The impact of cavaletti height on dogs' walking speed and its implications for ground reaction forces.

Objective: The objective of this study was to investigate the effects of cavaletti pole height on temporospatial (TPS) and ground reaction force (GRF) variables as compared to a walking gait in healthy dogs. Animals: A total of 25 client-owned dogs were included in this study. Procedures: This study used client-owned dogs to explore the effects of cavaletti pole height on TPS and GRF variables. Dogs were first walked over a validated pressure-sensitive walkway (PSW) and then walked over the PSW over which six cavaletti poles were set. Cavaletti pole height was initially set at 2 inches and then increased incrementally to 4 inches, 6 inches, and 8 inches. TPS and GRF variables were obtained for all dogs walking across a PSW without cavaletti poles and at each cavaletti height. TPS variables were then compared to those obtained at a normal walking gait. Results: Increasing cavaletti height resulted in significant decreases in walking gait velocity and the number of gait cycles per minute. Conversely, significant increases in gait cycle duration (duration of one complete cycle of gait, which includes the time from the initial contact of one paw to the subsequent contact of the same paw) and gait time (duration to walk the total distance on the PSW) were noted. Increases in stance time, normalized maximum force, and normalized vertical impulse were observed. Conclusion and clinical relevance: Cavaletti height does influence TPS variables in healthy dogs at a walking gait. The effects were most notable with regard to velocity. Due to the lack of consistent velocity for all cavaletti heights, no conclusions can be drawn regarding the effect of cavaletti height on ground reaction forces. Further investigation is needed to elucidate whether it is the velocity, cavaletti height, or combination of both that impacts ground reaction force variables. When selecting cavaletti pole heights for a therapeutic exercise program, an increase in cavaletti height results in a slower walking gait.

Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy.

OBJECTIVE: To evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors.  PATIENTS: We retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy.  MAIN OUTCOME MEASURES: Pathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment.  RESULTS: The incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%.  CONCLUSIONS: Preoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.

Quantifying future water resource vulnerability in a high-mountain third pole river basin under climate change.

Understanding the water resource vulnerability (WRV) in global mountain regions under climate change is crucial for water resources management and socio-economic development. However, the WRV in the high-mountain Third Pole region (with quite a few transboundary river basins) remains largely unclear. Here, we have applied a comprehensive assessment framework of WRV to a Third Pole high-mountain river basin (Nujiang-Salween River, NSR) and its dependent downstream. The framework consisted of sensitivity, exposure, adaptability, hazard, and water stress indices, considering climate change, socio-economics, government effectiveness, natural disasters, and water supply capacity of the target river basin. Our results indicate that the downstream area (with intensive human activities) often exhibited significantly higher WRV than the mountain region; while the WRV shows an M-shaped change with increasing elevation, with the highest vulnerability occurring in a relatively low elevation range (e.g., 500-1500 m for the NSR basin). In the near future, we find that the spatial pattern of WRV in the basin is alternately influenced by adaptation, water scarcity, and exposure; whereas climate change serves as the main driver affecting the WRV in the far future. These findings enhance our understanding of the WRV in high-mountain transboundary basins of the Third Pole under global change.

[Endometrial carcinoma: molecular classification in routine pathology]. / Endometriumkarzinom: molekulare Klassifikation in der Routinepathologie.

The molecular classification of endometrial carcinoma defines four main groups: polymerase­É›(PolE) gene mutated, microsatellite unstable (MSI), p53 abnormal tumors and tumors with no specific molecular profile (NSMP). This classification provides significant insights into the prognosis and therapeutic decisions. Each group exhibits unique genetic profiles identified through immunohistochemistry and molecular diagnostics, enabling personalized treatment. The identification of these molecular signatures necessitates precise analytical methods, selected based on the local circumstances at each site. The approach to molecular classification highlights the critical role of pathology in the diagnosis and emphasizes the necessity of collaboration between the clinic and pathology.

Breast reconstruction with TiLOOP® Bra: Another arrow in plastic surgeons' quiver?

