Evolutionary origin of the chordate nervous system revealed by amphioxus developmental trajectories.

The common ancestor of all vertebrates had a highly sophisticated nervous system, but questions remain about the evolution of vertebrate neural cell types. The amphioxus, a chordate that diverged before the origin of vertebrates, can inform vertebrate evolution. Here we develop and analyse a single-cell RNA-sequencing dataset from seven amphioxus embryo stages to understand chordate cell type evolution and to study vertebrate neural cell type origins. We identified many new amphioxus cell types, including homologues to the vertebrate hypothalamus and neurohypophysis, rooting the evolutionary origin of these structures. On the basis of ancestor-descendant reconstruction of cell trajectories of the amphioxus and other species, we inferred expression dynamics of transcription factor genes throughout embryogenesis and identified three ancient developmental routes forming chordate neurons. We characterized cell specification at the mechanistic level and generated mutant lines to examine the function of five key transcription factors involved in neural specification. Our results show three developmental origins for the vertebrate nervous system: an anterior FoxQ2-dependent mechanism that is deeply conserved in invertebrates, a less-conserved route leading to more posterior neurons in the vertebrate spinal cord and a mechanism for specifying neuromesoderm progenitors that is restricted to chordates. The evolution of neuromesoderm progenitors may have led to a dramatic shift in posterior neural and mesodermal cell fate decisions and the body elongation process in a stem chordate.

An evaluation of intervention appropriateness from the perspective of parents: A peer-mediated, play-based intervention for children with ADHD.

INTRODUCTION: A peer-mediated, play-based intervention has been developed to address social participation challenges experienced by children with ADHD. To facilitate implementation into clinical practice, interventions should be evaluated for appropriateness to the end-user, as well as effectiveness. Previous research demonstrated the approach is effective for improving children's social play skills. This study aimed to evaluate the appropriateness of the intervention for children with ADHD and their families. METHODS: Parents of children with ADHD who participated in the play-based intervention were interviewed 1 month after completion. Parents were asked about their perspective of parent and children's experiences of the intervention, the perceived benefits for children and parents, the logistics of participating, and recommended adaptations to the intervention. Interviews were analysed thematically, and themes were mapped to the elements of the adopted definition of appropriateness to understand whether parents supported the appropriateness of the intervention for their families. CONSUMER AND COMMUNITY INVOLVEMENT: Consumers were not directly involved in the decisions made about this study. FINDINGS: One core theme, 'collaborative efforts', emerged from the data. Major themes comprising the core theme were 'on the same page', 'therapeutic relationship', and 'getting the job done'. Three sub-themes of 'engagement and motivation', 'the effort was worth it for the reward', and 'Rome wasn't built in a day' were nested within the major themes. CONCLUSION: Parents largely supported the appropriateness of the intervention, indicating it addressed an important goal for their child, participation was a positive experience, and they perceived the intervention to be beneficial. Future adaptions of the intervention are needed to increase its ecological validity and to generalise the strategies to other social environments and playmates, such as peers at school. PLAIN LANGUAGE SUMMARY: This study looked at an intervention that uses play with peers to help children with ADHD develop their play skills. The researchers wanted to know if parents thought the intervention was a good fit for their families and if it helped their children. Parents gave an interview a month after the intervention ended. They were asked about their thoughts on the intervention, how it helped their children and themselves, how easy it was to take part, and what changes could be made to make the intervention better. After analysing parents' answers, the researchers found parents mostly agreed that the intervention was a good fit. They said it helped their children to play with their peers, and they had a good time doing it. Parents thought the intervention was helpful, they liked that it was a joint effort between them and the occupational therapist, and they felt it was worth the effort. However, they also suggested some changes. They wanted the intervention to fit into other real-life social situations, such as school, so their children could use the skills they learned in other places. Overall, parents thought the intervention was helpful and suitable for their children and themselves, but some changes might make it more helpful.

Six novel species of the genus Methanoculleus isolated from various environments in Taiwan.

