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Based on the fast kurtogram, many previous studies have focused on frequency band selection (FBS) affected by interference due to impulsive noise and varying speed conditions. Recently, machine learning algorithms have been considered effective for bearing diagnosis. However, most of these methods are supervised learning and thus suffer from data imbalance in the practical applications. This study proposes a semi-supervised learning indicator called outlier rate diagram (ORgram) based on the signal changes before and after bearing damage. ORgram is suitable for impulsive noise and varying speed conditions. First, the healthy bearing data is segmented by rotational speed and modeled with one-class support vector machine (SVM) for each frequency band. As bearing defects sprout, the defect response will produce the highest outlier rate in the informative frequency band (IFB). After selecting the IFB, techniques such as envelope analysis and order tracking are used to identify damaged bearing components for an alarm to reduce the losses caused by unplanned downtime. [ABSTRACT FROM AUTHOR]

As global climate change intensifies, the frequency and severity of wildfires affecting communities worldwide are on the rise. Therefore, the issue of residential safety for people is becoming increasingly crucial. During a fire, smoke particles and toxic emissions could infiltrate the refuge space through gaps in doors, making it a primary risk factor for casualties. It is worth conducting in‐depth research and investigation on how to effectively utilize available tools and facilities to enhance the probability of survival while waiting for rescue behind closed doors. This study uses iron, aluminum, and wooden doors as experimental samples. Thirty participants conducted a total of 1,620 experiments using six different qualities of tape to investigate the impact of applying different layers of tape on improving door leakage and the time required for tape application. This study proposes that in situations when people are waiting for rescue in refuge spaces, the most efficient course of action would involve the fastest available tape. The rationale behind this is that while different types of tape may vary in their smoke‐shielding effectiveness, using three layers of tape can meet the leakage effectiveness standards, specifically less than 25 m3/hr at a differential pressure of 25 Pa. [ABSTRACT FROM AUTHOR]

This study examines the dynamics of inbound tourism in China, utilizing a mixed-effects gravity model to analyze data from urban clusters around China's three major airports. The research methodology of the study includes applying advanced econometric techniques, such as the Poisson pseudo-maximum likelihood estimation, to ensure robust and accurate results. The study focuses on international tourist arrivals and foreign exchange earnings, identifying key drivers such as tourism resources, transportation safety, and service quality. Our findings indicate a 10% increase in per capita GDP correlates with a 0.88% rise in inbound tourist numbers. Additionally, proximity to major urban centers like Beijing, Shanghai, and Guangzhou significantly influences tourist arrivals, with every 100 km increase in distance resulting in a 5.56% decrease in tourist numbers. The study also explores the impact of environmental factors on tourism, suggesting that improvements in green coverage and reductions in industrial waste and traffic fatalities could enhance tourist arrivals. Conversely, environmental protection measures can both positively and negatively impact tourism. This research provides a strategic blueprint for policymakers and professionals in tourism and environmental sustainability, emphasizing the importance of integrated environmental sustainability in tourism development strategies. The model accounts for up to 79% of the variability in inbound tourism flows, offering robust evidence that economic and policy dimensions impact tourism. [ABSTRACT FROM AUTHOR]

We investigated the effects of periarticular multimodal drug injection (PMDI) on postoperative pain control, patients' mobilization, and length of hospital stay in patients undergoing total knee arthroplasty (TKA). We retrospectively enrolled patients who underwent unilateral TKA between 2019 and 2020. The formula for PMDI included 0.5 mL epinephrine (1 mg/mL), 1 mL ketorolac (30 mg/mL), 0.5 mL morphine (10 mg/mL), and 20 mL bupivacaine hydrochloride (5 mg/mL), mixed with 60 mL normal saline. The outcomes of interest included (1) the amount of patient-controlled anesthesia (PCA) consumption in the first 24 h after the surgery, (2) early mobilization within 24 h after the surgery, and (3) the length of hospital stay. A total of 127 patients were analyzed. Compared with patients who did not receive PMDI, those who received PMDI had lower consumption of PCA in the first 24 h (β coefficient −29.9, 95% CI −51.9 to −7.9, p = 0.008), higher odds of early mobilization within 24 h (odds ratio 8.263, 95% CI 3.041 to 22.453, p < 0.001), and shorter length of hospital stay (β coefficient −0.705, 95% CI −1.158 to −0.252, p = 0.003). We suggest that PMDI may be considered for patients undergoing TKA to improve the quality of care and shorten their length of hospital stay. [ABSTRACT FROM AUTHOR]

Background Oral cavity cancers requiring excision of the oral commissure and free flap reconstruction often requires commissuroplasty to manage oral incontinence. We aimed to evaluate the implications of primary versus delayed commissuroplasty on drooling, and interincisal distance outcomes in this cohort. Methods A retrospective query of head and neck cancer patients operated by a single surgeon from 2017 to 2020 was performed. Patients were included if they underwent free flap reconstruction of the oral commissure, had an immediate or delayed commissuroplasty, and had 2 years of follow-up data including Thomas-Stonell and Greenberg drooling rating scales and interincisal distance measurements. Results Thirty-five patients were included in the review. Twelve patients received immediate commissuroplasty and 23 patients had delayed commissuroplasty. Interincisal distance was similar at baseline, although significantly varied between immediate and delayed commissuroplasty groups at 1 month and 2 years postoperative. Drooling scores were significantly elevated in the group treated with delayed commissuroplasty, but eventually normalized after staged surgery and follow-up. Patients treated with adjunct radiation therapy had lower interincisal distance than patients who did not have radiation. Conclusion Delayed commissuroplasty increased interincisal distance and normalize drooling in patients who required full-thickness excision of the buccal mucosa and oral commissure and free tissue reconstruction. The presented data can help to educate patients on expected postoperative outcomes and likely advocates for a second-stage procedure after completion of adjunct radiotherapy to achieve optimal commissural placement and oral competence. [ABSTRACT FROM AUTHOR]

