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Using a Sendai Virus based vector delivering Yamanaka Factors, we generated induced Pluripotent Stem Cells (iPSCs) from peripheral blood mononuclear cells of a patient affected by Ataxia Telangiectasia (AT), caused by a novel homozygous deletion in ATM, spanning exons 5–7. Three clones were fully characterized for pluripotency and capability to differentiate. These clones preserved the causative mutation of parental cells and genomic stability over time (>100 passages). Furthermore, in AT derived iPSCs we confirmed the impaired DNA damage response after ionizing radiation. All these data underline potential usefulness of our clones as in vitro AT disease model.

Background Although there are effective evidence-based treatments for posttraumatic stress disorder (PTSD), many individuals drop out or do not benefit from treatment. There is a need for new treatments, including approaches that are nontrauma focused. Objective The purpose of this program evaluation was to investigate the acceptability of a Wellness Group designed to promote healthy behaviors and adaptive coping when offered to veterans with PTSD. Methods Nine veterans in a PTSD outpatient clinic enrolled in a 12-week, 24-session Wellness Group. Acceptability of the intervention was evaluated with attendance data, questionnaires, and interviews. Results Group attendance rates were high and no participants dropped out of treatment. Treatment satisfaction was high and all veterans reported gains in at least 3 of the 8 Wellness domains covered. Interview data supported the findings that veterans had positive reactions to the group. Conclusion A Wellness approach may offer a low-cost alternative or supplementary treatment for veterans with PTSD that is highly acceptable and may improve health behaviors, quality of life, and coping skills.

An overview is presented of the progress since 2021 in the construction and scientific programme preparation of the Divertor Tokamak Test (DTT) facility. Licensing for building construction has been granted at the end of 2021. Licensing for Cat. A radiologic source has been also granted in 2022. The construction of the toroidal field magnet system is progressing. The prototype of the 170 GHz gyrotron has been produced and it is now under test on the FALCON facility. The design of the vacuum vessel, the poloidal field coils and the civil infrastructures has been completed. The shape of the first DTT divertor has been agreed with EUROfusion to test different plasma and exhaust scenarios: single null, double null, X-divertor and negative triangularity plasmas. A detailed research plan is being elaborated with the involvement of the EUROfusion laboratories.

Earth's climate and water cycle are highly dependent on terrestrial evapotranspiration and the associated flux of latent heat. Although it has been hypothesized for over 50 years that land dryness becomes embedded in atmospheric conditions through evaporation, underlying physical mechanisms for this land–atmosphere coupling remain elusive. Here, we use a novel physically based evaporation model to demonstrate that near-surface atmospheric relative humidity (RH) fundamentally coevolves with RH at the land surface. The new model expresses the latent heat flux as a combination of thermodynamic processes in the atmospheric surface layer. Our approach is similar to the Penman–Monteith equation but uses only routinely measured abiotic variables, avoiding the need to parameterize surface resistance. We applied our new model to 212 in situ eddy covariance sites around the globe and to the FLUXCOM global-scale evaporation product to partition observed evaporation into diabatic vs. adiabatic thermodynamic processes. Vertical RH gradients were widely observed to be near zero on daily to yearly timescales for local as well as global scales, implying an emergent land–atmosphere equilibrium. This equilibrium allows for accurate evaporation estimates using only the atmospheric state and radiative energy, regardless of land surface conditions and vegetation controls. Our results also demonstrate that the latent heat portion of available energy (i.e., evaporative fraction) at local scales is mainly controlled by the vertical RH gradient. By demonstrating how land surface conditions become encoded in the atmospheric state, this study will improve our fundamental understanding of Earth's climate and the terrestrial water cycle.

