Miracle-dz/UniFAR-FTUs huggingface dataset:
Slow wave activity moderates the association between new learning and traumatic brain injury severity.

STUDY OBJECTIVES Sleep-wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate-severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep-wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate-severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity. METHODS Forty-two moderate-severe TBI participants, 12 to 47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performances. RESULTS We found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performances than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performances: higher SWA was more strongly associated to better memory performances in more severe TBI compared to milder TBI. CONCLUSIONS This study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.
Expansion of chronic lesions is linked to disease progression in relapsing–remitting multiple sclerosis patients

Background: Slow-burning inflammation is putatively associated with lesion expansion and leads to progressive loss of axons and disability worsening. Objective: To investigate the incidence and extent of chronic white matter lesion expansion in relapsing–remitting multiple sclerosis (RRMS) patients and to evaluate its relationship with biomarkers of disease progression. Methods: Pre- and post-gadolinium T1, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor images were acquired from 33 patients. Lesional activity were analysed between baseline and 48 months using custom-designed software. Results: A total of 569 lesions were identified as chronic at baseline, of which 261 were expanding, 236 were stable and 72 were shrinking. In addition, 139 new lesions (both confluent and free-standing) were observed. Chronic lesion expansion was associated with patient’s age and accounted for the bulk (67.3%) of total brain lesion volume increase, while only 32.7% was attributable to new lesion formation. Change in chronic lesion volume correlated with the rate of brain atrophy (r = −0.57, p = 0.001), change of Expanded Disability Status Scale (EDSS; r = 0.38, p = 0.03) and an increase of isotropic diffusivity inside the lesions (r = 0.75, p < 0.001). Conclusion: Expansion of chronic lesions in RRMS patients is the primary determinant of increased T2 total lesion load. It significantly contributes to disease progression and partially driving axonal loss inside the lesions and brain damage outside of lesional tissue.
Enhancing CDC and ADCC of CD19 Antibodies by Combining Fc Protein-Engineering with Fc Glyco-Engineering

Background: Native cluster of differentiation (CD) 19 targeting antibodies are poorly effective in triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are crucial effector functions of therapeutic antibodies in cancer immunotherapy. Both functions can be enhanced by engineering the antibody’s Fc region by altering the amino acid sequence (Fc protein-engineering) or the Fc-linked glycan (Fc glyco-engineering). We hypothesized that combining Fc glyco-engineering with Fc protein-engineering will rescue ADCC and CDC in CD19 antibodies. Results: Four versions of a CD19 antibody based on tafasitamab’s V-regions were generated: a native IgG1, an Fc protein-engineered version with amino acid exchanges S267E/H268F/S324T/G236A/I332E (EFTAE modification) to enhance CDC, and afucosylated, Fc glyco-engineered versions of both to promote ADCC. Irrespective of fucosylation, antibodies carrying the EFTAE modification had enhanced C1q binding and were superior in inducing CDC. In contrast, afucosylated versions exerted an enhanced affinity to Fcγ receptor IIIA and had increased ADCC activity. Of note, the double-engineered antibody harboring the EFTAE modification and lacking fucose triggered both CDC and ADCC more efficiently. Conclusions: Fc glyco-engineering and protein-engineering could be combined to enhance ADCC and CDC in CD19 antibodies and may allow the generation of antibodies with higher therapeutic efficacy by promoting two key functions simultaneously.
Implementing Mobile Health–Enabled Integrated Care for Complex Chronic Patients: Patients and Professionals’ Acceptability Study

