Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemical sympathectomy reduces peripheral inflammatory responses to acute and chronic sleep fragmentation.

Sleep loss contributes to the development of cardiovascular, metabolic and neurological disorders by promoting a systemic pro-inflammatory phenotype. The neuroendocrine-immune mechanisms contributing to such pathologies are poorly understood. The sympathetic nervous system (SNS) regulates immunity and is often activated following sleep disturbances. The aims of this study were to determine (i) the effect of SNS inhibition upon inflammatory responses to sleep fragmentation (SF) and (ii) whether homeostasis can be restored after 1 week of recovery sleep. We measured stress responses (norepinephrine and corticosterone), gene expression levels of pro- and anti-inflammatory cytokines in peripheral (heart, liver and spleen) tissues and protein levels of cytokines and chemokines in serum of female mice that were subjected to acute SF for 24 hours, chronic SF for 8 weeks, or 7 days of recovery after chronic SF. In each experiment, SF and control mice were chemically sympathectomized with 6-OHDA (6-hydroxydopamine) or injected with vehicle. Both acute and chronic SF elevated mRNA and protein levels of cytokines in peripheral tissues. Changes in inflammatory responses mirrored stress-axes activation, with increased corticosterone and norepinephrine in SF mice. 6-OHDA treatment significantly alleviated SF-induced inflammation, thus providing evidence of SNS regulation of peripheral inflammation from SF. Effects of chronic SF were more severe than acute SF, and 1 week of recovery from SF sufficiently alleviated peripheral inflammatory responses but not NE responses.
Influence of the Menstrual Cycle on Blood Markers of Muscle Damage and Inflammation Following Eccentric Exercise

The aim of this study was to evaluate whether the menstrual cycle and its underlying hormonal fluctuations affect muscle damage and inflammation in well-trained females following an eccentric exercise. Nineteen eumenorrheic women performed an eccentric squat-based exercise in the early follicular phase, late follicular phase and mid-luteal phase of their menstrual cycle. Sex hormones and blood markers of muscle damage and inflammation –creatine kinase, myoglobin, lactate dehydrogenase, interleukin-6, tumoral necrosis factor-α, and C reactive protein– were analyzed in each phase. No effect of menstrual cycle phase was observed (p > 0.05), while an interaction for interleukin-6 was shown (p = 0.047). Accordingly, a moderate effect size [0.68 (0.53)–0.84 (0.74)], indicated that interleukin-6 values 2 h post-trial (2.07 ± 1.26 pg/mL) were likely to be higher than baseline (1.59 ± 0.33 pg/mL), 24 h (1.50 ± 0.01 pg/mL) and 48 h (1.54 ± 0.13 pg/mL) in the mid-luteal phase. Blood markers of muscle damage and inflammation were not affected by the menstrual cycle in well-trained women. The eccentric exercise barely triggered muscle damage and hence, no inflammation was observed, possibly due to participants training status. The mid-luteal phase was the only phase reflecting a possible inflammatory response in terms of interleukin-6, although further factors than sex hormones seem to be responsible for this finding.
Neuroradiology in tuberculous meningitisdiagnostic significance and prognostic value.

Introduction:Tuberculous meningitis (TBM) is the most common and belligerent form of CNS TB.Prompt definitive diagnosis of TBM is arduous due to tedious microbiological procedures. This study was conducted to evaluate the neuroradiological findings in patients with TBM as a modality forearly diagnoses and predicting prognosis. Materials and methods: A successive series of 100 patients diagnosed with TBM admitted to the PIMS neurology ward were studied between March 2013 and April 2014. Cranial imaging results were obtained by non-contrast enhanced CT brain (NECT) and MRI (magnetic resonance imaging) brain with contrast. MRC staging on admission and in-hospital mortality were recorded.Results: The mean age was 34.86 ± 1.76 years with a female preponderance (55%, 55 out of 100). On admission, 72% were in MRC stages II or III. The in-hospital mortality was 16%. NECT was obtained in all the patients and was abnormal in 67% of the patients with hydrocephalus (58%), edema cerebral (24%) and infarcts (5%) being the commonestfindings.CT infarct had the highest mortality rate of 60%. MRI was obtained in 61% of the patients and was abnormal in 88.5% of these cases. Hydrocephalus (61%), tuberculomas (54%), leptomeningeal involvement (46%) and infarcts (13%) were the most frequent radiological signs on MRI. Mortality was significantly associated with infarcts but not with tuberculomas.Conclusion: Neuroimaging techniques are a handy tool in the early diagnosis of TBM. MRI is particularly helpful in defining findings such as infarcts and tuberculomas and in predicting mortality and morbidity.
Correction

