First X-ray spectral ptychography and resonant ptychographic computed tomography experiments at the SWING beamline from Synchrotron SOLEIL.

X-ray ptychography and ptychographic computed tomography have seen a rapid rise since the advent of fourth-generation synchrotrons with a high degree of coherent radiation. In addition to quantitative multiscale structural analysis, ptychography with spectral capabilities has been developed, allowing for spatial-localized multiscale structural and spectral information of samples. The SWING beamline of Synchrotron SOLEIL has recently developed a nanoprobe setup where the endstation's first spectral and resonant ptychographic measurements have been successfully conducted. A metallic nickel wire sample was measured using 2D spectral ptychography in XANES mode and resonant ptychographic tomography. From the 2D spectral ptychography measurements, the spectra of the components of the sample's complex-valued refractive index, δ and ß, were extracted, integrated along the sample thickness. By performing resonance ptychographic tomography at two photon energies, 3D maps of the refractive index decrement, δ, were obtained at the Ni K-edge energy and another energy above the edge. These maps allowed the detection of impurities in the Ni wire. The significance of accounting for the atomic scattering factor is demonstrated in the calculation of electron density near a resonance through the use of the δ values. These results indicate that at the SWING beamline it is possible to conduct state-of-the-art spectral and resonant ptychography experiments using the nanoprobe setup.

7.10 MAG. A Novel Host Monoacylglyceride for In Meso (Lipid Cubic Phase) Crystallization of Membrane Proteins.

A novel monoacylglycerol, 7.10 MAG, has been produced for use in the in meso (lipid cubic phase) crystallization of membrane proteins and complexes. 7.10 MAG differs from monoolein, the most extensively used lipid for in meso crystallization, in that it is shorter in chain length by one methylene and its cis olefinic bond is two carbons closer to the glycerol headgroup. These changes in structure alter the phase behavior of the hydrated lipid and the microstructure of the corresponding mesophases formed. Temperature-composition phase diagrams for 7.10 MAG have been constructed using small- and wide-angle X-ray scattering over a range of temperatures and hydration levels that span those used for crystallization. The phase diagrams include lamellar crystalline, fluid isotropic, lamellar liquid-crystalline, cubic-Ia3d, and cubic-Pn3m phases, as observed with monoolein. Conspicuous by its absence is the inverted hexagonal phase which is rationalized on the basis of 7.10 MAG's chemical constitution. The cubic phase prepared with the new lipid facilitates the growth of crystals that were used to generate high-resolution structures of intramembrane ß-barrel and α-helical proteins. Compatibility of fully hydrated 7.10 MAG with cholesterol and phosphatidylcholine means that these two lipids can be used as additives to optimize crystallogenesis in screening trials with 7.10 MAG as the host lipid.

Exploring the Performance of ChatGPT Versions 3.5, 4, and 4 With Vision in the Chilean Medical Licensing Examination: Observational Study.

Background: The deployment of OpenAI's ChatGPT-3.5 and its subsequent versions, ChatGPT-4 and ChatGPT-4 With Vision (4V; also known as "GPT-4 Turbo With Vision"), has notably influenced the medical field. Having demonstrated remarkable performance in medical examinations globally, these models show potential for educational applications. However, their effectiveness in non-English contexts, particularly in Chile's medical licensing examinations-a critical step for medical practitioners in Chile-is less explored. This gap highlights the need to evaluate ChatGPT's adaptability to diverse linguistic and cultural contexts. Objective: This study aims to evaluate the performance of ChatGPT versions 3.5, 4, and 4V in the EUNACOM (Examen Único Nacional de Conocimientos de Medicina), a major medical examination in Chile. Methods: Three official practice drills (540 questions) from the University of Chile, mirroring the EUNACOM's structure and difficulty, were used to test ChatGPT versions 3.5, 4, and 4V. The 3 ChatGPT versions were provided 3 attempts for each drill. Responses to questions during each attempt were systematically categorized and analyzed to assess their accuracy rate. Results: All versions of ChatGPT passed the EUNACOM drills. Specifically, versions 4 and 4V outperformed version 3.5, achieving average accuracy rates of 79.32% and 78.83%, respectively, compared to 57.53% for version 3.5 (P<.001). Version 4V, however, did not outperform version 4 (P=.73), despite the additional visual capabilities. We also evaluated ChatGPT's performance in different medical areas of the EUNACOM and found that versions 4 and 4V consistently outperformed version 3.5. Across the different medical areas, version 3.5 displayed the highest accuracy in psychiatry (69.84%), while versions 4 and 4V achieved the highest accuracy in surgery (90.00% and 86.11%, respectively). Versions 3.5 and 4 had the lowest performance in internal medicine (52.74% and 75.62%, respectively), while version 4V had the lowest performance in public health (74.07%). Conclusions: This study reveals ChatGPT's ability to pass the EUNACOM, with distinct proficiencies across versions 3.5, 4, and 4V. Notably, advancements in artificial intelligence (AI) have not significantly led to enhancements in performance on image-based questions. The variations in proficiency across medical fields suggest the need for more nuanced AI training. Additionally, the study underscores the importance of exploring innovative approaches to using AI to augment human cognition and enhance the learning process. Such advancements have the potential to significantly influence medical education, fostering not only knowledge acquisition but also the development of critical thinking and problem-solving skills among health care professionals.

