Full Resolution Research Articles

Full resolution reconstruction of whole-mount sections from digitized individual tissue fragments

Whole-mount sectioning is a technique in histopathology where a full slice of tissue, such as a transversal cross-section of a prostate specimen, is prepared on a large microscope slide without further sectioning into smaller fragments. Although this technique can offer improved correlation with pre-operative imaging and is paramount for multimodal research, it is not commonly employed due to its technical difficulty, associated cost and cumbersome integration in (digital) pathology workflows. In this work, we present a computational tool named PythoStitcher which reconstructs artificial whole-mount sections from digitized tissue fragments, thereby bringing the benefits of whole-mount sections to pathology labs currently unable to employ this technique. Our proposed algorithm consists of a multi-step approach where it (i) automatically determines how fragments need to be reassembled, (ii) iteratively optimizes the stitch using a genetic algorithm and (iii) efficiently reconstructs the final artificial whole-mount section on full resolution (0.25 µm/pixel). PythoStitcher was validated on a total of 198 cases spanning five datasets with a varying number of tissue fragments originating from different organs from multiple centers. PythoStitcher successfully reconstructed the whole-mount section in 86–100% of cases for a given dataset with a residual registration mismatch of 0.65–2.76 mm on automatically selected landmarks. It is expected that our algorithm can aid pathology labs unable to employ whole-mount sectioning through faster clinical case evaluation and improved radiology-pathology correlation workflows.

High-resolution photoelectron spectroscopy of the very weakly bound MgNe molecule

ABSTRACT We report on the characterisation of the X + 2 Σ + ground electronic state of MgNe + by photoionisation, mass-analysed threshold-ionisation (MATI) and pulsed-field-ionisation zero-kinetic-energy photoelectron (PFI-ZEKE-PE) spectroscopy and the observation of the metastable a 3 Π 0 state of MgNe. Rotationally cold MgNe was generated in a laser-ablation supersonic-beam source in both the X 1 Σ + ( v ″ = 0 ) ground state and a 3 Π 0 ( v ″ = 0 ) metastable electronic state. PFI-ZEKE-PE spectra with full resolution of the vibrational structure and partial resolution of the rotational structure were recorded from the X 1 Σ + ground state following resonant ( 1 + 1 ′ ) two-photon excitation via selected rovibrational levels of the C 1 Π intermediate state and from the a 3 Π 0 metastable state following single-photon excitation. The lowest six vibrational levels of the X + 2 Σ + state were observed, covering 80% of the X + 2 Σ + potential-well depth. The experimental data were used to determine potential-energy functions, dissociation energies, and molecular constants for the X 1 Σ + , a 3 Π 0 and C 1 Π states of MgNe and the X + 2 Σ + state of MgNe + . With dissociation energies D 0 of 12(3) cm−1 and 10(3) cm−1, respectively, the X 1 Σ + and a 3 Π 0 states of 24 Mg 20 Ne are extremely weakly bound. In contrast, the X + 2 Σ + state of 24 Mg 20 Ne + has a dissociation energy D 0 of 185(3) cm − 1 and 12 bound vibrational levels. From the difference between the adiabatic ionisation energies of the X 1 Σ + (61 498.5(4) cm − 1 ) and the a 3 Π 0 (39 645.1(3) cm − 1 ) states, the term value of the a 3 Π 0 ground vibrational level is determined to be 21 853.4(5) cm − 1 . These results are compared with those of earlier experimental studies and ab initio quantum-chemical calculations.

Surgically Induced Scleritis Associated With Suture Hypersensitivity Following Strabismus Surgery.

A 67-year-old woman with history of mild suture hyper-sensitivity presented with localized scleritis after strabismus surgery. After infection was ruled out, the patient was prescribed topical and systemic non-steroidal anti-inflammatory drugs and systemic steroids, which led to full clinical resolution. [J Pediatr Ophthalmol Strabismus. 2024;61(1):e4-e6.].