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Postnatal development of the entorhinal cortex: A stereological study in macaque monkeys

The entorhinal cortex is the main gateway for interactions between the neocortex and the hippocampus. Distinct regions, layers, and cells of the hippocampal formation exhibit different profiles of structural and molecular maturation during postnatal development. Here, we provide estimates of neuron number, neuronal soma size, and volume of the different layers and subdivisions of the monkey entorhinal cortex (Eo, Er, Elr, Ei, Elc, Ec, Ecl) during postnatal development. We found different developmental changes in neuronal soma size and volume of distinct layers in different subdivisions, but no changes in neuron number. Layers I and II developed early in most subdivisions. Layer III exhibited early maturation in Ec and Ecl, a two‐step/early maturation in Ei and a late maturation in Er. Layers V and VI exhibited an early maturation in Ec and Ecl, a two‐step and early maturation in Ei, and a late maturation in Er. Neuronal soma size increased transiently at 6 months of age and decreased thereafter to reach adult size, except in Layer II of Ei, and Layers II and III of Ec and Ecl. These findings support the theory that different hippocampal circuits exhibit distinct developmental profiles, which may subserve the emergence of different hippocampus‐dependent memory processes. We discuss how the early maturation of the caudal entorhinal cortex may contribute to path integration and basic allocentric spatial processing, whereas the late maturation of the rostral entorhinal cortex may contribute to the increased precision of allocentric spatial representations and the temporal integration of individual items into episodic memories.
Impact of age, body weight and metabolic risk factors on steroid reference intervals in men.

OBJECTIVE To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. DESIGN Cross-sectional study. METHODS 315 adult, drug-free and apparently healthy men underwent clinical and biochemical evaluation. 13 steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. RESULTS We observed lowering steroid precursors and testosterone, and increasing estrone levels in men showing increasing BMI levels. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, dehydroepiandrosterone, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29nmol/L lower (P=0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (-0.34nmol/L, P=0.045), cortisol (-87nmol/L, P=0.045-0.002) and corticosterone (-10.1nmol/L, P=0.048-0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. CONCLUSIONS Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.
Artificial intelligence and convolution neural networks assessing mammographic images: a narrative literature review

Studies have shown that the use of artificial intelligence can reduce errors in medical image assessment. The diagnosis of breast cancer is an essential task; however, diagnosis can include ‘detection’ and ‘interpretation’ errors. Studies to reduce these errors have shown the feasibility of using convolution neural networks (CNNs). This narrative review presents recent studies in diagnosing mammographic malignancy investigating the accuracy and reliability of these CNNs. Databases including ScienceDirect, PubMed, MEDLINE, British Medical Journal and Medscape were searched using the terms ‘convolutional neural network or artificial intelligence’, ‘breast neoplasms [MeSH] or breast cancer or breast carcinoma’ and ‘mammography [MeSH Terms]’. Articles collected were screened under the inclusion and exclusion criteria, accounting for the publication date and exclusive use of mammography images, and included only literature in English. After extracting data, results were compared and discussed. This review included 33 studies and identified four recurring categories of studies: the differentiation of benign and malignant masses, the localisation of masses, cancer‐containing and cancer‐free breast tissue differentiation and breast classification based on breast density. CNN's application in detecting malignancy in mammography appears promising but requires further standardised investigations before potentially becoming an integral part of the diagnostic routine in mammography.
Proline biosynthesis is a vent for TGFβ‐induced mitochondrial redox stress

The production and secretion of matrix proteins upon stimulation of fibroblasts by transforming growth factor‐beta (TGFβ) play a critical role in wound healing. How TGFβ supports the bioenergetic cost of matrix protein synthesis is not fully understood. Here, we show that TGFβ promotes protein translation at least in part by increasing the mitochondrial oxidation of glucose and glutamine carbons to support the bioenergetic demand of translation. Surprisingly, we found that in addition to stimulating the entry of glucose and glutamine carbon into the TCA cycle, TGFβ induced the biosynthesis of proline from glutamine in a Smad4‐dependent fashion. Metabolic manipulations that increased mitochondrial redox generation promoted proline biosynthesis, while reducing mitochondrial redox potential and/or ATP synthesis impaired proline biosynthesis. Thus, proline biosynthesis acts as a redox vent, preventing the TGFβ‐induced increase in mitochondrial glucose and glutamine catabolism from generating damaging reactive oxygen species (ROS) when TCA cycle activity exceeds the ability of oxidative phosphorylation to convert mitochondrial redox potential into ATP. In turn, the enhanced synthesis of proline supports TGFβ‐induced production of matrix proteins.
The glomerular crescent: triggers, evolution, resolution, and implications for therapy

