Miracle-dz/UniFAR-FTUs huggingface dataset:
Letter to the Editor

(1) The conclusion that only dentifrices at concentrations of 1000 ppm F and above are effective for caries control is not universal, since the same review (Walsh et al., 2010) acknowledges the uncertainty surrounding the benefits of low-fluoride dentifrices for the deciduous dentition. (2) It is surprising that the authors questioned the choice of whole plaque as the indicator of intra-oral fluoride levels, given that one of the letter’s authors recently concluded that “. uptake of F by dental plaque not removed by brushing may be the main cause of the anticaries effect of F dentifrices” (Tenuta et al., 2009). Moreover, contrary to our protocol, which better resembles the clinical situation, most of the studies cited by the authors were conducted in situ (Tenuta et al., 2006, 2009; Cury et al., 2010). (3) Power calculations were described in the manuscript. Significant differences were observed for many comparisons (Table 1 in our paper), but it should be noted that in our study we had water and dentifrices as sources of fluoride, which are both contributors to the total fluoride uptake by plaque. (4) Vogel et al. (2010) analyzed CaF2-like deposits in plaque 30 and 60 minutes after a fluoride rinse, and the authors acknowledge that such deposits could initially have been formed, dissolved, and subsequently retained by plaque bacteria, which is in accordance with our hypothesis. (5) The previous studies that support our hypothesis are described in the second paragraph of the manuscript.
miR‐128‐3p contributes to mitochondrial dysfunction and induces apoptosis in glioma cells via targeting pyruvate dehydrogenase kinase 1

Glioma, like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect, which is a dominant phenotype of most tumor cells. Glioma tumors exhibit high glycolytic metabolism with increased lactate production. Data derived from the gene expression profiling interactive analysis (GEPIA) database show that pyruvate dehydrogenase kinase 1 (PDK1) is significantly highly expressed in glioma tissues compared with corresponding normal tissues. PDK1 is a key enzyme in the transition of glycolysis to tricarboxylic acid cycle, via inactivating PDH and converting oxidative phosphorylation to Warburg effect, resulting in increment of lactate production. Silencing of PDK1 expression resulted in reduced lactate and ATP, accumulation of ROS, mitochondrial damage, decreased cell growth, and increased cell apoptosis. Aberrant expression of miR‐128 has been observed in many human malignancies. Mechanistically, we discover that overexpressed miR‐128‐3p disturbs the Warburg effect in glioma cells via reducing PDK1. Our experiments confirmed that the miR‐128‐3p/PDK1 axis played a pivotal role in cancer cell metabolism and growth. Collectively, these findings suggest that therapeutic strategies to modulate the Warburg effect, such as targeting of PDK1, might act as a potential therapeutic target for glioma treatment.
The −675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus, its clinical manifestations, and comorbidities in Mexican-Mestizo population

Abstract Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the −675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the −675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The −675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p < .001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p < .001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p < .001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p < .001). The 4G/5G genotype was associated with shorter disease duration (p = .039), as well as lower levels of haemoglobin (p = .001) and haematocrit (p = .009); the need for prednisone treatment (p = .001), higher BMI (p = .03), presence of type 2 DM (p = .015), clinical activity (Mex-SLEDAI = 57%; p = .047), Chronicity (SLICC-ACR = 0; p = .015) and CRP levels (p = .015) were associated with 5G/5G genotypes. In conclusion, the −675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.
Elevated Choline Kinase α–Mediated Choline Metabolism Supports the Prolonged Survival of TRAF3-Deficient B Lymphocytes

Key Points Chkα and choline metabolism are upregulated in mouse TRAF3–deficient B cells. Reconstitution of TRAF3 in human malignant B cells inhibits choline metabolism. Inhibition of Chkα reverses the survival phenotype of TRAF3-deficient B cells. Specific deletion of the tumor suppressor TRAF3 from B lymphocytes in mice leads to the prolonged survival of mature B cells and expanded B cell compartments in secondary lymphoid organs. In the current study, we investigated the metabolic basis of TRAF3-mediated regulation of B cell survival by employing metabolomic, lipidomic, and transcriptomic analyses. We compared the polar metabolites, lipids, and metabolic enzymes of resting splenic B cells purified from young adult B cell–specific Traf3−/− and littermate control mice. We found that multiple metabolites, lipids, and enzymes regulated by TRAF3 in B cells are clustered in the choline metabolic pathway. Using stable isotope labeling, we demonstrated that phosphocholine and phosphatidylcholine biosynthesis was markedly elevated in Traf3−/− mouse B cells and decreased in TRAF3-reconstituted human multiple myeloma cells. Furthermore, pharmacological inhibition of choline kinase α, an enzyme that catalyzes phosphocholine synthesis and was strikingly increased in Traf3−/− B cells, substantially reversed the survival phenotype of Traf3−/− B cells both in vitro and in vivo. Taken together, our results indicate that enhanced phosphocholine and phosphatidylcholine synthesis supports the prolonged survival of Traf3−/− B lymphocytes. Our findings suggest that TRAF3-regulated choline metabolism has diagnostic and therapeutic value for B cell malignancies with TRAF3 deletions or relevant mutations.
Nondigestible Oligosaccharides with Anti-obesity Effects.

