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Lipoprotein glomerulopathy (LPG) is a rare hereditary glomerular disease characterized by lipoprotein thrombi within dilated glomerular capillaries for which effective treatments remain limited. This report concerns a 25-year-old Japanese woman with an 8-year history of persistent proteinuria and severe dyslipidemia who presented with heavy proteinuria (3.31 g/gCr) despite preserved renal function. Kidney biopsy revealed features typical of LPG on light and electron microscopy, and serum apoE levels were markedly elevated. The patient was started on pemafibrate, a selective peroxisome proliferator-activated receptor-alpha modulator known to exert stronger triglyceride-lowering effects and to have a more favorable hepatic and renal safety profile compared with conventional fibrates. Following treatment, the patient's triglyceride levels decreased substantially and her proteinuria progressively improved. Complete remission (0.05 g/gCr) was achieved within 7 months, and she remained stable thereafter. Although partial remission with fibrates has been previously reported in patients with LPG, there have been no reports of complete remission in those treated with pemafibrate. To our knowledge, this is the first documented case of complete remission of proteinuria induced by pemafibrate in a patient with LPG. Pemafibrate may be a promising targeted therapy for this rare glomerular disorder.

Verification stages are recommended for maximal oxygen consumption (V̇O₂max) determination, but there is currently no standardization of verification stage design. We sought to determine if the length of recovery and the initial intensity of subsequent exercise influence the effectiveness of verification stages during testing for V̇O₂max. Twenty-seven participants (20 males, 7 females) completed four graded exercise tests (GXT). Each session included an identical incremental V̇O₂max (iV̇O₂max) protocol, followed by one of four verification stages with combinations of short (5 min) and long (15 min) rest periods, and submaximal (one stage below maximal workload) and supramaximal (one stage above maximal workload) starting intensities. Although iV̇O₂max and verification V̇O₂max (vV̇O₂max) were similar across all protocols, 11-19% of participants achieved higher values during verification. About 24% of individuals who did not exhibit a V̇O₂ plateau during the GXT exhibited a vV̇O₂max > iV̇O₂max in the submaximal verification protocols compared to 6-14% for the supramaximal protocols. Verification stages using initial submaximal intensities may increase the likelihood of achieving V̇O₂max.

Agentic AI systems have recently emerged as a critical and transformative approach in artificial intelligence, offering capabilities that extend far beyond traditional AI agents and contemporary generative AI models. This rapid evolution necessitates a clear conceptual and taxonomical understanding to differentiate this new paradigm. Our paper addresses this gap by providing a comprehensive review that establishes a precise definition and taxonomy for "agentic AI," with the aim of distinguishing it from previous AI paradigms. The concepts are gradually introduced, starting with a highlight of its diverse applications across the broader field of engineering. The paper then presents four detailed, state-of-the-art use-case applications within electrical power systems engineering, a domain where the impact of agentic AI systems is expected to be particularly significant. The high impact of agentic AI systems in the field of electrical power systems is primarily driven by global trends toward clean energy transition and higher levels of grid automations, all of which create an environment where agentic AI can be readily deployed and effectively leveraged. These case studies demonstrate current and innovative state-of-the-art, ranging from an advanced agentic framework for streamlining complex power system studies and benchmarking to a novel agentic AI system developed for survival analysis of dynamic pricing strategies in battery swapping stations. Finally, robust deployment of these autonomous agents brings a unique set of challenges that are discussed in this manuscript through detailed failure mode investigations. From these findings, we derive actionable recommendations for the design and implementation of safe, reliable, and accountable agentic AI systems, offering a critical resource for researchers and practitioners.

