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Background: To compare the characteristics of type 1 macular neovascularization (MNV) and the surrounding choriocapillaris (CC) perfusion in patients with neovascular age-related macular degeneration (nAMD) versus those with pachychoroid neovasculopathy (PNV) using swept-source optical coherence tomography angiography (SS-OCTA). Methods: This retrospective study included 64 treatment-naïve eyes (37 nAMD, 27 PNV) with type 1 MNV. SS-OCTA images were analysed to measure MNV area and perimeter, and CC flow deficits (FD) in five concentric rings surrounding the lesion. CC FD percentage (FD%), area (FDa), and number (FDn) were quantified. Intervortex anastomoses presence was also assessed. Results: MNV lesions in nAMD were significantly larger in area (2.94 vs 1.56 mm², p= 0.013) and perimeter (8.76 vs 5.85 mm, p= 0.004) compared to PNV. PNV eyes showed higher FD% and larger FDa across all rings (p< 0.05), while FDn did not differ significantly. Intervortex anastomoses were more prevalent in PNV (81.5% vs 35.1%, p= 0.0002). In nAMD, MNV size correlated positively with FD% in inner rings and FDn in all rings. In PNV, MNV size correlated only with FDn. Conclusions: Despite smaller MNV lesions, PNV eyes demonstrated more extensive CC flow deficits compared to nAMD. The distinct CC flow patterns and their correlations with MNV characteristics suggest different pathophysiological mechanisms underlying these conditions. These findings may have implications for differential diagnosis and tailored treatment approaches in nAMD and PNV.

Purpose: This study aims to develop a deep-learning-based software capable of detecting and differentiating microaneurysms (MAs) as hyporeflective or hyperreflective on structural optical coherence tomography (OCT) images in patients with non-proliferative diabetic retinopathy (NPDR). Methods: A retrospective cohort of 249 patients (498 eyes) diagnosed with NPDR was analysed. Structural OCT scans were obtained using the Heidelberg Spectralis HRA + OCT device. Manual segmentation of MAs was performed by five masked readers, with an expert grader ensuring consistent labeling. Two deep learning models, YOLO (You Only Look Once) and DETR (DEtection TRansformer), were trained using the annotated OCT images. Detection and classification performance were evaluated using the area under the receiver operating characteristic (ROC) curves. Results: The YOLO model performed poorly with an AUC of 0.35 for overall MA detection, with AUCs of 0.33 and 0.24 for hyperreflective and hyporeflective MAs, respectively. The DETR model had an AUC of 0.86 for overall MA detection, but AUCs of 0.71 and 0.84 for hyperreflective and hyporeflective MAs, respectively. Post-hoc review revealed that discrepancies between automated and manual grading were often due to the automated method’s selection of normal retinal vessels. Conclusions: The choice of deep learning model is critical to achieving accuracy in detecting and classifying MAs in structural OCT images. An automated approach may assist clinicians in the early detection and monitoring of diabetic retinopathy, potentially improving patient outcomes.

Background Recent advancements in imaging technologies, particularly structural optical coherence tomography (OCT), have improved the understanding of diabetic macular edema (DME) pathophysiology and provided valuable biomarkers for disease progression and visual outcomes. This prospective study aimed to investigate the association between specific retinal biomarkers identified through OCT imaging and reading performance metrics in patients with previously treated persistent versus resolved DME and good visual acuity.Methods Forty-nine eyes from 35 patients with a history of DME were enrolled. Reading performance was assessed using the Radner reading charts, which include standardized sentences with geometrically progressing print sizes. Structural alterations in the inner and outer retina, as well as the retinal pigment epithelium (RPE), were graded based on OCT images.Results Reading performance, measured as maximum reading speed, was associated with specific retinal biomarkers. The disruption of the ellipsoid zone (EZ) in the parafoveal region and the presence of disorganization of the inner retinal layers (DRIL) in the parafovea were correlated with reduced reading speed. These associations were independent of the presence of intraretinal or subretinal fluid.Conclusions Understanding the relationship between retinal biomarkers and reading performance could contribute to a comprehensive evaluation of visual function and quality of life in patients with DME, leading to better management strategies and treatment outcomes.

Objective: The anti-COVID vaccination campaign has led to a significant increase in the demand for allergology consultations in patients considered at risk of reaction to anti-COVID-19 vaccines. This study aims to describe the experience of the vaccination campaign held in Piedmont (Italy) which developed a new service of Allergy Call Center (ACC) thus providing for the screening and management of allergy high-risk patients during pandemic. Study Design: A retrospective analysis was performed on all patients considered at high risk for the development of allergic reactions who were referred by the Immunology and Allergy Unit of Azienda Ospedaliera Ordine Mauriziano in Turin, Italy, between December 2020 and December 2022 and also on ACC consultations. Methods: During the COVID-19 pandemic, Piedmont Region instituted the ACC, active from May 10th, 2021 to December 31st 2022, to allow vaccinating doctors to require a telephonic consultation for patients who were considered at high risk for the development of allergic reactions. If further diagnostic evaluations were required, the ACC scheduled a visit with a Consultant of the Unit to better assess the clinical situation of the patient. Furthermore, patients referred by General Practitioners, Occupational Doctors and other consultants were also evaluated by the Unit when required. Results: During the operational period the ACC received a total of 15,865 calls and referred only 336 patients to the unit (27.4% of the total referrals), while General Practitioners referred 499 patients (40.8%), Occupational Doctors referred 61 patients (4.9%), and other consultants referred 326 patients (26.6%). Conclusions: Evaluation and management of a large volume of requests seemed to be facilitated by a proactive framework for screening patients at high risk for allergic reactions as the ones referred by our ACC. This approach led to a prominent decrease in allergological visits to our tertiary care Centre, reducing the waiting times and providing additional support for both patients and healthcare providers, thus allowing the vaccinations to be more easily handled.

