Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of constipation in children using high-resolution anorectal manometry

This prospective, cross-sectional study, conducted from July 2018 to March 2019, aimed to determine the causes of constipation using high-resolution anorectal manometry. Among 33 children enrolled in the study, 31 (94%) children presented with complaints of constipation with mean duration of 2.3 ± 2.5 years and 12 (36.4%) children also had associated complaints of faecal incontinence with mean duration of 3.5 ± 2.8 years. Seven children (21.2%) had normal high-resolution anorectal manometry parameters; anal sphincter hypotonia with decreased squeeze in one child, anal sphincter hypertonia with other abnormal parameters were noted in 25 and absent recto-anal inhibitory reflex in two. The causes of constipation determined were functional constipation in 30 (91%) children, suspected Hirschsprung’s disease in two and suspected dyssynergic defecatory disorder in one. Almost 90% had functional constipation of which anal hypotension and anal hypertension may be a part of chronic functional constipation.
Structure, function and connectivity fingerprints of the frontal eye field versus the inferior frontal junction: A comprehensive comparison

The human prefrontal cortex contains two prominent areas, the frontal eye field and the inferior frontal junction, that are crucially involved in the orchestrating functions of attention, working memory and cognitive control. Motivated by comparative evidence in non‐human primates, we review the human neuroimaging literature, suggesting that the functions of these regions can be clearly dissociated. We found remarkable differences in how these regions relate to sensory domains and visual topography, top‐down and bottom‐up spatial attention, spatial versus non‐spatial (i.e., feature‐ and object‐based) attention and working memory and, finally, the multiple‐demand system. Functional magnetic resonance imaging (fMRI) studies using multivariate pattern analysis reveal the selectivity of the frontal eye field and inferior frontal junction to spatial and non‐spatial information, respectively. The analysis of functional and effective connectivity provides evidence of the modulation of the activity in downstream visual areas from the frontal eye field and inferior frontal junction and sheds light on their reciprocal influences. We therefore suggest that future studies should aim at disentangling more explicitly the role of these regions in the control of spatial and non‐spatial selection. We propose that the analysis of the structural and functional connectivity (i.e., the connectivity fingerprints) of the frontal eye field and inferior frontal junction may be used to further characterize their involvement in a spatial (‘where’) and a non‐spatial (‘what’) network, respectively, highlighting segregated brain networks that allow biasing visual selection and working memory performance to support goal‐driven behaviour.
In vitro antimetastatic activity of Momordica balsamina crude acetone extract in HT‐29 human colon cancer cells

Plant‐derived compounds and/or extracts have proven to be beneficial for the treatment of a broad spectrum of cancers with minimal side effects. In this study, we investigated whether a crude acetone extract of Momordica balsamina (MBE) can interfere with the metastatic ability of HT‐29 colorectal cancer (CRC) cells. The phytochemical composition of MBE was determined by ultra‐performance liquid chromatography and cytotoxic effects by the MTT and acridine orange/ethidium bromide staining assays. The effect of MBE on the formation of reactive oxygen species was assessed using the DCFH2‐DA assay. Wound healing assay, transwell cell invasion assay, cell adhesion assay, and the extracellular matrix‐cell adhesion array were used to assess the antimetastatic effects of MBE. The effect of MBE on the expression of TNF‐α, NF‐κB, TIMP‐3, MMP‐2, and MMP‐9 was assessed by western blot analysis. Our results showed that MBE consists of a mixture of compounds without a known anticancer activity in CRC and exhibits cytotoxicity against HT‐29 cells. MBE also suppressed reactive oxygen species formation, cell invasion, cell migration, and cell adhesion. The reduction of cell invasion was associated with the downregulation of TNF‐α, NF‐κB, MMP2, and MMP9 and upregulation of TIMP‐3 proteins. We concluded that MBE inhibits the metastatic ability of HT‐29 CRC cells in vitro.
Solubility of Nifedipine in Ethanol + Water and Propylene Glycol + Water Mixtures at 293.2 to 313.2 K