Rituximab (RTX) is an effective and safe treatment for rheumatoid arthritis (RA), but is associated with an increased risk of reactivation of hepatitis B virus (HBV) infection. Therefore, (inter)national guidelines recommend HBV screening prior to initiation of RTX treatment. However, the incidence of HBV in RA patients in nonendemic areas is expected to be very low, with known suboptimal screening adherence. This study aims to assess the added diagnostic value of routine serological HBV screening in RA patients initiating RTX. This retrospective single-centre cohort study included all patients with a clinical diagnosis of RA intending to initiate RTX between April 2012 and April 2024. Data on patient and disease characteristics, HBV screening results, and additional laboratory results were collected. Adherence to HBV screening, proportion of positive test results (hepatitis B surface antigen or core antibody positive), and incidence of HBV reactivation were assessed. Of 975 included patients, 270 (28 %) were serologically screened for HBV. Six of those (2.2 %) had a positive screening result, of whom 3 eventually did not receive RTX. All 6 had a known HBV history or risk factor. No active HBV infections were observed after initiating RTX (mean follow-up 6.97 years), regardless of screening. Routine serological HBV screening identified very few previously unrecognised infections, and-in spite of screening adherence being low-no HBV reactivations occurred. Routine serological HBV screening, therefore, seems redundant in a low-risk population and should be reserved for patients with known risk factors.

Dielectric capacitors offering ultrafast charge-discharge capability and superior reliability are essential for advanced electronic systems, but achieving both high energy density and efficiency within simple and eco-friendly compositions remains a great challenge. Here, guided by machine learning, we achieve high-efficiency and thermally stable capacitive energy storage in strontium titanate-based ceramics. Through synergistic local structural engineering and optimized fabrication process, the materials exhibit enhanced polarization, reduced hysteresis loss, and improved breakdown strength. The designed materials deliver an ultrahigh energy density of 10.69 J cm-3 with a near-ideal efficiency of ∼97% and a record high figure of merit of 392 J cm-3 at room temperature, and retains high performance at 150°C with a figure of merit of 152 J cm-3 and an efficiency of ∼94%. This remarkable performance arises from the incorporation of Bi3+ ions with high polarizability at the A-sites of strontium titanate quantum paraelectrics, which breaks structural symmetry and induces lattice and octahedral distortions, leading to the formation of nanoscale polar clusters with highly dynamic fluctuations. These findings establish a compositionally simple, environmentally benign pathway for developing dielectrics with superior energy storage capability and thermal stability, offering new opportunities for high-performance capacitive energy storage systems.

Because the body is commonly described in a six-layered structural hierarchy starting from molecules and cells to tissues, organs, organ systems, and finally to the whole organism, bodily functions (physiological and pathophysiological) are often approached in the same layered way. This is familiar and convenient, but it has clear limitations. Many important functions, such as homeostasis, thermoregulation, stress responses, and so on, emerge from coordinated causal processes that span multiple levels. They cannot be understood by assigning them to a single anatomical layer, yet integrative physiology still lacks a functional framework that is both conceptually coherent and practically useful for representing such multi-level interactions. This article introduces a 5-domain functional framework, developed through logical analysis of how intracellular fluid compartment(s) (ICF or ICFs) operate collectively within the shared extracellular fluid compartment (ECF). From this enveloping ECF-ICF relationship, five relational functional domains emerge. This perspective organizes bodily processes according to their operational logic rather than their anatomical position, allowing multi-level coordination to be visualized in a unified and flexible way. This framework and logic further lead to the development of a second functional platform that can organize bodily functions described by quantitative/mathematical relationships (e.g., oxygen-hemoglobin dissociation curve, Nernst equation, Michaelis-Menten equation, etc.). The platform is named Blueprint for Quantitative Functional Organization (BQFO). When mathematical expressions of function are placed into the BQFO, they form a systematically organized hierarchy rather than remaining scattered across topics. Together, the 5-domain functional framework and the BQFO provide not only practical tools for integrating complex functions but also a more realistic epistemology and methodology for understanding how bodily functions operate. These developments potentially establish new principles and offer new tools for integrative physiology and interdisciplinary teaching and research.

