Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivation of Foodborne Viruses by High-Pressure Processing (HPP)

High-pressure processing (HPP) is an innovative non-thermal food preservation method. HPP can inactivate microorganisms, including viruses, with minimal influence on the physicochemical and sensory properties of foods. The most significant foodborne viruses are human norovirus (HuNoV), hepatitis A virus (HAV), human rotavirus (HRV), hepatitis E virus (HEV), human astrovirus (HAstV), human adenovirus (HuAdV), Aichi virus (AiV), sapovirus (SaV), and enterovirus (EV), which have also been implicated in foodborne outbreaks in various countries. The HPP inactivation of foodborne viruses in foods depends on high-pressure processing parameters (pressure, temperature, and duration time) or non-processing parameters such as virus type, food matrix, water activity (aw), and the pH of foods. HPP was found to be effective for the inactivation of foodborne viruses such as HuNoV, HAV, HAstV, and HuAdV in foods. HPP treatments have been found to be effective at eliminating foodborne viruses in high-risk foods such as shellfish and vegetables. The present work reviews the published data on the effect of HPP processing on foodborne viruses in laboratory media and foods.
Structural polymorphism of collagen type I–heparin cofibrils

We report on the coexistence of 2 different supramolecular polymorphic forms of pepsin-digested collagen type I fibrils reconstituted in vitro in the presence of heparin. Detailed structural analysis using transmission electron microscopy and scanning force microscopy shows a hierarchy involving 3 different structural levels and banding patterns in the system: asymmetric segment longspacing (SLS) fibrils and symmetric segments with an average periodicity (AP) of 250–260 nm, symmetric fibrous longspacing (FLS IV) nanofibrils with AP of 165 nm, and cofibrils exhibiting an asymmetric D-periodicity of 67 nm with a striking resemblance to the native collagen type I banding pattern. The intercalation of the high negatively charged heparin in the fibrils is suggested as being the main trigger for the hierarchical formation of the polymorphic structures. We propose a model explaining the unexpected presence of a symmetric and asymmetric form in the system and the principles governing the symmetric or asymmetric fate of the molecules
Barriers to Obtaining a Timely Diagnosis in Human Papillomavirus–Associated Oropharynx Cancer

Objective Failure to recognize symptoms of human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) at presentation can delay diagnosis and treatment. This study aims to identify patient factors and provider patterns that contribute to delayed diagnosis. Study Design Retrospective case series. Setting Tertiary care center. Methods Patients with HPV(+)OPSCC receiving intent-to-cure treatment from 2006 to 2016. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations. Results Of 703 included patients, 627 (89%) were male, and mean (SD) age at diagnosis was 59 (9) years. The mean (SD) delay to diagnosis was 148.8 (243.51) days, with an average delay of 63 (154.91) days from symptom onset to first presentation and 82.8 (194.25) days from first presentation to diagnosis. Most patients visited at least 2 providers (n = 546, 78%) before diagnosis and saw their primary care physician at first presentation (n = 496, 71%). The most common imaging and biopsy obtained before diagnosis was neck computed tomography (n = 391, 56%) and neck fine-needle aspiration (n = 423, 60%), respectively. On multivariable linear regression, being a homemaker, being a current smoker, seeing 3 or more providers, and getting a magnetic resonance imaging scan were associated with significant delays in diagnosis (P < .01, all). Treatment with antibiotics and a suspicion for HPV(+)OPSCC at first presentation were associated with decreased delays in diagnosis (P < .01, both). Conclusions Patient delays in seeking medical attention and provider delays in recognizing the appropriate diagnosis both contribute to delays of care in HPV(+)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(+)OPSCC.
Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Endovascular Thrombectomy

