therapies.

MCT1-mediated transport of valeric acid promotes porcine preimplantation embryo development by improving mitochondrial function and inhibiting the autophagic AMPK-ULK1 pathway.

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.

Point-of-Care Bedside Brain Magnetic Resonance Imaging Is Safe in Extracorporeal Membrane Oxygenation Patients With Swan Ganz Catheters: A Phantom Experiment and Single Center Experience.

INTRODUCTION: More than 1.2 million pulmonary artery catheters (PACs) are used in cardiac patients per annum within the United States. However, it is contraindicated in traditional 1.5 and 3T magnetic resonance imaging (MRI) scans. We aimed to test preclinical and clinical safety of using this imaging modality given the potential utility of needing it in the clinical setting. METHODS: We conducted two phantom experiments to ensure that the electromagnetic field power deposition associated with bare and jacketed PACs was safe and within the acceptable limit established by the Food and Drug Administration. The primary end points were the safety and feasibility of performing Point-of-Care (POC) MRI without imaging-related adverse events. We performed a preclinical computational electromagnetic simulation and evaluated these findings in nine patients with PACs on veno-arterial extracorporeal membrane oxygenation. RESULTS: The phantom experiments showed that the baseline point specific absorption rate through the head averaged 0.4 W/kg. In both the bare and jacketed catheters, the highest net specific absorption rates were at the neck entry point and tip but were negligible and unlikely to cause any heat-related tissue or catheter damage. In nine patients (median age 66, interquartile range 42-72 y) with veno-arterial extracorporeal membrane oxygenation due to cardiogenic shock and PACs placed for close hemodynamic monitoring, POC MRI was safe and feasible with good diagnostic imaging quality. CONCLUSIONS: Adult ECMO patients with PACs can safely undergo point-of-care low-field (64 mT) brain MRI within a reasonable timeframe in an intensive care unit setting to assess for acute brain injury that might otherwise be missed with conventional head computed tomography.

Prevalence and characterization of aminoglycoside resistance gene aph(2")-If-carrying Campylobacter jejuni.

Campylobacter jejuni is recognized as a significant foodborne pathogen, and recent studies have indicated a rising trend of aminoglycosides resistance gene aph(2″)-If among C. jejuni isolates from food-producing animals in China. However, systematic information about aph(2″)-If-positive C. jejuni from food-producing animals and other sources worldwide based on whole-genome analysis remains a knowledge gap. In this study, we aimed to analyze the worldwide distribution, genetic environment and phylogenetic tree of aph(2″)-If by utilizing Whole Genome Sequencing (WGS) data obtained, coupled with information in the GenBank database. A total of 160C. jejuni isolates in the GenBank database and 14C. jejuni isolates in our laboratory carrying aph(2″)-If gene were performed for further analysis. WGS analysis revealed the global distribution of aph(2″)-If among C. jejuni from 6 countries. Multilocus Sequence Typing(MLST) results indicated that 70 STs were involved in the dissemination of aph(2″)-If, with ST10086 being the predominant ST. Whole-genome Multilocus Sequence Typing(wg-MLST) analysis according to times, countries, and origins of C. jejuni isolation further demonstrated a close relationship between aph(2″)-If carrying C. jejuni isolates from farm and food. The findings also revealed the existence of 32 distinct types of genetic environments surrounding aph(2″)-If among these isolates. Notably, Type 30, characterized by the arrangement ISsag10-deoD-ant(9)-hp-hp-aph(2″)-If, emerged as the predominant genetic environment. In conclusion, our analysis provides the inaugural perspective on the worldwide distribution of aph(2″)-If. This resistance gene demonstrates horizontal transferability and regional diffusion in a clonal pattern. The close association observed among aph(2″)-If-positive C. jejuni strains isolated from poultry, food, and clinical environments underscores the potential for zoonotic transmission from these isolates.