Background Integrated care (IC) can promote health and social care efficiency through prioritization of preventive patient-centered models and defragmentation of care and collaboration across health tiers, and mobile health (mHealth) can be the cornerstone allowing for the adoption of IC. Objective This study aims to assess the acceptability, usability, and satisfaction of an mHealth-enabled IC model for complex chronic patients in both patients and health professionals. Methods As part of the CONNECARE Horizon 2020 project, a prospective, pragmatic, 2-arm, parallel, hybrid effectiveness-implementation trial was conducted from July 2018 to August 2019 in a rural region of Catalonia, Spain. Home-dwelling patients 55 years and older with chronic conditions and a history of hospitalizations for chronic obstructive pulmonary disease or heart failure (use case [UC] 1), or a scheduled major elective hip or knee arthroplasty (UC2) were recruited. During the 3 months, patients experienced an mHealth-enabled IC model, including a self-management app for patients, a set of integrated sensors, and a web-based platform connecting professionals from different settings or usual care. The Person-Centered Coordinated Care Experience Questionnaire (P3CEQ) and the Nijmegen Continuity Questionnaire (NCQ) assessed person-centeredness and continuity of care. Acceptability was assessed for IC arm patients and staff with the Net Promoter Score (NPS) and the System Usability Scale (SUS). Results The analyses included 77 IC patients, 58 controls who completed the follow-up, and 30 health care professionals. The mean age was 78 (SD 9) years in both study arms. Perception of patient-centeredness was similarly high in both arms (usual care: mean P3CEQ score 16.1, SD 3.3; IC: mean P3CEQ score 16.3, SD 2.4). IC patients reported better continuity of care than controls (usual care: mean NCQ score 3.7, SD 0.9; IC: mean NCQ score 4.0, SD 1; P=.04). The scores for patient acceptability (UC1: NPS +67%; UC2: NPS +45%) and usability (UC1: mean SUS score 79, SD 14; UC2: mean SUS score 68, SD 24) were outstanding. Professionals’ acceptability was low (UC1: NPS −25%; UC2: NPS −35%), whereas usability was average (UC1: mean SUS score 63, SD 20; UC2: mean SUS score 62, SD 19). The actual use of technology was high; 77% (58/75) of patients reported physical activity for at least 60 days, and the ratio of times reported over times prescribed for other sensors ranged from 37% for oxygen saturation to 67% for weight. Conclusions The mHealth-enabled IC model showed outstanding results from the patients’ perspective in 2 different UCs but lacked maturity and integration with legacy systems to be fully accepted by professionals. This paper provides useful lessons learned through the development and assessment process and may be of use to organizations willing to develop or implement mHealth-enabled IC for older adults.
A Lower Sodium Neapolitan Pizza Prepared with Seawater in Place of Salt: Nutritional Properties, Sensory Characteristics, and Metabolic Effects

Seawater is rich in minerals which may help confer good palatability to foods, favouring the use of smaller amounts of salt, a recognized measure of cardiovascular prevention. The aim of this study was to investigate the nutritional properties, sensory characteristics and metabolic effects of a typical Neapolitan pizza prepared with seawater (SWP) in place of common salt, in comparison with Standard traditional Pizza (StP). The nutritional characteristics and the chemical profile of the SWP and StP were assessed by chemical analyses and the use of Food Composition Tables. Twelve healthy volunteers were recruited for a Randomized Controlled Trial, with the consumption of one StP and one SWP using a balanced crossover design. The satiating power and palatability of the two pizzas were tested by the administration of Visual Analogue Scales. Serum glucose, insulin and sodium were measured every 30 min and 3 h urines were collected after each meal. SWP contained nearly 50% less NaCl and a larger amount of micronutrients compared with StP. No significant differences were detected between the two pizzas with regard to satiating power, pleasantness and glycemic and insulinemic response. However, a significant difference was found in the urine volume collected over the 3 h after the two meals (194 mL after StP vs. 292 mL after SWP, p = 0.018) and in the 3 h sodium balance (+1.6 g after StP vs. +0.5 g after SWP, p = 0.002). Conclusions: SWP appears to be a food with favourable nutritional characteristics, very good acceptability and healthy metabolic properties: these results warrant confirmation by a larger intervention trial.
FTIR Spectroscopy to Reveal Lipid and Protein Changes Induced on Sperm by Capacitation: Bases for an Improvement of Sample Selection in ART

Although being a crucial step for Assisted Reproduction Technologies (ART) success, to date sperm selection is based only on morphology, motility and concentration characteristics. Considering the many possible alterations, there is a great need for analytical approaches allowing more effective sperm selections. The use of Fourier Transform Infrared (FTIR) may represent an interesting possibility, being able to reveal many macromolecular changes in a single measurement in a nondestructive way. As a proof of concept, in this observational study, we used a FTIR approach to reveal features related to sperm quality and chemical changes promoted by in vitro capacitation. We found indication that α-helix content is increased in capacitated sperm, while high percentages of the β-structures seem to correlate to poor-quality spermatozoa. The most interesting observation was related to the lipid composition, when measured as CH2/CH3 vibrations (ratio 2853/2870), which resulted in being strongly influenced by capacitation and well correlated with sperm motility. Interestingly, this ratio is higher than 1 in infertile samples, suggesting that motility is related to sperm membranes stiffness and lipid composition. Although further analyses are requested, our results support the concept that FTIR can be proposed as a new smart diagnostic tool for semen quality assessment in ART.
Inhibition of mechanistic target of rapamycin signaling decreases levels of O-GlcNAc transferase and increases serotonin release in the human placenta.