Taiwan is situated in the subtropical region and its geographical location and topographical features contribute to a rich ecological diversity and scenic landscapes. We investigated the diversity of methanogens in different environments of Taiwan using a culture-dependent method. This report presents the characterization and taxonomy of six hydrogenotrophic methanogens obtained from cold seep sediments (strain FWC-SCC1T and FWC-SCC3T), marine sediments (strain CWC-02T and YWC-01T), estuarine sediments (strain Afa-1T), and a hot spring well (strain Wushi-C6T) in Taiwan. The proposed names of the six novel species are Methanoculleus frigidifontis (type strain FWC-SCC1T=BCRC AR10056T=NBRC 113993T), Methanoculleus oceani (CWC-02T=BCRC AR10055T=NBRC 113992T), Methanoculleus methanifontis (FWC-SCC3T=BCRC AR10057T=NBRC 113994T), Methanoculleus nereidis (YWC-01T=BCRC AR10060T=NBRC 114597T), Methanoculleus formosensis (Afa-1T=BCRC AR10054T=NBRC 113995T), and Methanoculleus caldifontis (Wushi-06T=BCRC AR10059T= NBRC 114596T).

Towards Design Automation of Microfluidic Mixers: Leveraging Reinforcement Learning and Artificial Neural Networks.

Microfluidic mixers, a pivotal application of microfluidic technology, are primarily utilized for the rapid amalgamation of diverse samples within microscale devices. Given the intricacy of their design processes and the substantial expertise required from designers, the intelligent automation of microfluidic mixer design has garnered significant attention. This paper discusses an approach that integrates artificial neural networks (ANNs) with reinforcement learning techniques to automate the dimensional parameter design of microfluidic mixers. In this study, we selected two typical microfluidic mixer structures for testing and trained two neural network models, both highly precise and cost-efficient, as alternatives to traditional, time-consuming finite-element simulations using up to 10,000 sets of COMSOL simulation data. By defining effective state evaluation functions for the reinforcement learning agents, we utilized the trained agents to successfully validate the automated design of dimensional parameters for these mixer structures. The tests demonstrated that the first mixer model could be automatically optimized in just 0.129 s, and the second in 0.169 s, significantly reducing the time compared to manual design. The simulation results validated the potential of reinforcement learning techniques in the automated design of microfluidic mixers, offering a new solution in this field.

Pressure induces peritoneal fibrosis and inflammation through CD44 signaling.

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Amphiphilic NLC-Gel formulation loaded with Sebacoyl dinalbuphine ester and Nalbuphine for localized postoperative pain management.

Opioids are powerful analgesics; however, their significant systemic adverse effects and the need for frequent administration restrict their use. Nalbuphine (NA) is a κ-agonist narcotic with limited adverse effects, but needs to be frequently administrated due to its short elimination half-life. Whereas sebacoyl dinalbuphine ester (SDE) is a NA prodrug, which can effectively prolong the analgesic effect, but lacks immediate pain relief. Therefore, in this study, a rapid and sustained local delivery formulation to introduce NA and SDE directly into surgical sites was developed. An amphiphilic nanostructured lipid carrier (NLC) poloxamer 407 (P407) gel (NLC-Gel) was developed to permit concurrent delivery of hydrophobic SDE from the NLC core and hydrophilic NA from P407, offering a dual rapid and prolonged analgesic effect. Benefiting from the thermal-sensitive characteristic of P407, the formulation can be injected in liquid phase and instantly transit into gel at wound site. NLC-Gel properties, including particle size, drug release, rheology, and stability, were assessed. In vivo evaluation using a rat spinal surgery model highlighted the effect of the formulation through pain behavior test and hematology analysis. NLC-Gels demonstrated an analgesic effect comparable with that of commercial intramuscular injected SDE formulation (IM SDE), with only 15 % of the drug dosage. The inclusion of supplemental NA in the exterior gel (PA12-Gel + NA) provided rapid drug onset owing to swift NA dispersion, addressing acute pain within hours along with prolonged analgesic effects. Our findings suggest that this amphiphilic formulation significantly enhanced postoperative pain management in terms of safety and efficacy.

Risk factors affecting spinal fusion: A meta-analysis of 39 cohort studies.

