Miracle-dz/UniFAR-FTUs huggingface dataset:
LBA9Letrozole and palbociclib versus 3rd generation chemotherapy as neoadjuvant treatment of minal breast cancer. Results of the UNICANCER-eoPAL study

P. Cottu, V. D’Hondt, S. Dureau, F. Lerebours, I. Desmoulins, P-E. Heudel, F. Duhoux, C. Levy, M-A. Mouret-Reynier, F. Dalenc, J-S. Frenel, C. Jouannaud, L. Venat-Bouvet, S. Nguyen, J-M. Ferrero, J-L. Canon, J. Grenier, J. Lemonnier, A. Vincent-Salomon, S. Delaloge Medical Oncology, Institut Curie, Paris, France, Medical Oncology, ICM Regional Cancer Institute of Montpellier, Montpellier, France, Medical Oncology, Centre Georges-François Leclerc (Dijon), Dijon, France, Oncology, Centre Léon Bérard, Lyon, France, Medical Oncology, Cliniques Universitaires St. Luc, Brussels, Belgium, Medical Oncology, Centre Francois Baclesse, Caen, France, Medical Oncology, Centre Jean Perrin, Clermont-Ferrand, France, Medical Oncology, IUCT Oncopole Toulouse, Toulouse, France, Medical Oncology, UNICANCER, ICO Institut de Cancerologie de l’Ouest René Gauducheau, Saint-Herblain, France, Medical Oncology, Institut Jean Godinot, Reims, France, Medical Oncology, Limoges University Hospital, Limoges, France, Medical Oncology, CH Pau, Pau, France, Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France, Department of Oncology-Hematology, Grand Hopital de Charleroi, Charleroi, Belgium, Medical Oncology, Institut Ste Catherine, Avignon, France, R&D, UNICANCER, Paris, France, Tumor Biology, Institut Curie, Paris, France, Medical Oncology, Institut de Cancérologie Gustave Roussy, Villejuif, France
Comparison of Low- Versus High-Dose Four-Factor Prothrombin Complex Concentrate (4F-PCC) for Factor Xa Inhibitor–Associated Bleeding: A Retrospective Study

Background: Although andexanet alfa was recently approved as a specific reversal agent for apixaban and rivaroxaban, some providers still elect to administer 4-factor prothrombin complex concentrate (4F-PCC) instead, due to concerns surrounding efficacy, thrombotic risk, administration logistics, availability, and cost. Previous studies have described success with 4F-PCC doses ranging from 25 to 35 U/kg, with some guidelines recommending 50 U/kg. Objectives: The purpose of this study was to compare hemostasis between patients receiving low- (20-34 U/kg) versus high-dose (35-50 U/kg) 4F-PCC for the urgent reversal of apixaban and rivaroxaban. Patients/Methods: We performed a retrospective cohort study at a level one trauma center and comprehensive stroke center between January 2015 and December 2018. Main exclusion criteria included patients receiving less than 20 U/kg or if postreversal imaging were unavailable. Outcomes assessed included hemostasis for critical bleeding associated with apixaban or rivaroxaban and postoperative bleeding for reversal for emergent procedures. Results: The low-dose strategy was administered to n = 57 (57.6%) patients at a mean dose of 26.6 U/kg. The high-dose strategy was used in n = 42 (42.4%) patients at a mean dose of 47.6 U/kg. There was no difference in hemostasis by dosing strategy (75.4% vs 78.6%, P = .715) or hospital mortality (19.3% vs 35.7%, P = .067). No difference was found for secondary end points, including thrombotic events (5.3% vs 2.4%, P = .635) and hospital length of stay (11.3 vs 12.5 days, P = .070). Conclusions: Our comparison addresses a gap in the literature surrounding optimal dosing and supports a similar efficacy profile between dosing low- versus high-dose treatment.
Presentation of High-Flow Cerebral Proliferative Angiopathy With Adie's-Like Pupil and Proptosis.