Purpose of review Crescents are classical histopathological lesions found in severe forms of rapidly progressive glomerulonephritis, also referred to as crescentic glomerulonephritis (CGN). Crescent formation is a consequence of diverse upstream pathomechanisms and unraveling these mechanisms is of great interest for improving the management of patients affected by CGN. Thus, in this review, we provide an update on the latest insight into the understanding on how crescents develop and how they resolve. Recent findings Cellular crescents develop from activated parietal epithelial cells (PECs) residing along Bowman's capsule and their formation has as a consequence the decline in glomerular filtration rate (GFR). Cellular crescents can be reversible, but when multilevel growth of PECs associate with an epithelial--mesenchymal transition-like change in cell phenotype, fibrous crescents form, and crescents become irreversible also in terms of GFR recovery. Different molecular pathways trigger the activation of PECs and are a prime therapeutics target in CGN. First, crescent formation requires also vascular injury causing ruptures in the glomerular basement membrane that trigger plasmatic coagulation within Bowman's space. This vascular necrosis can be triggered by different upstream mechanisms, such as small vessel vasculitides, immune complex glomerulonephritis, anti-GBM disease, and C3 glomerulonephritis, that all share complement activation but involve diverse upstream immune mechanisms outside the kidney accessible for therapeutic intervention. Summary Knowing the upstream mechanisms that triggered crescent formation provides a tool for the development of therapeutic interventions for CGN.
Identification of signal peptide features for substrate specificity in human Sec62/Sec63‐dependent ER protein import

In mammalian cells, one‐third of all polypeptides are integrated into the membrane or translocated into the lumen of the endoplasmic reticulum (ER) via the Sec61 channel. While the Sec61 complex facilitates ER import of most precursor polypeptides, the Sec61‐associated Sec62/Sec63 complex supports ER import in a substrate‐specific manner. So far, mainly posttranslationally imported precursors and the two cotranslationally imported precursors of ERj3 and prion protein were found to depend on the Sec62/Sec63 complex in vitro. Therefore, we determined the rules for engagement of Sec62/Sec63 in ER import in intact human cells using a recently established unbiased proteomics approach. In addition to confirming ERj3, we identified 22 novel Sec62/Sec63 substrates under these in vivo‐like conditions. As a common feature, those previously unknown substrates share signal peptides (SP) with comparatively longer but less hydrophobic hydrophobic region of SP and lower carboxy‐terminal region of SP (C‐region) polarity. Further analyses with four substrates, and ERj3 in particular, revealed the combination of a slowly gating SP and a downstream translocation‐disruptive positively charged cluster of amino acid residues as decisive for the Sec62/Sec63 requirement. In the case of ERj3, these features were found to be responsible for an additional immunoglobulin heavy‐chain binding protein (BiP) requirement and to correlate with sensitivity toward the Sec61‐channel inhibitor CAM741. Thus, the human Sec62/Sec63 complex may support Sec61‐channel opening for precursor polypeptides with slowly gating SPs by direct interaction with the cytosolic amino‐terminal peptide of Sec61α or via recruitment of BiP and its interaction with the ER‐lumenal loop 7 of Sec61α. These novel insights into the mechanism of human ER protein import contribute to our understanding of the etiology of SEC63‐linked polycystic liver disease.
Time course changes in AQP4 expression patterns in progressive skeletal muscle atrophy during the early stage of denervation

Objectives: In the skeletal muscles, water metabolism is mainly regulated by water channel aquaporin 4 (AQP4). Although the expression level of AQP4 was reduced by long-term denervation, during denervation the relationship between muscle atrophy initiation and AQP4 expression decrease initiation remains unknown. The present study examined the relationship between the timing of muscle atrophy initiation and that of AQP4 expression decrease initiation, during the early stage of denervation. Methods: Female 344 rats (8 weeks of age) were randomly assigned to control (C), day 1 post-sciatic denervation (D1), day 4 post- sciatic denervation (D4) and day 7 post- sciatic denervation (D7) groups (n=6 per group). In the tibialis anterior (TA) muscles of each group, the expression levels of some target proteins were quantified by Western blot analysis. Results: The expression level of AQP4 significantly decreased on day 4 post-denervation (p<0.05). Moreover, the beginning of the decrease in AQP4 expression level was concurrent with the timing of muscle atrophy in the skeletal muscles during the early stage of denervation. Conclusions: The present study suggested that the progression of the decrease in the AQP4 expression level is partly related to the progression of muscle atrophy during the early stage of denervation.
Incidental findings in patients who underwent cone beam computed tomography for implant treatment planning