PURPOSE: We performed a meta-analysis to identify risk factors affecting spinal fusion. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library from inception to January 6, 2023, for articles that report risk factors affecting spinal fusion. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models for each factor for which the interstudy heterogeneity I2 was < 50%, while random-effects models were used when the interstudy heterogeneity I2 was ≥ 50%. Using sample size, Egger's P value, and heterogeneity across studies as criteria, we categorized the quality of evidence from observational studies as high-quality (Class I), moderate-quality (Class II or III), or low-quality (Class IV). Furthermore, the trim-and-fill procedure and leave-one-out protocol were conducted to investigate potential sources of heterogeneity and verify result stability. RESULTS: Of the 1,257 citations screened, 39 unique cohort studies comprising 7,145 patients were included in the data synthesis. High-quality (Class I) evidence showed that patients with a smoking habit (OR, 1.57; 95% CI, 1.11 to 2.21) and without the use of bone morphogenetic protein-2 (BMP-2) (OR, 4.42; 95% CI, 3.33 to 5.86) were at higher risk for fusion failure. Moderate-quality (Class II or III) evidence showed that fusion failure was significantly associated with vitamin D deficiency (OR, 2.46; 95% CI, 1.24 to 4.90), diabetes (OR, 3.42; 95% CI, 1.59 to 7.36), allograft (OR, 1.82; 95% CI, 1.11 to 2.96), conventional pedicle screw (CPS) fixation (OR, 4.77; 95% CI, 2.23 to 10.20) and posterolateral fusion (OR, 3.63; 95% CI, 1.25 to 10.49). CONCLUSIONS: Conspicuous risk factors affecting spinal fusion include three patient-related risk factors (smoking, vitamin D deficiency, and diabetes) and four surgery-related risk factors (without the use of BMP-2, allograft, CPS fixation, and posterolateral fusion). These findings may help clinicians strengthen awareness for early intervention in patients at high risk of developing fusion failure.

Analytical validation of the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis assay to diagnose spinal muscular atrophy.

OBJECTIVES: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous deletion and compound heterozygous mutations in survival motor neuron 1 (SMN1), with severity tied to the copy number of survival motor neuron 2 (SMN2). This study aimed to develop a rapid and comprehensive method for the diagnosis of SMA. METHODS: A total of 292 children with clinically suspected SMA and 394 family members were detected by the amplification refractory mutation system polymerase chain reaction-capillary electrophoresis (ARMS-PCR-CE) method, which targeted 19 reported mutations, and the results were compared with those in multiplex ligation-dependent probe amplification (MLPA). Individuals with identified point mutations were further confirmed by SMN1 long-range PCR and Sanger sequencing. RESULTS: A total of 202 children with SMA, 272 carriers, and 212 normal individuals were identified in this study. No difference was found in the R-value distribution of exons 7 and 8 in SMN1 and SMN2 among these cohorts, with coefficients of variation consistently below 0.08. To detect exon 7 and 8 copy numbers in SMN1 and SMN2, the ARMS-PCR-CE results were concordant with those of MLPA. Approximately 4.95 % (10/202) of the study patients had compound heterozygous mutations. CONCLUSIONS: The ARMS-PCR-CE assay is a comprehensive, rapid, and accurate diagnostic method for SMA that simultaneously detects copy numbers of exons 7 and 8 in SMN1/SMN2, as well as 19 point mutations in SMN1 and 2 enhancers in SMN2. This approach can effectively reduce the time frame for diagnosis, facilitating early intervention and preventing birth defects.

Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.

The management of renal cell carcinoma (RCC) has advanced significantly in the past two decades. Many promising functional imaging modalities such as radiolabeled tracer targeting carbonic anhydrase IX and prostate-specific membrane antigen are under development to detect primary kidney tumors, stage systemic disease, and assess treatment response in RCC. Immune checkpoint inhibitors targeting PD-1 and cytotoxic T-cell lymphocyte-4 have changed the treatment paradigm in advanced RCC. Trials investigating novel mechanisms such as LAG-3 immune checkpoint inhibition, chimeric antigen receptor T-cell therapies, and T-cell engagers targeting RCC-associated antigens are currently ongoing. With the rapidly changing treatment landscape of RCC, the treatment sequence strategies will continue to evolve. Familiarity with the toxicities associated with the therapeutic agents and how to manage them are essential to achieve optimal patient outcomes. This review summarizes the recent developments of functional imaging and immunotherapy strategies in RCC, and the evidence supports treatment sequencing.