The Ur III kingdom, which flourished in southern Mesopotamia at the end of the third millennium (ca. 2110–2003 BCE), produced and kept detailed administrative records from which historians can reconstruct the economic and social life of the period. Among these sources, we find household inventories of wealthy individuals, lists of temple treasures, receipts of luxury gifts, and accounts documenting allocations of prestige goods. Collectively, these documents shed light on the material culture of Babylonian society in the Early Bronze Age. Clothing, footwear, accessories, jewellery, weapons, and furniture feature among the objects most frequently associated with royals, priests, urban notables, and other elites. By combining data from these diverse textual sources and comparing them with possible parallels in glyptic iconography and the archaeological record, we will examine the elements that most clearly identify high-status individuals to determine the relationship between the economic and socio-cultural value of these objects, and reconstruct the context within which they were gifted and displayed.

This volume provides an interdisciplinary exploration of dress, textiles, furniture, and power accessories in the Aegean and ancient Near Eastern societies, examining their roles in expressing social status and identity. The introduction establishes the theoretical framework, drawing from studies on ancient material culture and identity construction. It investigates the role of these elements in social hierarchy, gender roles, and intercultural exchange by analyzing evidence from archaeological findings, iconographic representations, and textual sources. The introduction also outlines the structure of the volume and provides a summary of each contribution. Acknowledgements conclude the introduction, expressing gratitude to those who contributed to the realization of this work.

Soil erosion is a major land degradation process, threatening global agricultural sustainability and carbon cycling. Although geomorphic evidence confirms that human activities have significantly accelerated soil erosion, to what extent humans have altered soil erosion and how to attribute it to different land use changes and economic activities remains uncertain at the national scale. Here, by developing an integrated modeling framework to assess human-altered soil erosion (HASE) by water and its drivers, we estimate that nearly half of the total water erosion in China is dominated by HASE, rising to over 90% in agriculture-intensive areas. Household consumption emerges as a major hidden factor driving HASE. Conversely, human efforts, such as soil conservation practices like terraces, have effectively mitigated soil erosion. Our findings provide a starting point to evaluate the magnitude of human intervention in soil erosion at the regional or global scale, highlighting the importance of controlling accelerated soil erosion from a coupled social-ecological perspective.

Modeling the various properties of liquid water, particularly its reactivity, has been a longstanding challenge for simulation methods. Recently, ab initiosimulations based on density functional theory (DFT) have come to the fore as tenable methods for calculating the properties and reactivity of water, with varying degrees of success for different exchange-correlation functionals. In particular, hybrid-GGA and meta-GGA functionals have been shown to reproduce many of the structural, dynamical, and energetic properties of water to a high degree of accuracy relative to their computational cost. Here, we show that the dual descriptor (DD) measure of nucleophilicity and electrophilicity, which is sometimes used to elucidate organic chemistry reaction mechanisms, can also be used to characterize the reactivity of DFT-simulated liquid water. The DD is especially apt for understanding the reactivity of excess electrons with water as its calculation explicitly involves adding and removing an excess electron from a reference system. We use the DD to explore the reactivity of water simulated using three different DFT functionals: the LDA functional (LDA), a hybrid-GGA functional (PBE0), and a hybrid meta-GGA functional (SCAN0). Using the DD, we show that the SCAN0 functional with the standard 25% Hartree–Fock exchange produces simulated liquid water with many regions that are far more reactive than either PBE0 or LDA. To understand the implications of these highly reactive regions, we then add a strong nucleophile in the form of an excess electron and find that although PBE0 and LDA predict stable hydrated electrons, the excess electron reacts nearly instantaneously with SCAN0 water via proton abstraction to form a hydrogen atom and hydroxide ion. We show that the DD provides the ability to not only predict whether or not liquid water will react with a hydrated electron but also which particular waters will be involved solely from analyzing pure water configurations generated with each functional. We rationalize this result in terms of the known trap-seeking behavior of injected hydrated electrons, which are able to find the most electronegative region in bulk water. These results highlight the utility of the dual descriptor as a fast and interpretable method for investigating condensed-phase reactivity with excess electrons.