BACKGROUND: The use of lower-pole sling products has made immediate breast reconstruction a feasible option in women undergoing skin-nipple sparing and skin-reducing mastectomies. To date, available data on the comparative efficacy of biological and synthetic meshes regarding postoperative complications are scattered and limited. METHODS: A systematic literature search was performed to screen three different databases (PubMed, Web of Sciences, and Embase) using the following keywords: "breast reconstruction" AND "TiLOOP®" OR "Titanium-Coated Polypropylene Mesh" OR "TCPM". The perioperative and demographic characteristics of patients, complications profiles, and patient-reported outcomes were considered. RESULTS: We initially identified 234 articles, of which only 41, including 3923 patients and 5042 reconstructed breasts, fully satisfied the inclusion criteria. CONCLUSION: TiLOOP® Bra could be considered a safe and aesthetically valid alternative to Acellular Dermal Matrices (ADMs) in non-smokers patients undergoing skin-nipple sparing and skin-reducing mastectomies and immediate reconstruction. In such populations, complications are more likely to develop in patients with extreme body mass index values. The incidence of seroma with TiLOOP® Bra is comparable to that of ADMs as it is the beneficial effect in radiated patients, where TiLOOP® Bra seems superior to implant alone reconstruction. It has a good bio-integration with host tissues and resistance to infections in patients with a weakened immune system as a consequence of oncologic perioperative treatments.

Effortless Totem-Pole Converter Control Using a Power Factor Correction Peak Current-Mode Controller.

This paper expands a recently proposed peak current-mode (PCM) control method for a power factor correction (PFC) boost converter to include the totem-pole converter and solves the controller's compatibility problem with the totem-pole converter by proposing three input current sensing methods. Using MATLAB/Simulink 2023b, simulation experiments on a 2 kW totem-pole converter utilizing the PFC PCM controller were carried out to assess the performance of the controller with the proposed sensing methods. The findings indicate that under steady-state conditions, all three proposed sensing methods performed input current shaping successfully and yielded nearly identical THD% of about 4.4% in the input current waveform. However, it is noteworthy that method 2, referred to as the memory method, exhibited a sluggish and less robust transient response in comparison to the swift and resilient responses observed with method 1 and method 3. Additionally, the third proposed method, which involves a single current sensor positioned across the input inductor, emerged as the optimal and cost-effective sensing solution. This method achieved the same desirable attributes of fast and robust control while utilizing only a single current sensor, a notable advantage over method 1, which employs two current sensors.

Ecklonia cava Polyphenols Have a Preventive Effect on Parkinson's Disease through the Activation of the Nrf2-ARE Pathway.

Parkinson's disease (PD) is a degenerative neurological disorder defined by the deterioration and loss of dopamine-producing neurons in the substantia nigra, leading to a range of motor impairments and non-motor symptoms. The underlying mechanism of this neurodegeneration remains unclear. This research examined the neuroprotective properties of Ecklonia cava polyphenols (ECPs) in mitigating neuronal damage induced by rotenone via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Using human neuroblastoma SH-SY5Y cells and PD model mice, we found that ECP, rich in the antioxidant polyphenol phlorotannin, boosted the gene expression and functionality of the antioxidant enzyme NAD(P)H quinone oxidoreductase-1. ECP also promoted Nrf2 nuclear translocation and increased p62 expression, suggesting that p62 helps sustain Nrf2 activation via a positive feedback loop. The neuroprotective effect of ECP was significantly reduced by Compound C (CC), an AMP-activated protein kinase (AMPK) inhibitor, which also suppressed Nrf2 nuclear translocation. In PD model mice, ECPs improved motor functions impaired by rotenone, as assessed by the pole test and wire-hanging test, and restored intestinal motor function and colon tissue morphology. Additionally, ECPs increased tyrosine hydroxylase expression in the substantia nigra, indicating a protective effect on dopaminergic neurons. These findings suggest that ECP has a preventative effect on PD.

Band-Stop Frequency-Selective Surface (FSS) with Elliptic Response Designed by the Extracted Pole Technique.