Objective To determine whether pretreatment cerebral microbleeds (CMBs) presence and burden are correlated with an increased risk of intracranial hemorrhage (ICH) or poor functional outcome following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Methods Consecutive patients treated by EVT for anterior circulation AIS were retrospectively analyzed. Experienced neuroradiologists blinded to functional outcomes rated CMBs on T2*-MRI using a validated scale. We investigated associations of CMB presence and burden with ICH and poor clinical outcome at 3 months (modified Rankin Scale score >2). Results Among 513 patients, 281 (54.8%) had a poor outcome and 89 (17.3%) had ≥1 CMBs. A total of 190 (37%) patients experienced ICH; 66 (12.9%) were symptomatic. CMB burden was associated with poor outcome in a univariable analysis (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.03–1.36 per 1-CMB increase; p = 0.02), but significance was lost after adjustment for sex, age, stroke severity, hypertension, diabetes mellitus, atrial fibrillation, prior antithrombotic medication, IV thrombolysis, and reperfusion status (OR, 1.05; 95% CI, 0.92–1.20 per 1-CMB increase; p = 0.50). Results remained nonsignificant when taking into account CMB location or presumed underlying pathogenesis. CMB presence, burden, location, or presumed pathogenesis were not independently correlated with ICH. Conclusions Poor functional outcome or ICH were not correlated with CMB presence or burden on pre-EVT MRI after adjustment for confounding factors. Excluding such patients from reperfusion therapies is unwarranted. Classification of Evidence This study provides Class II evidence that in patients with AIS undergoing EVT, after adjustment for confounding factors, the presence of CMBs is not significantly associated with clinical outcome or the risk of ICH.
A High Amylose Wheat Diet Improves Gastrointestinal Health Parameters and Gut Microbiota in Male and Female Mice

High amylose wheat (HAW) contains more resistant starch than standard amylose wheat (SAW) and may have beneficial effects on gastrointestinal health. However, it is currently unclear whether these effects differ according to the level of HAW included in the diet or between males and females. Male and female C57BL/6 mice (n = 8/group/sex) were fed SAW65 (65% SAW; control), HAW35 (35% HAW), HAW50 (50% HAW) or HAW65 (65% HAW) diet for eight weeks. Female but not male, mice consuming any amount of HAW exhibited accelerated gastric emptying compared to SAW65 group. In both sexes, relative colon weights were higher in the HAW65 group compared to SAW65 group and in females, relative weights of the small intestine and cecum were also higher in the HAW65 group. In females only, colonic expression of Pyy and Ocln mRNAs were higher in the HAW65 group compared to HAW35 and HAW50 groups. In both sexes, mice consuming higher amounts of HAW (HAW50 or HAW65) had increased fecal bacterial load and relative abundance of Bacteroidetes phylum and reduced relative abundance of Firmicutes compared to SAW65 group. These data are consistent with a beneficial impact of HAW on gastrointestinal health and indicate dose-dependent and sex-specific effects of HAW consumption.
The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin–Detected Pregnancy, Pregnancy Loss, and Live Birth

BACKGROUND A previous large randomized trial indicated that preconception-initiated low-dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention-to-treat approach. OBJECTIVE To estimate per protocol effects of preconception-initiated LDA on pregnancy loss and live birth. DESIGN The EAGeR (Effects of Aspirin on Gestation and Reproduction) trial was used to construct a prospective cohort for a post hoc analysis. (ClinicalTrials.gov: NCT00467363). SETTING 4 university medical centers in the United States. PARTICIPANTS 1227 women between the ages of 18 and 40 years who had 1 or 2 previous pregnancy losses and were attempting pregnancy. MEASUREMENTS Adherence to LDA or placebo, assessed by measuring pill bottle weights at regular intervals during follow-up. Primary outcomes were human chorionic gonadotropin (hCG)-detected pregnancies, pregnancy losses, and live births, determined by pregnancy tests and medical records. RESULTS Relative to placebo, adhering to LDA for 5 of 7 days per week led to 8 more hCG-detected pregnancies (95% CI, 4.64 to 10.96 pregnancies), 15 more live births (CI, 7.65 to 21.15 births), and 6 fewer pregnancy losses (CI, -12.00 to -0.20 losses) for every 100 women in the trial. In addition, compared with placebo, postconception initiation of LDA therapy led to a reduction in the estimated effects. Furthermore, effects were obtained in a minimum of 4 of 7 days per week. LIMITATION The EAGeR trial data for this study were analyzed as observational data, thus are subject to the limitations of prospective observational studies. CONCLUSION Per protocol results suggest that preconception use of LDA at least 4 days per week may improve reproductive outcomes for women who have had 1 or 2 pregnancy losses. Increasing adherence to daily LDA seems to be key to improving effectiveness. PRIMARY FUNDING SOURCE National Institutes of Health.
Dbx2 regulation in limbs suggests interTAD sharing of enhancers