Directional BLUs for Full Resolution Field Alternative Auto-stereoscopic 3D/2D and 2D/3D LCDs

Switching-directional backlight units (BLUs) were designed and prototyped for full resolution field alternate auto-stereoscopic 3D liquid crystal displays (LCDs). Since the design concepts are different for 2D/3D and 3D/2D displays, the switching characteristic of BLU with two confronting illuminating sets, was applied to build 2D mode into 3D display, and 3D mode into 2D display. A design based on the 2D concept required a uniform bilateral prismatic structure with a cross-section of isosceles triangle on the back surface of the functional light-guide plate (LGP). This structure led to an increase in double-sided uniformity, i.e., for double-sided illuminations (2D as primary function of the 2D/3D display), and a decrease in single-sided uniformity, i.e. for single-sided illumination. However, a design that was based on the 3D concept required an angle gradation for the unilateral prisms with a cross-section of a scalene triangle on the back surface of the functional LGP that led to an increase in single-sided uniformity and a decrease in double-sided uniformity (3D as primary function of the 3D/2D display). Both switching concepts were used to display 3D and 2D on the LCDs of small size handheld game devices and still cameras.

On determining and breaking the gauge class in inverse problems for reaction-diffusion equations

Abstract We investigate an inverse boundary value problem of determination of a nonlinear law for reaction-diffusion processes, which are modeled by general form semilinear parabolic equations. We do not assume that any solutions to these equations are known a priori, in which case the problem has a well-known gauge symmetry. We determine, under additional assumptions, the semilinear term up to this symmetry in a time-dependent anisotropic case modeled on Riemannian manifolds, and for partial data measurements on ${\mathbb R}^n$ . Moreover, we present cases where it is possible to exploit the nonlinear interaction to break the gauge symmetry. This leads to full determination results of the nonlinear term. As an application, we show that it is possible to give a full resolution to classes of inverse source problems of determining a source term and nonlinear terms simultaneously. This is in strict contrast to inverse source problems for corresponding linear equations, which always have the gauge symmetry. We also consider a Carleman estimate with boundary terms based on intrinsic properties of parabolic equations.

Canadian Light Source beam position visualization tool

The Canadian Light Source orbit correction system acquires, collates, and publishes storage ring beam centroid position information from 48 beam position monitors (BPMs) at a rate of 1000 samples per second. We present a ”Beam Position Visualization Tool” that computes and displays dynamic Fast Fourier Transforms (FFTs) and Cumulative Power Spectral Densities (CPSDs) for all BPMs in real-time using full resolution data. The computed FFTs and CPSDs can be plotted in various combinations and in waterfall plots that allow visualization of changes over long periods of time. In addition, correlations between all BPM channel combinations are computed and ranked. Data from any two BPM channels can be selected for plotting in two dimensions wherein correlations are visually apparent. Computed CPSDs are further binned and archived for further analysis. Preliminary results from the Beam Position Visualization Tool have proven useful in identifying storage ring beam position noise at the Canadian Light Source.

Patella and Trochlea Osteochondritis Dissecans: Demographics and Treatment Paradigms.

Previous research on patellar and trochlear groove osteochondritis dissecans (OCD) is limited by small sample sizes. This study aims to describe the presentation of patients with OCD lesions of the patella and trochlea and characterize the outcomes of operative and nonoperative treatments. This retrospective cohort study identified all patients from a single institution from 2008 to 2021 with patellar and/or trochlear OCD lesions. Patients were excluded from the study if surgical records were unavailable or if the patient had knee surgery for a different injury at index surgery or in the 12 months postoperative. Minimum follow-up was 12 months. Outcomes included a return to sports (RTS), pain resolution, radiographic healing, and treatment "success" (defined as full RTS, complete pain resolution, and full healing on imaging). A total of 68 patients (75 knees) were included-45 (60%) with patellar OCD and 30 (40%) with trochlear. Of the patients, 69% were males. The median age at knee OCD diagnosis was 14 years. At the final follow-up, 62% of knees (n = 44) recovered sufficiently to allow a full RTS and 54% of knees (n = 39) had full pain resolution. Of the 46 knees with radiographic imaging at least 1 year apart, 63% had full healing of the lesion. There was no significant difference in RTS, pain resolution, radiographic healing, or overall success when comparing treatments. This study provides valuable epidemiologic demographic and outcome data regarding the scarcely reported patellar and trochlear OCD. While over half of patients fully returned to sports and reported full pain resolution, a large proportion continued to experience symptoms over a year after presentation. Future research should aim to better define the treatment algorithms for these OCD subtypes. Level III.

