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ABSTRACTIntroductionUpper and lower gastrointestinal (GI) dysfunctions frequently coexist, potentially mediated by gastrocolonic or cologastric neural reflexes. This study aims to assess the prevalence of impaired gastric accommodation (GA) and delayed gastric emptying (GE) among patients with slow colonic transit (CT), dyssynergic defecation (DD), and to evaluate relationships between CT or DD with impaired GA and delayed GE.MethodsWe reviewed records of 178 adult patients at Mayo Clinic (2005–2025) with documented slow CT or DD (respectively based on scintigraphy and high‐resolution anorectal manometry [ARM] and balloon expulsion [BE]) who underwent 99mTc‐SPECT measurement of GA and scintigraphic GE of 320‐kcal, 30% fat egg meal. Slow CT was defined by geometric center (GC) at 48 h < 2.1 for males and < 1.9 for females. Abnormal GA ratio was assessed as reduced < 2.62 or increased > 3.85, and delayed GE % < 75% at 4 h. Correlations were assessed using Spearman rank test.ResultsReduced GA was found in 23.7% with DD and 26.7% with slow CT, while increased GA was observed in 30.1% and 24.4%, respectively. Delayed GE was present in 20.5% DD patients and 35.6% slow CT patients. GC 48 h and 24 h were positively correlated with GE% 4 h (Rs = 0.279, and Rs = 0.294 respectively, both p < 0.001) suggesting slow CT retards GE. GC 48 h was moderately correlated with resting anal pressure (Rs = 0.259, p < 0.001) and negatively with the rectoanal pressure gradient (Rs = −0.166, p = 0.027). No significant correlations were observed between CT and GA.ConclusionSlow CT is associated with slower GE, suggesting cologastric reflex inhibition, but not with GA. There is a high prevalence of impaired GA and delayed GE in slow CT and DD.

Abstract Background Multiple guideline-based surgical treatment options for Peyronie’s disease (PD) exist, including penile plication and plaque incision or excision and grafting. Surgical incision type may differ depending upon location and severity of curve, planned concomitant procedures, and surgeon preference. Aim To evaluate postoperative wound complications comparing outcomes between ventral and subcoronal incisions in patients undergoing tunica albuginea plication (TAP) and plaque incision or partial excision and grafting (PG) for PD. Methods A single-surgeon, single-center retrospective chart review was conducted on all patients undergoing TAP or PG from 2019 to 2023. Patient demographics, including previous PD treatments, were recorded. A Mann–Whitney U test was utilized to determine differences in wound complication rate, median curvature improvement, and remaining postoperative curvature between ventral and subcoronal approaches. Outcomes Wound complication was classified as any dehiscence and/or wound exudate suspicious for infection within the first 3 months postoperatively. A secondary analysis was performed comparing these outcomes between TAP and PG. Results In the analysis, 189 patients were included, including PD straightening surgery, including 125 patients who underwent TAP (66%) and 64 patients (34%) who underwent PG. Among all cases, 49.7% underwent ventral incision (N = 94) and 50.3% (N = 95) underwent subcoronal incision. A total of 12 patients (6.3%) experienced a wound-related complication postoperatively (range 3-23 days), including 9/94 (9.6%) in the ventral incision cohort and 3/95 (3.2%) in the subcoronal cohort (P = 0.081). All the patients were treated with oral antibiotics and two patients required closure under local anesthesia (both in the ventral incision cohort). Secondary analysis did not reveal any significant difference in outcomes between TAP and PG cohorts with respect to wound complications. Clinical Implications While we did not identify a statistically significant difference, most of our wound complications, including infection and/or dehiscence, were seen in those undergoing a ventral penile raphe incision. Despite this, the rate of wound complications with either incisional approach as low. Strengths and Limitations Our report represents a large cohort of patients treated with surgical straightening for PD, and to our knowledge is one of the first to compare wound complications between ventral and subcoronal incisions. Limitations include the retrospective single-surgeon series without randomization, lack of power analysis, and heterogenous classification of wound complications. Conclusion Both ventral penile raphe and subcoronal (degloving) incisions can be considered for penile straightening procedures to correct PD curvature deformity with a low risk for serious wound-related complications.