Objective To evaluate the anatomical and functional macular results and rate of complications following surgical treatment of primary macular hole (MH) with autologous platelet rich plasma (a-PRP) use.Design retrospective, interventional, non-randomized case seriesPartecipants and methods A cohort of 9 consecutive patients from January 1, 2019 to August 31, 2021 who underwent vitrectomy with a-PRP use for primary MH were included. Anatomical results based on spectral domain- optical coherence tomography (SD-OCT) and visual acuity were analyzed.Results 10 pseudophakic eye of 9 patients were enrolled. Six patients were female and three patients were male. The mean age was 69.9 years ± 1.48. The baseline MH minimum diameter was 486.1 μm ± 37.1, and mean pre operative best-corrected visual acuity (BCVA) was 0.91 ± 0.03 logMAR (Snellen equivalent 20/160). Mean 1 month post operative BCVA was 0.81 ± 0.57 logMAR (Snellen equivalent 20/130; p= 1.000); mean 3 month post operative BCVA was 0.66 ± 0.04 logMAR (Snellen equivalent 20/90; p= 0.006); mean 6 month post operative BCVA was 0.6 ± 0.04 logMAR (Snellen equivalent 20/80; p< 0.001). In all eyes, 10/10 (100%), there was a complete MH closure at 6 months follow up: 5 eyes (50%) with a U-type closure pattern, 4 eyes (40%) with a V-type pattern and 1 eye (10%) with an irregular foveal contour closure at 6 month follow-up. No ocular and systemic complications were reported.Conclusion The a-PRP use is a successful and promising vitreoretinal surgical technique option for primary MH

This work presents a distributed method for multi-vehicle coordination based on nonlinear model predictive control (NMPC) and dual decomposition. Our approach allows the vehicles to coordinate in tight spaces (e.g., busy highway lanes or parking lots) by using a polytopic description of each vehicle's shape and formulating collision avoidance as a dual optimization problem. Our method accommodates heterogeneous teams of vehicles (i.e., vehicles with different polytopic shapes and dynamic models can be part of the same team). Our method allows the vehicles to share their intentions in a distributed fashion without relying on a central coordinator and efficiently provides collision-free trajectories for the vehicles. In addition, our method decouples the individual-vehicles' trajectory optimization from their collision-avoidance objectives enhancing the scalability of the method and allowing one to exploit parallel hardware architectures. All these features are particularly important for vehicular applications, where the systems operate at high-frequency rates in dynamic environments. To validate our method, we apply it in a vehicular application, that is, the autonomous lane-merging of a team of connected vehicles to form a platoon. We compare our design with the centralized NMPC design to show the computational benefits of the proposed distributed algorithm.

The electron beam powder bed fusion (PBF-EB) process has several advantages typical of additive manufacturing. However, at the end of the process, a large amount of powder is left that needs to be disposed of. Therefore, reusing powder for several build jobs may represent an interesting opportunity in the context of sustainable manufacturing. On the other hand, the reused powder differs from the virgin one in terms of chemical–physical characteristics due to the thermal history experienced in previous build jobs. As a consequence, the possible effects on the quality and mechanical properties of final PBF-EB parts need to be assessed to define reusing strategies that minimize these influences properly. In this study, the effect of reusing cycles on the physical/chemical properties of Ti6Al4V powder produced by plasma atomization and on the mechanical/microstructural properties of printed material was examined. The investigations showed that the powder reusing reduced the number of satellites and the porosity and induced grain coarsening. Moreover, an increase in oxygen content was found after several reusing cycles, resulting in an increase in the hardness of the printed material. The critical defect size was found to increase with reusing cycles, but no significant differences were observed in the fatigue behaviour.

Research has long-documented how Canada’s temporary foreign worker programs (TFWP) foster workers' precarity through their status as non-citizens and living and working conditions, ultimately, impacting their health. While studies point to limited supports and services for workers, their role in reinforcing or alleviating the precarious conditions that migrant agricultural workers experience remains largely unexplored. This paper draws on interviews with 35 service providers in three migrant-intensive regions in southwestern Ontario, to explore how service providers describe and construct support. We explore the barriers workers face in accessing services, challenges providers experience in supporting workers, and strategies employed to surmount these barriers. We argue that this multiregional analysis is important to illuminate how support shapes and is shaped by the larger structural context, namely common features of Canada’s TFWP. A more comprehensive understanding of support moreover, provides direction for sustainable interventions that can promote the health and wellbeing of this population.

Most of spectroscopic signals are specified by the nonlinear laser-induced polarization. In recent years, population-detection of signals becomes a trend in femtosecond spectroscopy. Polarization-detected (PD) and population-detected signals are fundamentally different, because they are determined by photoinduced processes acting on disparate time scales. In this work, we consider the fluorescence-detected (FD) N-wave-mixing (NWM) signal as a representative example of population-detected signals, derive a rigorous expression for this signal, and discuss its approximate variants suitable for numerical simulations. This leads us to the definition of the phenomenological FD (PFD) signal, which contains as a special case all definitions of FD signals available in the literature. Then we formulate and prove the population-polarization equivalence (PPE) theorem, which states that PFD NWM signals produced by (possibly strong) laser pulses can be evaluated as conventional PD signals in which the effective polarization is determined by the PFD transition dipole moment operator. We use the PPE theorem for the construction of the ab initioprotocol for the simulation of PFD 4WM signals. As an example, we calculate electronic two-dimensional (2D) PFD spectra of the gas-phase pyrazine and compare them with the corresponding PD 2D spectra.