SARS-CoV-2-Related Persistent Pulmonary Affection Case in A 55-Year-Old Gastric MALT Lymphoma Patient on Rituximab

Following a mild symptomatic SARS-CoV-2 infection, a 55-year-old patient with gastric MALT lymphoma, currently treated with rituximab, experienced persistent symptoms. Over subsequent months, the patient exhibited low-grade fever, dyspnea, and progressive desaturation, leading to respiratory failure necessitating home oxygen therapy. A PCR test confirmed SARS-CoV-2 infection, prompting suspicion of persistent COVID-19. Imaging and biopsy results were consistent with cryptogenic organizing pneumonia (COP), but the patient showed no response to treatment, including corticosteroids and immunosuppressants. Remdesivir treatment yielded partial improvement but failed to achieve full resolution. Plitidepsin (2.5 mg/day for 3 days) under compassionate use led to negative PCR tests and normal respiratory function restoration within 3 days after treatment. SARS-CoV-2's impact on immunocompromised patients is concerning due to unique clinical features, challenges in viral clearance and immunization, and varied responses to approved treatments. A phase II clinical trial is underway to assess plitidepsin's efficacy in immunocompromised COVID-19 adults requiring hospital care.

Impact of backtracking strategies on techno-economics of horizontal single-axis tracking solar photovoltaic power plants

Optimisation of horizontal single-axis tracking solar photovoltaic power plants is important for its optimal application. Commonly, standard backtracking has been applied to avoid mutual shading and improve the full load hours and levelised cost of electricity; however, this approach is not always the best solution for state-of-the-art modules with half cell technology. Backtracking has not yet been studied for different test sites with different solar and climatic conditions. This study aims to improve the knowledge on the techno-economic performance of horizontal single-axis tracking systems with half cell modules applying different backtracking strategies in full hourly resolution for nine test sites globally and varying row spacing. In addition to the standard backtracking algorithm, an advanced backtracking algorithm that varies the tracking angle only if the irradiance can be improved, and an advanced sophisticated backtracking algorithm simulating the irradiance for all possible tracking angles, are studied. The results confirm that standard backtracking is only superior for specific conditions. Compared to no backtracking, standard backtracking shows up to ca. 9% higher levelised cost of electricity due to lower full load hours. Advanced backtracking can lower the levelised cost of electricity by up to 9% and advanced sophisticated backtracking by up to 12%, due to improved full load hours. In general, results are similar and comparable for all test sites studied. This study highlights the importance of backtracking for optimised future horizontal single-axis tracking system planning.

Dichotomy of heavy and light pairs of holes in the t−J model

A key step in unraveling the mysteries of materials exhibiting unconventional superconductivity is to understand the underlying pairing mechanism. While it is widely agreed upon that the pairing glue in many of these systems originates from antiferromagnetic spin correlations, a microscopic description of pairs of charge carriers remains lacking. Here we use state-of-the art numerical methods to probe the internal structure and dynamical properties of pairs of charge carriers in quantum antiferromagnets in four-legged cylinders. Exploiting the full momentum resolution in our simulations, we are able to distinguish two qualitatively different types of bound states: a highly mobile, meta-stable pair, which has a dispersion proportional to the hole hopping t, and a heavy pair, which can only move due to spin exchange processes and turns into a flat band in the Ising limit of the model. Understanding the pairing mechanism can on the one hand pave the way to boosting binding energies in related models, and on the other hand enable insights into the intricate competition of various phases of matter in strongly correlated electron systems.

Replication of HLA‐DRB1*04:04 allele subtype protective effect against Alzheimer’s Disease in cognitively healthy centenarians using long‐read sequencing