Preparation of PANI/CuPc/PDMS Composite Elastomer with High Dielectric Constant and Low Modulus Assisted by Electric Fields.

Dielectric elastomer is a kind of electronic electroactive polymer, which plays an important role in the application of soft robots and flexible electronics. In this study, an all-organic polyaniline/copper phthalocyanine/silicone rubber (PANI/CuPc/PDMS) dielectric composite with superior comprehensive properties was prepared by manipulating the arrangement of filler in a polymer matrix assisted by electric fields. Both CuPc particles and PANI particles can form network structures in the PDMS matrix by self-assembly under electric fields, which can enhance the dielectric properties of the composites at low filler content. The dielectric constant of the assembled PANI/CuPc/PDMS composites can reach up to 140 at 100 Hz when the content of CuPc and PANI particles is 4 wt% and 2.5 wt%, respectively. Moreover, the elastic modulus of the composites remains below 2 MPa, which is important for electro-deforming. The strain of assembled PANI/CuPc/PDMS three-phase composites at low electric field strength (2 kV/mm) can increase up to five times the composites with randomly dispersed particles, which makes this composite have potential application in the field of soft robots and flexible electronics.

BMSC loaded photo-crosslinked hyaluronic acid/collagen hydrogel incorporating FG4592 for enhanced cell proliferation and nucleus pulposus differentiation.

Intervertebral disc degeneration arises from damage or degeneration of the nucleus pulposus (NP). In this study, we developed a photo-crosslinkable hydrogel incorporating FG4592 to support the growth and differentiation of bone-marrow-derived mesenchymal stem cells (BMSC). Initially, hyaluronic acid was modified with tyramine and combined with collagen to introduce riboflavin as a photo-crosslinker. This hydrogel transitioned from liquid to gel upon exposure to blue light in 3 min. The results showed that the hydrogel was biodegradable and had mechanical properties comparable to those of human NP tissues. Scanning electron microscopy after BMSC seeding in the hydrogel revealed an even distribution, and cells adhered to the collagen fibers in the hydrogel with minimal cell mortality. The effect of FG4592 on BMSC proliferation and differentiation was examined, revealing the capability of FG4592 to promote BMSC proliferation and direct differentiation resembling human NP cells. After cultivating BMSCs in the photo-crosslinked hydrogel, there was an upregulation in the expression of glycosaminoglycans, aggrecan, type II collagen, and keratin 19 proteins. Cross-species analyses of rat and human BMSCs revealed consistent results. For potential clinical applications, BMSC loaded with photo-crosslinked hydrogels can be injected into damaged intervertebral disc to facilitate NP regeneration.

Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

PIM1 inhibitor SMI-4a attenuated concanavalin A-induced acute hepatitis through suppressing inflammatory responses.

Background: Serine/threonine kinase 1 (PIM1) plays a crucial role in cell growth, differentiation, and apoptosis. However, its role in the pathogenesis of concanavalin A (ConA)-induced acute hepatitis is not well understood. PIM1 kinase inhibitor can reduce the expression of PIM1. This study aims to investigate the effects of PIM1 kinase inhibitor and its protective mechanism in ConA-induced acute hepatitis. Methods: C57/BL six mice were injected with ConA (20, 15, and 12 mg/kg) to induce acute hepatitis, and PIM1 kinase inhibitor SMI-4a (60 mg/kg) was administered orally 24 h before ConA injection. The survival rate of the mice was observed after ConA injection. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed on liver tissue collected at different time points. The major cytokines expression in liver tissue was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The number of macrophages, T-cell and neutrophils in liver tissue were detected by flow cytometry (FCM). PIM1 in liver tissue was detected by western blot (WB) and qRT-PCR. SMI-4a (80 µM) was pretreated for 24 h and ConA (400 µg/mL) was stimulated for 12 h in RAW264.7 cell model. Phosphorylated p65 (p-p65) and cleaved caspase-3 (c-caspase-3) in liver tissue and macrophages were detected by WB. Results: Different concentrations of ConA caused different acute hepatitis mortality, 12 mg/kg concentration within 24 h of the mortality showed a gradient increase. The levels of AST and ALT increased significantly at 12 h after ConA injection. PIM1 expression was upregulated at 12 h. SMI-4a can suppress the PIM1 expression. SMI-4a suppressed cytokines production, AST, and ALT in ConA-treated serum. SMI-4a suppressed the major cytokines in liver tissue. Tests in liver tissue showed that SMI-4a reduced the number of T cells, neutrophils, and macrophages. SMI-4a inhibited the inflammatory response by downregulating the expression of p-p65. Meanwhile, apoptosis was decreased by decreasing the expression of c-caspase-3. Conclusions: In conclusion, the protective effect of SMI-4a against acute hepatitis is by reducing the inflammatory response and apoptosis. These findings suggest that SMI-4a may have therapeutic potential in the treatment of autoimmune hepatitis.

