Tag: statistics

Oncogene. 2026 Jul 25. doi: 10.1038/s41388-026-03895-6. Online ahead of print.

ABSTRACT

Progression of cutaneous primary melanoma that arises from melanocytes leads to lethal metastatic disease. Molecular mechanisms that control the growth of primary melanoma in the skin and promote progression are not fully understood. Previously we showed that RAP guanine exchange factors EPAC1/2 (Exchange Proteins Activated by cyclic AMP) promote the growth of primary melanoma and loss of dependency on EPACs is associated with metastatic progression. In this study, we show that EPACs are activated during malignant transformation of melanocytes, and chemical inhibition or genetic deletion of EPAC inhibits melanomagenesis in Braf/Pten mice. Low expression of EPAC mRNA and its effector RAP1-GTP protein in primary melanoma correlate with better recurrence-free survival. RNAseq analysis of matched primary and metastatic melanoma cells treated with an EPAC inhibitor showed that TXNIP, an important regulator of redox homeostasis, is a downstream effector of EPAC signaling. We also show that EPACs promote melanoma growth by regulating redox homeostasis and mitochondrial ROS through activation of mechanistic target of rapamycin complex 1 (mTORC1) that stabilizes hypoxia-inducible factor 1-alpha (HIF-1α), a transcriptional activator of redox regulator TXNIP and glycolytic enzymes. Our data suggest that targeting mechanisms that melanoma cells employ to bypass EPAC dependency is a potential therapeutic approach.

PMID:42502103 | DOI:10.1038/s41388-026-03895-6

Ann Surg Oncol. 2026 Jul 25. doi: 10.1245/s10434-026-20288-x. Online ahead of print.

ABSTRACT

BACKGROUND: Early recurrence after curative resection for cT3 esophageal squamous cell carcinoma (ESCC) is strongly associated with poor long-term survival. Identifying patients at high risk of early recurrence may improve postoperative risk stratification and inform tailored surveillance or adjuvant therapy.

PATIENTS AND METHODS: We retrospectively analyzed patients who underwent en bloc esophagectomy with three-field lymphadenectomy. The log odds of positive lymph nodes (LODDS) were calculated as log([number of positive nodes + 0.5]/[number of negative nodes + 0.5]). Early recurrence was defined using maximally selected rank statistics. Independent risk factors for early recurrence were identified using multivariable Firth logistic regression, followed by decision tree analysis to establish hierarchical risk stratification.

RESULTS: Among 121 patients, 109 (90.1%) achieved R0 resection. The median numbers of dissected and metastatic lymph nodes were 67.0 and 2.0, respectively, with a median LODDS of – 3.46. Early recurrence was defined as recurrence within 16.6 months after surgery. Multivariable analysis identified higher LODDS, upper thoracic location, and resectability status (resectable or borderline resectable) as independent predictors of early recurrence. In the complementary tree-based analysis, early recurrence risk was primarily stratified by LODDS using a cut-off of – 2.69. Patients with LODDS > – 2.69 had significantly worse 5-year overall survival than those with LODDS ≤ -2.69 (30.0% versus 66.1%, p < 0.001). Among patients with LODDS ≤ – 2.69, tumor location further refined risk stratification.

CONCLUSIONS: LODDS provides a robust and clinically applicable metric for postoperative risk stratification of early recurrence in patients undergoing radical esophagectomy for cT3 ESCC.

PMID:42502093 | DOI:10.1245/s10434-026-20288-x

Ann Surg Oncol. 2026 Jul 25. doi: 10.1245/s10434-026-20294-z. Online ahead of print.

NO ABSTRACT

PMID:42502092 | DOI:10.1245/s10434-026-20294-z

Foot Ankle Surg. 2026 Jul 23:S1268-7731(26)00205-5. doi: 10.1016/j.fas.2026.07.011. Online ahead of print.

ABSTRACT

BACKGROUND: Pilon fractures are complex intra-articular injuries of the distal tibia often caused by high-energy trauma. Although ORIF remains the gold standard for restoring alignment and joint congruity, the influence of patient age on clinical and radiographic outcomes remains unclear. This study aimed to compare healing, complication rates, and functional outcomes between patients below and above 40 years old following ORIF of Pilon fractures.

MATERIALS AND METHODS: A prospective comparative study was conducted on 56 tibial Pilon fractures in 55 patients. Patients were stratified into two groups according to age: < 40 years (35 fractures) and ≥ 40 years (21 fractures). Functional outcomes were assessed using the AOFAS and Olerud-Molander scores. Radiographic union, alignment, and complications rates were assessed in both groups.

RESULTS: Among 56 included patients, both age groups showed comparable demographics and fracture characteristics. Falls were the most common mechanism of injury, followed by MVA. All fractures healed successfully, with a mean union time of 15.1 ± 2.7 weeks and no significant difference between both groups. Functional outcomes (AOFAS and OMS) were comparable between groups without statistical significance. Although postoperative complications were more frequent in older patients (47.6% vs. 22.9%), no significant difference was detected and no nonunion or implant failure occurred.