Changes in placental function, in particular down-regulation of placental O-GlcNAc transferase (OGT) in response to maternal stress and increased placental secretion of serotonin into the fetal circulation following maternal infection, have been mechanistically linked to adverse neurodevelopment in mice. We hypothesized that mTOR signaling is a key regulator of trophoblast serotonin synthesis and OGT protein expression and that serotonin is secreted by the human placenta into the fetal circulation. Placental homogenates (n=46) from elective terminations at 8-22 weeks of gestation and from healthy term women were sexed and the protein levels of OGT and enzymes involved in serotonin synthesis was determined. Primary human trophoblast (PHT) cells were isolated from normal term placenta (n=27), cultured and transfected (n=8) with siRNA targeting a scramble sequence (control), raptor (inhibits mTOR Complex 1), or rictor (inhibits mTOR Complex 2). Subsequently, conditioned media and PHT cell lysates were collected. Free serotonin concentration was measured using ELISA in cell culture media and in platelet-depleted normal term umbilical vein and artery plasma (n=38). Both mTORC1 and mTORC2 inhibition down-regulated OGT levels in PHT cells. The level of serotonin synthesis enzyme TPH-1 was higher in early gestation female placentas and at term serotonin concentration was 3-fold higher in the umbilical vein than in the umbilical artery. Inhibition of mTORC2, but not mTORC1, increased cultured PHT cell serotonin secretion. Our data is consistent with the model that mTOR signaling is a key regulator of trophoblast serotonin synthesis and OGT protein expression.
Real Life Prospective Evaluation of New Drug-Eluting Platform for Chemoembolization of Patients with Hepatocellular Carcinoma: PARIS Registry

Simple Summary Hepatocellular carcinoma treatment options depend on stage of disease. In intermediate stage transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended. DEM-TACE is simultaneous embolization of tumour feeding arteries and local delivery of anticancer drugs. We assessed real-life practice, safety, toxicity and efficacy of this therapy using new embolization microspheres in 97 patients. Toxicity of the treatment in our study was within or below rates reported so far, and the healthy liver parenchyma, the bile ducts and the portal vein were well preserved when compared with previous study using other type of DEM. Tumour response rate was high, achieving disease control in almost all patients. Hepatocellular carcinoma was controlled during 16.7 months with DEM-TCE as the only treatment. At one year 81% and at two years 66% of patients were alive. Our study showed that DEM-TACE in patients from every-day clinical practice is safe and efficient treatment modality. Abstract Background and aim: Transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended for patients with BCLC stage B hepatocellular carcinoma (HCC) and stage 0-A unsuitable for curative treatments. We assessed efficacy and safety along with hepatobiliary toxicities (HBT) of DEM-TACE using a novel microsphere, LifePearlTM, loaded with anthracyclines. Materials and methods: 97 patients diagnosed with HCC were prospectively enrolled and treated using LifePearlTM loaded with doxorubicin (77%) or idarubicin (23%). Safety and tolerability were assessed using CTCAE, HBT by CT/MRI scans, and tumor response by applying modified Response Evaluation Criteria in Solid Tumors (mRECIST). Follow-up was after 2 years. Results: Adverse events (AE) were reported in 73.2% of patients, majority being Grade 1–2. Grade ≥ 3 AE reported in 13.4% of patients were mainly related to postembolization syndrome. HBT were observed after 15.5% (29/187) of the DEM-TACEs. Objective response and disease control rates were 81% and 99%, respectively, as the best responses. Survival rates at one and two years were 81% and 66%, respectively, while the median overall survival (OS) was not reached. Median progression free survival was 13.7 months (95% CI: 11.3; 15.6) and median time to TACE untreatable progression was 16.7 months (95% CI: 12.7; not estimable (n.e.)). Conclusions: DEM-TACE using LifePearlTM provides a high tumor response rate in HCC patients. HBT rates within or below previously reported results for cTACE and DEM-TACE indicate a good safety profile for LifePearlTM. The trial was registered in National Library of Medicine (ID: NCT03053596).
Electronic Cigarette Use and Metabolic Syndrome Development: A Critical Review

The metabolic syndrome is a combination of several metabolic disorders, such as cardiovascular disease, atherosclerosis, and type 2 diabetes. Lifestyle modifications, including quitting smoking, are recommended to reduce the risk of metabolic syndrome and its associated complications. Not much research has been conducted in the field of e-cigarettes and the risk of metabolic syndrome. Furthermore, taking into account the influence of e-cigarettes vaping on the individual components of metabolic syndrome, i.e, abdominal obesity, insulin resistance, dyslipidemia and elevated arterial blood pressure, the results are also ambiguous. This article is a review and summary of existing reports on the impact of e-cigarettes on the development of metabolic syndrome as well as its individual components. A critical review for English language articles published until 30 June 2020 was made, using a PubMed (including MEDLINE), Cochrane, CINAHL Plus, and Web of Science data. The current research indicated that e-cigarettes use does not affect the development of insulin resistance, but could influence the level of glucose and pre-diabetic state development. The lipid of profile an increase in the TG level was reported, while the influence on the level of concentration of total cholesterol, LDL fraction, and HDL fraction differed. In most cases, e-cigarettes use increased the risk of developing abdominal obesity or higher arterial blood pressure. Further research is required to provide more evidence on this topic.
The Association between Material Deprivation and Avoidable Mortality in Lisbon, Portugal