Experiments show that the absorption spectrum of the hydrated electron (ehyd–) blue-shifts in electrolyte solutions compared with what is seen in pure water. This shift has been assigned to the ehyd–’s competitive ion-pairing interactions with the salt cation relative to the salt anion based on the ions’ positions on the Hofmeister series. Remarkably, little work has been done investigating the ehyd–’s behavior when the salts have chaotropic cations, which should greatly change the ion-pairing interactions given that the ehyd–is a champion chaotrope. In this work, we remedy this by using mixed quantum/classical simulations to analyze the behavior of two different models of the ehyd–in aqueous RbF and RbI electrolyte solutions as a function of salt concentration. We find that the magnitude of the salt-induced spectral blue-shift is determined by a combination of the number of chaotropic Rb+cations near the ehyd–and the number of salt anions near those cations so that the spectrum of the ehyd–directly reflects its local environment. We also find that the use of a soft-cavity ehyd–model predicts stronger competitive interactions with Rb+relative to I–than a more traditional hard cavity model, leading to different predicted spectral shifts that should provide a way to distinguish between the two models experimentally. Our simulations predict that at the same concentration, salts with chaotropic cations should produce larger spectral blue-shifts than salts with kosmotropic cations. We also found that at high salt concentrations with chaotropic cations, the predicted blue-shift is greater when the salt anion is kosmotropic instead of chaotropic. Our goal is for this work to inspire experimentalists to make such measurements, which will help provide a spectroscopic means to distinguish between simulations models that predict different hydration structures for the ehyd–.

Purpose To report clinical and imaging features of optic nerve and retinal involvement in a patient with mucopolysaccharidosis (MPS) type II B.Methods A 27-year-old man, diagnosed with MPS type II B and undergoing enzymatic substitution therapy for the past 19 years, was referred to the retina service. An ophthalmological evaluation, which included multimodal imaging, was conducted to investigate potential retinal and optic disc involvement.Results The eye examination revealed a pigmentary retinopathy with a predominant loss of the outer retinal loss, primarily in the parafoveal and perifoveal regions. Notably, multimodal imaging identified macular edema without any signs of leakage, implying an association between macular edema and retinal neurodegeneration. Additionally, both eyes exhibited an optic disc with blurred margins.Conclusion We herein describe the multimodal imaging findings of retinal and optic disc involvement in a patient with MPS type II B. This report describes for the first-time the presence of macular edema without leakage alongside photoreceptor damage and optic disc swelling.

An electron microscope study of the spermatocytes I of Scaptericus borrelli was performed using serial sections and tridimensional reconstruction. The stages examined were: mid-pachytene, early diplotene and the so-called “diffuse stage”. At mid-pachytene the nucleolus (associated to an autosome) shows a glomerular array formed of supernumerary synaptonemal complexes (extra-complexes, ECs). At early diplotene the autosomes still show remnants of synaptonemal complexes (SC) and the sex chromosome is formed by two substances: one is homogeneous (chromatin-like) the other is granular and dense. A short number of ECs occur in the latter. — At the “diffuse stage” (“lobulated” in this paper) the SCs remnants and the ECs have disappeared and the granular material is assembled in a nuclear lobule. This lobule was found associated with one centriole. — A tridimensional model of a diplotene nucleus and models of diplotene bivalents are shown. — The capacity to form repetitive components of the synaptonemal complex type by spermatocytes of the super-Family Grylloidea is discussed.

AbstractThe construct of sense of agency (SoA) has proven useful for understanding mechanisms underlying obsessive–compulsive disorder (OCD) phenomenology, especially in explaining the apparent dissociation in OCD between actual and perceived control over one’s actions. Paradoxically, people with OCD appear to experience both diminished SoA (feeling unable to control their actions) and inflated SoA (having “magical” control over events). The present review investigated the extent to which the SoA is distorted in OCD, in terms of both implicit (ie, inferred from correlates and outcomes of voluntary actions) and explicit (ie, subjective judgment of one’s control over an outcome) measures of SoA. Our search resulted in 15 studies that met the criteria for inclusion in a meta-analysis, where we also examined the potential moderating effects of the type of measure (explicit versus implicit) and of the actual control participants had over the outcome. We found that participants with OCD or with high levels of OCD symptoms show lower implicit measures of SoA and at the same time tend to overestimate their control in situations where they do not actually have it. Together, these findings support the hypothesized dissociation in OCD between actual and perceived control over one’s actions.

In the period from 2010 to 2014, the manufacture of components for the ITER Magnet System has started. Manufacturing of such complex components is associated not only with technical difficulties but also with managing an enormous amount of data and documentation. For example, the magnet feeders have more than 600,000 different parts, which need to be traced for quality control purposes. Another challenge is managing parts distribution among manufacturers. ITER Organization (IO) as a hub had received more than 20 thousand instrumentation components (sensors, cables, etc.) from its suppliers that needed to be stored and then distributed timely among components’ manufacturers. To solve these and other tasks, the Manufacturing Database (MDB) has been developed and deployed by the IO. The MDB consists of several modules that store information about raw materials, acceptance test results, drawings, procedures, electronic Manufacturing and Inspection Plans (MIPs), etc. When a component is being manufactured its related section of the MDB is filled with manufacturing records and reports and the Control Points (CPs) are approved online. When component manufacturing is completed, the final document is formed in the database with a full set of data and possibility to trace raw materials and easily find relevant manufacturing records. Brief description of the MDB modules and the interaction between them is provided in the article. The main advantages of its use are shown, as well as lessons learnt. The need for such a tool for the implementation in large and medium scientific or industrial projects, both local and international, is discussed.