Background During tetrapod limb development, the HOXA13 and HOXD13 transcription factors are critical for the emergence and organization of the autopod, the most distal aspect where digits will develop. Since previous work had suggested that the Dbx2 gene is a target of these factors, we set up to analyze in detail this potential regulatory interaction. Results We show that HOX13 proteins bind to eutherian-specific sequences at the vicinity of the Dbx2 locus that have enhancer activity in developing digits. However, the functional inactivation of the DBX2 protein did not elicit any particular phenotype related to Hox genes inactivation in digits, suggesting either redundant or compensatory mechanisms. We report that the neighboring Nell2 and Ano6 genes are also expressed in distal limb buds and are, in part, controlled by the same Dbx2 enhancers despite being localized into two different topologically associating domains (TADs) flanking the Dbx2 locus. Conclusions We conclude that Hoxa13 and Hoxd genes cooperatively activate Dbx2 expression in developing digits through binding to eutherian specific regulators elements in the Dbx2 neighborhood. Furthermore, these enhancers can overcome TAD boundaries in either direction to co-regulate a set of genes located in distinct chromatin domains. Bullet points Hoxa13 and Hoxd genes cooperatively regulate Dbx2 expression in developing digits via eutherian specific enhancers. Dbx2 is expressed in different digit joint precursors but its function there is not essential. Dbx2 enhancers also control the expression of the Nell2 and Ano6 genes, which are located in different TADs, thus overcoming the boundary effect. Dbx2 chromatin architecture and enhancers evolved in the mammalian lineage. Grant Sponsor and Number Swiss National Research Foundation #310030B_138662. European Research Council grants RegulHox #588029
Pediatric bipolar disorder: Executive, linguistic, mnemonic, and cognitive efficiency mapping

Abstract Neuropsychological assessment can enrich our understanding of Pediatric Bipolar Disorder (PB). This study aimed to: (1) analyze the occurrence of neuropsychological frequency of deficits and difficulties in children with PB; (2) verify whether there is a performance difference between PB type I (PB-I) and PB type II (PB-II)/unspecified, and between PB with and without ADHD; and (3) verify the cognitive efficiency differences within the PB group and control groups, and among clinical subgroups. Participants in the study were 16 children diagnosed with PB and 40 children with typical development (6–12 years old). The results indicated a high frequency of deficits/difficulties in verbal fluency, cognitive efficiency in performing basic abilities, inhibitory control, cognitive flexibility, and working memory, with emphasis on verbal and executive losses. There were indications that type PB-I and comorbidity with ADHD negatively impact a child’s neuropsychological development. The clinical group showed more cognitive efficiency losses compared with the control group, and greater losses were observed in PB-I and in PB with ADHD. The role of neuropsychological evaluation in multidomain and nonlinear statistical analysis is critical to gaining an understanding of the clinical and cognitive heterogeneity of PB.
Dynamics of Active Brownian Particles in Plasma

Experimental data on the active Brownian motion of single particles in the RF (radio-frequency) discharge plasma under the influence of thermophoretic force, induced by laser radiation, depending on the material and type of surface of the particle, are presented. Unlike passive Brownian particles, active Brownian particles, also known as micro-swimmers, move directionally. It was shown that different dust particles in gas discharge plasma can convert the energy of a surrounding medium (laser radiation) into the kinetic energy of motion. The movement of the active particle is a superposition of chaotic motion and self-propulsion.
Treatment with pembrolizumab in programmed death ligand 1–positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE‐028 trial

Current treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of the anti–programmed death 1 (anti–PD‐1) immunotherapy, pembrolizumab, in programmed death ligand 1 (PD‐L1)–positive, recurrent glioblastoma.
Recombinant high-mobility group box 1 induces cardiomyocyte hypertrophy by regulating the 14-3-3η, PI3K and nuclear factor of activated T cells signaling pathways

High-mobility group box 1 (HMGB1) is released by necrotic cells and serves an important role in cardiovascular pathology. However, the effects of HMGB1 in cardiomyocyte hypertrophy remain unclear. Therefore, the aim of the present study was to investigate the potential role of HMGB1 in cardiomyocyte hypertrophy and the underlying mechanisms of its action. Neonatal mouse cardiomyocytes (NMCs) were co-cultured with recombinant HMGB1 (rHMGB1). Wortmannin was used to inhibit PI3K activity in cardiomyocytes. Subsequently, atrial natriuretic peptide (ANP), 14-3-3 and phosphorylated-Akt (p-Akt) protein levels were detected using western blot analysis. In addition, nuclear factor of activated T cells 3 (NFAT3) protein levels were measured by western blot analysis and observed in NMCs under a confocal microscope. The results revealed that rHMGB1 increased ANP and p-Akt, and decreased 14-3-3η protein levels. Furthermore, wortmannin abrogated the effects of rHMGB1 on ANP, 14-3-3η and p-Akt protein levels. In addition, rHMGB1 induced nuclear translocation of NFAT3, which was also inhibited by wortmannin pretreatment. The results of this study suggest that rHMGB1 induces cardiac hypertrophy by regulating the 14-3-3η/PI3K/Akt/NFAT3 signaling pathway.
Drought by CO2 interactions in trees: a test of the water savings mechanism.