AbstractBackgroundGenomic‐Wide Association Studies (GWAS) of Alzheimer’s Disease (AD) have identified several single‐nucleotide‐polymorphisms (SNPs) in the Human Leukocyte Antigens (HLA) gene cluster. Fine mapping of the genetic signals, by means of model‐based HLA allele imputation from SNP‐array‐based genotyping data, was linked to a protective effect of three HLA‐DRB1*04 allele subtypes. These alleles would favor the binding of an aggregation‐prone Tau peptide by T‐cells, promoting early clearance of toxic Tau aggregate seeds, and reducing neurodegeneration. Here, we aim to replicate this association by means of HLA genotyping with long‐read sequencing.MethodWe used an HLA genotyping assay, [NGS‐go MX11‐3, GenDx], coupled with [PacBio] long‐read sequencing. This allows for genotyping of HLA genes at their full resolution of polymorphism. So far, we have genotyped HLA genes in 129 AD cases from the Amsterdam Dementia Cohort (ADC, mean age = 67.4 with SD = 7.56, N females = 85, N males = 44) and 138 cognitively healthy centenarians from the 100‐plus Study (mean age = 101.1 with SD = 3.33, N females = 92, N males = 46), thereby maximizing the analysis power. We then focused on the comparison of previously identified protective HLA‐DRB1*04 allele subtypes (DRB1*04:01, DRB1*04:04 and DRB1*04:07) between AD cases and centenarians.ResultFor all three HLA‐DRB1*04 allele subtypes, we observed no additional genetic variation concerning synonymous DNA substitutions in coding regions and changes in non‐coding regions. DRB1*04:04:01:02 had a frequency of 0.116 in centenarians, as compared to a 0.054 in AD cases (one‐sided Fisher’s exact test, p = 0.04). The frequency in centenarians was higher than the previously reported joint frequency of carriers in AD and controls, frequency = 0.073. DRB1*04:01:01:01 had similar frequencies in centenarians (0.174) and AD cases (0.178) (p>0.05). Similarly, DRB1*04:07:01:01 had a frequency of 0.014 in centenarians and 0.015 in AD (p>0.05).ConclusionWe confirmed a protective HLA‐DRB1*04:04 allele subtype, previously described by HLA imputation, with the use of long read sequencing. Genotyped at full resolution as DRB1*04:04:01:02, we observed an enrichment in cognitively healthy centenarians compared to the original AD vs controls setting. The HLA system could play a role in the enhanced immunity of centenarians, and how they are able to escape neurodegenerative diseases.

Recognizing protected and anthropogenic patterns in landscapes using interpretable machine learning and satellite imagery.

The accurate and comprehensive mapping of land cover has become a central task in modern environmental research, with increasing emphasis on machine learning approaches. However, a clear technical definition of the land cover class is a prerequisite for learning and applying a machine learning model. One of the challenging classes is naturalness and human influence, yet mapping it is important due to its critical role in biodiversity conservation, habitat assessment, and climate change monitoring. We present an interpretable machine learning approach to map patterns related to territorial protected and anthropogenic areas as proxies of naturalness and human influence using satellite imagery. To achieve this, we train a weakly-supervised convolutional neural network and subsequently apply attribution methods such as Grad-CAM and occlusion sensitivity mapping. We propose a novel network architecture that consists of an image-to-image network and a shallow, task-specific head. Both sub-networks are connected by an intermediate layer that captures high-level features in full resolution, allowing for detailed analysis with a wide range of attribution methods. We further analyze how intermediate layer activations relate to their attributions across the training dataset to establish a consistent relationship. This makes attributions consistent across different scenes and allows for a large-scale analysis of remote sensing data. The results highlight that our approach is a promising way to observe and assess naturalness and territorial protection.

Neuropsychiatric Developmental Disorders in Children Are Associated With an Impaired Response to Treatment in Bladder Bowel Dysfunction: A Prospective Multi-Institutional European Observational Study.

Bladder and bowel dysfunction is a common but underdiagnosed pediatric entity which may represent up to 47% of pediatric urology consults. The objectives of this observational study were to determine functional 1-year outcomes following standard treatment of bladder and bowel dysfunction in both control and neuropsychiatric developmental disorder groups using validated questionnaires, and to perform an initial cost analysis. This was a prospective observational study conducted across a number of academic European centers (July 2020-November 2022) for new bladder and bowel dysfunction patients. Parents completed a sociodemographic survey, information pertaining to prior neuropsychiatric developmental disorder diagnoses, as well as a number of validated functional scores. A total of 240 patients were recruited. In the control bladder and bowel dysfunction group, the baseline Dysfunctional Voiding Scoring System and Childhood Bladder and Bowel Dysfunction Questionnaire scores were 20% and 17.% lower, respectively, after 1 year compared to the neuropsychiatric developmental disorder group. The change in improvement was diminished for the neuropsychiatric developmental disorder cohort in both Dysfunctional Voiding Scoring System and Childhood Bladder and Bowel Dysfunction Questionnaire scores. The odds ratio of full symptom resolution was 5.7 in the control cohort compared to the neuropsychiatric developmental disorder cohort. A cost analysis on prescribed medications at referral led to a total cost of €32,603.76 (US $35,381.00) in the control group and €37,625.36 (US $40,830.00) in the neuropsychiatric developmental disorder group. This study demonstrates that pediatric patients with a neuropsychiatric developmental disorder exhibit more severe bladder and bowel dysfunction at baseline and throughout treatment with a lower overall quality of life, as well as 15.4% higher medication costs at referral. It is also important that parents' and caregivers' expectations are managed regarding higher levels of treatment resistance for functional bladder and bowel issues.