This paper describes and validates an advanced synthesis design process of Frequency-Selective Surfaces (FSSs) with elliptic band-stop responses. A systematic procedure based on the Generalized Chebyshev Function and the extracted pole technique enables control of the position of the transmission zeros and the attenuation level to obtain an equiripple rejection response. A systematic process is followed to obtain the lumped LC values of the resonator circuits extracted as poles and the impedance inverters. Then, equivalent dipoles and transmission lines are obtained to carry out the electromagnetic design at normal incidence for a linearly polarized field. The impact of the higher-order modes of the periodic structure on the electrical response of the FSS, which can be relevant due to the stringent selected specifications, has been also analyzed. A fourth-order band-stop filter with a 3 GHz bandwidth centered at 30 GHz and its attenuation at 50 dB has been designed considering three different implementations: two filters using a vacuum as a transmission line with different connection lengths and a third one using a dielectric substrate to enable its manufacturing. In order to verify the design procedure using experimental results, the third filter with printed dipoles in the dielectric substrate has been manufactured and measured, thus validating the developed process.

The Impact of Pelvicalyceal System Anatomy on Stone Formation in Patients with Single Lower Pole Calyceal Stone on Computed Tomography Urography.

BACKGROUND: To compare various lower pole pelvicalyceal anatomical factors of stone bearing kidney with contralateral normal kidneys and determine whether these factors predispose to stone formation in one kidney. METHODS: A descriptive study was done with Computed Tomography of 54 patients with solitary lower pole calculus in one kidney and normal contralateral kidney were included. Various lower pole pelvicalyceal anatomical factors like infundibulopelvic angle, infundibular width, infundibular length and calyceopelvic height of both stone bearing and contralateral kidneys were measured and compared for any differences Results: The mean infundibular width was 5.4±1.9mm on stone bearing kidneys and 5.2±2.05mm on contralateral normal kidneys. The mean infundibular length was 18.9±4.4mm on stone bearing kidneys and 18.8±3.9mm on contralateral normal kidneys. The mean infundibulopelvic angle was 47.9±10.8° on stone bearing kidneys and 47.6±11.2° on contralateral kidneys. The mean calyceopelvic height was 15.7±4.6mm on stone bearing kidneys and 15.5±3.9mm (range 7.5to 23.1mm) on contralateral kidneys. There were no statistically significant differences between stone bearing and contralateral normal kidneys in respect to these pelvicalyceal anatomical factors. CONCLUSIONS: In this study, we found no significant difference in lower pole pelvicalyceal anatomical factors between stone bearing kidneys and contralateral normal kidneys and therefore these factors do not seem to have significant role in stone formation in one kidney compared with the other.

A Comparison of Rib Osteochondral Graft to Medial Femoral Trochlear Osteocartilaginous Graft for the Salvage of the Fragmented Scaphoid Proximal Pole: A Single-Center Experience with Minimum 2-Year Follow-Up.

Purpose Fragmented fractures of the proximal pole of the scaphoid that cannot be internally fixed may be salvaged by four-corner arthrodesis or proximal row carpectomy. Replacement of the proximal scaphoid with costal-osteochondral graft (COG) or the medial femoral trochlea (MFT) graft are two alternative solutions for this clinical presentation. The purpose of this study was to compare the clinical and radiographic results of the COG and the MFT graft with a minimum 2-year follow-up from a single centre. Methods A retrospective study was performed to investigate the outcome of COG and MFT with a minimum 2 year follow up. Demographic data and clinical assessment including wrist range of motion and grip strength measurements and Oxford Knee score were collected. Patients completed the outcome measures of Disabilities of Arm, Shoulder, and Hand (DASH), the Patient-Rated Wrist Evaluation (PRWE), and a ten-point visual analogue score for pain (VAS). Radiological examination was performed on all wrists at follow-up. Results The visual analogue score, DASH and PRWE were similar between the two groups. There was radiographic evidence of arthritis between the radial styloid and distal scaphoid in all patients that underwent COG but no evidence in those that underwent MFT graft reconstruction. There were different complications in each group. Thirty percent of patients that underwent MFT reconstruction had persistent knee pain at follow up. Conclusion Though there are notable differences in the follow-up period, patients undergoing MFT risk developing knee pain, while those undergoing COG risk radiographic progression of wrist arthritis. Level of Evidence III - Comparative study.

Effect of infundibulopelvic angle on outcomes of ureteroscopy: a systematic review and meta-analysis.