The Southern California Bight is adjacent to one of the world's largest urban areas, Los Angeles. As a consequence, anthropogenic impacts could disrupt local marine ecosystems due to municipal and industrial waste discharge, pollution, flood control measures, and global warming. Santa Monica Basin (SMB), due to its unique setting in a low-oxygen and high-sedimentation environment, can provide an excellent sedimentary paleorecord of these anthropogenic changes. This study examined 10 sediment cores, collected from different parts of the SMB between spring and summer 2016, and compared them to existing cores in order to document changes in sedimentary dynamics during the last 250 years, with an emphasis on the last 40 years. The 210Pb-based mass accumulation rates (MARs) for the deepest and lowest oxygen-containing parts of the SMB basin (900–910 m) have been remarkably consistent during the past century, averaging 17.1±0.6 mg cm−2 yr−1. At slightly shallower sites (870–900 m), accumulation rates showed more variation but yield the same accumulation rate, 17.9±1.9 mg cm−2 yr−1. Excess 210Pb sedimentation rates were consistent with rates established using bomb test 137Cs profiles. We also examined 14C profiles from two cores collected in the deepest part of the SMB, where fine laminations are present up to about 450 yr BP. These data indicate that the MAR was slower prior to ∼1900 CE (rates obtained were 9 and 12 mg cm−2 yr−1). The δ13Corg profiles show a relatively constant value where laminations are present, suggesting that the change in sediment accumulation rate is not accompanied by a change in organic carbon sources to the basin. The increase in sedimentation rate towards the Recent occurs at about the time previous studies predicted an increase in siltation and the demise of a shelly shelf benthic fauna on the SMB shelf. X-radiographs show finely laminated sediments in the deepest part of the basin only, with centimeter-scale layering of sediments or no layering whatsoever in shallower parts of the SMB basin. The absence of finely laminated sediments in cores MUC 10 (893 m) and MUC 3 (777 m) suggests that the rate at which anoxia is spreading has not increased appreciably since cores were last analyzed in the 1980s. Based on core top data collected during the past half century, sedimentary dynamics within SMB have changed minimally during the last 40 years. Specifically, mass accumulation rates, laminated sediment fabric, extent of bioturbation and % Corg have not changed. The only parameter that appeared to have changed in the last 450 years was the MAR, with an apparent > 50 % increase occurring between ∼1850 CE and the early 1900s. The post-1900 CE constancy of sedimentation through a period of massive urbanization in Los Angeles is surprising.

Water authorities responsible for water quantity and water quality management may strongly influence the magnitude of greenhouse gas emissions from the surface waters and the adjacent peat areas within their territories. Climate smart water management (reducing influx of organic matter and improving water quality) is therefore a potentially strong mitigation tool. We hypothesize that climate smart water management has a stronger mitigation potential than reducing emissions from the operational management of a Water Authority. Based on literature data on greenhouse gas emissions from ditches and agricultural peatlands, we present a case study of a Dutch Water Authority – Amstel, Gooi and Vecht (operated by Waternet). We estimate that greenhouse gas emissions from the 195 km2 large peat area within its territory are 470 kt CO2-eq per year. An additional 231 kt CO2-eq yr−1 is emitted from the water bodies within the 102 km2 large water area territory. Both emissions are considerably higher than the estimated climate footprint of the operational management of the water board (∼62 kt CO2-eq per year in 2017). While Waternet strives to have a net zero emission of greenhouse gases related to its operational management by 2020, we postulate that measures (to be taken before 2030) such as the prevention of organic matter and nutrients entering surface waters, the removal of organic carbon from ditches and higher groundwater levels in agricultural peatlands, may reduce greenhouse gas emissions in ditches and agricultural peat meadows with 26 and 27 kt CO2-eq per year, respectively. Measures that are taken to reduce greenhouse gas emissions in water bodies are expected to have a positive impact on water quality as well.

Repetitive corrugation and straightening (RCS) is a process that induces cyclic plastic deformation on sheet geometries, reporting promising improvements in mechanical properties in metals and alloys. Alternative die geometries, as well as the effect of the process over strain-hardenable alloys, have not been widely studied. In this work, sheets of the aluminum 5754 alloy were processed by RCS, using a novel die design to induce heterogeneous repetitive plastic deformation at room temperature. Numerical 3D Finite Element Analysis (FEA) was performed using the new die; the changes in the homogeneity of deformation, ductility and mechanical strength due to the process were studied. The processed samples were mechanically characterized by means of microhardness and tensile tests. Global and local XRD peak broadening were measured for determining the microstrain evolution during the process. After the initial heterogeneous RCS pass, a decrement in ductility was observed, but the increase in yield strength was significant. The microhardness mapping showed a heterogeneous distribution of the deformation with good agreement with the numerical simulation. XRD peaks width enlarged with the heterogeneous RCS passes in concordance with the mechanical results. Keywords: Aluminum alloys, Repetitive corrugation and straightening, Finite element analysis, Micro-hardness, Stress/strain measurements, X-ray analysis