Harm reduction vending machines (HRVMs) can expand low-barrier access to overdose prevention, sexual health, safer-use, and basic self-care supplies; however, practical guidance for implementing HRVMs in health system and supportive housing settings is limited. This practice report describes a clinical pharmacist practitioner (CPP)-led deployment of 15 HRVMs across a Veterans Affairs (VA) system and Veterans supportive housing in California. Beginning in December 2021, the CPP conducted site engagement, market research, and funding applications; convened cross-departmental stakeholders (logistics, engineering, biomedical, environmental management, information security/technology); and completed contracting. Contracts were awarded to VendNovation, LLC, for HRVMs which were placed in 7 community-based outpatient clinics, 6 supportive-housing sites, and 2 hospital locations. The CPP designed the HRVM wrap and interior layout; curated product assortments (eg, fentanyl/xylazine test strips, syringes, safer-sex supplies, wound-care, and hygiene items; naloxone added after launch) based on prior quality improvement interventions and Veteran feedback surveys; and established barcode-based user access and software-enabled inventory management. Implementation challenges included staff concerns (eg, stigma, not in my backyard attitudes), connectivity barriers (eg, Wi-Fi requirements), and added costs for deliveries to non-VA locations. HRVMs within VA clinics were accessible during business hours; supportive-housing HRVMs operate 24/7. Planning and installation required nearly 2 years, underscoring the need for dedicated staffing (CPP plus logistics technician), braided funding for start-up and recurring costs, and standardized purchasing and installation pathways. HRVMs seem feasible and acceptable in VA clinical and housing settings and may increase anonymous, low-barrier access to harm-reduction supplies. Implications for scale-up include development of centralized or prevetted procurement pathways, clearer implementation guidance, and operational supports to reduce site-level contracting burden.

We describe the case of a 44-year-old female with a history significant for only hypertension who presented to the emergency department with symptoms of aphasia and difficulty concentrating, persisting for six hours. Work-up revealed evidence of a multifocal infarct suggestive of embolic etiology, along with evidence of a large 6.0 × 6.0 ascending thoracic artery and simultaneous aneurysm of the transverse arch. The patient subsequently underwent open surgical repair with placement of a Dacron graft, which she tolerated well without complications. Surgical pathology was positive for granulomatous inflammation suggestive of autoimmune or infectious etiology, and the patient was readmitted post-surgical discharge for an extensive work-up, which was found to be negative. A new diagnosis of Takayasu arteritis (TA) was made. During her subsequent hospitalization, she developed an episode of unstable atrial fibrillation with rapid ventricular response and acute hypotension requiring medical ICU observation. She was started on high-dose steroids, trimethoprim-sulfamethoxazole prophylaxis, and amiodarone with a positive clinical response. She underwent a cardiac MRI to evaluate for evidence of myocardial infiltration, which was determined to be normal. The development of atrial fibrillation was considered a postoperative complication, and amiodarone was discontinued at eight weeks. The patient received a gradual steroid taper with initiation of daily low-dose prednisone and methotrexate and made a full recovery.