28.02 W LD side-pumped CW laser operated at 2.8†µm in YSGG/Er:YSGG/YSGG crystal.

We demonstrated a 978 nm laser diode (LD) side-pumped YSGG/Er:YSGG/YSGG composite crystal with a size of Ф 3 mm × 65 mm and continuous-wave (CW) mode. By optimizing resonator length and output mirror transmittance, a maximum output power of 28.02 W is generated, corresponding to slope efficiency of 17.55% and optical-optical efficiency of 12.29%, respectively. The thermal focal lengths are obtained by resonator stability condition. The laser wavelength is centered near 2.8 µm. Moreover, the beam quality factors M x2/M y2 are fitted to be 8.14 and 7.35, respectively. The above results indicate that a high-performance 2.8 µm CW laser can be achieved by LD side-pumped YSGG/Er:YSGG/YSGG composite crystal with excellent heat dissipation ability, which promotes effectively the development and applications of the mid-infrared solid-state lasers.

Versatile Deprotonation-Induced Exfoliation and Functionalization of Biological Nanofibrils for Actuation and Fluorescence.

Biological nanofibrils not only are characteristic of many species of biomasses but also serve as a promising type of sustainable nanomaterials for various applications. However, their production has long relied on an invasive and energy-consuming mechanical shear. A noninvasive and versatile approach remains challenging to exfoliate different types of biomasses into nanofibrils. In this study, we showed a versatile and nonaggressive intercalative deprotonation agent of organic base, which could efficiently deprotonate various biomasses for energy-saving exfoliation and functionalization, including cellulose, chitin, and silk. Both carboxylic nanofibrils and nanofibrils with pristine chemical structures could be produced in high yields through manual shaking or sonication. By further grafting photoresponsive groups via transesterification, intelligent NFs were generated featuring ultraviolet-responsive fluorescence and hydrophilicity. These responsive fluorescence and actuation behaviors promised their potential as green encryption and anticounterfeiting nanomaterials.

A composite score based on cardiovascular parameters can predict the mortality risk of patients with newly diagnosed interstitial lung disease: A prospective observational study.

BACKGROUND: It is crucial to identify factors that can predict the risk of mortality in patients newly diagnosed with interstitial lung disease (ILD). This study sought to develop and assess a composite scoring system for mortality prediction among ILD patients based on cardiovascular parameters, which were previously reported as predictors of survival. METHODS: We prospectively enrolled patients with newly diagnosed ILD and monitored their survival status for 24 months. Surviving and deceased patients were compared regarding their baseline characteristics including clinical, pulmonary, and cardiovascular parameters. A system of composite scores was established based on significant cardiovascular parameters and the Gender-Age-Physiology (GAP) score. Receiver operating characteristic curves were generated to identify their optimal cut-off values. Univariate as well as multiple multivariate regression models were built to investigate the mortality prediction of different individual and combined parameters. RESULTS: Ninety-six patients newly diagnosed with ILD underwent cardiovascular evaluation. In univariate analysis, three cardiovascular parameters were identified as significant predictors of mortality risk in ILD patients, either individually or as a combination of composite scores: tricuspid regurgitation velocity > 3.1 m/s; N-terminal pro-B-type natriuretic peptide level > 300 pg/ml and computed tomography pulmonary artery/ascending aorta diameter ratio > 0.9. In multivariate analysis, a composite score of those parameters [hazard ratio (HR) = 2.37 (confidence interval [CI]:1.06-5.33); p = 0.037; Score 1] and GAP score [HR = 1.62 (CI: 1.11-2.36); p = 0.012] were the most significant predictors for mortality among ILD patients. Combination of Score 1 and GAP score (Score 2) can increase the accuracy of survival predictions (area under the curve 0.83; p < 0.001). CONCLUSIONS: A composite score based on cardiovascular parameters and the GAP score can be used to predict the risk of mortality of patients with ILD. Such a score achieved better diagnostic accuracy than the GAP score alone. Nevertheless, further larger-scale randomized controlled trials are required for evaluation of the newly proposed score and confirmation of our results.