Most subscapularis and serratus anterior muscles lie between the scapula and the thoracic cage. Evaluation of this area in patients with scapulothoracic dyskinesis, snapping scapular syndrome, or interscapular pain can provide valuable information to clinicians. However, ultrasound scanning of pathologies in this area is hindered by anatomical limitations. In this study, we described a simple patient setup position and scanning method for ultrasound evaluation and guided intervention of the subscapularis and serratus anterior muscles between the scapula and thoracic cage. [ABSTRACT FROM AUTHOR]

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95–11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30–20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49–13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18–11.34) and 10.9 (95% CI: 9.18–11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59–12.69), 13.6 (95% CI: 10.89–16.3), and 9.2 (95% CI: 7.8–10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85–4.79), 10.5 (95% CI: 8.59–20.26) and 8.7 (95% CI: 7.21–16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC. [ABSTRACT FROM AUTHOR]

MTX-211 is a first-in-class dual inhibitor of epidermal growth factor receptor (EGFR) and phosphoinositide-3 kinase (PI3K) signaling pathways with a compelling pharmaceutical profile and could enhance the effectiveness of mitogen-activated protein kinase kinase (MEK) inhibitor therapy in colorectal tumors with KRAS mutations. However, the specific mechanisms contributing to the acquired resistance to MTX-211 in human cancers remain elusive. Here, we discovered that the overexpression of the ATP-binding cassette (ABC) drug transporter ABCG2, a prevalent mechanism associated with multidrug resistance (MDR), could diminish the effectiveness of MTX-211 in human cancer cells. We showed that the drug efflux activity of ABCG2 substantially decreased the intracellular accumulation of MTX-211 in cancer cells. As a result, the cytotoxicity and effectiveness of MTX-211 in suppressing the activation of the EGFR and PI3K pathways were significantly attenuated in cancer cells overexpressing ABCG2. Moreover, the enhancement of the MTX-211-stimulated ATPase activity of ABCG2 and the computational molecular docking analysis illustrating the binding of MTX-211 to the substrate-binding sites of ABCG2 offered a further indication for the interaction between MTX-211 and ABCG2. In summary, our findings indicate that MTX-211 acts as a substrate for ABCG2, underscoring the involvement of ABCG2 in the emergence of resistance to MTX-211. This finding carries clinical implications and merits further exploration. [ABSTRACT FROM AUTHOR]

Cupping therapy is a popular intervention for improving muscle recovery after exercise although clinical evidence is weak. Previous studies demonstrated that cupping therapy may improve microcirculation of the soft tissue to accelerate tissue healing. However, it is unclear whether the cupping size could affect the spatial hemodynamic response of the treated muscle. The objective of this study was to use 8-channel near-infrared spectroscopy to assess this clinical question by assessing the effect of 3 cupping sizes (35, 40, and 45 mm in inner diameter of the circular cup) under −300 mmHg for 5 min on the muscle hemodynamic response from the area inside and outside the cup, including oxyhemoglobin and deoxy-hemoglobin in 18 healthy adults. Two-way factorial design was used to assess the interaction between the cupping size (35, 40, and 45 mm) and the location (inside and outside the cup) and the main effects of the cupping size and the location. The two-way repeated measures ANOVA demonstrated an interaction between the cupping size and the location in deoxy-hemoglobin (P = 0.039) but no interaction in oxyhemoglobin (P = 0.100), and a main effect of the cup size (P = 0.001) and location (P = 0.023) factors in oxyhemoglobin. For the cupping size factor, the 45-mm cup resulted in a significant increase in oxyhemoglobin (5.738±0.760 μM) compared to the 40-mm (2.095±0.312 μM, P<0.001) and 35-mm (3.134±0.515 μM, P<0.01) cup. Our findings demonstrate that the cupping size and location factors affect the muscle hemodynamic response, and the use of multi-channel near-infrared spectroscopy may help understand benefits of cupping therapy on managing musculoskeletal impairment. [ABSTRACT FROM AUTHOR]

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti‐ vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real‐world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR‐TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first‐line EGFR‐TKI with anti‐VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high‐grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti‐VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR‐TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large‐scale registry‐based cohort studies may be needed to validate our findings. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end‐stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at‐risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre‐implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD‐specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision‐making among these patients. Summary at a glance: From an evidence‐based perspective, we synthesize information for screening, diagnosis and management of patients with autosomal dominant polycystic kidney disease (ADPKD) in Taiwan. We provide useful strategies regarding how to provide optimal care for patients with ADPKD. This is the first national consensus from Taiwan to focus on this topic. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) is a by‐product of the Maillard reaction, which occurs when food reacts at high temperatures. Occupational exposure is a risk factor for chronic ACR toxicity. ACR may cause neurotoxicity and depressive symptoms with high concentration in the blood; however, the underlying mechanism remains unknown. We showed the rats developed neurotoxic symptoms after being fed with ACR for 28 days, such as reduced activity and hind limb muscle weakness. We investigated whether ACR exposure causes gene expression differences by blood RNA sequencing and analyzed the differential expression of depressive symptoms‐associated genes. The result indicated that IFN‐γ the key regulator of neurotoxicity and depressive symptoms was induced by ACR. ACR induced the ubiquitin‐mediated proteolysis pathway and JAK/STAT pathways gene expression. ACR upregulated the expression of IFN‐γ, inducing neuroinflammation and neurotoxicity. ACR also upregulated the expression of JAK2, STAT1, PI3K, AKT, IκBα, UBE2D4, NF‐κB, TNF‐α, and iNOS in rat brain tissues and Neuro‐2a cells. Thus, IFN‐γ induction by ACR may induce depressive symptoms, and the ubiquitin‐mediated proteolysis pathway and JAK/STAT pathways may involve in ACR neurotoxicity and depressive symptoms. [ABSTRACT FROM AUTHOR]

Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR Acinetobacter infection in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B- and T-cell epitopes from proteins associated with A. baumannii pathogenesis. A novel Acinetobacter Multi-Epitope Vaccine (AMEV2) was constructed using an A. baumannii thioredoxin A (TrxA) leading protein sequence followed by five identified peptide antigens. Antisera from A. baumannii infected mice demonstrated reactivity to rAMEV2, and subcutaneous immunization of mice with rAMEV2 produced high antibody titer against the construct as well as peptide components. Immunization results in increased frequency of IL-4-secreting splenocytes indicative of a Th2 response. AMEV2-immunized mice were protected against intranasal challenge with a hypervirulent strain of A. baumannii and demonstrated reduced bacterial burden at 48 h. In contrast, all mock vaccinated mice succumbed to infection within 3 days. Results presented here provide insight into the effectiveness of immunoinformatic-based vaccine design and its potential as an effective strategy to combat the rise of MDR pathogens. [ABSTRACT FROM AUTHOR]

The paraspinal muscles of the cervical, thoracic, and lumbar spine are important pain generators because muscle strains or myofascial pain syndrome caused by trigger points are common during clinical practice. Ultrasonography is the most convenient imaging tool for evaluating these muscles due to its advantages, such as providing good delineation of soft tissues, easy accessibility, and zero radiation. Additionally, ultrasound can serve as a useful guiding tool for paraspinal muscle intervention to prevent inadvertent injuries to vital axial neurovascular structures. This pictorial essay presents ultrasound scanning protocols for the paraspinal and other associated muscles as well as a discussion of their clinical relevance. Axial magnetic resonance imaging has also been used to elucidate reciprocal anatomy. In conclusion, ultrasound imaging proves to be a valuable tool that facilitates the differentiation of individual paraspinal muscles. This capability significantly enhances the precision of interventions designed to address myofascial pain syndrome. [ABSTRACT FROM AUTHOR]

The objectives were to investigate whether cupping therapy improves muscle quality and the interaction between duration and negative pressure of cupping therapy affects muscle quality. A 2×2 factorial design with repeated measures was used to examine the efficacy of cupping therapy on improving muscle quality. The independent factors were cupping pressures at −225 and −300 mmHg and cupping durations at 5 and 10 min, and the dependent factor was texture of B-mode ultrasound image of the triceps. Four cupping protocols were applied to 12 participants at 4 different days. Texture analysis including contrast, correlation, energy, and homogeneity was applied to assess muscle quality from 480 ultrasound images. The two-way repeated measures ANOVA showed that there was an interaction between the pressure and duration factors on the superficial layer of the triceps in contrast (F = 5.434, P = 0.004) and correlation (F = 6.274, P = 0.029). In contrast texture, the superficial layer of the triceps showed a significant increase in three protocols: −225 mmHg for 5 min (1.0434 ± 0.130), −300 mmHg for 5 min (1.0339 ±0.1407), and −300 mmHg for 10 min (1.0563 ±0.1432) except −225 mmHg for 10 min (0.9704 ±0.0985). In correlation texture, the superficial layer of the triceps showed a significant decrease in all protocols: −225 mmHg for 5 min (0.9556 ± 0.07), −225 mmHg for 10 min (0.9831 ± 0.0708), −300 mmHg for 5 min (0.9976 ± 0.055), and −300 mmHg for 10 min (0.9406 ± 0.0809). The results indicate that the interaction between the pressure and duration factors of cupping therapy significantly increases contrast texture and significantly decreases correlation texture of the superficial layer of the triceps after cupping therapy. Cupping therapy decreases homogeneity among soft tissues of the treated muscle. [ABSTRACT FROM AUTHOR]

Although relative performance evaluation (RPE) represents an important compensation practice, selecting a relevant peer firm poses a challenge for compensation committees. We study the implications of a committee's peer-specific knowledge for the peer group property (i.e., RPE relevance). Committees likely know more about firms within their networks, and such peer-specific knowledge increases with their connections to potential peer firms. Our findings suggest that peer-specific knowledge facilitates not only the inclusion of more relevant peer firms, but also the exclusion of less relevant ones. Moreover, the committees incorporate connected peers' performance information to a greater extent for risk removal. We address identification challenges by including an intensive set of fixed effects to control for characteristics of the focal and the peer firms and by exploiting exogenous changes to the connections between the committees and the peer firms. Our findings suggest that the compensation committee's peer-specific knowledge facilitates the RPE practice. Data Availability: All data used in this study are publicly available. JEL Classifications: D22; M52; I19. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is an important fungal disease that is found in many desert regions of the western hemisphere. The inhaled organisms are highly pathogenic, but only half of infected, immunologically intact people develop symptomatic pneumonia; most symptomatic infections resolve spontaneously, although some resolve very slowly. Furthermore, second infections are very rare and natural immunity after infection is robust. Therefore, the host response to this organism is very effective at resolving the infection in most cases and immunizing to prevent second infections. People who are immunocompromised are much more likely to develop disseminated infection. This is a comprehensive review of the innate and acquired immune responses to Coccidioides spp., the genetics of resistance to severe infection, and the search for an effective vaccine. [ABSTRACT FROM AUTHOR]