The solubility of nifedipine (NIF) in binary mixtures of ethanol (EtOH) + water and propylene glycol (PG) + water at 293.2, 298.2, 303.2, 308.2, and 313.2 K was measured. The Jouyban–Acree model and its combination with van’t Hoff equation was used to predict the solubility of NIF in the mixed solvents at different temperatures. The solubility of NIF in EtOH + water mixtures have a maximum at 0.90 mass fraction of EtOH, but the solubility of NIF in PG + water reaches to the maximum value in neat PG. Both mixtures (EtOH + water and PG + water) have a maximum solubility at 313.2 K. A mean relative deviation (MRD) for the fitted data to the Jouyban–Acree model of 8.1% and for combined method of 7.4% was obtained. The predicted MRDs for the solubility data using previously trained models were 38.8%, 43.0%, and 43.9%, and the MRD for predicted density value was 7.3%.
Hepatitis E virus egress and beyond – the manifold roles of the viral ORF3 protein

Although the hepatitis E virus represents an uprising threat to the global community by representing the commonest cause of an acute viral hepatitis worldwide, its life cycle is grossly understudied. Albeit HEV is a non‐enveloped virus, its progeny is released as quasi‐enveloped virions. Thus, the responsible accessory protein pORF3 gained rising attention in the past years. It mediates viral release via the exosomal route by targeting the viral capsid to the endosomal system, more precisely to multivesicular bodies. As this is followed by quasi‐envelopment, pORF3 may in terms represent a substitute to a conventional envelope protein. This feature proofs to be rather unique with respect to other enteric viruses, although the protein's role in the viral life cycle seems to reach far beyond simply maintaining release of progeny viruses. How pORF3 affects viral morphogenesis, how it mediates efficient viral release and how it supports viral spread is summarised in this microreview. With this, we aim to shed light on functions of pORF3 to gain further insights in still enigmatic aspects of the HEV life cycle.
Heterozygous HTRA1 nonsense or frameshift mutations are pathogenic.

Heterozygous missense HTRA1 mutations have been associated with an autosomal dominant cerebral small vessel disease whereas the pathogenicity of heterozygous HTRA1 stop codon variants is unclear. We performed a targeted high throughput sequencing of all known cerebral small vessel disease genes, including HTRA1, in 3,853 unrelated consecutive CSVD patients referred for molecular diagnosis. The frequency of heterozygous HTRA1 mutations leading to a premature stop codon in this patient cohort was compared with their frequency in large control databases. An analysis of HTRA1 messenger RNA was performed in several stop codon carrier patients. Clinical and neuroimaging features were characterized in all probands. Twenty unrelated patients carrying a heterozygous HTRA1 variant leading to a premature stop codon were identified. A highly significant difference was observed when comparing our patient cohort with control databases (gnomAD v3.1.1 (p = 3.12 x 10-17, OR = 21.9), TOPMed freeze 5 (p = 7.6 x 10-18, OR = 27.1) and 1000 Genomes (p = 1.5 x 10-5). Messenger RNA analysis performed in eight patients showed a degradation of the mutated allele strongly suggesting a haploinsufficiency. Clinical and neuroimaging features are similar to those previously reported in heterozygous missense mutation carriers, except for penetrance, which seems lower. Altogether, our findings strongly suggest that heterozygous HTRA1 stop codons are pathogenic through a haploinsufficiency mechanism. Future work will help to estimate their penetrance, an important information for genetic counseling.
PREPARATION AND DETERMINATION OF THE FUNCTIONAL PROPERTIES OF THE TRUPILLO PROTEIC CONCENTRATED (Prosopis juliflora)

The main food shortages in the world are protein products, what has become a great problem of food security since they are difficult production, availability, high cost, and very low fuel consumption. In the present work was obtained a protein concentrate, having suspended a sample of while keeping the system with constant mechanical agitation during one hour at 40°C and subsequently acidify the supernatant with HCI 1N up to ted the functional properties, which compared with the concentrate of soybeans were similar in the following parameters of industrial interest, in the rate of absorption of lipids (334-306) respectively. It was concluded that the trupillo can be constituted as a new source of protein. This is important because it is a native plant, whose raw material costs are significantly lower than the traditional.
Schwann Cells Provide Iron to Axonal Mitochondria and Its Role in Nerve Regeneration