Objectives: The aim of this study is to determine the type, frequency, and location of incidental findings in the maxillofacial region in patients undergoing cone beam computed tomography (CBCT) scan for implant treatment. [5]Methods: In this study, 300 patients who underwent CBCT imaging for implant treatment planning were evaluated retrospectively. Patients were evaluated in four different categories, namely, maxillary sinus pathologies, temporomandibular joint (TMJ) findings, dentoalveolar findings, and soft-tissue calcifications. In maxillary sinus pathologies, we categorized patients by mucosal thickening, polypoidal lesion, air–liquid level, total opacification, oroantral fistula, periapical lesion related with maxillary sinus, antrolith, hypoplasia, and foreign body presence. In the TMJ findings category, we evaluated patients for erosion, osteophyte, sclerosis, flattening, and bifid condyle. For dentoalveolar findings, we looked for the residual root and impacted tooth. In soft-tissue calcifications, we examined patients for tonsillolith, sialolith, lymph node calcification, styloid ligament calcification, carotid artery calcifications, and osteoma cutis. Results: Mucosal thickening was mostly seen in maxillary sinus pathology. One hundred and forty-eight (49.3%) of the patients had at least one TMJ incidental finding. We detected at least one impacted tooth in 17 (5.7%) patients' maxilla and 14 (4.7%) patients' mandibles. The most frequently seen calcification was styloid ligament calcification. There was no statistically significant relationship between the age groups and incidental findings (P > 0.05). Conclusions: Oral radiologists should be aware of incidental findings and evaluate the possibilities of underlying diseases in a comprehensive way, and if there is a concern about the finding, they should refer the patient to the relevant specialist.
STXBP5/tomosyn regulates the small RhoA GTPase to control the dendritic stability of neurons and the surface expression of AMPA receptors

Tomosyn, a protein encoded by syntaxin-1-binding protein 5 (STXBP5) gene, has a well-established presynaptic role in the inhibition of neurotransmitter release and the reduction of synaptic transmission by its conical interaction with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) machinery. The postsynaptic role of tomosyn in dendritic arborization, spine stability, and trafficking of ionotropic glutamate receptors remains to be elucidated. We used short hairpin RNA (shRNA) to knock down tomosyn in mouse primary neurons to evaluate the postsynaptic cellular function and molecular signaling regulated by tomosyn. Knockdown of tomosyn led to an increase of RhoA GTPase activity accompanied by compromised dendritic arborization, loss of dendritic spines, decreased surface expression of AMPA receptors, and reduced miniature excitatory postsynaptic current (mEPSC) frequency. Inhibiting RhoA signaling was sufficient to rescue the abnormal dendritic morphology and the surface expression of AMPA receptors. The function of tomosyn regulating RhoA is mediated through the N-terminal WD40 motif, where two variants each carrying a single nucleotide mutation in this region, were found in individuals with autism spectrum disorder (ASD). We demonstrated that these variants displayed loss-of-function phenotypes. Unlike the wild-type tomosyn, these two variants failed to restore the reduced dendritic complexity, spine density, as well as decreased surface expression of AMPA receptors in tomosyn knockdown neurons. This study uncovers a critical role of tomosyn, independent of its interaction with the SNARE machinery, in maintaining neuronal function by inhibiting RhoA activity. Further analysis of tomosyn variants also provides a potential mechanism for explaining cellular pathology in ASD. Significance Statement This study unveils a vital role of tomosyn in the maintenance of neuronal morphology, basal synaptic transmission, and AMPA receptor surface expression that is distinct from its presynaptic role. Tomosyn affects dendritic stability and glutamate receptor trafficking via the regulation of the Rho signaling pathway and this interaction is likely independent of the interaction with the dendritic SNARE complex, such as syntaxin-4. The WD40 domain of tomosyn is necessary to conduct the Rho regulation and two autism-associated variants localized at the WD40 domain perturb this function. The current study reveals a novel molecular link between dendritic stability and synaptic function, which could advance a greater understanding of the cellular pathologies involved in neurodevelopmental disorders, such as ASD.