Inflammatory cerebral amyloid angiopathy with poor outcome – case report

The article presents a clinical case of a 62-year-old patient diagnosed with inflammatory amyloid angiopathy after extensive diagnostic imaging and based on the characteristic radiological picture. Inflammatory amyloid angiopathy is a rare condition with intermediate features between the classic form of amyloid angiopathy and primary central nervous system angiitis. Multiple characteristic features suggesting the diagnosis may be seen on brain magnetic resonance imaging. There are no laboratory markers of the disease. Knowledge of this disease is important as it allows for a quick diagnosis and initiation of appropriate treatment. The response to treatment varies, with full symptom resolution in some patients, and resistance to treatment in others, such as the patient described in this case report.

Allogeneic Hematopoietic Stem Cell Transplantation for Adult Metachromatic Leukodystrophy (MLD): A Case Series

Introduction Adult Metachromatic Leukodystrophy (MLD) is a rare neurological disorder leading to devastating and progressive cognitive impairment and motor impairment with ataxia, spasticity and neuropathy as well as incontinence resulting in complete disability and reduced life expectancy. MLD is caused by autosomal recessive mutations of the ARSA gene, resulting in reduced arylsulfatase A enzyme (ARSA) activity and consecutive accumulation of galactosylceramide-3-0-sulfate in the central nervous system (CNS). Potential therapies in infantile and juvenile MLD include allogeneic hematopoietic stem cell transplantation (allo-HCT), ex-vivo gene therapy (Atidarsagen autotemcel), and (intrathecal) enzyme replacement as tested in ongoing trials. Allo-HCT may slow down or stop MLD progression. However, the outcome in adult patients treated with allo-HCT has been only reported in a few case reports. In this case series, we report our experience of allogeneic transplantation in four patients with adult MLD. Methods Four patients (2 male and 2 female) with a genetically confirmed diagnosis of adult MLD, with enzyme deficiency detectable in peripheral blood (ARSA activity range 0.00-0.06 E514nm/10 -6), evidence of white matter lesions on MRI and demyelinating polyneuropathy in EMG were treated with allo-HCT. One patient was still clinically asymptomatic at the treatment timepoint. Allo-HCT was performed at an age between 18 and 37 years (mean 25.75 years) and within one year after diagnosis. Bone marrow (n=2) or mobilized peripheral blood stem cells (n=2) from 10/10 matched related (n=1) or unrelated (n=3) donors were infused at a dose of 2.2-7.82x10 6 CD34+/kg after a reduced intensity conditioning regime with Fludarabine (150 mg/m²) and Treosulfane (10 or 14 g/m²). Three patients received further infusions with allogeneic mesenchymal stem cells (MSCs) manufactured in the hospital´s own GMP laboratory around day 30 after transplantation. One patient received a second MSC infusion at day 182. MSCs are able to secrete ARSA and were used to consolidate enzyme levels. In case of transplant failure donor lymphocytes (DLI) were given. For posttransplant immunosuppression Tacrolimus, Methotrexate, Mycophenolate mofetil or Anti-thymocyte globulin (ATG, Grafalon®, Neovii 10 mg/kg) were used. Results All patients engrafted 16-21 days after HCT. Platelets regenerated within 14 to 21 days (mean 16 days), neutrophils recovered within 16 to 21 days (mean 18.5 days). In two patients hepatitis and exanthema associated with ATG administration were observed as transient adverse events. Other therapy-associated adverse events were innappetence, hyperkalemia and diarrhea. A mild Graft-versus-host disease of the skin occurred only in one patient with full resolution on a course of steroids and Tacrolimus. After allo-HCT, an increase in ARSA levels reaching normal range values within the first 12 months after treatment was already documented in 3 out of 4 patients; measurements are pending in the 4 th more recently transplanted patient. Three out of four patients developed consistent full donor chimerism within 11 (1-11 ) months after HCT. In the fourth 18-year-old patient autologous chimerism increased to 60-80%, while ARSA activity decreased from 1.05 to 0.61 E514nm/10 -6. Consequently, the patient received DLIs. However, an improvement in chimerism has not be achieved so far. Longer follow-up data will be reported at the meeting. Discussion and Conclusion Allo-HCT in patients with MLD can be used to restore normal range ARSA activity. Donor-derived macrophages with an adequate secretion of ARSA migrate to the central nervous system and release ARSA. To our knowledge, there have been only a few individual case reports on allo-HCT in adult MLD so far. Our case series indicates that allo-HCT can be performed with tolerable risks and evident efficacy in adult patients with MLD. Based on this experience and previously reported cohorts in juvenile and infantile MLD allo-HCT should be thus also considered as a therapeutic option for adult patients with MLD. Longer clinical follow-up, higher patient numbers and ultimately a prospective randomised trial containing an untreated group would be needed to evaluate allo-HCT as a treatment option for adult MLD.