ObjectiveTo evaluate changes in antipsychotic treatment patterns and healthcare utilization before and after initiation of long-acting injectable antipsychotics (LAI-APs) in a large Québec population cohort, comparing individuals with schizophrenia (SCZ) to those with other psychotic disorders (non-SCZ).MethodWe conducted a retrospective cohort study using linked Québec administrative databases (RAMQ, MED-ECHO, and public drug insurance) to identify 6,221 adults who initiated a LAI-AP between April 2013 and December 2016, after a 12-month LAI-free period. Participants were followed for 12 months before and after the index date. The cohort was stratified into SCZ and non-SCZ, and were further divided by regimen at initiation (LAI only; LAI + clozapine; LAI + other oral antipsychotic). Antipsychotic exposure and health-service usage (hospitalizations, emergency visits, outpatient and community care) trajectories were analyzed weekly using state-sequence analysis; pre- versus post-initiation comparisons used paired statistical tests.ResultsOf 6,221 patients (63.4% male; mean age 41.6 years), initial treatments consisted of paliperidone LAI (55.7%), aripiprazole LAI (21.5%), risperidone LAI (6.9%), first-generation LAI (15.6%), and LAI combinations (0.2%); 40% received LAI only, 5% LAI + clozapine, 55% LAI + an oral antipsychotic. SCZ patients were more often male, economically disadvantaged, and more likely to receive clozapine. After LAI initiation, hospital days fell sharply by almost 70% and outpatient and community-care visits increased substantially. Use of oral antipsychotics decreased overall post-initiation, except for clozapine (which rose) and first-generation oral drugs (which remained stable).ConclusionsIn this real-world Québec cohort, LAI-AP initiation was followed by a marked reduction in hospitalizations and a shift toward outpatient and community care, regardless of diagnosis. Observed differences in sociodemographic and clinical profiles between SCZ and non-SCZ patients-and among SCZ treatment subgroups-suggest the need for tailored care pathways. These findings support LAI-AP effectiveness in reducing healthcare utilization and inform resource planning. How Injectable Medications Reduce Hospital Visits for Patients With PsychosisA Quebec study of 6,221 patients reveals that starting long-acting injectable antipsychotics (LAIs) reduces hospital stays by 70% while increasing community-based follow-ups. These results demonstrate the effectiveness of LAIs in improving patient stability and highlight the need to tailor care according to the diagnosis, whether for schizophrenia or other psychotic disorders. This research supports the use of LAIs to optimize the use of healthcare services.