PURPOSE: The infundibulo-pelvic angle (IPA) is reportedly a predictor of successful ureteroscopy for lower pole renal stones, however there is uncertainty at which IPA success is likely. We therefore aimed to perform a meta-analysis and determine at which the angle of likely success and failure. METHODS: We performed a systematic review and meta-analysis as per Cochrane guidelines in accordance to the PRISMA statement. The review was registered with PROSPERO prior to commencement (ID: CRD42022296732). We included studies reporting on outcomes of ureteroscopy for lower pole stones, with IPA. We excluded patients undergoing alternative treatments for lower pole stones, anatomical abnormalities and studies with < 10 patients. We assessed bias with the Newcastle-Ottawa scale. We performed meta-analysis in R, and summarised the findings as per GRADE. RESULTS: Overall, there were 13 studies included, with 10 included for meta-analysis. These studies covered n = 1964 patients (71% stone free). Overall, the stone free patients had a significantly less acute mean IPA (52o ± 9o), compared to the non-stone free patients (39o ± 7o), on meta-analysis (REM MD = -13.0, 95% CI: -18.7 to -7.2, p < 0.001). On examination of forest plots, at IPA < 30o no patients were stone free, whilst > 50o all were stone free. Risk of bias was moderate, and certainty of evidence was 'very low'. CONCLUSION: With a very low certainty of evidence, we demonstrate that at an IPA of < 30o no patient is stone free, whilst > 50o all patients (in this review) are stone free. More evidence is therefore needed.

Clinical comparative study of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones: a retrospective case-controlled study.

OBJECTIVES: To compare the clinical efficacy and safety of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones. METHODS: We enrolled 135 patients underwent reusable flexible ureteroscopy (FURS) and 78 patients underwent single-use digital FURS. Demographic, clinical variables, anatomical parameters of the lower calyx and perioperative indicators were compared in the two groups. RESULTS: Thirty-six patients in the infundibuloureter angle (IPA) < 45° subgroup had a mini-percutaneous nephrolithotomy (mini-PCNL), including 25 patients in the reusable FURS group and 11 patients in the single-use FURS group. The demographic and clinical variables in the two FURS groups were comparable. There was no statistical difference in the success rate of stone searching (P > 0.05). In terms of the success rate of lithotripsy, there was also no statistical difference in the IPA ≥ 45° subgroup (P > 0.05), whereas single-use FURS was superior in the IPA < 45° subgroup (χ2 = 6.513, P = 0.011). The length of the working fiber in the reusable FURS and single-use FURS groups was 3.20 ± 0.68 mm and 1.75 ± 0.47 mm, respectively (t = 18.297, P < 0.05). The use of a stone basket in the reusable FURS (31/135, 23.0%) was significantly higher than that in the single-use FURS (8/78, 10.3%) (χ2 = 5.336, P = 0.021). Compared with the reusable FURS group, the single-use FURS group had shorter operation times (P < 0.05) and higher stone-free rate (SFR) (χ2 = 4.230, P = 0.040). There was no statistical difference in the intraoperative transfer of mini-PCNL and postoperative complications between the two groups (P > 0.05). CONCLUSIONS: Single-use and reusable FURS are alternative methods for removal of lower pole stones (i.e., 2 cm or less). Single-use FURS has a high success rate of lithotripsy, shorter operation time, and high stone-free rate.

The structure of the γ-TuRC at the microtubule minus end - not just one solution.

In cells, microtubules (MTs) assemble from α/ß-tubulin subunits at nucleation sites containing the γ-tubulin ring complex (γ-TuRC). Within the γ-TuRC, exposed γ-tubulin molecules act as templates for MT assembly by interacting with α/ß-tubulin. The vertebrate γ-TuRC is scaffolded by γ-tubulin-interacting proteins GCP2-6 arranged in a specific order. Interestingly, the γ-tubulin molecules in the γ-TuRC deviate from the cylindrical geometry of MTs, raising the question of how the γ-TuRC structure changes during MT nucleation. Recent studies on the structure of the vertebrate γ-TuRC attached to the end of MTs came to varying conclusions. In vitro assembly of MTs, facilitated by an α-tubulin mutant, resulted in a closed, cylindrical γ-TuRC showing canonical interactions between all γ-tubulin molecules and α/ß-tubulin subunits. Conversely, native MTs formed in a frog extract were capped by a partially closed γ-TuRC, with some γ-tubulin molecules failing to align with α/ß-tubulin. This review discusses these outcomes, along with the broader implications.

An uncommon case of POLE mutated uterine carcinosarcoma - complemented by a review of literature.