Post-Transplant Pain and Paralysis: Neurologic Amyotrophy As an Atypical Cause of Shoulder Dysfunction Following Hematopoietic Stem Cell Transplant

Introduction: Neuralgic amyotrophy (NA), also known as Parsonage-Turner Syndrome, brachial neuritis, or idiopathic brachial plexopathy, is a rare inflammatory peripheral nervous system disorder affecting the brachial plexus, typically presenting as sudden and abrupt unilateral shoulder pain followed by progressive painless weakness and occasionally reflex and sensory abnormalities. Diagnosis is clinical - based on history and detailed neuromuscular physical examination. Electrodiagnostic studies (EDX) and advanced imaging are supportive to confirm diagnosis and exclude alternative etiologies. While the pathogenesis is not entirely understood, the idiopathic form is thought to be secondary to immune or vascular mediated effects with only a few case reports after hematopoietic stem cell transplantation (HCT). Given under recognition and misdiagnosis, a high degree of suspicion is necessary in patients developing acute onset of shoulder pain after HCT. While no curative treatment is available, early diagnosis will result in appropriate management, patient education, pain control, and timely focused rehabilitation. Methods: We retrospectively collected demographics, HCT details, clinical characteristics, imaging studies, and EDX on patients with acute shoulder pain post-HCT at a single institution. Descriptive statistics were utilized to summarize the collected data. Results: Between 8/2020 -7/2022, nine patients (44% male, median age 60 years) were diagnosed with NA following autologous (n=4, for multiple myeloma (n=2), non-Hodgkin lymphoma (n=1), or germ cell tumor (n=1)) or allogeneic HCT (n=5, for myelodysplastic syndrome (n=3) and acute myelogenous leukemia (n=2)). Each patient acutely developed severe shoulder pain at a median of 9 days (range 1-21) mean. Shoulder pain was bilateral in 3 patients. Neurological weakness involving the shoulder (s) was observed on average 5.1 days after pain onset (range 1-15 days). All but one patient developed sensory deficits in the affected upper extremity. Shoulder pain subsided after a median of 23 days (range 8-40 days). MRI of the shoulder and/or brachial plexus was performed in all patients and showed periscapular muscle edema, atrophy and enhancement in six patients. These signal abnormalities were observed in varying distributions including supraspinatus, infraspinatus, deltoid, teres minor, serratus anterior and intercostals (Figure 1). Of the 6 patients who had EDX, findings were consistent with NA in 5 patients (axillary neuropathy in 2 patients, upper trunk plexopathy in 1 patient, bilateral posterior cord plexopathy in 1 patient and diffuse bilateral brachial plexopathy in 1 patient). All patients were treated with pain medications and received optimal rehabilitative care including consult with physical medicine and rehabilitation physicians and physical and occupational therapy. Upon long term follow up (>1 year), three patients experienced full or near-full resolution of symptoms, four patients partially recovered, and two patients had little to no improvement of their neurological symptoms. Conclusion: Patients undergoing HCT are susceptible to neurological insults, potentially driven by immune-mediated mechanisms. In individuals experiencing acute shoulder pain accompanied by neurological symptoms early post-HCT, it is important to maintain a high level of suspicion for the diagnosis of NA. A timely diagnosis is essential to facilitate early intervention and ensure optimal functional recovery. MRI of the shoulder and/or brachial plexus and EDX are valuable diagnostic tools for assessing the presence and distribution of neuromuscular involvement. While recovery is possible, comprehensive long-term follow-up is necessary to ascertain the extent of symptom resolution and functional restoration.