Opioid use disorder (OUD) and overdoses represent critical challenges linked to the widespread availability of opioid medications. To address these risks, the French National Authority for Health convened a multidisciplinary working group to develop comprehensive guidelines on the prevention and management of OUD and overdoses. These recommendations expand on the second part of the guidelines, which specifically addressed the prevention and management of OUD and overdoses. Grounded in the highest level of international evidence and developed through a rigorous formal consensus process, the guidelines emphasize appropriate opioid prescribing as the cornerstone of prevention. They provide practical recommendations for identifying patients at risk, detecting problematic use early, and initiating opioid agonist treatment when indicated. The role of naloxone as an essential tool to prevent fatal overdoses is highlighted, along with strategies for coordinated and multidisciplinary care across diverse healthcare settings. By integrating prevention, treatment, and harm reduction measures, these guidelines seek to balance legitimate access to opioid analgesics with robust safeguards against opioid use disorder and overdose. Although developed within the French healthcare system, their strong evidence base and underlying clinical principles make them applicable to international practice. Together with the first part on pain management, they constitute one of the most comprehensive and up-to-date sets of recommendations on the safe and effective use of opioid medications. Opioid medicines are important for treating pain, but they also carry risks of opioid use disorder and overdose, which can sometimes be fatal. These risks have increased as opioids have become more widely available. Clear national guidance is needed to help patients and healthcare professionals use these medicines safely. This second part of the French national practice guidelines focuses on the prevention and management of opioid use disorder and overdoses. The recommendations were developed with input from doctors, pharmacists, addiction specialists, patients, and public agencies, and are based on international scientific evidence. The guidelines stress the importance of safe prescribing from the start of treatment and educating patients about benefits and risks. They highlight how to recognize early warning signs of problematic use and recommend substitution treatments, such as buprenorphine or methadone, which reduce cravings and lower the risk of overdose. Another key recommendation is to make naloxone, the emergency medicine that reverses an opioid overdose, widely available to patients, relatives, and first responders. These guidelines also call for coordinated, multidisciplinary care that addresses medical, psychological, and social needs. Together with Part 1 of the guidelines, which focuses on clinical use of opioids for pain, they provide a comprehensive and consistent framework to ensure safe access to opioids while reducing harm.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is critical for diagnosing solid lesions. The wet-suction technique, which pre-fills the needle lumen with saline, has been proposed to improve specimen quality compared with conventional dry suction. This study aimed to evaluate the efficacy of wet suction versus dry suction in EUS-TA. This study aimed to evaluate the efficacy of wet suction versus dry suction in EUS-TA. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA 2020 guidelines. Electronic searches of PubMed, Embase, Cochrane CENTRAL, and additional databases were performed through January 2025. Primary outcomes were blood contamination, cellularity, and integrity scores; secondary outcomes were diagnostic accuracy and specimen adequacy. Effect sizes were calculated using Hedges' g or risk ratios (RRs) with 95% confidence intervals (CIs). Seven RCTs (784 patients; 1566 specimens) were included. Wet suction significantly reduced blood contamination (Hedges' g&#x2009;=&#x2009;0.289, 95% CI: 0.178-0.401, p&#x2009;<&#x2009;0.0001) and improved cellularity (Hedges' g&#x2009;=&#x2009;0.420, 95% CI: 0.241-0.599, p&#x2009;<&#x2009;0.0001) with low heterogeneity. Integrity score showed no significant difference (p&#x2009;=&#x2009;0.054). Overall diagnostic accuracy was similar between techniques (RR&#x2009;=&#x2009;1.025, p&#x2009;=&#x2009;0.548), but subgroup analysis revealed higher accuracy for wet suction in EUS-fine needle aspiration (FNA; RR&#x2009;=&#x2009;1.162, p&#x2009;=&#x2009;0.001). Specimen adequacy did not differ significantly (p&#x2009;=&#x2009;0.074). Wet suction improves sample quality by reducing blood contamination and increasing cellularity, with potential diagnostic benefit in FNA procedures. Effects on integrity and adequacy remain inconclusive. Larger, standardized trials are warranted to confirm these findings. Better samples, better results: using water to improve ultrasound-guided biopsies Improving biopsy quality: the &#x201c;wet suction&#x201d; advantage The challenge: When doctors need to diagnose a suspicious growth inside the body (such as in the pancreas), they use Endoscopic Ultrasound-Guided Tissue Acquisition (EUS-TA). A thin needle is guided by ultrasound to collect tissue samples. However, these samples often contain too much blood or too few diagnostic cells, making it difficult for pathologists to provide a clear answer. The &#x201c;wet suction&#x201d; technique: Traditionally, the biopsy needle is filled with air (Dry Suction). The Wet Suction technique is a simple modification: the needle is pre-filled with sterile saline (salt water) before the procedure. This saline replaces the air to create a more stable vacuum, helping to pull in more tissue while reducing blood interference. Our study and findings: We analyzed data from 7 clinical trials involving 784 patients and 1,566 tissue samples. Our goal was to confirm if the &#x201c;wet&#x201d; method is truly superior to the standard &#x201c;dry&#x201d; method. Cleaner Samples: Wet suction significantly reduced blood contamination, making samples easier to read under a microscope. Higher Cell Yield: Samples collected with wet suction contained a higher concentration of the actual target cells (better cellularity). Greater Accuracy: For specific needle types (FNA), wet suction significantly improved the accuracy of the final diagnosis. Better for Large Lesions: Larger growths showed a particularly strong benefit from the reduction in blood contamination. Why this matters: For patients, a better-quality sample means a higher chance of an accurate diagnosis on the first try. This simple, low-cost adjustment reduces the need for repeat procedures and helps patients start the correct treatment sooner, providing more certainty and less anxiety during the diagnostic process.