Aims: Sodium‐glucose cotransporter 2 inhibitors (SGLT‐2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT‐2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan. Materials and Methods: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT‐2is during 2016–2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP‐4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use. Results: After controlling for relevant variables, the SGLT‐2i cohort (aHR = 0.90, 95% CI = 0.87–0.93) had a significantly lower risk of developing cancer than the DPP‐4i cohort, particularly when the SGLT‐2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87–0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86–0.94). Regarding cancer type, the SGLT‐2i cohort's risk of cancer was significantly lower than that of the DPP‐4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer. Conclusions: SGLT‐2i use was associated with a significantly lower risk of cancer than DPP‐4i use. [ABSTRACT FROM AUTHOR]

Background: Safinamide (SAF), an α-aminoamide derivative and a selective, reversible monoamine oxidase (MAO)-B inhibitor, has both dopaminergic and nondopaminergic (glutamatergic) properties. Several studies have explored the potential of SAF against various neurological disorders; however, to what extent SAF modulates the magnitude, gating, and voltage-dependent hysteresis [Hys(V)] of ionic currents remains unknown. Methods: With the aid of patch-clamp technology, we investigated the effects of SAF on voltage-gated sodium ion (NaV) channels in pituitary GH3 cells. Results: SAF concentration-dependently stimulated the transient (peak) and late (sustained) components of voltage-gated sodium ion current (INa) in pituitary GH3 cells. The conductance–voltage relationship of transient INa [INa(T)] was shifted to more negative potentials with the SAF presence; however, the steady-state inactivation curve of INa(T) was shifted in a rightward direction in its existence. SAF increased the decaying time constant of INa(T) induced by a train of depolarizing stimuli. Notably, subsequent addition of ranolazine or mirogabalin reversed the SAF-induced increase in the decaying time constant. SAF also increased the magnitude of window INa induced by an ascending ramp voltage Vramp. Furthermore, SAF enhanced the Hys(V) behavior of persistent INa induced by an upright isosceles-triangular Vramp. Single-channel cell-attached recordings indicated SAF effectively increased the open-state probability of NaV channels. Molecular docking revealed SAF interacts with both MAO and NaV channels. Conclusion: SAF may interact directly with NaV channels in pituitary neuroendocrine cells, modulating membrane excitability. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as Coccidioides species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on coccidioidal virulence and pathogenesis primarily employs murine models typically associated with low lethal doses (LD100 < 100 spores). However, the Galleria model has recently garnered attention due to its immune system bearing both structural and functional similarities to the innate system of mammals. Our findings indicate that Coccidioides posadasii can convert and complete the parasitic cycle within the hemocoel of the Galleria larva. In Galleria, the LD100 is between 0.5 and 1.0 × 106 viable spores for the clinical isolate Coccidioides posadasii C735. Furthermore, we demonstrated the suitability of this model for in vivo antifungal susceptibility tests to validate the bioreactivity of newly discovered antifungals against Coccidioides. Additionally, we utilized this larva model to screen a Coccidioides posadasii mutant library showing attenuated virulence. Similarly, the identified attenuated coccidioidal mutants displayed a loss of virulence in a commonly used murine model of coccidioidomycosis. In this study, we demonstrated that Galleria larvae can be applied as a model for studying Coccidioides infection. [ABSTRACT FROM AUTHOR]

A new method is developed to derive the hydrometer's bulk density and bulk water fraction from collocated measurements from Micro-Rain Radar (MRR) and Particle Size and Velocity disdrometer (Parsivel). Rigorous particle scattering simulation, namely the T-matrix method, is applied to particle size distribution data of Parsivel to calculate the reflectivity (ZHH). The possible combinations of the particle's ice, air, and water are derived to compare them with the MRR-measured ZHH. The combination of minimum water fraction subsequently determines the bulk density (ρbulk). The proposed method is applied to the data collected from the International Collaborative Experiments for Pyeongchang 2018 Olympic and Paralympic Winter Games (ICE-POP 2018) Projects and its pre-campaign. The estimated was examined by self-evaluation of reflectivity weighted fall velocity (Vz) of MRR and independent comparison of the liquid-equivalent snowfall rate (SR) of collocated Pluvio. The bias values are adequately low (Vz: -0.27~0.14 m s-1, SR: 0.52~0.74 mm hr-1). The correlation coefficient of calculated SR from estimated ρbulk and observed SR from Pluvio can be up to 0.74. The results indicate the capability to derive reliable ρbulk through the proposed method, leveraging the compact and easily deployable designs of MRR and Parsivel. The derived bulk density of the two warm-low cases (28 February and 07 March 2018) shares a similar transition as the systems were decaying. The particles with higher bulk density and bulk water fraction were found in the coastal sites (BKC and GWU: mean ρbulk values are 0.12 to 0.25 g cm-3), typically accompanied by higher liquid-water constituents (mean values of the top 5 % bulk water fraction are 0.33 to 0.50) than the inland sites (YPO and MHS: mean ρbulk values are 0.09 to 0.08 and mean values of the top 5 % bulk water fraction are 0.001 to 0.029) during such synoptic conditions. [ABSTRACT FROM AUTHOR]