2837. Impact of Regulatory Guidelines on Therapeutic, Clinical, and Microbiological Success Rates in Uncomplicated Urinary Tract Infection: Results from a Two Phase 3 Randomized Controlled Trials of Oral Gepotidacin (EAGLE-2 and EAGLE-3)

Abstract Background For noninferiority RCTs in uUTIs, the latest US Food and Drug Administration (FDA; 2019)/European Medicines Agency (EMA; 2018) guidance recommends a primary endpoint of therapeutic response (combined clinical and microbiologic response) with success defined by full symptom resolution plus microbiological eradication from ≥ 105 to < 103 CFU/mL. Historically, less stringent criteria (clinical or microbiological [not combined], allowing symptom improvement/resolution) and various endpoints were used; success rates of 70–92% have been reported for NTF (Table 1). Gepotidacin, a novel, first-in-class, triazaacenaphthylene, bactericidal ABX has been investigated for uUTI treatment in 2 RCTs, EAGLE-2 (E-2; NCT04020341) and -3 (E-3; NCT04187144) following FDA/EMA guidance. Here, we demonstrate the impact of new endpoint guidance on the RCT results. Methods E-2 and -3 were global Phase 3, parallel-group, double-blind, noninferiority (10% margin) RCTs comparing the efficacy and safety of oral gepotidacin (1500mg BID, 5 days) vs NTF (100mg BID, 5 days) in female patients (≥ 12 years) with uUTI. Using the complete study dataset, we assessed all patients who received ≥ 1 dose of study drug and had 1–2 qualifying uropathogens (≥ 105 CFU/mL) susceptible to NTF. TOC was 10–13 days post first dose, FU was 28 (±3) days. Results In E-2/-3, the primary endpoint was assessed in 634/567 patients (41/35% of ITT; Table 2). At TOC in E-2/-3, clinical success was 66.7/68.2% for gepotidacin, and 65.8/63.6% for NTF. Microbiological success in E-2/-3 was 72.6/72.9% for gepotidacin, and 66.8/57.5% for NTF. TOC therapeutic success rates (E-2/E-3) were lower than clinical or microbiological rates for both treatments: 51.8/58.9% for gepotidacin, 47.0/44.0% NTF (Table 3). Exploratory analysis replacing clinical ‘resolution’ with ‘near success’ increased TOC therapeutic success rates by 6.2–9.5% (Table 3). Use of non-study ABX for uUTI was substantially lower than the overall rate of therapeutic failure at TOC and FU. Conclusion In these 2 RCTs using recent regulatory criteria that set a high threshold for uUTI treatment efficacy, therapeutic and clinical success rates were lower than some historic studies. Contemporary study results using new guidance cannot be directly compared with historical studies. Disclosures Florian Wagenlehner, MD, Achaogen: Advisory Board member, study participation|Astellas: Honoraria|AstraZeneca: Honoraria|AstraZeneca: Advisory Board member|Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Bionorica: Honoraria|Bionorica: Meeting/travel support, study participation|Deutsches Zentrum für Infektionsforschung (DZIF): Study participation|Enteris BioPharma: Study participation|Everest Medicines: Grant/Research Support|German S3 guideline Urinary tract infections: Board Member|Glaxo Smith Kline: Advisor/Consultant|Glaxo Smith Kline: Honoraria|Glaxo Smith Kline: Consulting fees, meeting/travel support, advisory board member, principal investigator in a GSK-sponsored study|Global Antibiotic Research and Development Partnership (GARDP Foundation): Grant/Research Support|Guidelines European Association of Urology: Infections in Urology: Board Member|Helperby Therapeutics: Study participation|Janssen: Honoraria|Janssen: Advisory Board member|Klosterfrau: Honoraria|LeoPharma: Advisory Board member|MerLion: Advisory Board member|MIP Pharma: Honoraria|MSD: Advisory Board member|OM Pharma/Vifor Pharma: Advisory Board member, study participation|OM-Pharma: Honoraria|Pfizer: Honoraria|Pfizer: Advisory Board member|RosenPharma: Advisory Board member|Shionogi: Advisory Board member, study participation|Speaker research group German research foundation (DFG) Bacterial Renal Infections and Defense (FOR 5427): Study participation|Spero Therapeutics: Advisor/Consultant|Spero Therapeutics: Consulting fees|University Hospital Giessen and Marburg GmbH, and Justus Liebig University, Germany: Employee|Venatorx Pharmaceuticals, Inc.: Advisor/Consultant|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Consulting fees, Advisory Board member Caroline R. Perry, PhD, GSK: Employee and shareholder Thomas M. Hooton, MD, GSK: Advisor/Consultant Nicole E. Scangarella-Oman, MS, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder

Hiatal hernia repair after previous laparoscopic Roux-en-Y gastric bypass

BackgroundSymptomatic hiatal hernia (HH) with pouch migration after previous laparoscopic Roux-en-Y gastric bypass (RYGB) is an uncommon complication, with limited extant evidence for the utility of surgical repair. ObjectiveTo evaluate the presentation and resolution of symptoms in patients with HH repair after previous RYGB. SettingMulticenter University Hospital. MethodsA retrospective review was conducted from 2010 to 2022. Patients with prior RYGB who were undergoing subsequent isolated HH repair were included. Patients undergoing incidental HH repair during concomitant revisional bariatric surgery were excluded. Baseline characteristics and surgical outcomes were evaluated and presented as medians (25th–75th percentile). ResultsForty-four patients met the inclusion criteria. The time from RYGB to HH repair was 59 months (39–88). Body mass index at HH repair was 31 kg/m2 (27–39). The most common presenting symptoms of hernia were dysphagia (52%), gastric reflux (39%), and abdominal pain (36%). All HH repairs were completed with a minimally invasive approach (98% laparoscopic, 2% robotic). Nonabsorbable suture was used in 98% of patients, with bioabsorbable mesh in 30%. At a median 28-day (12–117) follow-up, 70% of patients reported full symptom resolution and 23% partial resolution. At follow-up, 2 patients had radiologic HH recurrence, with 1 requiring reoperation. ConclusionsThis is the largest series of isolated HH repair for symptomatic pouch migration after previous RYGB. Common presenting symptoms are dysphagia and reflux, and surgical repair yields a high rate of symptom resolution in the short term. Longer follow-up is needed to evaluate the durability of this intervention.

Dyke swarm history in Belet-ili and Gaia (Gaya) Coronae Region (13°–26°E, 0°–10°N), Central Eistla Regio, Venus

Eistla Regio, Venus, is a locus of major plume-generated magmatism and tectonics. We focus on the central portion, termed Central Eistla Regio. More than 19,000 extensional lineaments (grabens, fissures and fractures) were mapped in the area 13°-26°E, 0°-10°N, at 1:500,000 scale using full resolution Magellan SAR (radar) images. These structures are interpreted to represent the surface expression of underlying mafic dykes and have been grouped, on the basis of trend, into radiating, circumferential and linear dyke swarms. Thirty-two swarms are identified and linked to 20 magmatic centres, most of which are located within or near two coronae, Belet-ili and Gaia (Gaya) coronae, while others are linked to magmatic centres outside the study area. These magmatic centres are interpreted to be linked to underlying mantle plumes, and the sizes of the underlying flattened plume heads are estimated from the interpreted dyke swarms: for radiating swarms, the radius of the transition from proximal radiating to more distal linear pattern, and for circumferential dykes, the radial distance to the outer boundary of the circumferential pattern. Plume heads for the largest centres, Belet-ili and Gaia coronae are estimated at about 230 km and 275 km in radius, respectively. These sizes are less than the 1200 km radii predicted for a plume arriving from the deep mantle, and would suggest an origin at a shallower level (likely a mid-mantle boundary, i.e. between upper and lower mantle). The NW alignment of Belet-ili and Gaia corona and other magmatic centres in our study area potentially represents structural control by a rift zone, which can be traced further north to Anala Mons (one of two main plume centres of Central Eistla Regio).

Artificial Intelligence for Image-Based Breast Cancer Risk Prediction Using Attention.

Accurate prediction of individual breast cancer risk paves the way for personalised prevention and early detection. The incorporation of genetic information and breast density has been shown to improve predictions for existing models, but detailed image-based features are yet to be included despite correlating with risk. Complex information can be extracted from mammograms using deep-learning algorithms, however, this is a challenging area of research, partly due to the lack of data within the field, and partly due to the computational burden. We propose an attention-based Multiple Instance Learning (MIL) model that can make accurate, short-term risk predictions from mammograms taken prior to the detection of cancer at full resolution. Current screen-detected cancers are mixed in with priors during model development to promote the detection of features associated with risk specifically and features associated with cancer formation, in addition to alleviating data scarcity issues. MAI-risk achieves an AUC of 0.747 [0.711, 0.783] in cancer-free screening mammograms of women who went on to develop a screen-detected or interval cancer between 5 and 55 months, outperforming both IBIS (AUC 0.594 [0.557, 0.633]) and VAS (AUC 0.649 [0.614, 0.683]) alone when accounting for established clinical risk factors.