Plasmonic nanoparticles have generated great attention due to their potential applications in photocatalysis. The dissociation of hydrogen on Au nanoparticles has served as a useful model for this process, but despite many previous studies, there are important details of the dynamics which remain uncertain, such how single-photon absorption triggers dissociation. This paper addresses these issues through the study of gold clusters interacting with H2, explicitly examining the effects of cluster size, shape, and excitation energy on the dissociation dynamics. By using time-dependent density functional theory (TDDFT) interfaced with trajectory surface hopping, we have examined the Au + H2 system for states with excitation energies similar to the plasmon energy in gold. Three distinct outcomes are observed: H-H bond dissociation, H2 desorption, and nonreactive relaxation. Trajectories starting in excited states of the cluster relax through extensive nonadiabatic surface hopping to lower excited states that couple to antibonding states where repulsion drives dissociation. In addition, hopping converts metal excitation to increased kinetic energy in H-H stretching that helps overcome dissociation barriers on reactive adiabats. This provides a detailed picture of the evolution of hot carriers into antibonding states of physisorbed molecules after extensive surface hopping that dissociate in &#x223c;100 fs. Desorption and nonreactive relaxation compete with this picture. Our findings provide insights to photoinduced processes involving plasmonic nanoparticles showing how nonadiabatic dynamics plays a crucial role in accessing repulsive states while also releasing kinetic energy that drives dissociation.

While proteasomes are best known for eliminating defective proteins or turning off signaling pathways, they also enable crucial cellular activities. Critical among these, proteasomes allow cells to initiate gene expression, but underlying targets and regulatory mechanisms remain poorly understood. Here, we report that proteasomes drive the systemic degradation of repressive trans-cription factors to eject TLE/Groucho-family co-repressors from chromatin and thereby constantly free transcription start sites for activator binding. This circuitry requires the E3 ligase SCF FBXL14 , which modifies its targets dependent on presentation by TLEs, but independently of their identity. The continuous cycling of co-repressors off chromatin, as achieved by systemic turnover of a protein family, is essential for stem cells to translate developmental cues into lineage-specific gene expression, and it is disrupted by cancer mutations in TLE1 that impair SCF FBXL14 -recruit-ment. We conclude that systemic degradation of repressive transcription factors establishes co-repressor dynamics required for genes expression and cell fate specification.

Gastric cancer (GC) is a highly malignant tumor with significant morbidity and mortality rates globally. Recent studies have shown that RUNX2, a member of the RUNX family known for its role in osteoblast differentiation and bone morphogenesis, is associated with the pathogenesis and progression of GC, while the underlying mechanisms of the pathogenesis and progression of GC are largely unknown. In this study, we investigated the role of RUNX2 in GC progression by analyzing its effects on gene expression and alternative splicing (AS) in HGC-27 cells. We silenced RUNX2 by small interfering RNA (siRUNX2), and then analyzed the globally regulated transcriptome profile by sequencing method (RNA-seq) to identify the differentially expressed genes (DEGs) and alternative splicing (AS) genes. The downstream targets of RUNX2 were identified by performing CUT&Tag and sequencing experiment in HGC-27 cells. Using RNA-seq, we identified 314 DEGs and 1120 regulated AS events (RASEs) in HGC-27 cells upon RUNX2 knockdown. The DEGs were enriched in pathways related to cell cycle regulation and apoptosis, while the RASEs were predominantly involved in cell cycle processes. These findings suggest that RUNX2 not only modulates gene expression but also extensively influences AS, which is crucial for cellular processes such as proliferation and survival. Notably, we found that RUNX2 regulates the expression of the splicing factor SF3B6 by binding to its promoter region. Our results showed that SF3B6 expression was significantly decreased in siRUNX2 samples, and its downregulation was associated with altered AS profiles of genes involved in the cell cycle. Our findings demonstrate that RUNX2 modulates the transcriptome and AS profile in GC cells, with a particular focus on its regulation of SF3B6. This study highlights the multifaceted role of RUNX2 in GC progression and suggests that targeting the RUNX2-SF3B6 axis could be a promising therapeutic strategy for GC.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, especially in patients with distant metastases. However, recent advances in multidisciplinary treatment strategies, including surgical resection, have led to successful outcomes even in patients with metastatic PDAC. Nevertheless, few cases have been reported with 2 or more resections of metachronous distant metastases. Herein, we report a case of PDAC in which a metachronous hepatic metastasis was successfully resected following prolonged chemotherapy after curative pancreatectomy and in which a metachronous pulmonary metastasis was subsequently resected following additional chemotherapy. A 69-year-old man was diagnosed with PDAC and received neoadjuvant chemotherapy in October 2019. In March 2020, a subtotal stomach-preserving pancreaticoduodenectomy was performed. The patient received 1 year of adjuvant chemotherapy following surgery. In September 2021, 18 months after surgery, CT showed a 10-mm nodule in segment (S) 6 of the liver, which was diagnosed as a hepatic recurrence of PDAC. After 19 months of chemotherapy, the metastatic liver lesion remained solitary and showed no change in size, suggesting that the tumor was well-controlled. In June 2023, a partial hepatectomy of S6 was performed. Chemotherapy with S-1 was continued after hepatic resection; however, a metastatic pulmonary lesion in the right lower lobe was identified on CT 15 months after the liver surgery. Right lower lobe partial resection was performed using video-assisted thoracoscopic surgery in January 2025. The patient remains alive and recurrence-free 1 year after the last surgery, 6 years and 1 month after the initial surgery, and 6 years and 6 months after the start of treatment. This report describes a case of long-term survival achieved with a multidisciplinary approach, including 2 surgical resections, for recurrent disease following a diagnosis of PDAC.