Background The goals of this study were to understand the trends in recent and past rhinology fellows concerning their demographics, goals, and experiences.Methods An anonymous web-based survey was sent to graduates of the 35 rhinology fellowship programs. The survey included questions regarding the scope of practice, research contribution, societal involvement, fellow satisfaction with training, and current practice patterns. Chi-square testing and logistic regression were used to compare variables across cohorts: 0-5 years versus 6+ years from fellowship graduation, gender, and practice settings.Results Based on 171 respondents, we found no significant differences in 0-5 versus 6+ year graduates in their desire for an academic job post-fellowship. However, those who graduated 6+ years ago had significantly more success securing one (74% vs 96%, P= 0.004). Between males and females, there were no differences in goal of obtaining an academic job or success in obtaining an academic career. Females were more likely to report they attend academic society meetings regularly. Female rhinologists also reported less satisfaction with overall work-life balance and decreased satisfaction with clinical practice. Physicians in academic settings have poorer work-life balance.Conclusions Our findings suggest that finding an academic job may be more difficult for recent rhinology fellowship graduates, although still very possible for the majority of graduates. Understanding the reason for these changes may provide insight to current rhinology fellowship directors and trainees interested in pursuing fellowship training.

Purpose To report a case of pitchfork sign following pars plana vitrectomy for idiopathic epiretinal membrane.Study design Case report.Results A 75-year-old man was referred to the surgical retina service due to a quantitative and qualitative decline in vision in the left eye (LE) for several months. Optical coherence tomography (OCT) examination revealed the presence of a stage III epiretinal membrane (ERM) according to the Govetto classification. Seven days after undergoing a 25-gauge pars plana vitrectomy (PPV) with ERM peeling and balanced salt solution (BSS) tamponade, OCT examination revealed the presence of the ‘pitchfork sign’ in the macular region, along with the detection of a choroidal neovascularization (CNV) through OCT-A examination. After receiving two monthly intravitreal anti-VEGF injections, a complete regression of the MNV was observed.Conclusions We reported, for the first time, the iatrogenic onset of the pitchfork sign following vitreoretinal surgery. This discovery highlights the unique presentation of the pitchfork sign in the context of surgical procedures, expanding our comprehension of its range of causes.

Age-related macular degeneration (AMD) is a complex and multifactorial disease characterized by the damage of the unit comprised of the photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. Although the outer retina appears to be mainly affected in this disorder, several evidences exhibit that also the inner retina may be impaired. In this review we will provide a description of the prominent histologic and imaging findings suggesting an inner retinal loss in these eyes. In details, structural optical coherence tomography (OCT) technology proved either the inner and outer retina is impacted by AMD and that these two impairments are associated. Therefore, the purpose of this review is to provide a description of the role of neurodegeneration in AMD in order to better understand the relationship between neuronal loss and the outer retinal damage in this disease.

Diagnosis of rumination syndrome (RS) relies on Rome IV criteria. Oesophageal high‐resolution impedance manometry (HRIM) can objectively demonstrate the episodes of rumination, but its role in the diagnostic pathway is not yet established. We aimed to demonstrate the clinical contribution of this tool for the timely diagnosis of RS and diagnostic work‐up of children with unexplained foregut symptoms deemed to be due to other conditions. HRIMs performed between 2012 and 2021 were searched to retrieve all diagnoses of RS. Medical records were reviewed for clinical data. Out of 461 HRIMs performed, 76 children had manometric diagnosis of RS (35 male, median age: 13 years). Of them, 47% were not clinically suspected as the symptoms did not fulfil clinical criteria for RS. The indications for HRIM in these cases were investigation of unexplained foregut symptoms (37%), suspected refractory gastroesophageal reflux disease (8%) and dysphagia (2%). Among all HRIMs performed for investigations of unexplained foregut symptoms (n= 80), 35% demonstrated rumination episodes. Identification of characteristic patterns of rumination on HRIM in children with unexplained foregut symptoms enables the immediate diagnosis of RS. Thus, in situations of diagnostic uncertainty, the use of HRIM at early stages of the diagnostic pathway would reduce unnecessary investigations and treatments. Diagnosis of rumination syndrome (RS) is based on Rome IV criteria.Heterogeneity of symptomatology, overlap with other functional gastrointestinal disorders and symptom miscommunication make its diagnosis challenging.Despite high‐resolution impedance manometry (HRIM) can detect rumination episodes, its role in diagnosing RS is not well established. Diagnosis of rumination syndrome (RS) is based on Rome IV criteria. Heterogeneity of symptomatology, overlap with other functional gastrointestinal disorders and symptom miscommunication make its diagnosis challenging. Despite high‐resolution impedance manometry (HRIM) can detect rumination episodes, its role in diagnosing RS is not well established. HRIM enables diagnosis of RS in more than one‐third of children with unexplained upper GI symptoms.Almost half of the patients diagnosed with RS on HRIM are not clinically identified as these cases do not fulfil Rome criteria for RS.HRIM can facilitate diagnosis of RS in children with unexplained foregut symptoms and avoid excessive investigations and treatments. HRIM enables diagnosis of RS in more than one‐third of children with unexplained upper GI symptoms. Almost half of the patients diagnosed with RS on HRIM are not clinically identified as these cases do not fulfil Rome criteria for RS. HRIM can facilitate diagnosis of RS in children with unexplained foregut symptoms and avoid excessive investigations and treatments.