Iron is an essential cofactor for several metabolic processes, including the generation of ATP in mitochondria, which is required for axonal function and regeneration. However, it is not known how mitochondria in long axons, such as those in sciatic nerves, acquire iron in vivo. Because of their close proximity to axons, Schwann cells are a likely source of iron for axonal mitochondria in the PNS. Here we demonstrate the critical role of iron in promoting neurite growth in vitro using iron chelation. We also show that Schwann cells express the molecular machinery to release iron, namely, the iron exporter, ferroportin (Fpn) and the ferroxidase ceruloplasmin (Cp). In Cp KO mice, Schwann cells accumulate iron because Fpn requires to partner with Cp to export iron. Axons and Schwann cells also express the iron importer transferrin receptor 1 (TfR1), indicating their ability for iron uptake. In teased nerve fibers, Fpn and TfR1 are predominantly localized at the nodes of Ranvier and Schmidt-Lanterman incisures, axonal sites that are in close contact with Schwann cell cytoplasm. We also show that lack of iron export from Schwann cells in Cp KO mice reduces mitochondrial iron in axons as detected by reduction in mitochondrial ferritin, affects localization of axonal mitochondria at the nodes of Ranvier and Schmidt-Lanterman incisures, and impairs axonal regeneration following sciatic nerve injury. These finding suggest that Schwann cells contribute to the delivery of iron to axonal mitochondria, required for proper nerve repair. SIGNIFICANCE STATEMENT This work addresses how and where mitochondria in long axons in peripheral nerves acquire iron. We show that Schwann cells are a likely source as they express the molecular machinery to import iron (transferrin receptor 1), and to export iron (ferroportin and ceruloplasmin [Cp]) to the axonal compartment at the nodes of Ranvier and Schmidt-Lanterman incisures. Cp KO mice, which cannot export iron from Schwann cells, show reduced iron content in axonal mitochondria, along with increased localization of axonal mitochondria at Schmidt-Lanterman incisures and nodes of Ranvier, and impaired sciatic nerve regeneration. Iron chelation in vitro also drastically reduces neurite growth. These data suggest that Schwann cells are likely to contribute iron to axonal mitochondria needed for axon growth and regeneration.
Genotypic analysis of the female BPH/5 mouse, a model of superimposed preeclampsia

Animal models that recapitulate human diseases and disorders are widely used to investigate etiology, diagnosis, and treatment of those conditions in people. Disorders during pregnancy are particularly difficult to explore as interventions in pregnant women are not easily performed. Therefore, models that allow for pre-conception investigations are advantageous for elucidating the mechanisms involved in adverse pregnancy outcomes that are responsible for both maternal and fetal morbidity, such as preeclampsia. The Blood Pressure High (BPH)/5 mouse model has been used extensively to study the pathogenesis of preeclampsia. The female BPH/5 mouse is obese with increased adiposity and borderline hypertension, both of which are exacerbated with pregnancy making it a model of superimposed preeclampsia. Thus, the BPH/5 model shares traits with a large majority of women with pre-existing conditions that predisposes them to preeclampsia. We sought to explore the genome of the BPH/5 female mouse and determine the genetic underpinnings that may contribute to preeclampsia-associated phenotypes in this model. Using a whole genome sequencing approach, we are the first to characterize the genetic mutations in BPH/5 female mice that make it unique from the closely related BPH/2 model and the normotensive background strain, C57Bl/6. We found the BPH/5 female mouse to be uniquely different from BPH/2 and C57Bl/6 mice with a genetically complex landscape. The majority of non-synonymous consequences within the coding region of BPH/5 females were missense mutations found most abundant on chromosome X when comparing BPH/5 and BPH/2, and on chromosome 8 when comparing BPH/5 to C57Bl/6. Genetic mutations in BPH/5 females largely belong to immune system-related processes, with overlap between BPH/5 and BPH/2 models. Further studies examining each gene mutation during pregnancy are warranted to determine key contributors to the BPH/5 preeclamptic-like phenotype and to identify genetic similarities to women that develop preeclampsia.
Exposure to Low (≤10 cGy) Doses of 4He Particles Leads to Increased Social Withdrawal and Loss of Executive Function Performance