Fluid Flow to Electricity: Capturing Flow-Induced Vibrations with Micro-Electromechanical-System-Based Piezoelectric Energy Harvester.

We introduce a micro-electromechanical system (MEMS) energy harvester, designed for capturing flow energy. Moving beyond traditional vibration-based energy harvesting, our approach incorporates a cylindrical oscillator mounted on an MEMS chip, effectively harnessing wind energy through flow-induced vibration (FIV). A highlight of our research is the development of a comprehensive fabrication process, utilizing a 5.00 µm thick cantilever beam and piezoelectric film, optimized through advanced micromachining techniques. This process ensures the harvester's alignment with theoretical predictions and enhances its operational efficiency. Our wind tunnel experiments confirmed the harvester's capability to generate a notable electrical output, with a peak voltage of 2.56 mV at an 8.00 m/s wind speed. Furthermore, we observed a strong correlation between the experimentally measured voltage frequencies and the lift force frequency observed by CFD analysis, with dominant frequencies identified in the range of 830 Hz to 867 Hz, demonstrating the potential application in actual flow environments. By demonstrating the feasibility of efficient energy conversion from ambient wind, our research contributes to the development of sustainable energy solutions and low-power wireless electron devices.

Health Care Utilization for Common Shoulder Disorders: Analysis of the 2010-2019 National Patient Sample Data from the Health Insurance Review and Assessment Service in Korea.

Background and Objective: The aim of this study was to analyze trends in surgical and non-surgical service utilization for common shoulder disorders in Korea from 2010 to 2019. Methods and Materials: This retrospective, cross-sectional, descriptive study utilized National Patient Sample data from the Health Insurance and Review Assessment Service (HIRA) of Korea. These data constitute a 2% sample out of the entire Korean population and include data for a variety of parameters instrumental for health care research. Patients with at least one medical service use for rotator cuff syndrome or tear, impingement syndrome, or adhesive capsulitis between January 2010 and December 2019 were included. Trends in healthcare utilization by disorder type, patient demographics, seasonal service use, and treatment details were examined. Results: There was an upward trend in the total number of patients and costs for shoulder disorders, from 35,798 patients and USD 5,485,196 in 2010 to 42,558 and USD 11,522,543 in 2019, respectively. The number of patients aged ≥60 and hospital visits increased. March had the highest number of claims. Physical therapy was the most common non-surgical procedure, while nerve block claims more than doubled. Opioid prescription rates also tripled. Surgical treatments were dominated by shoulder rotator cuff repair and acromioplasty. Conclusions: There was a significant increase in healthcare utilization for shoulder disorders, marked by rising costs and patient numbers. The use of nerve blocks and opioids notably increased. These data are valuable for clinicians, researchers, and policymakers.

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.

Purpose: Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. Materials and Methods: We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Results: Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Conclusion: Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

A Case Report of Acute Bilateral Mydriasis Induced by Herbal Medication.

Ma Huang (Ephedra), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.

Philadelphia chromosome-positive acute myeloid leukemia successfully treated by allogeneic hematopoietic stem cell transplantation: A case report and review of the literature.

RATIONAL: The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute myeloid leukemia (Ph + AML) is a rare entity with a poor prognosis and a short median survival period. To date, there have been few clinical reports on this disease. And the treatment regimen of this disease has not been uniformly determined. PATIENT CONCERNS: We report a case of a Ph + AML. A 32-year-old male who was admitted to our hospital with weakness for 2 months. DIAGNOSIS: Philadelphia chromosome-positive acute myeloid leukemia. INTERVENTIONS: The patient achieved complete remission by the administration of a tyrosine kinase inhibitor, combined with low-intensity chemotherapy and a B-cell lymphoma 2 inhibitor. Then, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his sister was successfully performed. OUTCOMES: The patient has been in a continuous remission state for 6 months after transplantation. LESSONS: We reported a rare Ph + AML case, successfully treated with allo-HSCT. This case provided strong support for treating Ph + AML with allo-HSCT.