A 32-year-old man presented because of gradual protrusion of his left eye progressing over the course of a year. He reported mild pulsatile tinnitus in the left ear. He denied any blurry vision, diplopia, eye pain, headache, dizziness, or nausea. On initial assessment, visual acuity was 20/25 in each eye, with intraocular pressures of 18 mm Hg in the right eye and 20 mm Hg in the left eye by Goldmann applanation tonometry. External examination indicated 5 mm left exophthalmos by Hertel exophthalmometry (right eye, 15 mm; left eye, 20 mm) (Fig. 1A). Extraocular movements were normal. Both pupils were round, and there was no relative afferent pupillary defect. Anisocoria was present; the left pupil was larger, demonstrated a poor light response and a slightly better near response, but constricted only slightly to an even higher than usual percentage of pilocarpine used to detect an Adie’s pupil, essentially ruling out this diagnosis (Fig. 1B, C) (1). On anterior segment examination of the left eye, although frank helicity or corkscrewing of the conjunctival blood vessels was not commented on, tortuosity was certainly present (Fig. 1D). The failure of such vessels to blanch after the administration of phenylephrine drops suggested the possibility of raised episcleral pressure as causative. Ophthalmoscopy demonstrated small cup/disc ratio and no venous stasis in the left fundus. There was no abnormality found in the right eye. The patient did not manifest any neurological deficit, and his systemic review was negative. Ultrasonography and MRI of brain and orbits (Fig. 2A, B) showed a dilated left superior ophthalmic vein with otherwise normal orbital structures. Exophthalmos can clearly be noted on the MRI axial view on the left, along with dilated vasculature in the left anterior hemisphere. Ultrasonography seems to reveal a thickened retinal/ choroidal complex. A left frontal lobe lesion was found, and cerebral angiography (Fig. 2C, D) helped to define a vascular malformation with diffuse nidus, which was
Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO‐grade II—Report from the German/Swiss SIOP‐LGG 2004 cohort

Reports on pediatric low‐grade diffuse glioma WHO‐grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2‐entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub‐entities proved unfavorable for survival. Within the prospectively registered, population‐based German/Swiss SIOP‐LGG 2004 cohort 100 patients (age 0.8‐17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event‐free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3‐K27M‐mutation in 4, IDH1‐mutation in 11, BRAF‐V600‐mutation in 12, KIAA1549‐BRAF‐fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549‐BRAF‐fusions. Histone3‐K27M‐mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2‐entities, with the exemption of Histone3‐K27M‐mutant tumors that require a HGG‐related treatment strategy. Our data confirm the importance to genetically define pediatric low‐grade diffuse gliomas for proper treatment decisions and risk assessment.
Research Progress Regarding Surgical Margins, Molecular Margins, and Prognosis of Laryngeal Carcinoma

Background: Laryngeal carcinoma is one of the most common malignant tumors of the head and neck. Researchers have refined the study of surgical margin in the anatomical subarea of the larynx to determine the most appropriate distance of the surgical margin for laryngeal carcinoma, to achieve accurate resection of laryngeal carcinoma and to improve the possibility of retention of laryngeal function. Methods: A comprehensive review of the primary literature was performed from 2009 to 2019 utilizing keywords laryngeal carcinoma, surgical margin, molecular margin, and prognostic factor. Articles were included at the discretion of the authors based on novel and/or contributions to the literature. Results: The prognosis of laryngeal carcinoma significantly correlates with the status of surgical margins. Patients with positive surgical margins have higher recurrence and metastasis rates and worse prognosis. Patients with negative pathological surgical margin but with the expression or altered expression levels of one or more tumor-related molecular biomarkers had high rates of recurrence and metastasis, and poor prognosis. Conclusions: Clinical intervention can improve the prognosis of patients with positive surgical margins. Patients with close margins should be followed closely. Among patients with negative surgical margins, patients with abnormal molecular margin results should be closely followed up. However, the specific selection of one or several molecular biomarkers as the detection index of molecular margin currently requires multicenter prospective or retrospective large sample study as guidance.
Common therapeutic advances for Duchenne muscular dystrophy (DMD)

Abstract Background and purpose: Duchenne muscular dystrophy (DMD), a lethal X-linked recessive muscle dystrophy, is resulted in by different mutations including mostly frame-shifting gross deletions and duplications and rarely point mutations in DMD gene. Increasing weakness, progressive loss of skeletal muscle mass, and later-onset cardiomyopathy are serious clinical symptoms which ultimately lead to cardiac and respiratory failure, and premature death in DMD patients by age of 30. DMD is a prevalent genetic disorder and considers as an interesting target for gene therapy approaches. Massive gene size and existence of enormous number of muscle tissues are terrific hindrance against DMD treatments, nevertheless enormous efforts have been executed in the fields of gene replacement therapy, gene editing strategies, cell-based treatments, and small drug medications. Hot spot exons skipping and suppression of premature stop codons are the most interesting treatments for restoring functional DMD product, dystrophin protein. Clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas) systems are the most interesting genome editing platforms that are able to restore open reading frame of DMD gene. CRISPR-Cas9 and CRISPR-Cpf1 are two main genome editing sub-types that successfully used in mdx mice. Conclusions: This review aims to present recent progresses and future prospects over three main DMD therapeutic subgroups including gene therapy, cell therapy, and pharmacological therapy.
Microbial and Fungal Phytases Can Affect Growth Performance, Nutrient Digestibility and Blood Profile of Broilers Fed Different Levels of Non-Phytic Phosphorous