CONCLUSION: Age did not significantly influence healing or functional outcomes after ORIF of Pilon fractures. Despite slightly longer union time and a higher rate of complications in older patients, both groups achieved comparable recovery. These findings suggest that satisfactory outcomes can be achieved across different age groups when appropriate staged management and fixation principles are applied.

LEVEL OF EVIDENCE: Level 4.

PMID:42502050 | DOI:10.1016/j.fas.2026.07.011

ISA Trans. 2026 Jul 21:S0019-0578(26)00382-4. doi: 10.1016/j.isatra.2026.07.016. Online ahead of print.

ABSTRACT

This paper investigates the distributed resource allocation problem in second-order nonlinear multi-agent systems (MASs) and proposes an integrated adaptive dynamic programming (ADP) framework with a dynamic event-triggered mechanism. A coupled performance index based on resource allocation errors is first formulated, embedding a positive-definite quadratic form to transform the resource allocation control problem into the design of optimal control policies for all agents. Within this framework, a fixed-time single-critic learning law is developed to approximate the Hamilton-Jacobi-Bellman (HJB) equation online. The dynamic event-triggered mechanism updates the control input only when the adaptive triggering condition is violated. Theoretical analysis guarantees the uniform ultimate boundedness of all closed-loop signals. Numerical simulations verify the effectiveness of the proposed framework in achieving accurate resource allocation while balancing allocation errors and control efforts.

PMID:42502010 | DOI:10.1016/j.isatra.2026.07.016

Int J Oral Maxillofac Surg. 2026 Jul 25:S0901-5027(26)00307-3. doi: 10.1016/j.ijom.2026.07.008. Online ahead of print.

ABSTRACT

The study investigated vertical orbital dystopia in patients with dentofacial deformities and its impact on coronal plane orientation. This retrospective analysis included 79 patients (52 females, 27 males, mean age 27.64 years) with dentofacial deformity who underwent orthognathic surgery from 2019 to 2022 with preoperative cone-beam computed tomography. Bilateral hard tissue measurements were performed using virtual orthognathic planning software (NemoFAB, Nemotec, Spain). Two anatomical landmarks were measured vertically to assess the severity and direction of orbital asymmetry. Of the 79 patients, 56 had class III and 23 had class II skeletal deformity. There were no significant differences between patients based on gender or Angle classification. Orbital dystopia was statistically significant (73.4%) among the study population (P = 0.05). The severity and the direction were analysed, respectively; no correlation was found between the orbitalis inferior (r = 0.052, P = 0.73) and the orbitalis superior (r = -0.060, P = 0.67). The study suggests that focusing solely on the orbital region in orthognathic surgery planning may lead to inaccuracies due to the prevalence of orbital dystopia in dentofacial deformity patients.

PMID:42502006 | DOI:10.1016/j.ijom.2026.07.008

Gut. 2026 Jul 25:gutjnl-2026-338385. doi: 10.1136/gutjnl-2026-338385. Online ahead of print.

ABSTRACT

BACKGROUND: Hypnotherapy is an evidence-based therapy recommended for IBS, but access to therapist-led hypnotherapy is limited by costs and availability.

OBJECTIVE: We studied the effectiveness of smartphone-based self-guided hypnotherapy versus in-person therapist-delivered hypnotherapy.

DESIGN: This multicentre, three-armed non-inferiority randomised controlled trial (RCT) included patients with IBS (Rome IV, 16-75 years). Patients were randomised to 12-week in-person therapist-delivered hypnotherapy, smartphone-based self-guided hypnotherapy or online self-guided psychoeducation. The primary endpoint was abdominal pain response per Food and Drug Administration (FDA) definition (≥30% reduction from baseline in weekly average of worst daily abdominal pain in at least 2 out of 4 weeks follow-up). The non-inferiority margin was 10%. Secondary endpoints included ≥50 points IBS-symptom severity scale reduction and changes in psychological symptoms.

RESULTS: A total of 230 patients (mean±SD age 38.2±13.8 years, 70.4% female) were randomised. FDA abdominal pain response rates were 48% for in-person therapist-delivered hypnotherapy, 33% for smartphone-based self-guided hypnotherapy and 22% for psychoeducation. Non-inferiority of online to in-person hypnotherapy could not be shown (-14.7%, 95% CI -29.3% to 0.9%). In-person hypnotherapy was more effective than psychoeducation (OR 3.48, 95% CI 1.68 to 7.20, p<0.001) at week 16, both hypnotherapy groups were more effective at 6-month follow-up (OR 3.11, 95% CI 1.37 to 7.09, p=0.007 and OR 4.68, 95% CI 2.07 to 10.57, p<0.001). There were no significant treatment effects on psychological symptoms between groups.

CONCLUSION: This multicentre RCT could not demonstrate non-inferiority of smartphone-based self-guided hypnotherapy compared with in-person therapist-delivered hypnotherapy in reducing abdominal pain. However, substantial response rates for smartphone-based self-guided hypnotherapy highlight its potential as a broadly applicable and cost-effective alternative.

TRIAL REGISTRATION NUMBER: NCT03899779.