Obesity has an important influence on health conditions, causing multitude complications and comorbidities, and drug therapy is considered as one of the treatment strategies. Nowadays, there is an increasing interest in the study of intestinal microbiota regulation of obesity, as well as an increasing number of agricultural and sideline products are found to have anti-obesity potential. In the present review, we summarize an overview of current known and potential anti-obesity oligosaccharides and their molecular structures. We describe their anti-obesity potential activity and the molecular structure associated with this activity, the regulation of intestinal microbiota composition and its mechanism of action, including regulation of short-chain fatty acids (SCFAs) pathway and altering bile acids (BAs) pathway. This review will provide new ideas for us to develop new anti-obese functional foods.
Understanding barriers to women seeking and receiving help for perinatal mental health problems in UK general practice: development of a questionnaire

Abstract Aim: To develop a questionnaire to measure quantitatively barriers and facilitators to women’s disclosure of perinatal mental health problems in UK primary care. To pilot and evaluate the questionnaire for content validity and internal consistency. Background: Around 15% of women develop a mental illness in the perinatal period, such as depression, anxiety or post-traumatic stress disorder. In the United Kingdom, 90% of these women will be cared for in primary care, yet currently in as many as 50% of cases, no discussion of this issue takes place. One reason for this is that women experience barriers to disclosing symptoms of perinatal mental illness in primary care. These have previously been explored qualitatively, but no tool currently exists with which to measure these barriers quantitatively. Methods: Questionnaire items, drawn from qualitative literature and accounts of women’s experiences, were identified, refined iteratively and arranged in themes. The questionnaire was piloted using cognitive debriefing interviews to establish content validity. Women completed a refined version online. Responses were analysed using descriptive statistics. Internal consistency of subscales was calculated using Cronbach’s alpha. Findings: Cognitive debriefing interviews with five women showed the majority of questionnaire items were relevant, appropriate and easy to understand. The final questionnaire was completed by 71 women, and the majority of subscales had good internal consistency. The barrier scoring most highly was fear and stigma, followed by willingness to seek help and logistics of attending an appointment. Family/partner support and general practitioners’ (GPs) reaction were the lowest scoring barriers. Factors facilitating disclosure were GPs being empathetic and non-judgemental and listening during discussions. In the future, this questionnaire can be used to examine which barriers are most important for particular groups of women. This may enable the development of strategies to improve acknowledgement and discussion, and prevent under-recognition and under-treatment, of perinatal mental health problems in primary care.
Impact of NPM1/FLT3-ITD genotypes defined by the2017 European LeukemiaNet in patients with acute myeloid leukemia.

Patients with AML harboring FLT3 internal tandem duplications (ITD) have poor outcomes, in particular AML with a high ({greater than or equal to}0.5) mutant-to-wildtype allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined four distinct FLT3-ITD genotypes based on the ITD-AR and the NPM1 mutational status. In this retrospective, exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial evaluating the addition of midostaurin to standard chemotherapy. The four NPM1/FLT3-ITD genotypes significantly differed with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after one or two induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly between ELN risk groups with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate- and adverse-risk groups, respectively (P<0.001). Multivariate Cox model for OS using allogeneic hematopoietic-cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.
Morphology and Incidence of Torus Palatinus and Mandibularis in Brazilian Indians

The incidence and morphology of torus platinus and mandibularis was verified in 200 Indians, residents of two Brazilian Indian Reserves in São Paulo State, Brazil. A low incidence of both types of exostoses was observed, with torus palatinus occurring more frequently than mandibularis. These structures did not occur in individuals less than 10 years of age. Flattened torus palatinus predominated in relation to the other forms.
Multiscale Imaging Reveals Aberrant Functional Connectome Organization and Elevated Dorsal Striatal Arc Expression in Advanced Age