Abstract Background Metaplastic breast cancer (MBC) is a rare form of breast cancer characterized by an aggressive clinical presentation, with a poor response to standard chemotherapy. MBCs are typically triple-negative breast cancers (TNBCs), frequently with alterations to genes of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective of this study was to determine the response to PI3K and MAPK pathway inhibitors in patient-derived xenografts (PDXs) of MBCs with targetable alterations. Methods We compared survival between triple-negative MBCs and other histological subtypes, in a clinical cohort of 323 TNBC patients. PDX models were established from primary breast tumors classified as MBC. PI3K-AKT-mTOR and RTK-MAPK pathway alterations were detected by targeted next-generation sequencing (NGS) and analyses of copy number alterations. Activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways was analyzed with reverse-phase protein arrays (RPPA). PDXs carrying an activating mutation of PIK3CA and genomic changes to the RTK-MAPK signaling pathways were treated with a combination consisting of a PI3K inhibitor and a MEK inhibitor. Results In our clinical cohort, the patients with MBC had a worse prognosis than those with other histological subtypes. We established nine metaplastic TNBC PDXs. Three had a pathogenic mutation of PIK3CA and additional alterations to genes associated with RTK-MAPK signaling. The MBC PDXs expressed typical EMT and stem cell genes and were of the mesenchymal or mesenchymal stem-like TNBC subtypes. On histological analysis, MBC PDXs presented squamous or chondroid differentiation. RPPA analysis showed activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. In vivo, the combination of PI3K and MAPK inhibitors displayed marked antitumor activity in PDXs carrying genomic alterations of PIK3CA, AKT1, BRAF, and FGFR4. Conclusion The treatment of metaplastic breast cancer PDXs by activation of the PI3K-AKT-mTOR and RTK-MAPK pathways at the genomic and protein levels with a combination of PI3K and MEK inhibitors resulted in tumor regression in mutated models and may therefore be of interest for therapeutic purposes.

Carbon (C) and nitrogen (N) cycling under future climate change is associated with large uncertainties in litter decomposition and the turnover of soil C and N. In addition, future conditions (especially altered precipitation regimes and warming) are expected to result in changes in vegetation composition, and accordingly in litter species and chemical composition, but it is unclear how such changes could potentially alter litter decomposition. Litter transplantation experiments were carried out across six European sites (four forests and two grasslands) spanning a large geographical and climatic gradient (5.6–11.4 °C in annual temperature 511–878 mm in precipitation) to gain insight into the climatic controls on litter decomposition as well as the effect of litter origin and species. The decomposition k rates were overall higher in warmer and wetter sites than in colder and drier sites, and positively correlated with the litter total specific leaf area. Also, litter N content increased as less litter mass remained and decay went further. Surprisingly, this study demonstrates that climatic controls on litter decomposition are quantitatively more important than species or site of origin. Cumulative climatic variables, precipitation, soil water content and air temperature (ignoring days with air temperatures below zero degrees Celsius), were appropriate to predict the litter remaining mass during decomposition (Mr). Mr and cumulative air temperature were found to be the best predictors for litter carbon and nitrogen remaining during the decomposition. Using mean annual air temperature, precipitation, soil water content and litter total specific leaf area as parameters we were able to predict the annual decomposition rate (k) accurately.

Se evalúan las prestaciones sismorresistentes de un edificio de uso sanitario proyectado con la normativa española actual. La evaluación ha sido realizada en el marco de una metodología probabilística que provee una base consistente con las incertidumbres del proceso de evaluación. Un prototipo de edificio sanitario sirve como base para discutir una estimación realista de las implicaciones de terremotos raros y ocasionales en edificios de importancia especial. Para este fin, el estudio comprende un análisis dinámico no lineal de la estructura del edificio, la identificación de grupos de prestaciones estructurales y no estructurales, la expresión probabilística de la respuesta de la estructura y la cuantificación de daños y costes de reparación mediante relaciones de fragilidad. Este trabajo revela que las prestaciones sismorresistentes del edificio analizado son inapropiadas en términos de daños, pérdida de funcionalidad y costes de reparación.