Background: Adolescent idiopathic scoliosis (AIS) is the most common developmental spine disorder among children. It is characterized by a lateral deviation of the spine that gives rise to the distinctive "S" or "C" shaped bending of the spine. The Lin School of Lingnan Region (LSLR), one of the prominent schools for bare-handed orthopaedic manipulation in southern China, provides preliminary evidences that the orthopaedic manipulation techniques help to correct deviations of the spine. Previous research found that Orthopaedic Manipulation Techniques of LSLR (OMT-LSLR) could reduce the Cobb's angles in patients with AIS. Therefore, the current study aims to investigate the effectiveness and safety of the OMT-LSLR in treating teenagers with AIS. Methods: In this participant-and-assessor-blinded randomized controlled clinical trial, 50 participants identified AIS without surgical indications will be recruited and randomized into two groups to receive physiotherapy scoliosis-specific exercises training with either orthopaedic manipulation or sham manipulation treatment for 16 weeks, followed by post-treatment visits at week 24. Primary outcome measure is the change of Scoliosis Research Society-22 (SRS-22) questionnaire score. Secondary outcome measures include Traditional Chinese version of Spinal Appearance Questionnaire (TC-SAQ) score, Italian Spine Youth Quality of Life (ISYQOL) score, the change of Cobb's angle measured by Xray, and the change of Cobb's angle, spinal rotation and muscle volume measured by three-dimensional (3D) ultrasound. The trial will be conducted at the Chinese University of Hong Kong Chinese Medicine Specialty Clinic cum Clinical Teaching and Research Centre in Hong Kong (CUHK-CMSCTRC). Discussion: The results of this study will establish comprehensive clinical evidence about the efficacy and safety of the Orthopaedic Manipulation Techniques of the Lin School of Lingnan Region in the Treatment of Adolescent Idiopathic Scoliosis. One of the characteristics of this trial is that it is a participant-and-assessor-blinded randomized controlled clinical trial with sham manipulation. The study would also apply three-dimensional (3D) ultrasound technology to investigate the relationship between the change of the muscle volume and the spinal curve. Trial registration: The trial is registered on ClinicalTrials.gov (Identifier: NCT05639023) on December 6, 2022. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci), which have a 4–5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from Cp isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1-based vaccine against both species of Coccidioides. DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of Cp and Ci, respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against five highly virulent isolates of Cp and Ci. There are total of seven amino acid substitutions in the rCpa1 antigen between Cp and Ci. Both C57BL/6 and HLA-DR4 mice that were vaccinated with an rCpa1 vaccine had a significant reduction of fungal burden and increased numbers of IFN-γ- and IL-17-producing CD4+ T cells in the first 2 weeks post challenge. These data suggest that rCpa1 has cross-protection activity against Cp and Ci pulmonary infection through activation of early Th1 and Th17 responses. [ABSTRACT FROM AUTHOR]

The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies. To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection. We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109). Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010–0.020; p <.001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727–198.160), the HCV genotype 3–genotype 1 IRR was 4.13 (95% confidence interval: 1.52–11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration. Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary. [ABSTRACT FROM AUTHOR]

Recent post-SOX studies have consistently found that the presence of audit committee (AC) directors with multiple directorships is associated with lower financial reporting quality. An implicit assumption of these studies is that AC directors distribute their effort equally across all their directorships. Using a firm size-based proxy and firm risk-based (i.e. probabilities of litigation and of misstatements) proxies to measure relative directorship importance, we investigate (1) whether and how AC directors who serve on multiple AC directorships allocate their effort to different directorships unequally, and (2) whether the unequal prioritization of effort across multiple AC directorships relates to AC monitoring effectiveness. We find a positive (no) relation between the risk-based (firm size-based) directorship importance measures and AC effectiveness, suggesting that AC directors serving on multiple boards unequally allocate their effort to different directorships based on incentives related to firm risk and not to firm size. Our results have relevance for regulators, boards of directors, investors, and other stakeholders. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the association between salivary matrix metalloproteinase‐1 (MMP‐1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP‐1 and other established circulating markers for OSCC. Methods: Saliva specimens from 479 OSCC subjects were examined using an enzyme‐linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP‐1 and other markers were calculated, and survival analyses were conducted using Kaplan–Meier and multivariate regression methods. Results: Salivary MMP‐1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p =.021) and Charlson comorbidity index (0.568, p =.048) and comparable with neutrophil‐to‐lymphocyte ratio (0.620, p =.987), platelet‐to‐lymphocyte ratio (0.575, p =.125), and squamous cell carcinoma antigen (0.609, p =.605). Elevated levels of salivary MMP‐1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth (p all <.05). Multivariate analyses indicated that a higher level of salivary MMP‐1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 [95% confidential interval: 1.014–1.989], p =.041). Conclusion: The study found that the salivary MMP‐1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post‐treatment outcome. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

The effects of lipid‐lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end‐stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non‐LLD users; the final follow‐up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub‐distribution hazard regression models adjusted for multivariables, including time‐varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65–0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62–0.93) than did non‐LLD users. After adjusting for time‐varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65–0.93) and MACEs (aHR, 0.77, 95% CI, 0.60–0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non‐LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects. [ABSTRACT FROM AUTHOR]

Purpose: Coronavirus disease pandemic makes high requirements in delivering remote and efficient communication, and patient education. Because of the increases of digital and social media applications in Taiwan, we aim to apply Artificial Intelligence of LINE Chatbot to improve the self‐care ability of patients undergoing peritoneal dialysis. Materials and Methods: We conducted the project since 1 May 2021 to 30 April 2022. We designed an automatically replied Chatbot system, and divided into six scopes of interaction interfaces, including peritoneal dialysis technique operation video, clinical reminder, home caring, hospital registration service, dietary guideline, and Automatic Peritoneal dialysis guidance. We surveyed patients' satisfaction with the LINE Chatbot 3 months later by the Likert 1–5 score‐based questionnaire and the higher score indicated higher satisfaction. Results: There were 440 patients who joined the PD AI Chatbot study and use the Chatbot, but the satisfaction questionnaire recovery rate was only 297 patients. We found that 91.7% of participants agreed 'Overall satisfaction with patient intelligent Chatbot application'. More than 4 points accounted for 86.6%. We traced every click in each section of the Chatbot and explored the potential scenario patients face. The Chatbot statistically significant reduced infection rate of exit site and tunnel infection before using (p =.049 and.024). Furthermore, peritonitis rate decreased from 0.93 to 0.8/100 patient month after using Artificial Intelligence technique. Peritoneal dialysis Artificial Intelligence Chatbot had similar effect with face‐to‐face education. Conclusion: The innovative Chatbot allowed delivering remote and digital information's to improve patients' self‐care ability. Peritoneal dialysis patients were highly recognized and satisfied with the tools. It deserves to further explore the long‐term impact of Artificial Intelligence Chatbot in peritoneal dialysis care. [ABSTRACT FROM AUTHOR]