Effects of antidiabetic drugs on bone metabolism.

Objectives: The prevalence of diabetes mellitus type 2 (DMT2) is increasing exponentially worldwide. DMT2 patients have been found to be at a higher risk for bone fractures than the healthy population. Hence, improving our understanding of the impact of antidiabetic drugs on bone metabolism is crucial. Methods: A descriptive, retrospective study involving 106 patients receiving six groups of antidiabetic drugs: insulin; dipeptidylpeptidase four inhibitors (DPP4i); glucagon-like peptide type 1 receptor agonists (GLP1ra); sulfonylureas; sodium-glucose cotransporter two inhibitors (SGLT2i); and pioglitazone, in which osteocalcin (OC), bone alkaline phosphatase (BAP) and C-terminal telopeptide of collagen type 1 or beta-crosslaps (ß-CTx) were determined. Results: ß-CTx concentrations were higher in the patients treated with pioglitazone, as compared to patients treated with DPP4i (p=0.035), SGLT2i (p=0.020) or GLP1ra (p<0.001). The lowest ß-CTx concentrations were observed in the patients treated with GLP1ra. Conclusions: Bone remodeling is influenced by the type of antidiabetic drug administered to DMT2 patients. In our study, the patients who received pioglitazone showed higher ß-CTx concentrations, as compared to patients treated with other types of antidiabetic drugs. This finding highlights the convenience of avoiding these drugs, especially in postmenopausal women with DMT2. GLP1ra drugs were associated with the lowest ß-CTx concentrations, which suggests that these agents could exert beneficial effects on bone metabolism.

Mechanisms Underlying Memory Impairment Induced by Fructose.

Fructose consumption has increased over the years, especially in adolescents living in urban areas. Growing evidence indicates that daily fructose consumption leads to some pathological conditions, including memory impairment. This review summarizes relevant data describing cognitive deficits after fructose intake and analyzes the underlying neurobiological mechanisms. Preclinical experiments show sex-related deficits in spatial memory; that is, while males exhibit significant imbalances in spatial processing, females seem unaffected by dietary supplementation with fructose. Recognition memory has also been evaluated; however, only female rodents show a significant decline in the novel object recognition test performance. According to mechanistic evidence, fructose intake induces neuroinflammation, mitochondrial dysfunction, and oxidative stress in the short term. Subsequently, these mechanisms can trigger other long-term effects, such as inhibition of neurogenesis, downregulation of trophic factors and receptors, weakening of synaptic plasticity, and long-term potentiation decay. Integrating all these neurobiological mechanisms will help us understand the cellular and molecular processes that trigger the memory impairment induced by fructose.

Residential exposure to traffic pollution and mammographic density in premenopausal women.

BACKGROUND: Mammographic density (MD) is the most important breast cancer biomarker. Ambient pollution is a carcinogen, and its relationship with MD is unclear. This study aims to explore the association between exposure to traffic pollution and MD in premenopausal women. METHODOLOGY: This Spanish cross-sectional study involved 769 women attending gynecological examinations in Madrid. Annual Average Daily Traffic (AADT), extracted from 1944 measurement road points provided by the City Council of Madrid, was weighted by distances (d) between road points and women's addresses to develop a Weighted Traffic Exposure Index (WTEI). Three methods were employed: method-1 (1dAADT), method-2 (1dAADT), and method-3 (e1dAADT). Multiple linear regression models, considering both log-transformed percentage of MD and untransformed MD, were used to estimate MD differences by WTEI quartiles, through two strategies: "exposed (exposure buffers between 50 and 200 m) vs. not exposed (>200 m)"; and "degree of traffic exposure". RESULTS: Results showed no association between MD and traffic pollution according to buffers of exposure to the WTEI (first strategy) for the three methods. The highest reductions in MD, although not statistically significant, were detected in the quartile with the highest traffic exposure. For instance, method-3 revealed a suggestive inverse trend (eßQ1 = 1.23, eßQ2 = 0.96, eßQ3 = 0.85, eßQ4 = 0.85, p-trend = 0.099) in the case of 75 m buffer. Similar non-statistically significant trends were observed with Methods-1 and -2. When we examined the effect of traffic exposure considering all the 1944 measurement road points in every participant (second strategy), results showed no association for any of the three methods. A slightly decreased MD, although not significant, was observed only in the quartile with the highest traffic exposure: eßQ4 = 0.98 (method-1), and eßQ4 = 0.95 (methods-2 and -3). CONCLUSIONS: Our results showed no association between exposure to traffic pollution and MD in premenopausal women. Further research is needed to validate these findings.