Background: Posttraumatic stress disorder (PTSD) is a debilitating psychological disorder that is associated with a host of psychosocial and health ailments, including chronic pain. Although evidence-based psychological therapies are recommended as first-line PTSD treatments, a large proportion of individuals either drop out and/or do not achieve a therapeutic response. PTSD is increasingly recognized as a systemic disorder that impacts both physical and mental health, and mind-body approaches, such as Tai Chi, have shown promise. However, to date there have been no randomized clinical trials examining Tai Chi as a treatment for PTSD.Objective: To conduct a fully remote two-phased study designed to adapt, refine, and standardize two group treatments, Tai Chi and a Wellness comparison, for Veterans diagnosed with PTSD and chronic pain.Method: We deploy the project in two phases. In Phase One, we adapt both interventions for delivery via a videoconferencing platform. We then pilot the interventions in a ‘dry run’ with non-random assignment of 12 participants to Tai Chi or a Wellness comparison group. In Phase Two, we randomize 36 participants to one of the two group interventions. The feasibility and acceptability of the two remotely delivered interventions and assessment protocols are evaluated.Conclusions: This is the first study to our knowledge to evaluate the feasibility, acceptability, adherence, and participant burden of the Tai Chi and Wellness comparison interventions for PTSD and chronic pain in Veterans. This information will facilitate the development of a future large, randomized control trial to evaluate the efficacy of Tai Chi to address PTSD and chronic pain in Veterans.

Los ecosistemas mediterráneos son clásicamente considerados como pobres en nutrientes. La disponibilidad de nutrientes para las plantas depende de varios mecanismos complejos y mutuamente dependientes. En primer lugar dependerá del retorno de necromasa al suelo, y de la eficiencia que las plantas muestren en la conservación de los nutrientes en sus tejidos, lo que va a determinar la cantidad y calidad de necromasa a descomponer y el equilibrio entre mineralización e inmovilización microbiana. En segundo lugar de las condiciones climáticas, cuyo elemento diferenciador en ecosistemas mediterráneos son los ciclos cortos y frecuentes de secado-rehumedecido. En este escenario, la inmovilización microbiana juega un papel crucial, y la posibilidad de que las plantas adquieran el temporalmente abundante nitrógeno orgánico disuelto es una posibilidad escasamente explorada. Por otra parte, las altas tasas de deposición atmosférica de N, junto con los cambios en temperatura y humedad como resultado del cambio global, plantean nuevos escenarios nutricionales para los ecosistemas mediterráneos.

CLINICAL CASE A 43-year-old Romanian woman was referred with the clinical suspicion of gastric lymphoma; she had complained from two months nausea, vomiting and weight loss (7 kg); 3 esophagogastroduodenoscopic examinations had evidenced reduced distensibility of stomach body and antrum, ulcered and congestive mucosa, the histopathological examinations revealed a non specific inflammation. There was no response to therapy with omeprazolo. A computer-assisted tomoghraphy scan of the thorax and abdomen, obtained after the oral and intravenous administration of contrast material, showed diffuse thickening of the gastric wall, lymphadenopathies were seen in the retrocrural space, lesser curvature, and paraaortic region. It was performed another upper endoscopy with “deep” biopsy specimen, comprehensive of spirochetal immunohistochemistry, that was diagnostic for gastric syphilis. DISCUSSION Even though gastritis is a rare clinical manifestations of the secondary stage of syphilis, it must be considered in the differential diagnosis of erosive gastritis unresponsive to medical therapy, especially in young patients; screening tests like VDRL (routinely used until few years ago in internal medicine divisions) may be useful to identify those patients needing a further diagnostic evaluation.