The assessment of reading performance metrics is characterized by good values of intersession repeatability in patients with neovascular age-related macular degeneration with good best-corrected visual acuity. These findings are important if these measures be employed in trials assessing the visual outcome in patients with neovascular age-related macular degeneration.

Objectives: Among patients with chronic rhinosinusitis (CRS), gender differences in epidemiology as well as quality of life have been reported. However, whether gender differences in endoscopic sinus surgery (ESS) preoperative concerns exist is unclear.Methods: CRS patients undergoing ESS at 3 tertiary care centers in Los Angeles completed the validated Western Surgical Concern Inventory - ESS assessing ESS preoperative concerns.Results: Of the 75 patients included, female patients expressed greater concern than male patients in regard to nasal packing, undergoing anesthesia, impact of surgery on daily activities, and pain and discomfort following surgery.Conclusion: This study suggests there are gender differences in ESS preoperative concerns and otolaryngologists should be aware of these possible concerns during preoperative discussions.

Different simulation models of the hydrated electron produce different solvation structures, but it has been challenging to determine which simulated solvation structure, if any, is the most comparable to experiment. In a recent work, Neupane et al. [J. Phys. Chem. B2023, 127, 5941–5947] showed using Kirkwood–Buff theory that the partial molar volume of the hydrated electron, which is known experimentally, can be readily computed from an integral over the simulated electron–water radial distribution function. This provides a sensitive way to directly compare the hydration structure of different simulation models of the hydrated electron with experiment. Here, we compute the partial molar volume of an ab-initio-simulated hydrated electron model based on density-functional theory (DFT) with a hybrid functional at different simulated system sizes. We find that the partial molar volume of the DFT-simulated hydrated electron is not converged with respect to the system size for simulations with up to 128 waters. We show that even at the largest simulation sizes, the partial molar volume of DFT-simulated hydrated electrons is underestimated by a factor of 2 with respect to experiment, and at the standard 64-water size commonly used in the literature, DFT-based simulations underestimate the experimental solvation volume by a factor of ∼3.5. An extrapolation to larger box sizes does predict the experimental partial molar volume correctly; however, larger system sizes than those explored here are currently intractable without the use of machine-learned potentials. These results bring into question what aspects of the predicted hydrated electron radial distribution function, as calculated by DFT-based simulations with the PBEh-D3 functional, deviate from the true solvation structure.

In athletes with right bundle branch block (RBBB) morphology non-sustained ventricular arrhythmias (VAs), the presence of a non-ischaemic left ventricular scar (NLVS) may be highly suspected if one or more of the following electrocardiogram (ECG) characteristics are present at the 12-lead resting ECG: low QRS voltages in limb leads, negative Twaves in inferior leads, negative Twaves in limb leads I–aVL, negative Twaves in precordial leads V4–V6, presence of left posterior fascicular block, presence of pathologic Qwaves, and poor R-wave progression in right precordial leads. This score should be externally validated in a larger population of athletes with VAs.In athletes with RBBB morphology non-sustained Vas, attention should be placed on the 12-lead resting ECG to suspect the presence of an NLVS.In athletes with RBBB VAs and the presence of one or more of the identified ECG characteristics, a cardiac magnetic resonance with late gadolinium enhancement is useful to rule out an NLVS.Graphical Abstract

This case involves a 30-year-old female who suffered extensive facial burns as an outcome of a horrific assault. The patient subsequently underwent 2 surgeries with the ultimate goal of reducing the cosmetic, physical, and thus mental burden the assault caused. The technique of choice was the novel trapezius fasciocutaneous flap for burn reconstruction of the neck. It is discussed that while this technique is still deemed a novel procedure, its unique characteristics make it an excellent choice for cases similar to this one. While this approach has not been widely popularized in the treatment of patients with burn contracture requiring reconstruction, the donor site characteristics and ideal functionality make the trapezius fasciocutaneous flap such an excellent choice. This particular type of graft yields a hidden donor site, contains rich vascularity with physical qualities similar to those of facial skin, specifically in regard to thickness, color, and texture, and ultimately produces the most ideal cometic outcome. Further, the wide arc of rotation unique to this flap allows for better manipulation and mobility at the transplanted location. While the anatomic implications are very relevant to head and neck surgery, this method also produces exemplary cosmetic outcomes when compared to other graft procedures.

Extraskeletal Ewing sarcoma (EES) is a relatively rare primary tumor of the soft tissues predominantly affecting men in the second and third decades of life. They are a less common form of the cancerous growth known as an Ewing sarcoma, which occurs in bones or soft tissue such as cartilage. Head and neck ESS can require intervention including endoscopic sinus surgery, septoplasty, inferior turbinectomy, and left internal nasal valve repairs with septal cartilage This is a case report on an unusual presentation of ESS in the sinonasal region.