This article discusses the importance of emphasizing probabilistic reasoning education for nephrology trainees in the era of AI-assisted clinical practice. Probabilistic reasoning involves constructing conclusions based on one's beliefs and prior knowledge, which is crucial in navigating clinical uncertainty. The use of artificial intelligence (AI) and clinical decision support (CDS) systems in nephrology has increased the need for trainees to interpret probabilities and tolerate ambiguity. The article proposes strategies to enhance trainees' ability to cope with uncertainty, including integrating probabilistic reasoning into education, focusing on the limitations and applicability of AI-assisted algorithms, and engaging in discussions to refine algorithm usage. The authors believe that emphasizing probabilistic reasoning in nephrology education can help trainees effectively navigate the challenges of clinical uncertainty in the AI era. [Extracted from the article]

Background: Previous research has examined the use of augmented reality (AR) and virtual reality (VR) in English language teaching. However, to the best of our knowledge, none of the earlier studies that investigated integrating AR and VR "wearables" into teaching and learning English based on the attention, relevance, confidence, and satisfaction (ARCS) motivation model compared the differences in learning motivation and performance between traditional teaching methods and those using AR‐ and VR‐based using wearables. Objectives: To create a thematic learning environment based on learners' lived experiences and provide them with an immersive English course that extends textbook knowledge using a technology‐assisted real‐life learning context. Method: This study used a quasi‐experimental research design. A total of 119 participants were spilt into three learning groups based on teaching tools: traditional methods and AR‐ and VR‐based wearable devices. The performance of each group was evaluated through three stages using appropriate educational tools for traditional, AR‐, and VR‐based classrooms, followed by semistructured interviews. Multiple regression analysis was conducted to investigate the inference learning performance (remembering and analysing) of the four ARCS dimensions with the three teaching methods. Results: The results showed that confidence and relevance were positively correlated with learning performance in the VR‐based wearable group. In the context of the ARCS model, learners' confidence predicted learning performance and the remembering subdimension when VR‐based learning materials were used. Implications: These results suggest that, compared to traditional teaching methods, VR‐based wearables make it easier to create a highly immersive learning environment and are more likely to help learners find the correct words, improve their accuracy, and increase their confidence and sense of accomplishment in the entire learning process. Lay Description: Augmented reality (AR) and virtual reality (VR) allow learners to apply memorized subject knowledge to real‐life scenarios.The attention, relevance, confidence, and satisfaction (ARCS) motivation model enhances learning. What this paper adds: The study proposed the integration of AR and VR with "wearables" for teaching English.The study investigated the differences between how the teaching materials designed to incorporate different technological devices with the four ARCS dimensions predict their learning performance (remembering and analysing). Implications for practice and/or policy: The ARCS motivation model‐based design allows learners using VR‐based wearables to learn English through multiple interactions in real‐time.Integrating daily life experiences with course materials can attract learners' attention in the early stages of teaching.VR‐based learning creates a virtual learning environment relevant to the learners, allows them to learn English thematically in an immersive environment, and allows them to interact with the system. [ABSTRACT FROM AUTHOR]

In this digital era, digital service trade has brought significant benefits to the global economy. However, this trade also poses considerable challenges to international trade regulations. This study aims to analyze the impact of cross-border digital service trade on the economic growth of importing countries while determining how digital trade barriers moderate this effect. We established a theoretical model that meticulously delineates various restrictive regulatory measures that can hinder digital service inputs. We further developed a comprehensive and detailed trade barrier index based on these measures. A three-dimensional fixed effects panel regression model was used to analyze data from six types of digital services in 48 economies from 2005 to 2021. The findings indicated that cross-border digital service inputs enhance importing countries' economic growth, highlighting the substantial economic value of these inputs. However, trade barriers in digital services were also found to diminish this positive effect. Specifically, an increase in the digital service trade barriers in importing countries constricts the range and quality of selectable digital services, which might adversely impact national economic growth. The inhibitory effect is stronger for countries with a "Limited Model" for personal data transfers and processing. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis (PD)-associated peritonitis is a common cause of mortality among patient undergoing PD. Although nontuberculous mycobacteria (NTM) account for only 1%-3% and 0.4% of PD-associated peritonitis worldwide and in Taiwan respectively, the mortality of affected individuals can reach 30%-40%.[[1], [3]] There is no consensus on the choice of empirical treatment regimen for NTM peritonitis currently.[4] We described a case of I Mycobacterium mageritense i PD-associated peritonitis treated successfully for the first time. ISPD guideline recommends screening for possible NTM infection among patients with refractory culture-negative PD peritonitis.[4] Surgical source control and tailored antimycobacterial therapy on the basis of in vitro antimicrobial susceptibilities of isolated species are suggested. [Extracted from the article]