Objetivo: El objetivo de este trabajo es describir el nivel de adecuación nutricional de la dieta habitual en gestantes pertenecientes a nuestra área sanitaria. Ámbito: Área Sanitaria Valme. Sevilla. Diseño: Estudio descriptivo aleatorio transversal. Sujetos: Cuarenta y nueve gestantes de primer trimestre. Intervenciones: Se valoró la ingesta diaria, por recordatorio de 24 horas y por encuesta de consumo semanal. Los datos obtenidos se comparan con las ingestas diarias recomendadas de nutrientes y con las raciones diarias recomendadas para determinados grupos de alimentos. Al mismo tiempo, se realizó una valoración antropométrica y analítica básica. Resultados: La ingesta calórica fue la recomendada (2.208 ± 475 kcal/día). La dieta contenía un exceso de proteínas (88 ± 21 g/día), de grasa (97 ± 27 g/día), con predominio de grasas monoinsaturadas (46,9 ± 5,5%) sobre las saturadas (36,6 ± 7,2%) y poliinsaturadas (15,1 ± 7%), (p Goal: The purpose of the present paper is to describe the level of nutritional adequacy of the regular diet of pregnant women belonging to our health-care area. Scope: Health-care area of Valme Hospital, Seville. Design: Randomized transversal descriptive study. Subjects: Forty-nine pregnant women during their first trimester. Interventions: The daily intake was assessed by means of a 24-hour reminder sheet and a weekly consumption survey. The data obtained were compared with the recommended daily intake of nutrients and with the recommended daily allowances for various foods. At the same time, an anthropometric and basic analysis were also carried out. Results: The calorie intake was as recommended (2,208 ± 475 kcal/day). The diet contained excessive amounts of proteins (88 ± 21 g/day) and fat (97 ± 27 g/day), with a predominance of monounsaturated fats (46.9 ± 5.5%) over saturated (36.6 ± 7.2%) or polyunsaturated fats (15.1 ± 7%), (p

Abstract This study aimed to evaluate the effect of two restrictive cumulative fluid balance (CFB) trends on survival and on major clinical outcomes in invasively ventilated patients with moderate to severe respiratory distress syndrome (ARDS) due to SARS-CoV-2. Prospective data collection was conducted on patients in the intensive care unit (ICU) originating from a tertiary university hospital. The primary outcomes were the risk association between the CFB trend during D0 to D7 and 28-day survival. The secondary outcomes were ICU mortality, in-hospital mortality, the need for invasive ventilation at D28, administration of vasoactive drugs at D7, time on invasive ventilation after D7, and length of ICU and hospital stay. 171 patients were enrolled in the study and divided according to their CFB trends during seven days of follow-up using model-based clustering [median CFB negative trend (n = 89) – 279 ml (− 664 to 203) and (n = 82) median CFB positive trend 1362 ml (619–2026)]. The group with CFB negative trend showed a higher chance of surviving 28-day in the ICU (HR: 0.62, 95% CI 0.41–0.94, p = 0.038). Moreover, this group had a reduced length of stay in the ICU, 11 (8–19) days versus 16.5 (9–29) days p = 0.004 and presented lower rates (OR = 0.22; 95% CI 0.09–0.52) of invasive ventilation after 28-days in the ICU. In patients invasively ventilated with moderate to severe ARDS due to COVID-19, the collective who showed a negative trend in the CFB after seven days of invasive ventilation had a higher chance of surviving 28 days in the ICU and lower length of stay in the ICU.

ObjectiveTo evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit.MethodsA single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated.Results121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement ( 50% lung involvement (≥14 points) on Chest-CT at ICU admission.ConclusionCOVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia.

Brief Abstract: Small cell carcinoma of the urinary tract is an aggressive malignancy that comprises less than 1% of urinary bladder cancers. The renal pelvis and ureter, also lined by urothelium, are rare sites for small cell carcinoma. The diagnosis and staging of upper tract cancer are difficult due to the need for small, atraumatic instrument to access the upper tract. There are fewer than 40 reported cases of upper urinary tract small cell carcinoma. These include both pure and variant histologies. We present the management of a 72 year old male with small cell carcinoma of the upper urinary tract. Keywords: Small cell carcinoma, Neuroendocrine tumor, Renal pelvis and ureter cancer

Patients diagnosed with bladder cancer are most frequently older adults who have multiple chronic conditions. Frequently, new conditions are unmasked during preoperative evaluation for surgery such as radical cystectomy. We report the case of an 85 year old male with muscle invasive bladder cancer who was concurrently diagnosed with cold agglutinin hemolytic anemia. This case demonstrates the importance of close attention to underlying chronic conditions in older adults considering major cancer surgery and the need for multidisciplinary management in medically complex cases. Keywords: Bladder cancer, Aging, Multiple chronic conditions, Hemolytic anemia