Simple Summary To reduce the environmental pollution is a must to preserve the health of the world. The environmental impact of poultry farming is receiving an increasing attention due to several emissions among these is phosphorus. This element is in general present in the commercial diets of broilers or laying hens in an amount exceeding the real needing of the animals, and, therefore, a great amount of phosphorus ends in the excreta. Thus, optimizing the amount of phosphorous in the diets of poultry could partially alleviate the environmental impact of these farms. Abstract A total of 420 day old chicks were divided into seven groups (5 replicates of 12 chicks/group) fed isoproteic and isoenergetic diets. The control group was fed diets containing 0.50%, 0.45% and 0.40% of non-phytic phosphorous (nPP) in starter (1–35), grower (37–56) and finisher (57–64 d) periods, respectively. The three intermediate nPP (IntnPP) groups were fed diets with 0.40%, 0.35% and 0.30% nPP according to the growth period and were submitted to three dietary treatments: unsupplemented; supplemented with 500 FTU/kg diet of an Aspergillus niger phytase (IntnPP_fp) and supplemented with 500 FTU/kg diet of an Escherichia coli phytase (IntnPP_bp). The three low nPP groups fed diets contained 0.30%, 0.25% and 0.20% nPP and were submitted to the same dietary treatments than IntnPP to obtain LnPP, LnPP_fp and LnPP_bp groups. IntnPP and LnPP groups had lower body weight gain and feed, crude protein (CP) and metabolizable energy (ME) intake (p < 0.05) than the control. Feed conversion ratio of IntnPP was more favorable (p < 0.01) than the LnPP group. CP and ME conversion ratios worsened (p < 0.01) in IntnPP and LnPP groups in comparison to the control. The nPP conversion ratio improved (p < 0.01) from the control to the LnPP group. Fungal phytase reduced (p < 0.05) feed, CP, ME and nPP intake than the bacterial one. IntnPP and LnPP diets had a lower digestibility of CP (p < 0.01) and CF (p = 0.01) than the control. IntnPP and LnPP groups showed a higher (p < 0.05) economic efficiency than the control. Blood total protein was the lowest (p < 0.05) in the LnPP group, the control group showed the lowest (p < 0.05) level of albumin and IntnPP group had the lowest (p < 0.01) globulin level. The use of bacterial phytase increased (p < 0.01) total protein and globulin and decreased (p < 0.05) the plasma cholesterol in comparison to fungal phytase. Decreasing nPP levels in colored slow-growing broilers diet negatively affects growth performance and the use of phytase can partly alleviate these negative effects, but the efficiency of different enzyme sources (bacterial or fungal) was tied to the dietary nPP levels.
Frequent FOXA1-Activating Mutations in Extramammary Paget’s Disease

Extramammary Paget’s disease (EMPD) is a neoplastic skin disease of indeterminate origin with an unknown genetic cause. We performed a comprehensive genetic analysis or targeted gene sequencing in 48 patients with EMPD. We identified FOXA1 mutations, a GAS6–FOXA1 fusion gene, and somatic hotspot mutations in the FOXA1 promoter region in 11 of the 48 EMPD patients (11/48, 23%). Additional mutations were identified in PIK3CA (six patients) and in HIST1H2BB, HIST1H2BC, and SMARCB1 (one patient each), but none were found in other frequently mutated genes in cancer. A global gene expression analysis using EMPD clinical samples found the upregulation of PI3 kinase–AKT–mTOR signaling. ABCC11, which is specifically expressed in the apocrine secretory cells and is necessary for their sweat secretion, was upregulated in the EMPD samples. This upregulation suggests that Paget cells originate from apocrine secretory cells. Immunohistochemical staining revealed that FOXA1 expression was prevalent in all of the EMPD samples analyzed and was associated with estrogen receptor expression. Our genetic analysis indicates that EMPD frequently involves FOXA1 mutations. FOXA1 is a transcriptional pioneer factor for the estrogen receptor, and the present results suggest that certain treatments for hormone-dependent cancers could be effective for EMPD.
A calcified chronic total occlusion preclinical model

To create an experimental chronic total occlusion (CTO) model with calcification by dietary modification (cholesterol, calcium carbonate, vitamin D) and local injection of pro‐calcification factors (dipotassium phosphate, calcium chloride, and bone morphogenetic protein‐2 [BMP‐2]).
Evaluation of weight retention four weeks after delivery as a risk factor for gestational diabetes mellitus in a subsequent pregnancy

