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Abstract The Marine Predator Algorithm (MPA) has unique advantages as an important branch of population-based algorithms. However, it emerges more disadvantages gradually, such as traps to local optima, insufficient diversity, and premature convergence, when dealing with complex problems in practical industrial engineering design applications. In response to these limitations, this paper proposes a novel Improved Marine Predator Algorithm (IMPA). By introducing an adaptive weight adjustment strategy and a dynamic social learning mechanism, this study significantly improves the encounter frequency and efficiency between predators and preys in marine ecosystems. The performance of the IMPA was evaluated through benchmark functions, CEC2021 suite problems, and engineering design problems, including welded beam design, tension/compression spring design, pressure vessel design, and three-bar design. The results indicate that the IMPA has achieved significant success in the optimization process over other methods, exhibiting excellent performance in both solving optimal parameter solutions and optimizing objective function values. The IMPA performs well in terms of accuracy and robustness, which also proves its efficiency in successfully solving complex industrial engineering design problems.

BackgroundThe Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies.Material and methodsTOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment).ResultsA total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy.ConclusionThese findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

Foodborne diseases are major global public health issues. Among microbial hazards， foodborne diseases are the most serious problem caused by pathogenic bacteria. Under the risk-based food safety management system， identifying the priority hazards and their important food sources is the premise and key to the prevention and control foodborne diseases. Currently， Europe， the United States， and other countries have established two categories of source attribution methods based on microbial subtyping. The results of these methods were transformed on a scientific basis to formulate food safety risk control measures. China is in the preliminary exploration stage of source attribution method research of foodborne disease. This study aimed to systematically sort the methodological principles and models of source attribution methods widely used internationally， combine the basis and current situation of foodborne disease source attribution research in China， and suggest four work directions for constructing the next stage of foodborne disease source attribution system in China. These directions include developing methods， combining data， building platforms and strong exchanges， which involves the development of localized source attribution model based on microbial subtyping to solve the challenges associated with confirming control and preventing and controlling foodborne diseases in China， and achieving food safety and protecting the lives and health of individuals.

Objective: To explore the short-and long-term efficacy and toxic and side effects of hyperfractionated radiotherapy with different fractionated doses in patients with limited stage small cell lung cancer (SCLC). Methods: From August 2017 to August 2019, 70 patients with limited stage SCLC admitted to Zhangye People’s Hospital were selected and divided into control group (n=35) and observation group (n=35) according to the random number table method. Conventional chemotherapy and hyperfractionated radiotherapy were used in both groups, with a total dose of 45 Gy in the control group and 60 Gy in the observation group. A three-year follow-up was carried out to compare the short- and long-term efficacy (survival and local control rate), and the occurrence of toxic and side effects between the two groups. Results: The total effective rate in the observation group was obviously higher than that in the control group (91.43% vs 71.43%, χ2=4.629, P=0.031). The 1-, 2-, and 3-year local control rates and survival rates of patients in the observation group were significantly higher than those in the control group (P＜0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P＞0.05), and most of adverse reactions were grade Ⅰ-Ⅱ, which did not affect the course of treatment. After treatment, the scores of life quality in both groups increased significantly (P＜0.01), and the observation group showed a significant increase compared to the control group (P＜0.01). Conclusion: Hyperfractionnated radiotherapy with appropriately increased fractionated dose for patients with limited stage SCLC has better short- and long-term efficacy, higher local control rate and survival, and no significant increase in toxic and side effects, which is safe and can improve the quality of patients' life.

Abstract Background The oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated. Results Here, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription. Conclusions We identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% of adult pan-cancer samples had KRAS alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, and prevalence was similar in liquid biopsies. Co-alteration landscapes were largely similar across KRAS mutations but distinct from KRAS wild-type, though differences were observed in some tumor types for tumor mutational burden, PD-L1 expression, microsatellite instability, and other mutational signatures. Prognosis of KRAS-mutant versus other genomic cohorts of lung, pancreatic, and colorectal cancer were assessed using a real-world clinicogenomic database. As specific KRAS inhibitors and combination therapeutic strategies are being developed, genomic profiling to understand co-alterations and other biomarkers that may modulate response to targeted or immunotherapies will be imperative.

Background and objectivesDiffuse-tenosynovial giant cell tumor (D-TGCT) is a rare, locally aggressive, typically benign neoplasm affecting mainly large joints, representing a wide clinical spectrum. We provide a picture of the treatment journey of D-TGCT patients as a 2-year observational follow-up.MethodsThe TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study at tertiary sarcoma centers spanning seven European countries and two US sites. Histologically confirmed D-TGCT patients were categorized as either those who remained on initial treatment strategy (determined at baseline visit) or those who changed treatment strategy with specific changes documented (e.g., systemic treatment to surgery) at the 1-year and/or 2-year follow-up visits.ResultsA total of 176 patients were assessed, mean diagnosis age was 38.4 (SD ± 14.6) years; most patients had a knee tumor (120/176, 68.2%). For the 2-year observation period, most patients (75.5%) remained on the baseline treatment strategy throughout, 54/79 patients (68.4%) remained no treatment, 30/45 patients (66.7%) remained systemic treatment, 39/39 patients (100%) remained surgery. Those who changed treatment strategy utilized multimodal treatment options.ConclusionsThis is the first prospectively collected analysis to describe D-TGCT patient treatments over an extended follow-up and demonstrates the need for multidisciplinary teams to determine an optimal treatment strategy.

Background, Natural orifice specimen extraction (NOSE) via the anus or vagina is an alternative to conventional transabdominal specimen extraction in laparoscopic colorectal cancer surgery. NOSE has been shown to be safe and effective, resulting in decreased postoperative pain, analgesia use, and improved recovery, without oncological compromise. We aimed to demonstrate the feasibility of NOSE for combined colectomy with liver metastasectomy.Methods, From July 2022 to April 2024, all cases of laparoscopic colorectal cancer resection and synchronous liver metastasectomy with NOSE were included in the study. Selection criteria included a maximum specimen diameter of less than 5 cm and patient body mass index of less than 35 kg/m2.Results, Over the 22-month duration, four consecutive patients (two males, two females) underwent combined resection with NOSE. Mean age and BMI were 74.8 (range 63–81) years and 20.9 (range 19.5–22.3) kg/m2 respectively. Patient A and D underwent anterior resection for sigmoid cancer, Patient B underwent D3 right hemicolectomy for cecal cancer, and Patient C underwent subtotal colectomy for synchronous cecal and descending colon cancer. All patients underwent liver metastasectomy at the same sitting. Patient A and D had transanal NOSE while Patients B and C underwent transvaginal NOSE. Mean operative time and blood loss was 416 (range 330–535) minutes and 338 (range 50–500) ml respectively. All patients recovered gastrointestinal function within the first two postoperative days. Infected seroma of the liver bed occurred in one patient requiring percutaneous drainage. The average maximum colon tumor diameter was 2.9 (range 1.3–4.0) cm. All resection margins were clear. Mean duration of follow-up was 7.5 (range 2–12) months.Conclusions, Simultaneous colectomy and liver metastasectomy with NOSE for colorectal cancer is feasible and safe in highly selected patients, resulting in good postoperative outcomes. This proof-of-concept analysis paves the way for larger studies to draw definitive conclusions.