Purpose: To explore the use of autologous platelet-rich plasma (PRP) as a potential therapeutic adjuvant strategy for treating degenerative lamellar macular holes (LMHs). Design: A prospective interventional case series. Methods: Seven consecutive patients (8 eyes) with a diagnosis of LMH underwent a pars-plana vitrectomy with PRP injection under air tamponade. Anatomical results based on spectral domain optical coherence tomography (SD-OCT) and functional results, in terms of best corrected visual acuity (BCVA) and reading performance, were analyzed. Results: At 12 months postoperatively, 7 out of 8 eyes (88%) presented a complete closure of the LMH. The ellipsoid zone (EZ) was restored in 3 eyes (37.5%). The mean (±SD) postoperative BCVA was 0.39 (±0.56) LogMAR, resulting in a statistically significant visual acuity improvement (p= 0.007). The mean (±SD) maximum reading speed (MaxRS) improved to 133.48 (±41.47) wpm, with a significant increase compared to the baseline (p= 0.029). The mean (±SD) reading acuity score (RA score) resulted in 0.44 (±0.04) LogRAD, with an improvement in reading acuity that did not reach statistical significance (p= 0.129). Conclusions: The utilization of the PRP technique with a no-retina-touch approach safeguards the delicate retinal tissues, minimizing the possibility of iatrogenic trauma or post-operative complications, while maintaining a high rate of efficacy in enabling the improvement of the foveal defect in lamellar macular holes.

PurposeTo develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD).Methods300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients.ResultsThe model obtained a mean (±SD) AUC of 0.93 (±0.04) per slice and 0.88 (±0.07) per volume for fluid detection. The correlation score (R2) between automatic and manual segmentation obtained by the model resulted in a mean (±SD) of 0.89 (±0.05). The mean (±SD) 2D correlation score was 0.69 (±0.04). The mean (±SD) Dice score resulted in 0.61 (±0.10).ConclusionsWe present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians’ assessments.

Background: To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small idiopathic macular hole. Methods: Retrospective, multicentre cohort study including consecutive eyes with a ≤250 μm idiopathic macular hole treated with primary vitrectomy. The primary outcome was best-corrected visual acuity (BCVA) change and macular hole closure rate. Closure patterns on optical coherence tomography (OCT) and rates of external limiting membrane (ELM) and ellipsoid zone (EZ) recovery were considered as secondary outcomes. Results: A total of 389 and 250 eyes were included in the conventional ILM peeling group and in the inverted flap group, respectively. Hole closure rate was comparable between the two groups (98.5% in the ILM peeling group and 97.6% in the inverted flap group). Mean BCVA was comparable between the two groups at baseline (p= 0.331). At 12 months, mean BCVA was 0.14 ± 0.19 logMAR in the conventional ILM peeling group and 0.17 ± 0.18 logMAR in the inverted flap group (p= 0.08). At 12 months, 73% of eyes had a U-shape closure morphology in the conventional ILM peeling group versus 55% in the inverted flap group. At 12 months, ELM recovery rate was 96% and 86% in the conventional ILM peeling group and in the inverted flap group, respectively (p&lt; 0.001); EZ recovery rate was 78% and 69%, respectively (p= 0.04). Conclusions: The inverted flap technique provides no advantages in terms of visual outcome and closure rate in small idiopathic macular hole surgery. Additionally, this technique seems to impair postoperative restoration of external retinal layers compared with conventional peeling.

We present an interactive visual analysis tool for analyzing the spread of wildfires and what influences their evolution. Multiple time-varying 3-D scalar and vector fields are investigated and related to each other to identify causes of atypical fire spread. We present a visual analysis approach that allows for a comparative analysis of multiple runs of a simulation ensemble on different levels of detail. Overview visualizations combined with volume renderings and flow visualizations provide an intuitive understanding of the fire spread.

It is estimated that only 0.02% of disseminated tumour cells are able to seed overt metastases1. While this suggests the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unclear. Here, combining transposon technology2and fluorescence niche labelling3, we developed an in vivo CRISPR activation screen to systematically investigate the interactions between hepatocytes and metastatic cells. We identify plexin B2 as a critical host-derived regulator of liver colonization in colorectal and pancreatic cancer and melanoma syngeneic mouse models. We dissect a mechanism through which plexin B2 interacts with class IV semaphorins on tumour cells, leading to KLF4 upregulation and thereby promoting the acquisition of epithelial traits. Our results highlight the essential role of signals from the liver parenchyma for the seeding of disseminated tumour cells before the establishment of a growth-promoting niche. Our findings further suggest that epithelialization is required for the adaptation of CRC metastases to their new tissue environment. Blocking the plexin-B2–semaphorin axis abolishes metastatic colonization of the liver and therefore represents a therapeutic strategy for the prevention of hepatic metastases. Finally, our screening approach, which evaluates host-derived extrinsic signals rather than tumour-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints to metastasis in other organs and cancer types.

Eosinophils are a class of granulocytes with pleiotropic functions in homeostasis and various human diseases. Nevertheless, they are absent from conventional single-cell RNA sequencing atlases owing to technical difficulties preventing their transcriptomic interrogation. Consequently, eosinophil heterogeneity and the gene regulatory networks underpinning their diverse functions remain poorly understood. We have developed a stress-free protocol for single-cell RNA capture from murine tissue-resident eosinophils, which revealed distinct intestinal subsets and their roles in colitis. Here we describe in detail how to enrich eosinophils from multiple tissues of residence and how to capture high-quality single-cell transcriptomes by preventing transcript degradation. By combining magnetic eosinophil enrichment with microwell-based single-cell RNA capture (BD Rhapsody), our approach minimizes shear stress and processing time. Moreover, we report how to perform genome-wide CRISPR pooled genetic screening in ex vivo-conditioned bone marrow-derived eosinophils to functionally probe pathways required for their differentiation and intestinal maturation. These protocols can be performed by any researcher with basic skills in molecular biology and flow cytometry, and can be adapted to investigate other granulocytes, such as neutrophils and mast cells, thereby offering potential insights into their roles in both homeostasis and disease pathogenesis. Single-cell transcriptomics of eosinophils can be performed in 2–3 d, while functional genomics assays may require up to 1 month.