Aim We aimed to assess the association between postpartum weight retention (PPWR) in the fourth week after delivery and the risk of gestational diabetes mellitus (GDM) in a subsequent pregnancy. Methods We performed a retrospective cohort study of the obstetric records of women who gave birth to their second singleton between 32 and 41 weeks of gestation at the National Hospital Organization Kofu National Hospital between January 2013 and September 2019. The exclusion criteria were missing data, twin pregnancy, diabetes in pregnancy, and delivery before 22 weeks in the first pregnancy. We calculated PPWR as the BMI 4 weeks after the first birth minus the BMI before the first pregnancy and grouped the subjects into the stable PPWR (gain of <1 BMI unit) and non-stable PPWR groups (gain of ≥1 BMI units). We used the χ2 test and multivariable logistic regression analysis to investigate the association between weight retention at the postpartum checkup and GDM. Results We included 566 women in this study (mean age, 31.7±4.8 years; mean maternal pre-pregnancy BMI, 21.3±3.5 kg/m2; term delivery, n = 544 [96.1%]). The overall prevalence of GDM during the second pregnancy was 7.4% (42/566), and 33.9% (192/566) of women had stable PPWR. Non-stable PPWR was not significantly associated with GDM in the second pregnancy (adjusted odds ratio, 1.93; 95% confidence interval, 0.84–4.46) after controlling for each variable. Conclusion PPWR measured in the fourth week after delivery was not associated with an increased risk of GDM in the second pregnancy.
Integrating Modes of Transport in a Dynamic Modelling Approach to Evaluate Population Exposure to Ambient NO2 and PM2.5 Pollution in Urban Areas

To evaluate the effectiveness of alternative policies and measures to reduce air pollution effects on urban citizen’s health, population exposure assessments are needed. Due to road traffic emissions being a major source of emissions and exposure in European cities, it is necessary to account for differentiated transport environments in population dynamics for exposure studies. In this study, we applied a modelling system to evaluate population exposure in the urban area of Hamburg in 2016. The modeling system consists of an urban-scale chemistry transport model to account for ambient air pollutant concentrations and a dynamic time-microenvironment-activity (TMA) approach, which accounts for population dynamics in different environments as well as for infiltration of outdoor to indoor air pollution. We integrated different modes of transport in the TMA approach to improve population exposure assessments in transport environments. The newly developed approach reports 12% more total exposure to NO2 and 19% more to PM2.5 compared with exposure estimates based on residential addresses. During the time people spend in different transport environments, the in-car environment contributes with 40% and 33% to the annual sum of exposure to NO2 and PM2.5, in the walking environment with 26% and 30%, in the cycling environment with 15% and 17% and other environments (buses, subway, suburban, and regional trains) with less than 10% respectively. The relative contribution of road traffic emissions to population exposure is highest in the in-car environment (57% for NO2 and 15% for PM2.5). Results for population-weighted exposure revealed exposure to PM2.5 concentrations above the WHO AQG limit value in the cycling environment. Uncertainties for the exposure contributions arising from emissions and infiltration from outdoor to indoor pollutant concentrations range from −12% to +7% for NO2 and PM2.5. The developed “dynamic transport approach” is integrated in a computationally efficient exposure model, which is generally applicable in European urban areas. The presented methodology is promoted for use in urban mobility planning, e.g., to investigate on policy-driven changes in modal split and their combined effect on emissions, population activity and population exposure.
Optical Coherence Tomography Angiography (OCT-A) in Choroideremia (CHM) carriers

ABSTRACT Purposes: To explore OCT-A abnormalities in CHM carriers Methods: CHM carriers and age-matched controls were consecutively enrolled at the Eye Clinic in Florence. All patients underwent a complete ophthalmic examination, fundus photography, fundus autofluorescence (FAF) and OCT examinations. OCT-A images of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris slab (CC) were acquired and analyzed using ImageJ software to detect and quantify vascular density. Results: Six patients (12 eyes) and 8 age-matched controls (16 eyes) were included in our study. The mean age was 45.5 ± 16.3 years (range 15–61) for the CHM carriers and 46.6 ± 12.2 (range 18–54) for controls. All CHM carriers showed fundus abnormalities. The detected mean central retinal thickness (CRT) (220 ± 18.34 vs 227 ± 15.46; p = .342) and choroidal central thickness (CCT) (271 ± 54.28 vs 275 ± 38.36; p = .760) did not differ between the carrier and the control group, respectively. Quantitative analysis of the inner retinal vasculature disclosed no significant difference of both SCP (p = .437) and DCP (p = .859) vessel density compared to the control group. Of note, a mild reduction on the vascular flow of the CC could be detected in the carrier group compared to the control group (78.896 ± 13.972 vs 80.008 ± 10.862; p = .045). Conclusions: OCT-A allows us to underline the role of the retinal pigment epithelium in the CHM pathophysiology. Central inner retinal and choriocapillaris vascularization were preserved although the RPE was always involved in the CHM carrier: this could support a secondary role of vascular impairment in the natural history of the disease.
Rifaximin Alleviates Endotoxemia with Decreased Serum Levels of Soluble CD163 and Mannose Receptor and Partial Modification of Gut Microbiota in Cirrhotic Patients

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (ΔsCD163: Correlation coefficient (R) = 0.680, p = 0.023; ΔsMR: R = 0.613, p = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change.