A Self-Adaptive Automatic Incident Detection System for Road Surveillance Based on Deep Learning.

We present an automatic road incident detector characterised by a low computational complexity for easy implementation in affordable devices, automatic adaptability to changes in scenery and road conditions, and automatic detection of the most common incidents (vehicles with abnormal speed, pedestrians or objects falling on the road, vehicles stopped on the shoulder, and detection of kamikaze vehicles). To achieve these goals, different tasks have been addressed: lane segmentation, identification of traffic directions, and elimination of unnecessary objects in the foreground. The proposed system has been tested on a collection of videos recorded in real scenarios with real traffic, including areas with different lighting. Self-adaptability (plug and play) to different scenarios has been tested using videos with significant scene changes. The achieved system can process a minimum of 80 video frames within the camera's field of view, covering a distance of 400 m, all within a span of 12 s. This capability ensures that vehicles travelling at speeds of 120 km/h are seamlessly detected with more than enough margin. Additionally, our analysis has revealed a substantial improvement in incident detection with respect to previous approaches. Specifically, an increase in accuracy of 2-5% in automatic mode and 2-7% in semi-automatic mode. The proposed classifier module only needs 2.3 MBytes of GPU to carry out the inference, thus allowing implementation in low-cost devices.

Draft genome of the Klebsiella pneumoniae 24Kpn33 and complete sequence of its pCOL-1, a plasmid related to the blaKPC-2 acquisition in Pseudomonas aeruginosa.

We report the draft genome of a clinical multi-resistant Klebsiella pneumoniae (24Kpn33) isolate, whose genome (5.7 Mbp) harbored 17 antibiotic resistance genes, including blaKPC-2. Notably, this gene was mobilized within the IncP-6 pCOL-1 plasmid, the first genetic platform related to the acquisition and dissemination of the blaKPC-2 in Pseudomonas aeruginosa.

Finding neural correlates of depersonalisation/derealisation disorder via explainable CNN-based analysis guided by clinical assessment scores.

Mental health disorders are typically diagnosed based on subjective reports (e.g., through questionnaires) followed by clinical interviews to evaluate the self-reported symptoms. Therefore, considering the interconnected nature of psychiatric disorders, their accurate diagnosis is a real challenge without indicators of underlying physiological dysfunction. Depersonalisation/derealisation disorder (DPD) is an example of dissociative disorder affecting 1-2 % of the population. DPD is characterised mainly by persistent disembodiment, detachment from surroundings, and feelings of emotional numbness, which can significantly impact patients' quality of life. The underlying neural correlates of DPD have been investigated for years to understand and help with a more accurate and in-time diagnosis of the disorder. However, in terms of EEG studies, which hold great importance due to their convenient and inexpensive nature, the literature has often been based on hypotheses proposed by experts in the field, which require prior knowledge of the disorder. In addition, participants' labelling in research experiments is often derived from the outcome of the Cambridge Depersonalisation Scale (CDS), a subjective assessment to quantify the level of depersonalisation/derealisation, the threshold and reliability of which might be challenged. As a result, we aimed to propose a novel end-to-end EEG processing pipeline based on deep neural networks for DPD biomarker discovery, which requires no prior handcrafted labelled data. Alternatively, it can assimilate knowledge from clinical outcomes like CDS as well as data-driven patterns that differentiate individual brain responses. In addition, the structure of the proposed model targets the uncertainty in CDS scores by using them as prior information only to guide the unsupervised learning task in a multi-task learning scenario. A comprehensive evaluation has been done to confirm the significance of the proposed deep structure, including new ways of network visualisation to investigate spectral, spatial, and temporal information derived in the learning process. We argued that the proposed EEG analytics could also be applied to investigate other psychological and mental disorders currently indicated on the basis of clinical assessment scores. The code to reproduce the results presented in this paper is openly accessible at https://github.com/AbbasSalami/DPD_Analysis.

One vs. two-stage arteriovenous loops in lower extremity reconstruction with free flaps: Systematic review and metanalysis.