Automated imaging techniques have been in increasing demand for the more advanced analysis and efficient characterization of cellular phenotypes. The success of the image-based profiling method hinges on assays that can rapidly and simultaneously capture a wide range of phenotypic features. We have developed an automated image acquisition method for fungal cytological profiling (FCP) using an imaging flow cytometer that can objectively measure over 250 features of a single fungal cell. Fungal cells were labeled with calcofluor white and FM4-64FX, which bind to the cell wall and lipophilic membrane, respectively. Images of single cells were analyzed using IDEAS® software. We first acquired FCPs of fungal cells treated with fluconazole, amphotericin B, and caspofungin, each with a distinct mode of action, to establish FCP databases of profiles associated with specific antifungal treatment. Once fully established, we investigated the potential application of this technique as a screening methodology to identify compounds with novel antifungal activity against Candida albicans and Cryptococcus neoformans. Altogether, we have developed a rapid, powerful, and novel image-profiling method for the phenotypic characterization of fungal cells, also with potential applications in antifungal drug development. [ABSTRACT FROM AUTHOR]

Chemotherapy, in combination with immune checkpoint blockade (ICB) targeting to programmed death‐1 (PD‐1) or its ligand PD‐L1, is one of the first‐line treatments for patients with advanced non–small‐cell lung cancer (NSCLC). However, a large proportion of patients, especially those with PD‐L1 negative tumors, do not benefit from this treatment. This may be due to the existence of multiple immunosuppressive mechanisms other than the PD‐1/PD‐L1 axis. Human leukocyte antigen‐G (HLA‐G) has been identified as an immune checkpoint protein (ICP) and a neoexpressed tumor‐associated antigen (TAA) in a large proportion of solid tumors. In this study, we evaluated the induction of HLA‐G as well as PD‐L1 using sublethal doses of chemotherapeutics including pemetrexed in different NSCLC cell lines. Except for gefitinib, most of the chemotherapeutic agents enhanced HLA‐G and PD‐L1 expression in a dose‐dependent manner, whereas pemetrexed and carboplatin treatments showed the most consistent upregulation of PD‐L1 and HLA‐G in each cell line. In addition to protein levels, a novel finding of this study is that pemetrexed enhanced the glycosylation of HLA‐G and PD‐L1. Pemetrexed potentiated the cytotoxicity of cytotoxic T lymphocytes (CTLs) to treat NSCLC. Both in vitro and in vivo experiments revealed that CTL‐mediated cytotoxicity was most pronounced when both anti‐PD‐L1 and anti‐HLA‐G ICBs were combined with pemetrexed treatment. In conclusion, anti‐HLA‐G could be an intervention strategy in addition to the anti‐PD‐1/PD‐L1 pathway for NSCLC. Moreover, dual targeting of PD‐L1 and HLA‐G combined with pemetrexed might have a better extent of CTL‐based immunotherapy. [ABSTRACT FROM AUTHOR]

1,5,9‐Tribromo‐2,3,6,7,10,11‐hexamethoxy‐4b1‐methyltribenzotriquinacene, a C3‐symmetric TBTQ derivative, can be prepared conveniently and with high regioselectivity from readily available starting materials. It is a versatile key compound for the synthesis of other chiral 1,5,9‐trifunctionalized TBTQ derivatives and π‐extended congeners in which the bays of the TBTQ skeleton are bridged by vinylene and 1,2‐arylene units. X‐ray crystal structure analysis and UV‐vis spectroscopy show that vinylene bay‐bridging enables better π‐conjugation with the arene rings of the TBTQ core than 1,2‐arylene bay‐bridging does. [ABSTRACT FROM AUTHOR]

A significant amount of research has been conducted on applying functional materials as surgical sutures. Therefore, research on how to solve the shortcomings of surgical sutures through available materials has been given increasing attention. In this study, hydroxypropyl cellulose (HPC)/PVP/zinc acetate nanofibers were coated on absorbable collagen sutures using an electrostatic yarn winding technique. The metal disk of an electrostatic yarn spinning machine gathers nanofibers between two needles with positive and negative charges. By adjusting the positive and negative voltage, the liquid in the spinneret is stretched into fibers. The selected materials are toxicity free and have high biocompatibility. Test results indicate that the nanofiber membrane comprises evenly formed nanofibers despite the presence of zinc acetate. In addition, zinc acetate can effectively kill 99.9% of E. coli and S. aureus. Cell assay results indicate that HPC/PVP/Zn nanofiber membranes are not toxic; moreover, they improve cell adhesion, suggesting that the absorbable collagen surgical suture is profoundly wrapped in a nanofiber membrane that exerts antibacterial efficacy and reduces inflammation, thus providing a suitable environment for cell growth. The employment of electrostatic yarn wrapping technology is proven effective in providing surgical sutures with antibacterial efficacy and a more flexible range of functions. [ABSTRACT FROM AUTHOR]

Machine learning profoundly impacts every aspect of our lives. As machine learning evolves, many techniques, such as deep learning, are improving its accuracy and performance. Nonetheless, large data computations with large memory footprints will always be a bottleneck for deep learning applications. One of the most computationally demanding DNN operations is matrix multiplication, such as the convolution layer and fully connected layer, which preserve the image arrangement and obtain a partial image as an input feature. Our goal is to find an effective method for programmers to improve the performance of such matrix multiplication layers. Halide is an image processing programming language that separates the algorithm from its schedule. With the use of Halide, one can easily enhance the performance of their code with built-in scheduling primitives. In this paper, we propose sparse matrix compression schedule primitives with different compression schemes in Halide and find a method to improve convolution with the im2col method. With this design, we can compress the matrix to enhance the performance of convolution. We can also optimize natural language processing (NLP) with proposed compression scheduling. The word embedding training model can convert words into multidimensional vectors and transform words that do not have meaning into vectors with meaning. We focus on the word representation application in FastText, in which general matrix-vector multiplication (GEMV) is one of the most computationally intensive operations. We refine the software architecture of FastText and preprocess the pretrained model ahead of time. Our experiments show that the convolution and GEMV performance can be enhanced by the proposed design. [ABSTRACT FROM AUTHOR]