The functional connectome reflects a network architecture enabling adaptive behavior that becomes vulnerable in advanced age. The cellular mechanisms that contribute to altered functional connectivity in old age, however, are not known. Abstract The functional connectome reflects a network architecture enabling adaptive behavior that becomes vulnerable in advanced age. The cellular mechanisms that contribute to altered functional connectivity in old age, however, are not known. Here we used a multiscale imaging approach to link age-related changes in the functional connectome to altered expression of the activity-dependent immediate-early gene Arc as a function of training to multitask on a working memory (WM)/biconditional association task (BAT). Resting-state fMRI data were collected from young and aged rats longitudinally at three different timepoints during cognitive training. After imaging, rats performed the WM/BAT and were immediately sacrificed to examine expression levels of Arc during task performance. Aged behaviorally impaired, but not young, rats had a subnetwork of increased connectivity between the anterior cingulate cortex (ACC) and dorsal striatum (DS) that was correlated with the use of a suboptimal response-based strategy during cognitive testing. Moreover, while young rats had stable rich-club organization across three scanning sessions, the rich-club organization of old rats increased with cognitive training. In a control group of young and aged rats that were longitudinally scanned at similar time intervals, but without cognitive training, ACC–DS connectivity and rich-club organization did not change between scans in either age group. These findings suggest that aberrant large-scale functional connectivity in aged animals is associated with altered cellular activity patterns within individual brain regions.
Elderly caregiver: knowledge, attitudes and practices about falls and its prevention.

OBJECTIVE investigate the knowledge, attitudes and practices of informal elderly caregivers about falls and its prevention. METHOD this is a descriptive cross-sectional study conducted with 97 informal elderly caregivers residents in areas covered by five Health Strategy Units (ESF) in Cuiabá. RESULTS more than half of the participants are aware of falls and identify them as a problem, as well as they identify some risk factors and prevention measures. Regarding attitudes, more than half of the caregivers do not seem to act effectively to prevent falls. Most of them report adopting practices to prevent falls of the elderly, supervising the activities of their daily lives. CONCLUSION caregivers know about falls and its prevention, but in a superficial way, and it seems to influence their attitudes and practices regarding the prevention of this event.
Twenty five years of UK trials in acute myeloid leukaemia: what have we learned?

There have been national trials in acute leukaemia in the United Kingdom since the 1960. As haematology developed into a clinical specialty direct care move into the ambit of clinical haematology. Participation in trials reflected this evolution as did the expansion to include both Teaching and District General hospitals. More intensive chemotherapy combinations have been facilitated by better supportive care, including support from other medical disciplines, and nursing expertise. With the median age of acute myeloid leukaemia patients being 68 years, the intensive approach is not suitable for the majority of older patients where a different approach is needed. The UK has a creditable record in delivering improved care in recent years through a portfolio of prospective randomised trials. In a sequence from 1988 to 2014 of many of the largest trials ever undertaken in acute myeloid leukaemia (AML), a number of improvements to treatment have developed. Of major parallel importance has been the improvement in supportive care which, particularly in younger patients, has permitted more intensive treatment including transplantation to be assessed. The large recruitment has enabled several questions to be asked in a single trial. This experience is reviewed here exclusively in patients considered to be fit for an intensive chemotherapy approach. An additional portfolio in elderly unfit patients is not included. In the first 10 years children could participate, but the introduction of unlicensed drugs to the protocols was not permissible in younger patients. The sequence of treatments tested in the trials within the programme evolved over the years (Fig 1A, B). This includes a review of 16 959 patients who participated a programme of seven randomised trials which delivered a total of 33 249 randomisations from, at different times, >190 institutions in the UK, Ireland, Denmark, New Zealand and, for children, the Netherlands. Several treatment schedules were assessed (Table I). An additional 1758 young patients, who were high-risk or in relapse entered six randomisations in sequential trials, 2394 older patients who were not considered fit for intensive treatment entered 12 randomised comparisons. These interventions are not discussed here.These trials of intensive treatments have delivered important improvements in survival in children and younger adults, (Fig 2A, B) but less so in older patients (Fig 2C).
Normal and altered masticatory load impact on the range of craniofacial shape variation: An analysis of pre-Hispanic and modern populations of the American Southern Cone