Kidney cancer is the ninth most common malignancy in the United States. Most kidney cancers are clear cell renal cell carcinoma (RCC) and arise as solid tumors from kidney parenchyma. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are often to lung, bone, liver, and brain. Metastatic RCC without an identifiable solid kidney tumor is exceedingly rare. We report the case of a 52 year old male with a rare cutaneous RCC metastasis without an identifiable primary renal tumor. Keywords: Kidney cancer, Renal cell carcinoma

Renal transplantation has profound improvements in mortality, morbidity, and overall quality of life compared to renal replacement therapy. This report aims to illustrate the use of ex-vivo partial nephrectomy in a patient with a renal angiomyolipoma prior to living donor transplantation. The surgical outcomes of the donor nephrectomy and recipient transplantation are reported with 2 years of follow-up. Both the donor and recipient are healthy and without any significant comorbidities. In conclusion, urologic techniques such as partial nephrectomy can be used to expand the living donor pool in carefully selected and well informed transplant recipients. Our experience demonstrated a safe and positive outcome for both the recipient and donor, and is consistent with other reported outcomes in the literature.

Phytoplankton is an essential resource in aquatic ecosystems, situated at the base of aquatic food webs. Plastic pollution can impact these organisms, potentially affecting the functioning of aquatic ecosystems. The interaction between plastics and phytoplankton is multifaceted: while microplastics can exert toxic effects on phytoplankton, plastics can also act as a substrate for colonisation. By reviewing the existing literature, this study aims to address pivotal questions concerning the intricate interplay among plastics and phytoplankton/phytobenthos and analyse impacts on fundamental ecosystem processes (e.g. primary production, nutrient cycling). This investigation spans both marine and freshwater ecosystems, examining diverse organisational levels from subcellular processes to entire ecosystems. The diverse chemical composition of plastics, along with their variable properties and role in forming the "plastisphere", underscores the complexity of their influences on aquatic environments. Morphological changes, alterations in metabolic processes, defence and stress responses, including homoaggregation and extracellular polysaccharide biosynthesis, represent adaptive strategies employed by phytoplankton to cope with plastic-induced stress. Plastics also serve as potential habitats for harmful algae and invasive species, thereby influencing biodiversity and environmental conditions. Processes affected by phytoplankton-plastic interaction can have cascading effects throughout the aquatic food web via altered bottom-up and top-down processes. This review emphasises that our understanding of how these multiple interactions compare in impact on natural processes is far from complete, and uncertainty persists regarding whether they drive significant alterations in ecological variables. A lack of comprehensive investigation poses a risk of overlooking fundamental aspects in addressing the environmental challenges associated with widespread plastic pollution., (© 2024 The Author(s). Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Induced Pluripotent Stem Cells (iPSCs) are nowadays a common starting point for wide-ranging applications including 3D disease modeling (i.e. organoids) and in future regenerative medicine. Physiological processes like homeostasis, cell differentiation, development and reproduction are tightly regulated by hormones through binding to their transmembrane or nuclear receptors of target cells. Considering their pleiotropic effect, take into account also their expression in an iPSCs-based disease modeling would better recapitulate the molecular events leading to 3D organoid development and disease study. Here we reported the expression pattern of estrogen receptor (ERα) and progesterone receptor (PR) in four different iPSCs, obtained from CD34 + progenitor cells and skin fibroblasts with four different methods. Expression of ERα and PR mRNA were significantly downregulated in iPSCs as well as fibroblasts compared to MCF7 positive control. Immunofluorescence (IF) staining detected only the expression of PR protein in all the different iPSCs cell lines, while ERα was not detectable. By flow cytometry analysis we observed that the ~ 65% of the total population of iPSCs cells expressed only PR, with 100% fold increase compared to HSPCs and fibroblasts, while ERα was not expressed. Our results collectively demonstrated for the first time that the reprogramming of somatic cells into iPSCs leads to the expression of PR receptor., Competing Interests: Declarations Conflicts of Interest The authors declare no conflict of interest. Data Availability The data supporting the findings of this study are contained within the contents of this article. The datasets generated during this study will be freely provided by the corresponding author upon request. Informed Consent Informed consent was obtained from all subjects involved in the study. Institutional Review Board Statement The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committees of ASST Spedali Civili of Brescia (NP3426)., (© 2024. The Author(s).)