Carcinosarcomas are high-grade endometrial cancers which enclose mesenchymal and epithelial differentiated components. The vast majority of these cancers belong to the p53 abnormal molecular subgroup and usually come with an unfavorable prognosis. POLE mutant carcinosarcomas are a rarity and only make up about 5% of this histologic subtype. Recent literature even suggests that this number is still an overestimation and the result of misclassification of undifferentiated or dedifferentiated endometrial cancers. Here we present a case of a 56-years old patient diagnosed with carcinosarcoma of the uterus. Hysterectomy, bilateral salpingo-oophorectomy with pelvic lymph node staging was performed and complete molecular workup of the tumor revealed an abnormal p53 expression as well as a pathologic POLE mutation. NGS was performed separately on the epithelial and mesenchymal component of this high-grade cancer and both components shared two identical POLE mutations, a known pathologic mutation, and a variant of unknown significance (VUS). This finding hints to a clonal origin of both histologic components of this tumor and supports conversion theory as mechanism of carcinosarcoma emergence. The cancer was correctly staged as FIGO 2023 Stage IAmPOLEmut and according to ESGO-ESTRO-ESP guidelines adjuvant chemotherapy no longer considered and our patient entered follow-up after a detailed discussion.

Plasticity of the mitotic spindle in response to karyotype variation.

Karyotypes, composed of chromosomes, must be accurately partitioned by the mitotic spindle for optimal cell health. However, it is unknown how underlying characteristics of karyotypes, such as chromosome number and size, govern the scaling of the mitotic spindle to ensure accurate chromosome segregation and cell proliferation. We utilize budding yeast strains engineered with fewer chromosomes, including just two "mega chromosomes," to study how spindle size and function are responsive to, and scaled by, karyotype. We determined that deletion and overexpression of spindle-related genes are detrimental to the growth of strains with two chromosomes, suggesting that mega chromosomes exert altered demands on the spindle. Using confocal microscopy, we demonstrate that cells with fewer but longer chromosomes have smaller spindle pole bodies, fewer microtubules, and longer spindles. Moreover, using electron tomography and confocal imaging, we observe elongated, bent anaphase spindles with fewer core microtubules in strains with mega chromosomes. Cells harboring mega chromosomes grow more slowly, are delayed in mitosis, and a subset struggle to complete chromosome segregation. We propose that the karyotype of the cell dictates the microtubule number, type, spindle pole body size, and spindle length, subsequently influencing the dynamics of mitosis, such as the rate of spindle elongation and the velocity of pole separation. Taken together, our results suggest that mitotic spindles are highly plastic ultrastructures that can accommodate and adjust to a variety of karyotypes, even within a species.

Current Management Practices for Endometrial Cancer (EC) in the UK: A National Healthcare Professional Survey (KNOW-EC).

The clinical landscape for endometrial cancer in the UK is evolving to include new management guidelines and targeted treatment options. An understanding of current treatment and management practices in the UK will help services plan and adapt to upcoming changes. AIM: The purpose of this survey was to understand current and anticipated real-world practices for endometrial cancer care in the UK and potential areas for optimisation. MATERIALS AND METHODS: Telephone interviews were conducted in November/December 2021 with UK-based healthcare professionals involved in endometrial cancer management. Questions were aligned with the British Gynaecological Cancer Society/European Society for Medical Oncology recommendations, covering the pathway from diagnosis and treatment to follow-up. RESULTS: A total of 63 healthcare professionals (HCPs) involved in the management of patients with endometrial cancer participated in telephone interviews. The results highlighted variations in management and treatment practices for endometrial cancer and suggest that current UK practice appears to diverge from national and international guidance in some instances. While somatic mismatch repair deficiency testing was used by 89.7% of respondents as mainstream testing, the survey highlighted a lack of access to other key molecular biomarker tests, such as polymerase epsilon (POLE) sequencing (used by only 9.8% of HCPs at the time of the survey). CONCLUSION: The results highlighted several perceived practical barriers to the swift adoption of new therapeutic options, including funding access, limited staff, treatment-related resources, staff education, and support. Our findings support the need for better access to biomarkers that could enable more effective and targeted treatments.

Frontal pole-precuneus connectivity is associated with a discrepancy between self-rated and observer-rated depression severity in mood disorders: a resting-state functional magnetic resonance imaging study.