PMID:42502003 | DOI:10.1136/gutjnl-2026-338385

Rev Gastroenterol Peru. 2026 Apr-Jun;46(2):144-151.

ABSTRACT

Chronic constipation is a frequent gastrointestinal disorder that significantly impairs quality of life and has a multifactorial etiology. High-resolution anorectal manometry (HR-ARM) allows for an objective evaluation of anorectal function. In Peru, evidence regarding its findings in the adult population is scarce.

OBJECTIVE: To describe the findings obtained through high-resolution anorectal manometry in adults with primary chronic constipation, according to the London Classification, in three private institutions in Lima, Peru.

MATERIALS AND METHODS: A retrospective descriptive study was conducted in three private institutions in Lima between January 2020 and December 2024. Reports of manometry from patients over 18 years old with a diagnosis of functional chronic constipation and normal colonoscopy findings were included. Data were analyzed using STATA v.18, applying descriptive statistics and the Chi-square test.

RESULTS: A total of 122 patients were evaluated (81.2% women). According to the London Classification, the most frequent findings were anal normotension with hypocontractility (62.3%), normal expulsion with abnormal coordination (43.4%), and preserved anorectal inhibitory reflex (97.5%). Regarding rectal sensitivity, hyposensitivity was the most common finding (38.5%), followed by normal parameters (37.8%). Analysis by age and sex showed significant differences in resting anal pressure (p=0.045), desire to defecate (p=0.048), and rectal urgency (p=0.007).

CONCLUSIONS: The most frequent manometric findings in patients with primary chronic constipation were anal hypocontractility, impaired anorectal coordination, and rectal hyposensitivity. These results highlight differences according to age and sex, underscoring the importance of incorporating the London Classification to achieve a more accurate diagnosis and personalized clinical management.

PMID:42501992

Int J Phytoremediation. 2026 Jul 25:1-11. doi: 10.1080/15226514.2026.2703734. Online ahead of print.

ABSTRACT

Arsenic pollution of water and soil is a global environmental and public health issue that requires sustainable remediation. Metal-tolerant plant species are used in phytoremediation to significantly remove metals from contaminated locations. This study tested Hydrocotyle umbellata L. against five Arsenic concentrations (500,750,1000,1250,1500 µg L^-1 from T1 to T5 respectively,) in Hoagland solution for 10 days to assess its phytoextraction potential. This was done using triplicate randomized block design. Pearson Correlation analysis, ANOVA, Multivariate Regression, and CART models are used for statistical analyses. These statistical characteristics were used to examine H. umbellata’s Arsenic uptake and its effects on factors like fresh and dry weight, translocation factor (TF), bio-concentration factor (BCF), chlorophyll content (Chl.), and electrolyte leakage. All treatments had BCF greater than 1 and a maximum BCF value was shown by T5 as 32.65. The strong metal uptake, greatest BCF reduced dry weight indicates physiological stress in H. umbellata, which can collect and translocate Arsenic from roots to stolon. Highest BCF and TF values accompanying As translocation to shoots indicate H. umbellata’s phytoextraction capacity and adaptation to Arsenic stress.

PMID:42500851 | DOI:10.1080/15226514.2026.2703734

Cancer Control. 2026 Jan-Dec;33:10732748261470289. doi: 10.1177/10732748261470289. Epub 2026 Jul 25.

ABSTRACT

IntroductionIn Mexico, delays in pediatric cancer diagnosis remain a major barrier to timely care and are partly driven by inefficiencies in referral pathways. This study aimed to evaluate the impact of a direct pathway on referral intervals for patients with suspected childhood cancer treated at a high-specialty hospital in Mexico.MethodsWe conducted a retrospective observational cohort study based on a comprehensive review of medical records of patients referred to a high-specialty hospital in Mexico between 2017 and 2022. Patients’ characteristics, along with dates from symptom recognition to diagnosis, were collected. The exposure was the referral pathway: standard versus direct (Golden Code strategy) pathway, which enables access to pediatric oncology through a zero-rejection policy. The primary outcome was the time attributable to oncological referral (TAOR), analyzed as a continuous variable and a dichotomous outcome. Secondary intervals were calculated using standardized definitions. Regression models were used to evaluate factors associated with untimely (>7 days) referral.ResultsA total of 399 patients were included. The direct pathway was associated with a shorter TAOR compared to the standard pathway (median 2.0 vs. 7.0 days; p<0.001). The proportion of timely referrals was substantially higher in the direct pathway (91.3%) than in the standard (50.6%) and reduced the likelihood of an untimely referral (OR = 0.098, 95% CI: 0.055-0.173; p<0.001). No differences were observed in other diagnostic intervals.ConclusionThe direct referral pathway improves the timeliness and consistency of access to pediatric oncology care by reducing referral delays and increasing the proportion of patients evaluated within recommended referral intervals. However, the absence of changes in the secondary intervals, such as time to oncological diagnosis, highlights the need for complementary actions targeting downstream diagnostic processes. Strengthening referral systems represents a feasible and impactful strategy to address delays in pediatric cancer care in middle-income settings.

PMID:42500849 | DOI:10.1177/10732748261470289