accurate assessment of maximum oxygen uptake (VO2max) is fundamental to exercise physiology and cardiorespiratory fitness evaluation. While treadmills are the gold standard, there is a growing need for standardized vertical loading devices. This study aimed to evaluate the concurrent validity, construct validity, and reliability of the novel Tianyu climbing machine during progressive load exercise testing. Thirty-one male physical education students (mean age: 20.45 years) were recruited to perform maximal graded exercise tests on both a treadmill (using the Bruce protocol) and the Tianyu climbing machine (starting at 0.05&#xa0;m/s with 0.01&#xa0;m/s increments every minute). Physiological indicators, including VO2max, heart rate (HR), and respiratory exchange ratio (RER), were monitored. Concurrent validity was assessed using Bland-Altman plots and mean relative percentage error (MRPE), while construct validity was examined through canonical correlation analysis (CCA). Test-retest reliability of the machine's speed was evaluated via intraclass correlation coefficients (ICC).The climbing machine demonstrated high concurrent validity with the treadmill, with a mean relative percentage error (MRPE) of less than 10%.CCA revealed a significant linear relationship between physiological markers and climbing performance indicators (r&#xa0;=&#xa0;0.779, P <&#xa0;0.01). Furthermore, the device exhibited excellent speed accuracy (error < 1%) and high test-retest reliability (ICC&#xa0;=&#xa0;0.74 - 0.85) across standardized speed ranges. The Tianyu climbing machine is a scientifically valid and reliable tool for assessing cardiorespiratory function. Its ability to provide precise, controllable vertical loads makes it an effective alternative to traditional modalities for standardized metabolic testing in athletic and clinical settings.

In the pursuit of multifunctional therapeutic agents, a new series of thiocarbamoylpyrazoline derivatives were synthesized starting from chalcones, and all synthesized compounds (1-12) were structurally characterized using spectroscopic methods (NMR, FT-IR, and Q-TOF-LC-MS) and elemental analysis. The anticancer properties of the test compounds were evaluated in vitro against human bone cancer cell lines MG63 and SW1353 using MTT and LDH assays. LDH assay results demonstrated that the compounds exhibited no detectable cytotoxicity toward normal human chondrocyte (HC) cells. Compared to the reference drug 5-fluorouracil (5-FU), several compounds displayed notable antiproliferative activity. Tumor selectivity index (TSI) analysis identified compounds 1, 2, 4, and 10 as having high tumor selectivity, indicating a preferential cytotoxic effect toward cancer cells over normal cells. Among these, compounds 4 and 10 exhibited the most favorable anticancer profiles, combining potent antiproliferative activity with minimal toxicity to normal cells. Furthermore, to support the experimental anticancer findings, in silico molecular docking studies were performed using the crystal structures of caspase-3 (1GFW), human metalloproteinase-13 (3KEJ), human estrogen receptor (3ERT), and EGFR (1M17) against compounds 1, 2, 4, and 10, and their binding modes were analyzed.