Discrepancies in self-rated and observer-rated depression severity may underlie the basis for biological heterogeneity in depressive disorders and be an important predictor of outcomes and indicators to optimize intervention strategies. However, the neural mechanisms underlying this discrepancy have been understudied. This study aimed to examine the brain networks that represent the neural basis of the discrepancy between self-rated and observer-rated depression severity using resting-state functional MRI. To examine the discrepancy between self-rated and observer-rated depression severity, self- and observer-ratings discrepancy (SOD) was defined, and the higher and lower SOD groups were selected from depressed patients as participants showing extreme deviation. Resting-state functional MRI analysis was performed to examine regions with significant differences in functional connectivity in the two groups. The results showed that, in the higher SOD group compared to the lower SOD group, there was increased functional connectivity between the frontal pole and precuneus, both of which are subregions of the default mode network that have been reported to be associated with ruminative and self-referential thinking. These results provide insight into the association of brain circuitry with discrepancies between self- and observer-rated depression severity and may lead to more treatment-oriented diagnostic reclassification in the future.

The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway.

BACKGROUND: BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear. AIMS: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA). OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease. METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays. RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels. CONCLUSION: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.

Disturbance rejecting PID-FF controller design of a non-ideal buck converter using an innovative snake optimizer with pattern search algorithm.

The optimal design of a proportional-integral-derivative controller with two cascaded first-order low-pass filters (PID-FF) for non-ideal buck converters faces significant challenges, including effective disturbance rejection, robustness to parameter variations, and the mitigation of high-frequency signal noise, with existing approaches often struggling and leading to suboptimal performance in practical applications. This study addresses these challenges by introducing a constraint on the open-loop crossover frequency to mitigate high-frequency noise and ensuring the controller prioritizes maintaining constant output voltage and robust responsiveness to input voltage and load current variations. This study also introduces an innovative metaheuristic algorithm, the opposition-based snake optimizer with pattern search (OSOPS), designed to address these limitations. OSOPS enhances the Snake Optimizer (SO) by integrating opposition-based learning (OBL) and Pattern Search (PS), thereby improving its exploration and exploitation capabilities. The proposed algorithm design includes a crossover frequency constraint aimed at counteracting high-frequency noise and ensuring robust performance under diverse disturbances. The efficacy of the OSOPS algorithm is demonstrated through rigorous statistical box plot analysis and convergence response comparisons with the original SO algorithm. Additionally, we systematically compare the performance of the OSOPS-based PID-FF-controlled non-ideal buck converter system against systems utilizing the original SO algorithm and the classical pole placement (PP) method. This evaluation encompasses transient and frequency responses, disturbance rejection, and robustness analysis. The results reveal that the OSOPS-based system outperforms the SO- and PP-based systems with 14.21 % and 32.10 % faster rise times, along with 15.38 % and 84.95 % faster settling times, respectively. The OSOPS and SO systems also exhibit higher bandwidths, exceeding the PP-based system by 18.74 % and 17.03 %, respectively. By addressing the key challenges in PID-FF controller design for non-ideal buck converters, this study provides a substantial advancement in control strategy, promising enhanced performance in practical applications.

Accelerated clinical response achieved by combining short-term tumor-directed photodynamic therapy with immunotherapy-based systemic therapies in synchronous colorectal cancer with MSI-H and POLE mutation: a case report.

Genetic sequencing has revolutionized immunotherapy in colorectal cancer (CRC). Recent clinical trials have revealed a positive response to immunotherapy-based systemic therapies in CRC patient subgroups with microsatellite instability (MSI)-High or DNA polymerase epsilon (POLE) mutation. However, the unsatisfactory response rates was the major limitation in real-world practice of the precision immunotherapy in CRC. Adding photodynamic therapy (PDT) to systemic immunotherapy has showed synergetic anti-tumor effect by modulating tumor microenvironment, while the eligible patient's subgroups which would benefit from this combination remained equivocal. Here we reported a synchronous colorectal cancer patient with MSI-High and POLE mutation who had accelerated response in less than 2 cycles (42 days) of immunotherapy-based systemic therapies after tumor-directed PDT and has remained progression-free by far. This case enlightened the synergetic effect of PDT in immunotherapy-treated CRC patients, with the MSI and POLE-mutation status as predictors of survival benefits.