Abstract Background Breast cancer genome-wide association studies (GWAS) have identified more than 200 susceptibility loci, but most studies are dominated by European and East Asian populations. Methods We analyzed breast cancer GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR), and Hispanic/Latina (H/L) samples (159,297 cases and 212,102 controls). We estimated logit-scale SNP-based heritability, polygenicity, and cross-ancestry genetic correlation, partitioned heritability across functional annotations, and integrated GWAS results with the Tabula Sapiens single-cell atlas using scDRS+. Results The logit-scale heritability of breast cancer ranged from ℎ 2 =0.47 (SE = 0.07) in EAS to AFR ℎ 2 =0.61 (SE = 0.10), with no significant differences across ancestries (p=0.63). The estimated number of susceptibility markers in a sparse normal-mixture effects model also varied from 4,446 (SE = 3,100) in EAS to 8,308 (SE = 2,751) in AFR, but differences were not significant across ancestries (p=0.55). Cross-sample genetic correlations varied, with the strongest correlation between EUR and EAS (𝜌 = 0.79, SE = 0.08) and weakest between AFR and H/L (𝜌 = 0.26, SE = 0.24). Regulatory annotations were enriched for breast cancer heritability across samples. Integration with single-cell expression profiles implicated ancestry-shared associations with innate immune, secretory epithelial, and stromal cell types. Conclusion These results indicate substantial cross-ancestry sharing of breast cancer polygenic architecture, highlight a consistent contribution of regulatory variation, and identify convergent cellular contexts that motivate functional follow-up and inform expectations for the transferability and attainable performance of common-variant risk prediction across populations.

Rubella is typically a mild viral illness, but it can lead to severe complications when contracted during pregnancy, such as pregnancy loss or developmental defects in the fetus (congenital rubella syndrome). Therefore, it is crucial to develop and maintain protective immunity in women of childbearing age. In this study, we assessed the transcriptional factors associated with rubella-specific immune outcomes (IgG binding antibody and avidity, neutralizing antibody, and memory B cell ELISpot response) following a third MMR vaccine dose in women of reproductive age to identify key factors/signatures impacting the immune response. We identified baseline (Day 0) and differentially expressed (Day 28–Day 0) genes associated with several RV-specific immune outcomes, including the transferrin receptor 2 (TFR2), which is an important factor regulating iron homeostasis and macrophage functional activity, and a close functional homolog of TFR1, the cellular receptor of the New World hemorrhagic fever arenaviruses. We also identified enriched KEGG pathways, “cell adhesion molecules”, “antigen processing and presentation”, “natural killer cell-mediated cytotoxicity”, and “immune network for IgA production”, relevant to immune response priming and immune activation to be associated with RV-specific immune outcomes. This study provides novel insights into potential biomarkers of rubella-specific immunity in women of childbearing age.

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity.

Abstract Objectives To enable users with modest technical background to perform biomedical natural language processing (NLP). Materials and Methods We developed medspacyV using the Python graphical programming tkinter library, following the model-view-controller (MVC) design pattern. The interface wraps around a rule-based pipeline for sentence splitting, section segmentation, concept identification, and negation detection. Results The primary window allows the user to configure the project and NLP rules, execute the pipeline, and save the outputs into a table. A separate annotation viewer window can be launched to inspect the immediate or previous NLP outputs. Discussion We developed medspacyV with three rationales: controllability, explainability, and economy. The rule-based approach is sufficient for many NLP use cases. Conclusion The medspacyV program is publicly available at https://github.com/medspacy/medspacyV, targeting use by healthcare professionals and researchers in their NLP projects.