Gold nanomaterials have been shown to augment radiation therapy both in vitro and in vivo. However, studies on these materials are mostly phenomenological due to nanoparticle heterogeneity and the complexity of biological systems. Even accurate quantification of the particle dose still results in bulk average biases; the effect on individual cells is not measured but rather the effect on the overall population. To perform quantitative nanobiology, we coated glass coverslips uniformly at varying densities with Au nanoparticle preparations with different morphologies (45 nm cages, 25 nm spheres, and 30 nm rods). Consequently, the effect of a specific number of particles per unit area in contact with breast cancer cells growing on the coated surfaces was ascertained. Gold nanocages showed the highest degree of radiosensitization on a per particle basis, followed by gold nanospheres and gold nanorods, respectively. All three materials showed little cytotoxic effect at 0 Gy, but clonogenic survival decreased proportionally with the radiation dose and particle coverage density. A similar trend was seen in vivo in the combined treatment antitumor response in 4T1 tumor-bearing animals. The presence of gold affected the type and quantity of reactive oxygen species generated, specifically superoxide and hydroxyl radicals, and the concentration of nanocages correlated with the development of more numerous double-stranded DNA breaks and increased protein oxidation as measured by carbonylation. This work demonstrates the dependence on morphology and concentration of radiation enhancement by gold nanomaterials and may lead to a novel method to differentiate intra- and extracellular functionalities of gold nanomedicine treatment strategies. It further provides insights that can guide the rational development of gold nanomaterial-based radiosensitizers for clinical use.

Background: Multiple sclerosis (MS) is associated with high prevalence of cognitive impairment, ranging from 40 to 80%. The purpose of this single-center retrospective study was to examine the relation between cognitive function, as measured by Symbol Digit Modalities Test (SDMT), with fatigue, anxiety, and depression symptoms in a Belgian cohort of patients with MS. Methods: Sociodemographic and clinical data were analyzed in 66 (F:40, M:26) Belgian patients with a diagnosis of MS. The cognitive function was assessed with the oral version of SDMT, depression and anxiety symptoms with the Hospital Anxiety and Depression scale (HAD), fatigue symptoms with the French valid version of the Fatigue Impact Scale in MS (EMIF-SEP), which is a scale composed of four dimensions (cognitive, physical, social, and psychological) allowing a multidimensional evaluation of fatigue. Results: The multivariate linear regression analysis demonstrated that lower SDMT scores were associated with higher EDSS score and psychological dimension of fatigue symptoms. No association were found between SDMT and anxiety or depression symptoms. Conversely, higher depression and anxiety symptoms were associated with higher total fatigue symptoms, but lower physical dimension of fatigue symptoms. Higher anxiety symptoms were also independently associated with higher social dimension of fatigue symptoms. Conclusion: A complex relationship exists between cognitive performance, fatigue, and neuropsychiatric symptoms in Belgian people with MS. The level of disability and fatigue adversely affects the cognitive function in MS, whereas depression and anxiety seem to not have a significant effect. A more complex relationship exists between fatigue and neuropsychiatric symptoms, with a divergent interplay between the different dimensions of fatigue that supports the multidimensional approach to assessing fatigue in MS.

Purpose To evaluate short-term peripapillary structural and vascular changes in DME after treatment with dexamethasone implant (DEX-I) and anti-VEGFs using OCT-A.Methods Sixty-five patients with naïve center-involving DME were enrolled. 33 of sixty five patients (group 1) underwent with single DEX-I 0.7 mg (Ozurdex, Allergan, Inc., USA), 32 of sixty-five (group 2) underwent with intravitreal injection of aflibercept 0.5 mg (Eylea, Bayer, Genentech, San Francisco, USA). The OCT acquisition was completed at the following visits: (i) “T1 visit” corresponding to the intravitreal injection of DEX-I or aflibercept in patients with naïve center-involving DME (ii) “T2 visit” corresponding to the examination performed 2 weeks after intravitreal injection of aflibercept and 1 month after DEX-I. The parameters analyzed were: (i) RPC vasculature density (VD); (ii) peripapillary retinal nerve fiber layer (pRNFL) thickness, and (iii) intraocular pressure (IOP).Results The RPC analysis showed a VD increase at T2 in both groups, although values did not reach statistical significance (48.12± 4.17 and 49.04 ± 4.23; P = 0.081 in Group 1 and 46.93± 3.16 and 47.17 ± 3.70; P = 0.087 in Group 2). Likewise, the pRNFL thickness and IOP fluctuations did not show statistically significant changes in in both groups among the different study visits.Conclusions After intravitreal injection (anti-VEGF or DEX-I), no significant short-term changes were found in peripapillary microvasculature, IOP and pRNFL thickness in diabetic eyes treated with anti-VEGF or DEX-I.

El descubrimiento de autoanticuerpos específicos es un hito muy importante en el diagnóstico de las miopatías inflamatorias idiopáticas (MII), permitiendo a los nuevos consensos de clasificación incluir en los criterios diagnósticos los hallazgos serológicos junto a los clínicos e histopatológicos usados tradicionalmente.