Astronauts on the planned mission to Mars will be exposed to galactic cosmic radiation (GCR), with proton and He particles accounting (in approximately equal amounts) for ∼75% of the equivalent dose. Exposure to ≤15 cGy of space radiation ions with Z ≥ 15 particles has been shown to impair various executive functions, including attentional set shifting and creative problem-solving in rats. Executive functions also regulate social interactions and mood. Should space radiation exposure alter these executive functions as it does cognitive flexibility, there is the possibility of altered interactions among crew members and team cooperativity during prolonged space exploration. This study characterized the effects of ≤10 cGy 400 MeV/n of 4He particles on cognitive flexibility and social interaction (within freely interacting dyads) in male Wistar rats. Exposure to ≥1 cGy 4He ions induced deficits in the SD and/or CD stages of the attentional set shifting (ATSET) task, as reported after exposure to Z ≥ 15 space radiation ions. Should similar effects occur in astronauts, these data suggest that they would have a reduced ability to identify key events in a new situation and would be more easily distracted by extraneous variables. The irradiated rats were also screened for performance in a task for unconstrained cognitive flexibility (UCFlex), often referred to as creative problem-solving. There was a marked dose-dependent change in UCFlex performance with ∼30% of rats exposed to 10 cGy being unable to solve the problem, while the remaining rats took longer than the sham-irradiated animals to resolve the problem. Importantly, performance in the ATSET test was not indicative of UCFlex performance. From a risk assessment perspective, these findings suggest that a value based on a single behavioral end point may not fully represent the cognitive deficits induced by space radiation, even within the cognitive flexibility domain. Rats that received 5 cGy 4He ion irradiation had a significantly lower level of interaction toward their sham-irradiated partners in a non-anxiogenic (uncaged) dyad interactions study. This is consistent with the social withdrawal previously observed in space radiation-exposed male mice in a three-chamber test. 4He-irradiated rats exhibited a significantly higher incidence and duration of self-grooming, which is even more concerning, given that their dyad partners were able to physically interact with the irradiated rats (i.e., touching/climbing over them). This study has established that exposure of male rats to “light” ions such as He affects multiple executive functions resulting in deficits in both sociability and cognitive flexibility, and possibly affective behavior (reward valuation). Further studies are needed to determine if these space radiation-induced co-morbidities are concomitantly induced within individual rats.
What is normal bone health? A bioarchaeological perspective on meaningful measures and interpretations of bone strength, loss, and aging

Bioarchaeological (the study of archeological human remains together with contextual and documentary evidence) offers a unique vantage point to examine variation in skeletal morphology related to influences such as activity, disease, and nutrition. The human skeleton is composed of a dynamic tissue that is forged by biocultural factors over the entire life course, providing a record of individual, and community history. Various aspects of adult bone health, particularly bone maintenance and loss and the associated skeletal disease osteoporosis, have been examined in numerous past populations. The anthropological study of bone loss has traditionally focused on the signature of postmenopausal aging, costs of reproduction, and fragility in females. The a priori expectation of normative sex‐related bone loss/fragility in bioanthropological studies illustrates the wider gender‐ideological bias that continues in research design and data analysis in the field. Contextualized data on bone maintenance and aging in the archeological record show that patterns of bone loss do not constitute predictable consequences of aging or biological sex. Instead, the critical examination of bioarchaeological data highlights the complex and changing processes that craft the human body over the life course, and calls for us to question the ideal or “normal” range of bone quantity and quality in the human skeleton, and to critically reflect on what measures are actually biologically and/or socially meaningful.
Characteristics and Outcomes of Over 300,000 Patients with COVID-19 and History of Cancer in the United States and Spain

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.
ICD‐11 ‘mixed depressive and anxiety disorder’ is clinical rather than sub‐clinical and more common than anxiety and depression in the general population

Background The new International Classification of Diseases was published in 2018 (ICD‐11; World Health Organization, 2018) and now includes ‘Mixed depressive and anxiety disorder’ (6A73: MDAD) designated as a mood disorder. This disorder is defined by symptoms of both anxiety and depression occurring more days than not, for a period of two weeks, and neither set of symptoms considered separately reaches a diagnostic threshold for either disorder. However, to date no study has examined the validity of these guidelines in a general population sample. Methods Using Goldberg et al.’s (2017) guidelines regarding measurement of depression and anxiety, this study used factor mixture modelling (FMM) to examine the validity of the ICD‐11 criteria of MDAD. Symptom endorsement rates are provided as well as demographic predictors and somatization outcomes. Results Fit indices suggested the two‐factor four‐class solution was the best balance between model complexity and model fit. The results did not support a class that is subsyndromal to both anxiety and depression. On the contrary, we suggest that there exists a ‘Comorbid’ class that represents endorsement of both anxiety and depression symptoms at a higher level when compared to both ‘anxiety’ and ‘depression’ groups. Demographic predictors, as well as somatization and functional impairment outcomes, provided support for this FMM solution. Conclusions The ‘Comorbid’ group was the largest symptomatic group and had the highest levels of both anxiety and depression symptoms. Importantly, this group was larger than either the ‘anxiety’ or ‘depression’ group and was associated with high levels of functional impairment and somatization.