Introduction: Treatment of cutaneous warts with intralesional vitamin D3 has demonstrated promising results in over 35 studies with methodological limitations. Methods: We conducted a randomized, double-blind, placebo-controlled trial in our primary care procedure clinic of intralesional vitamin D3 12 000 IU vs placebo in cutaneous warts every 4 weeks up to 3 times. Warts were assessed 4, 8, 12, and 24 weeks after the initial injection. The primary outcome was complete wart resolution. Reduction in wart size was a secondary outcome. Results: Between October 2020 and April 2023, we enrolled 77 participants with 1 or more cutaneous warts (41 and 36 in vitamin D3 and placebo groups, respectively) with untreated (32%) and recalcitrant (69%) warts. At 24 weeks, the index wart had resolved in 12 (30%) of vitamin D3 and 10 (31%) placebo participants. Treatment with vitamin D3 had no effect on wart surface area in an adjusted model nor wart resolution in analysis adjusted for baseline wart size, multiple warts, and the vehicle (OR 0.31 [95% CI] 0.01-10.3; P = 0.51). Conclusions: These results demonstrate a lack of benefit of intralesional vitamin D3 in cutaneous warts. ( ClinicalTrials.gov number NCT04278573)

Background: Flexor pollicis longus (FPL) palsy following both-bone forearm fracture (BBFF) is a rare complication. Methods: A retrospective review of acute BBFF treated with open reduction internal fixation by a single surgeon from 2005 to 2023 was performed. Injury and surgical characteristics of patients with documented FPL palsy were reviewed. In addition, 10 cadaveric dissections were performed to evaluate the anatomy of the anterior interosseous nerve (AIN) and its branches. The distance of these branches from palpable elbow landmarks and variability in branching pattern were evaluated. Results: Twenty-nine patients underwent surgery for acute BBFF. Of these, 5 (17%) had evidence of an FPL palsy either at the time of injury presentation (n = 2) or immediately following surgery (n = 3). All patients with FPL palsy sustained fractures in the middle one-third of the radius. All palsies resolved after an average of 33 days of observation. In cadaveric dissections, the average distance from the lateral epicondyle to the AIN takeoff and branch to the FPL was 5.5 and 7.6 cm, respectively. The AIN takeoff and branch to the FPL were never less than 4 and 7 cm from the lateral epicondyle, respectively. Conclusion: Flexor pollicis longus palsy following BBFF can occur at the time of injury or following surgery. All FPL palsies involved midshaft radial fractures and were likely neurapraxia. The etiology of FPL palsy remains unclear, but cadaveric dissection suggests the FPL motor branch may be at risk from mid-to-proximal radius fracture fragments or excessive traction during surgery.

Abstract Post-translational modifications (PTM) of tau are implicated in Alzheimer disease (AD) progression and are established biomarkers in cerebrospinal fluid and plasma; however, the labor-intensive nature of conventional proteomics limits their investigation in histology-specific contexts. We describe the findings of an artificial intelligence-guided laser capture microdissection (LCM) pipeline for harvesting neurofibrillary tangles (NFTs) by maturation level into pretangles (pre-NFTs), mature tangles (iNFTs), and ghost tangles (eNFTs) using 38 cases obtained from 2 independent biobanks. We evaluated the performance characteristics of proprietary machine learning algorithms for the subclassification of these NFT categories in anti-pTau217-stained whole slide images of entorhinal cortex, hippocampus, frontal, and parietal cortex sections. Overall precision/recall/F1 scores were highest for Classifier A (0.6/0.46/0.5). The best performing algorithm was used to guide LCM capture and inform NFT enrichment. Targeted proteomics on tau signature peptides (pTau181, pTau217, and TauMTBR) was performed on approximately 1250 NFT collections. The results demonstrated that their abundance increased from pretangles to mature tangles (∼2-11-fold increase), and that this was followed by a sharp reduction in ghost tangles (∼3-116-fold decrease), with pTau217 showing the most drastic change. Pathologist-trained NFT classifiers represent an objective albeit imperfect means to enrich specific morphologic forms permitting coupled LCM-MS (mass spectrometry) to investigate AD-associated PTM.