BACKGROUND: Arteriovenous loops are one of the main therapeutic alternatives to address the absence of recipient vessels in lower extremity microsurgical reconstruction. However, there is no consensus on whether to perform them in one or two surgical stages. The objective of this work is to determine whether the outcome of lower limb free flaps anastomosed to vascular loops depends on the number of surgical stages. MATERIALS AND METHODS: A literature review was conducted, following PRISMA guidelines, on vascular loops and free flaps in lower limb. Survival rate, as well as major and minor complications were studied. A forest plot and Pearson's chi-square were used for statistical analysis. Study quality was assessed in duplicate using Methodological Index for Non-Randomized Studies (MINORS) and Joanna Briggs Institute (JBI) tool. This study was registered on PROSPERO. RESULTS: Thirty-two articles using free flaps anastomosed to vascular loops in lower limb, either one or two-stage, were selected. A total of 296 flaps were included, 52% (n = 154) in one and 48% (n = 142) in two surgical times. No statistically significant differences were found in the survival rate (OR = 1.85, 95% CI 0.62; 5.47, p = .09 and p = .344) or major complications (OR = 0.70, 95% CI 0.31; 1.57, p = .56 and p = .92) of flaps between both groups. CONCLUSIONS: According to the available evidence, the outcome of free flaps anastomosed to vascular loops in the lower limb does not depend on the number of surgical stages they undergo. Although there is some heterogeneity in the groups studied, the decision on the number of procedures to be performed should be determined by the surgeon, concerning the clinical situation of the patient, as well as to the vascular, bone and soft tissue status of the extremity.

Retinal Function in Long-Term Type 1 Diabetes without Retinopathy: Insights from Pattern Electroretinogram and Pattern Visual Evoked Potentials Assessments.

BACKGROUND: To evaluate changes in pattern electroretinogram (pERG) and pattern visual evoked potentials (pVEP) in patients with long-lasting type 1 diabetes without diabetic retinopathy (DR). METHODS: Prospective study involving 92 eyes divided into two groups. The diabetic group included 46 eyes of 23 patients with type 1 diabetes (T1DM); the control group included 23 age-matched healthy subjects. pERG and pVEP were assessed using the RETI-port/scan21 recording software (version 1021.3.0.0). RESULTS: Mean age was 48 ± 9.77 years for the diabetic group and 51.7 ± 4.75 years for the control group. The mean duration of diabetes was 28.88 ± 8.04 years. The mean HbA1c value was 7.29 ± 0.89%. There were no differences in the age or sex distribution. Regarding the pERG, T1DM patients exhibited a significant decrease in the amplitude of the P50 and N95 waves compared to the control group (p = 0.018 and p = 0.035, respectively), with no differences in the peak time of each component. pVEP showed no significant changes in either peak time or amplitude of the different components. CONCLUSIONS: Long-term T1DM patients without DR showed changes in the amplitude of pERG waves with preserved peak times. We did not observe modifications in pVEP. pERG may serve as a subclinical marker of ganglion cell damage in long-term T1DM patients.

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature.

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.

Sensitization to textile dyes in Spain: Epidemiological situation (2019-2022).

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.

2-Hydroxyethyl methacrylate (2-HEMA) sensitization, a global epidemic at its peak in Spain?

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.

ProSPyX: software for post-processing images of X-ray ptychography with spectral capabilities.

X-ray ptychography is a coherent diffraction imaging technique based on acquiring multiple diffraction patterns obtained through the illumination of the sample at different partially overlapping probe positions. The diffraction patterns collected are used to retrieve the complex transmittivity function of the sample and the probe using a phase retrieval algorithm. Absorption or phase contrast images of the sample as well as the real and imaginary parts of the probe function can be obtained. Furthermore, X-ray ptychography can also provide spectral information of the sample from absorption or phase shift images by capturing multiple ptychographic projections at varying energies around the resonant energy of the element of interest. However, post-processing of the images is required to extract the spectra. To facilitate this, ProSPyX, a Python package that offers the analysis tools and a graphical user interface required to process spectral ptychography datasets, is presented. Using the PyQt5 Python open-source module for development and design, the software facilitates extraction of absorption and phase spectral information from spectral ptychographic datasets. It also saves the spectra in file formats compatible with other X-ray absorption spectroscopy data analysis software tools, streamlining integration into existing spectroscopic data analysis pipelines. To illustrate its capabilities, ProSPyX was applied to process the spectral ptychography dataset recently acquired on a nickel wire at the SWING beamline of the SOLEIL synchrotron.

Transcriptional profiling of peripheral blood mononuclear cells identifies inflammatory phenotypes in Ataxia Telangiectasia.

INTRODUCTION: Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy. METHODS: Participants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features. RESULTS: People with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls. CONCLUSION: Using a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.