Introduction: Local treatment can be distressful to breast cancer patients. We aimed to evaluate how different types of local treatment impact the quality of life of patients., Methods: In this retrospective cohort study, one-year postoperative Breast-Q Satisfaction with Breasts scores were used as a surrogate for Quality of Life. Linear regression was used to estimate the impact of breast conservation, oncoplastic surgery, breast reconstruction, and radiation therapy on Breast-Q scores. All analyses were adjusted for multiple covariates., Results: Of the 711 eligible patients, 349 female patients answered both the pre- and one-year postoperative questionnaires and were included in the final analysis. In total, 237 (68%) patients underwent breast-conserving surgeries and 112 (32%) underwent mastectomies. All mastectomy patients underwent breast reconstruction and 176 (74% of breast-conserving surgeries) underwent concomitant oncoplastic surgery. After multivariate analysis, mastectomy was associated with lower scores compared to breast-conserving surgery (-21.3; 95%CI: -36.2, -6.4, p=0.005), and oncoplastic surgery was associated with higher scores (9.2; 95%CI: 0.8, 17.6, p=0.032). There was a tendency for higher scores with the use of flaps in breast reconstruction and a tendency for lower scores with the use of radiation therapy, but the difference was not significant., Conclusions: Breast-conserving surgery is associated with better quality of life than mastectomy. Additionally, oncoplastic surgery is associated with a better quality of life than standard breast-conserving surgery. Patients should be counseled whenever multiple options for surgery are possible, and efforts should be made to increase the availability of trained surgeons in oncoplastic techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barbalho, Polidorio, Mori, Barros, Sampaio, Melo, Assis, Bioni, Miziara, Fraga and Andrade.)

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for multiple sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the STORMS pilot feasibility study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for multiple sclerosis patients.

Nutrition is vital for athletic performance, especially in ultra-endurance sports, which pose unique nutritional challenges. Despite its importance, there exist gaps in the nutrition knowledge among athletes, and emerging digital tools could potentially bridge this gap. The ULTRA-Q, a sports nutrition questionnaire adapted for ultra-endurance athletes, was used to assess the nutritional knowledge of ChatGPT-3.5, ChatGPT-4, Google Bard, and Microsoft Copilot. Their performance was compared with experienced ultra-endurance athletes, registered sports nutritionists and dietitians, and the general population. ChatGPT-4 demonstrated the highest accuracy (93%), followed by Microsoft Copilot (92%), Bard (84%), and ChatGPT-3.5 (83%). The averaged AI model achieved an overall score of 88%, with the highest score in Body Composition (94%) and the lowest in Nutrients (84%). The averaged AI model outperformed the general population by 31% points and ultra-endurance athletes by 20% points in overall knowledge. The AI model exhibited superior knowledge in Fluids, outperforming registered dietitians by 49% points, the general population by 42% points, and ultra-endurance athletes by 32% points. In Body Composition, the AI model surpassed the general population by 31% points and ultraendurance athletes by 24% points. In Supplements, it outperformed registered dietitians by 58% points and the general population by 55% points. Finally, in Nutrients and in Recovery, it outperformed the general population only, by 24% and 29% points, respectively. AI models show high proficiency in sports nutrition knowledge, potentially serving as valuable tools for nutritional education and advice. AI-generated insights could be integrated with expert human judgment for effective athlete performance optimization., (Copyright © Institute of Sport – National Research Instutite.)