Aims: Despite the declining incidence of acute post‐streptococcal glomerulonephritis (APSGN) in Australia, there is still a significant burden of disease amongst Aboriginal and Torres Strait Islander people in the Northern Territory. Childhood APSGN has been highlighted as a predictor of chronic kidney disease in this population. We aimed to describe clinical characteristics and outcomes of hospitalised children with APSGN in the Northern Territory. Methods: Single‐centre, retrospective cohort study of children (<18 years) with APSGN admitted to a tertiary hospital in the Top End of the Northern Territory between January 2012 and December 2017. Cases were confirmed using the Centre for Disease Control case definition guidelines. Data were extracted from the case notes and electronic medical records. Results: There were 96 cases of APSGN with median age of 7.1 years (interquartile range (IQR) 6.7–11.4). Majority were Aboriginal and Torres Strait Islander (90.6%) and from rural and remote areas (82.3%). Preceding skin infections were identified in 65.5% and sore throat in 27.1%. Severe complications included hypertensive emergencies (37.4%), acute kidney injury (43.8%) and nephrotic‐range proteinuria (57.7%). All children improved from their acute illness with supportive medical therapy; however, only 55 out of 96 (57.3%) children were followed up within 12 months of their acute illness. Conclusions: APSGN disproportionately affects Aboriginal and Torres Strait Islander children and highlights the need for continued and improved public health response. There is room for significant improvement in the medium‐ and long‐term follow‐up of affected children. [ABSTRACT FROM AUTHOR]

Constitutive activation of the phosphoinositide-3-kinase (PI3K)/Akt signaling pathway is crucial for tumor growth and progression. As such, this pathway has been an enticing target for drug discovery. Although HS-173 is a potent PI3K inhibitor that halts cancer cell proliferation via G2/M cell cycle arrest, the resistance mechanisms to HS-173 have not been investigated. In this study, we investigated the susceptibility of HS-173 to efflux mediated by the multidrug efflux transporters ABCB1 and ABCG2, which are two of the most well-known ATP-binding cassette (ABC) transporters associated with the development of cancer multidrug resistance (MDR). We found that the overexpression of ABCB1 or ABCG2 significantly reduced the efficacy of HS-173 in human cancer cells. Our data show that the intracellular accumulation of HS-173 was substantially reduced by ABCB1 and ABCG2, affecting G2/M arrest and apoptosis induced by HS-173. More importantly, the efficacy of HS-173 in multidrug-resistant cancer cells could be recovered by inhibiting the drug-efflux function of ABCB1 and ABCG2. Taken together, our study has demonstrated that HS-173 is a substrate for both ABCB1 and ABCG2, resulting in decreased intracellular concentration of this drug, which may have implications for its clinical use. [ABSTRACT FROM AUTHOR]

Simple Summary: Afatinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used to treat patients with advanced EGFR-mutant lung cancer. In this study, we retrospectively enrolled patients with lung adenocarcinomas harboring susceptible EGFR mutations, who were diagnosed and treated with first-line afatinib in three Kaohsiung Medical University-affiliated hospitals. Patients who received local consolidative therapy (LCT) had a significantly longer PFS than those who did not. Patients who received LCT also had significantly longer OS. Multivariable analysis showed LCT was an independent prognostic factor for improved PFS and OS. The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib. Further large-scale prospective trials are warranted. Afatinib is an irreversible tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), which is utilized for the treatment of patients with advanced lung cancer that harbors EGFR mutations. No studies have evaluated the clinical efficacy of LCT in patients treated with first-line afatinib. In this study, we retrospectively enrolled patients with advanced lung adenocarcinomas harboring susceptible EGFR mutations who were diagnosed and treated with first-line afatinib in three hospitals. A total of 254 patients were enrolled, including 30 (12%) patients who received LCT (15 patients received definitive radiotherapy for the primary lung mass and 15 patients received curative surgery). Patients who received LCT had a significantly longer PFS than those who did not (median PFS: 32.8 vs. 14.5 months, p = 0.0008). Patients who received LCT had significantly longer OS than those who did not (median OS: 67.1 vs. 34.5 months, p = 0.0011). Multivariable analysis showed LCT was an independent prognostic factor for improved PFS (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 0.44 [0.26–0.73], p = 0.0016) and OS (aHR [95% CI]: 0.26 [0.12–0.54], p = 0.0004). The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib. [ABSTRACT FROM AUTHOR]

Frailty is the incremental accumulation of minute defects that progressively impair health and performance. Frailty is commonly observed in older adults; however, secondary frailty may also occur in patients with metabolic disorders or major organ failure. In addition to physical frailty, several distinct types of frailty have been identified, including oral, cognitive, and social frailty, each of which is of practical importance. This nomenclature suggests that detailed descriptions of frailty can potentially advance relevant researches. In this narrative review, we first summarize the clinical value and plausible biological origin of frailty, as well as how to appropriately assess it using physical frailty phenotypes and frailty indexes. In the second part, we discuss the issue of vascular tissue as a relatively underappreciated organ whose pathologies contribute to the development of physical frailty. Moreover, when vascular tissue undergoes degeneration, it exhibits vulnerability to subtle injuries and manifests a unique phenotype amenable to clinical assessment prior to or accompanying physical frailty development. Finally, we propose that vascular frailty, based on an extensive set of experimental and clinical evidence, can be considered a new frailty type that requires our attention. We also outline potential methods for the operationalization of vascular frailty. Further studies are required to validate our claim and sharpen the spectrum of this degenerative phenotype. [ABSTRACT FROM AUTHOR]