The reduction of masticatory load intensity resulting from dietary changes in human evolution has been proposed as an important factor that alters craniofacial shape in past and current populations. However, its impact on craniofacial variation and on the perceived differences among populations is unclear. The maxillomandibular relationship, which alters masticatory force direction, is a factor often neglected but it can contribute to variation in craniofacial morphology, particularly among modern/urban populations where the prevalence of dental malocclusions is greater than in prehistoric populations. This study investigates the influence of masticatory load intensity and maxillomandibular relationship as a proxy for force direction on the human craniofacial skeleton. By using 3D imaging and geometric morphometrics, we analyzed craniofacial shape variation among 186 individuals from pre-Hispanic and modern Chilean and Argentinean populations that differ in diet consistency (a proxy for masticatory load intensity) and maxillomandibular relationship. We predicted that masticatory load would have a subtle effect on the upper craniofacial bones and that this would be more marked in the maxilla. Our results showed no clear influence of masticatory load on craniofacial shape, particularly in modern/urban populations. Allometry, on the contrary, shows a stronger effect. The degree of integration between the upper craniofacial bones and the load-bearing maxilla depends on masticatory load intensity, decreasing from high to low but showing a conservative pattern of covariation among the groups. The degree of variation in the shape of the maxilla is greater than the upper craniofacial bones. These results suggest that masticatory load has a limited effect in determining differences in craniofacial morphology among populations. This effect is slightly greater for the maxillary region of the face. We propose that the reduction of functional constraints is key to greater shape variation found in modern/urban populations.
$Ex~Vivo$ Assessment of Cortical Bone Properties Using Low-Frequency Ultrasonic Guided Waves

The early diagnosis of osteoporosis through bone quality assessment is a major public health challenge. Research in axial transmission using ultrasonic guided waves has shown the method to be sensitive to the geometrical and mechanical properties of the cortical layer in long bones. However, because of the asymmetric nature of cortical bone, the introduction of a more elaborate numerical model than the analytical plate and cylinder models, as well as its inversion, continues to be challenging. The aim of this article is, therefore, to implement a bone-like geometry using semianalytical finite-element (SAFE) modeling to perform the inverse characterization of ex vivo radii at low frequencies (< 60 kHz). Five cadaveric radiuses were taken from donors aged between 53 and 88 and tested using a typical axial transmission configuration at the middle of the diaphysis. The dispersion curves of the propagating modes were measured experimentally and then systematically compared with the solutions obtained with the SAFE method. For each sample, four parameters were estimated using a parameter identification procedure: 1) the bulk density; 2) the thickness; 3) the outer diameter; and 4) a shape factor (SF). The results showed a moderate agreement between the predicted bulk density and the average voxel value calculated from X-ray computed tomography images. Furthermore, a good agreement was observed between the geometrical parameters (thickness, outer diameter, and SF) and the reference images.
Anatomically correct assessment of the orientation of the cardiomyocytes using diffusion tensor imaging

Diffusion tensor imaging has been used for assessing the orientation of cardiac myocytes for decades. Striking methodological differences exist between studies when quantifying these orientations. This limits the comparability between studies, and impedes collaboration and the drawing of appropriate physiological conclusions. We have sought to elucidate these differences, permitting us to propose a standardised “tool set” that might better establish consensus in future studies.
The discrimination of quick Paediatric Early Warning Scores in the pre‐hospital setting

In our previous study, a Paediatric Early Warning Score could be calculated for only one‐fifth of 102,993 children transported by ambulance to hospital, as components other than supplemental oxygen were not reliably measured: respiratory rate 90,358 (88%); Glasgow Coma Score 83,648 (81%); heart rate 83,330 (81%); time to capillary reperfusion 81,685 (79%); oxygen saturation 71,372 (69%); temperature 60,402 (59%); systolic blood pressure 37,088 (36%). We tested 12 abbreviated scores with 3–5 components. The discrimination of these 12 scores for the primary outcome (30‐day mortality or admission to paediatric intensive care), as measured by the area under the receiving operator characteristic curve, ranged from 0.69 to 0.80. Scores could be calculated for at most 74,508 (72%) children when heart rate, conscious level and respiratory rate were measured, with or without supplemental oxygen: the discrimination of these two versions was 0.75 and 0.77, respectively. Optimal threshold scores of 3 and 2 for these two abbreviated versions discriminated an outcome rate of 2–3% in about one third of children from the other children who had < 1% rate of outcome.