●Elevated atmospheric CO2 (eCa ) may benefit plants during drought by reducing stomatal conductance (gs ) but any 'water savings effect' could be neutralized by concurrent stimulation of leaf area. We investigated whether eCa enhanced water savings, thereby ameliorating the impact of drought on carbon and water relations in trees. ●We report leaf-level gas exchange and whole-plant and soil water relations during a short-term dry-down in two Eucalyptus species with contrasting drought tolerance. Plants had previously been established for 9-11 months in steady-state conditions of ambient (aCa ) and eCa , with half of each treatment group exposed to sustained drought for 5-7 months. ●The lower stomatal conductance under eCa did not lead to soil moisture savings during the dry-down due to the counteractive effect of increased whole-plant leaf area. Nonetheless, eCa -grown plants maintained higher photosynthetic rates and leaf water potentials, making them less stressed during the dry-down, despite being larger. These effects were more pronounced in the xeric species than the mesic species, and in previously water-stressed plants. ●Our findings indicate that eCa may enhance plant performance during drought despite a lack of soil water savings, especially in species with more conservative growth and water-use strategies.
Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease

Objective To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Methods Multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing–based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. Results Prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C–like progression (SARA points 2.5–5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. Conclusions RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials. Classification of Evidence This study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC.
Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies

Purpose: In preclinical studies, the lysine-specific histone demethylase 1A (LSD1) inhibitor tranylcypromine (TCP) combined with all-trans retinoic acid (ATRA) induces differentiation and impairs survival of myeloid blasts in non-acute promyelocytic leukemia acute myeloid leukemia (AML). We conducted a phase I clinical trial (NCT02273102) to evaluate the safety and activity of ATRA plus TCP in patients with relapsed/refractory AML and myelodysplasia (MDS). Patients and Methods: Seventeen patients were treated with ATRA and TCP (three dose levels: 10 mg twice daily, 20 mg twice daily, and 30 mg twice daily). Results: ATRA-TCP had an acceptable safety profile. The MTD of TCP was 20 mg twice daily. Best responses included one morphologic leukemia-free state, one marrow complete remission with hematologic improvement, two stable disease with hematologic improvement, and two stable disease. By intention to treat, the overall response rate was 23.5% and clinical benefit rate was 35.3%. Gene expression profiling of patient blasts showed that responding patients had a more quiescent CD34+ cell phenotype at baseline, including decreased MYC and RARA expression, compared with nonresponders that exhibited a more proliferative CD34+ phenotype, with gene expression enrichment for cell growth signaling. Upon ATRA-TCP treatment, we observed significant induction of retinoic acid–target genes in responders but not nonresponders. We corroborated this in AML cell lines, showing that ATRA-TCP synergistically increased differentiation capacity and cell death by regulating the expression of key gene sets that segregate patients by their clinical response. Conclusions: These data indicate that LSD1 inhibition sensitizes AML cells to ATRA and may restore ATRA responsiveness in subsets of patients with MDS and AML.
Spin–spin coupling constants and triplet instabilities in Kohn–Sham theory

Indirect nuclear spin–spin coupling constants calculated using restricted Hartree–Fock theory are unreliable since the usually dominant Fermi-contact (FC) contribution arises from a triplet perturbation of the electronic system, poorly described in the Hartree–Fock theory – in particular, at geometries close to the onset of triplet instabilities. These problems are usually but not invariably overcome in Kohn–Sham theory, which typically provides good spin–spin coupling constants. We here examine the sensitivity of spin–spin coupling constants to triplet instabilities in Kohn–Sham and Hartree–Fock theories by correlating the quality of the spin–spin coupling constants and the quality of the lowest triplet excitation energy for a number of small molecules. In general, the FC contributions are most stable in the local density approximation (LDA) and slightly less stable in the generalised gradient approximation (GGA); on the other hand, GGA coupling constants are usually more accurate than LDA constants. Importantly, although hybrid theory often gives better results than the GGA theory, it is also more susceptible to triplet instabilities (inheriting some of the problems of the Hartree–Fock theory) and therefore less reliable than the GGA theory for spin–spin coupling constants. For calculations of spin–spin coupling constants, we recommend the Perdew–Burke–Ernzerhof GGA exchange-correlation functional, which provides a good compromise of accuracy and robustness.