The MHC class I-related molecule MR1 is ubiquitously expressed, is highly conserved among mammals, and presents bacterial and endogenous antigens in tumor cells. These features indicate that tumor-specific T cells restricted to MR1 may represent ideal candidates for novel cancer-directed T-cell immunotherapy. The very low expression of the MR1 protein at the cell surface is a potential challenge limiting the possible use of MR1-directed immunotherapies. To overcome this challenge, it is important that understanding of the mechanisms regulating MR1 expression is increased, as little is known about this currently. This study identified ERK1/2 as negative regulators of the MR1 gene and protein expression. Inhibition of ERK1/2 in tumor cells or treatment of BRAF-mutant tumor cells with drugs specific for mutated BRAF increased MR1 protein expression and recognition by tumor-reactive and MR1-restricted T cells. The ERK1/2 inhibition of MR1 was mediated by the ELF1 transcription factor, which was required for MR1 gene expression. The effects of ERK1/2 inhibition also occurred in cancer cell lines of different tissue origins, cancer cell lines resistant to drugs that inhibit mutated BRAF, and primary cancer cells, making them potential targets of specific T cells. In contrast to tumor cells, the recognition of healthy cells was very poor or absent after ERK1/2 inhibition. These findings suggest a pharmaceutical approach to increase MR1 protein expression in tumor cells and the subsequent activation of MR1-restricted T cells, and they have potential therapeutic implications., (©2024 American Association for Cancer Research.)

External motivational stimuli have been shown to improve athletic performance. However, the neurophysiological mechanisms underlying this improvement remain poorly understood. This randomized crossover study investigated the effects of music and verbal encouragement on measures of muscle excitation and myoelectric manifestations of fatigue in the biceps brachii and brachioradialis muscles during an endurance task. Fifteen untrained (mean age 29.57 ± 2.77 years) and 13 trained individuals (mean age 32.92 ± 2.90 years) were included. The endurance task, performed to exhaustion, consisted of keeping the dominant arm flexed to 90 degrees while holding a dumbbell loaded to 80% of 1RM with a supine grip in three randomized conditions: standard, with self-selected music, and with verbal encouragement. The untrained subjects showed an increase in task duration of 15.26% ( p < 0.003) with music and 15.85% ( p < 0.002) with verbal encouragement compared to the condition without external stimuli. There were no significant differences in the myoelectric manifestations of fatigue between the different conditions. Regarding the muscle excitation metrics, although the mean amplitude, peak value, and area under the curve remained unchanged across conditions, a significant reduction in the trend coefficient, indicating motor unit recruitment over time, was observed with both music (biceps brachii: -10.39%, p < 0.001; brachioradialis: -9.40%, p < 0.001) and verbal encouragement (biceps brachii: -7.61%, p < 0.001; brachioradialis: -6.51%, p < 0.001) compared to the standard condition. For the trained participants, no significant differences were observed between conditions in terms of task duration and outcome measures related to muscle excitation and myoelectric manifestations of fatigue, suggesting the possible presence of a ceiling effect on motivation. These results highlight the important role of external motivational stimuli, such as music and verbal encouragement, in improving task performance in untrained subjects, probably through more effective and efficient recruitment of motor units.

Standardized treatment options are lacking for patients with unresectable or multifocal follicular dendritic cell sarcoma (FDCS) and disease-related mortality is as high as 20%. Applying whole-genome sequencing (WGS) in one case and whole-exome sequencing (WES) in additional twelve cases, this study adds information on the molecular landscape of FDCS, expanding knowledge on pathobiological mechanisms and identifying novel markers of potential theragnostic significance. Massive parallel sequencing showed high frequency of mutations on oncosuppressor genes, particularly in RB1, CARS and BRCA2 and unveiled alterations on homologous recombination DNA damage repair-related genes in 70% (9/13) of cases. This indicates that patients with high-stage FDCS may be eligible for poly ADP ribose polymerase inhibition protocols. Low tumor mutational burden was confirmed in this study despite common PDL1 expression in FDCS arguing on the efficacy of immune checkpoint inhibitors. CDKN2A deletion, detected by WGS and confirmed by fluorescence in situ hybridization in 41% of cases (9/22) indicates that impairment of cell cycle regulation may sustain oncogenesis in FDCS. Absence of mutations in the RAS/RAF/MAPK pathway and lack of clonal hematopoiesis-related mutations in FDCS sanction its differences from dendritic cell-derived neoplasms of hematopoietic derivation. WGS and WES in FDCS provides additional information on the molecular landscape of this rare tumor, proposing novel candidate genes for innovative therapeutical approaches to improve survival of patients with multifocal disease.