There is considerable evidence pointing to the existence of a socioeconomic gradient in mortality, which tends to be steeper in urban areas. Similar to other European cities, Lisbon is far from homogeneous since considerable geographical inequalities exist between the more advantaged and the more deprived neighborhoods. The main goals of this study are to describe the geographical pattern of premature deaths (before 65 years old), avoidable deaths (preventable and amenable to healthcare) and cause-specific mortality (HIV/AIDS and suicide) in Lisbon, at the lower administrative level (civil parish, in Portuguese: Freguesia), and analyze the statistical association between mortality risk and deprivation, before (1999–2003) and during the economic crisis (2008–2012). Smoothed Standardized Mortality Ratios (sSMR) and Relative Risk (RR) with 95% credible intervals were calculated to identify the association between mortality and deprivation. The analysis of the geographical distribution of cause-specific mortality reveals that civil parishes with high sSMR in the first period continued to present higher mortality rates in the second. Moreover, a significant statistical association was found between all the causes of death and deprivation, except suicide. These findings contribute to understanding how social conditions influence health outcomes and can offer insights about potential policy directions for local government.
Intrinsic non-stomatal resilience to drought of the photosynthetic apparatus in Coffea spp. is strengthened by elevated air [CO2].

Growing water restrictions associated with climate changes constitute daunting challenges to crop performance. This study unveils the impacts of moderate (MWD) or severe (SWD) water deficit, and their interaction with air [CO2], on the photosynthetic apparatus of Coffea canephora cv. Conilon Clone 153 (CL153) and C. arabica cv. Icatu. Seven year-old potted plants grown under 380 (aCO2) or 700 μL L-1 (eCO2) [CO2] gradually reached predawn water potentials between -1.6 to -2.1 MPa (MWD), and below -3.5 MPa (SWD). Under drought, stomata closure was chiefly related to ABA rise. Increasing drought severity progressively affected gas exchange and fluorescence parameters in both genotypes, with non-stomatal limitations becoming gradually dominating, especially regarding the photochemical and biochemical components of CL153 SWD plants. In contrast, Icatu plants were highly tolerant to SWD, with minor, if any, negative impacts on the potential photosynthetic functioning and components (e.g., Amax, Fv/Fm, electron carriers, photosystems (PSs) and RuBisCO activities). Besides, drought-stressed Icatu plants displayed increased abundance of a large set of proteins associated with the photosynthetic apparatus (photosystems, light harvesting complexes, cyclic electron flow, RuBisCO activase) regardless of [CO2]. Single eCO2 did not promote stomatal and photosynthetic down-regulation in both genotypes. Instead, eCO2 increased photosynthetic performance, moderately reinforced photochemical (PSs activity, electron carriers) and biochemical (RuBisCO, Ru5PK) components, whereas photoprotective mechanisms and protein abundance remained mostly unaffected. In both genotypes, under MWD, eCO2 superimposition delayed stress severity and promoted photosynthetic functioning with lower energy dissipation and PSII impacts, whereas stomatal closure was decoupled from increases in ABA. In SWD plants most impacts on the photosynthetic performance were reduced by eCO2, especially in the moderately drought affected CL153 genotype, although maintaining RuBisCO as the most sensitive component, deserving special breeder's attention to improve coffee sustainability under future climate scenarios.
Consumer knowledge and behaviors regarding food safety risks associated with wheat flour.

Consumers do not consider flour, a low-moisture food product, a high-risk for microbial contamination. In the past ten years, however, flour has been identified as a source of pathogenic bacteria, including Salmonella and E. coli . Online surveys were conducted to study consumers' flour-handling practices and their knowledge about food safety risks related to flour. The survey also evaluated message impact on three food safety messages in communicating information and convincing consumers to adopt safe flour handling practices. Flour-using consumers (n = 1,045) from the United States reported they used flour to make cakes, cookies, and bread. Most consumers stored flour in sealed containers. Less than 1% kept a record of product identification numbers, like lot numbers, and less than 11% kept brand and use-by-date information. Many consumers (85%) were unaware of flour recalls, or outbreaks, and few (17%) believed they would be affected by flour recalls or outbreaks. If the recall affected the flour they bought, nearly half of the consumers (47%) would buy the same product from a different brand for a few months before they returned to the recalled brand. Among consumers who use flour to bake, 66% said they ate raw cookie dough or batter. Raw dough "eaters" were more difficult to convince to avoid eating and playing raw flour than "non-eaters. " Food safety messages were less impactful on those raw dough "eaters" than "non-eaters. " Compared with the food safety message with only recommendations, those messages with recommendations and an explanation as to the benefits of the practice were more effective in convincing consumers to change their practices. These findings provide insight into effective consumer education about safe flour-handling practices and could assist in the accurate development of risk assessment models related to flour handling.