Elastic and Self-Healing Copolymer Coatings with Antimicrobial Function.

The revolutionary self-healing function for long-term and safe service processes has inspired researchers to implement them in various fields, including in the application of antimicrobial protective coatings. Despite the great advances that have been made in the field of fabricating self-healing and antimicrobial polymers, their poor transparency and the trade-off between the mechanical and self-healing properties limit the utility of the materials as transparent antimicrobial protective coatings for wearable optical and display devices. Considering the compatibility in the blending process, our group proposed a self-healing, self-cross-linkable poly{(n-butyl acrylate)-co-[N-(hydroxymethyl)acrylamide]} copolymer (AP)-based protective coating combined with two types of commercial cationic antimicrobial agents (i.e., dimethyl octadecyl (3-trimethoxysilylpropyl) ammonium chloride (DTSACL) and chlorhexidine gluconate (CHG)), leading to the fabrication of a multifunctional modified compound film of (AP/b%CHG)-grafted-a%DTSACL. The first highlight of this research is that the reactivity of the hydroxyl group in the N-(hydroxymethyl)acrylamide of the copolymer side chains under thermal conditions facilitates the "grafting to" process with the trimethoxysilane groups of DTSACL to form AP-grafted-DTSACL, yielding favorable thermal stability, improvement in hydrophobicity, and enhancement of mechanical strength. Second, we highlight that the addition of CHG can generate covalent and noncovalent interactions in a complex manner between the two biguanide groups of CHG with the AP and DTSACL via a thermal-triggered cross-linking reaction. The noncovalent interactions synergistically serve as diverse dynamic hydrogen bonds, leading to complete healing upon scratches and even showing over 80% self-healing efficiency on full-cut, while covalent bonding can effectively improve elasticity and mechanical strength. The soft nature of CHG also takes part in improving the self-healing of the copolymer. Moreover, it was discovered that the addition of CHG can enhance antimicrobial effectiveness, as demonstrated by the long-term superior antibacterial activity (100%) against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and the antifouling function on a glass substrate and/or a silica wafer coated by the modified polymer.

The incidence, pathogenesis, and management of non-clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and is divided into two distinct subtypes, clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC). Although many treatments exist for RCC, these are largely based on clinical trials performed in ccRCC and there are limited studies on the management of nccRCC. Non-clear cell RCC consists of multiple histological subtypes: papillary, chromophobe, translocation, medullary, collecting duct, unclassified, and other rare histologies. Due to variations in pathogenesis and therapeutic response, therapy should be tailored to specific variant histologies. For patients with localized nccRCC, surgical resection remains the gold standard. In the metastatic setting, the standard of care has yet to be clearly defined, and most guidelines recommend clinical trial participation. General therapeutic options include immunotherapy, either as monotherapy or in combination, targeted therapies such as vascular endothelial growth factor tyrosine kinase inhibitors and MET inhibitors, and chemotherapy in certain subtypes. Here we present a review of the incidence and pathogenesis of the various subtypes, as well as available clinical data to support therapeutic recommendations for these subtypes. We also highlight currently available clinical trials in nccRCC and future directions in investigating novel treatment modalities tailored to patients with variant histology.

Exercise capacity-hemodynamics mismatch in elderly patients with pulmonary hypertension: A nationwide multicenter study from Taiwan Society of Cardiology Pulmonary Hypertension Registry (TAIPANS).

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.