To compare the efficacy of pre-emptive antifungal therapy (PAT) and empirical antifungal therapy (EAT) in patients with febrile neutropenic acute leukaemia (AL) with/without anti-mold prophylaxis. We included 92 patients with AL and neutropenia with fever unresponsive to empiric antibiotics, stratified by posaconazole prophylaxis to receive EAT (n&#x200a;=&#x200a;40) or PAT (n&#x200a;=&#x200a;52). In the PAT group, a standardized diagnostic workup for the detection of invasive fungal infection (IFI) was performed. The study endpoints were antifungal therapy initiation, IFI documentation, safety, and cost. Posaconazole prophylaxis was equally distributed among the patients (overall 55.4%). Antifungal therapy was started in 58% of the patients in the PAT group versus 100% in the EAT group (P&#x200a;<&#x200a;0.01; 95% CI: 0.42 [0.28-0.55]). In the EAT and PAT groups, overall proven/probable IFI rates were 2% and 17%, respectively (P&#x200a;=&#x200a;0.02; 95%CI: -0.14 [-0.26 to -0.03]) and 4% and 10% in patients with posaconazole prophylaxis, respectively (P&#x200a;=&#x200a;0.3; 95% CI: -0.06 [-0.20-0.07]). At hospital discharge, mortality was 19% in the EAT and 5% in the PAT groups (P&#x200a;=&#x200a;0.02; 95% CI: -0.14 [-0.26 to -0.03]), unrelated to the use of posaconazole prophylaxis, and no IFI-related death was observed. The mean costs per patient were &#x20ac;7681 and &#x20ac;3344 in the EAT and PAT groups, respectively (P&#x200a;=&#x200a;0.003; 95% CI: &#x20ac;4337 [&#x20ac;1814-6860]). Adverse reactions to antifungals were similar between the groups. In patients with persistently febrile neutropenic AL, PAT was safe and effective and reduced the use and costs of antifungals, irrespective of anti-mold prophylaxis, compared with empirical treatment.

Chlorophylls (Chls) harvest the solar energy that drives photosynthesis, which underpins most of the food chains on our planet. Starting from protoporphyrin IX, just seven biosynthetic reactions culminate in the synthesis of Chl a, the major light-absorbing pigment on Earth. Other such pigments, Chls b, c, d and f, widen the absorption range in the visible and red regions of the spectrum, and several bacteriochlorophylls (BChls), BChls a, b and g in particular, open new spectral windows allowing organisms to harvest near infra-red light. This perspective surveys the structural features of porphyrins, chlorins and bacteriochlorins that impart their characteristic absorption features, then presents a similar analysis of the biosynthetic intermediates leading to Chls a, b, c, d and f. The interlinked Chl and BChl biosynthetic pathways are summarised, then the rest of the perspective focusses on the enzymes that synthesise Chls a, b, c, d and f. AlphaFold 3 was used to model a complete set of structures for Chl biosynthesis enzymes, predicting intersubunit associations and the arrangements of cofactors and bound substrates, and providing insights into catalytic mechanisms. A new scheme for binding substrates and transferring products between pathway enzymes suggests how synthetic biology approaches can assemble hybrid Chl and BChl pathways to expand the spectral range for harvesting and using solar energy.