Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic predictors of survival in behavioral variant frontotemporal degeneration

Objective To determine autosomal dominant genetic predictors of survival in individuals with behavioral variant frontotemporal degeneration (bvFTD). Methods A retrospective chart review of 174 cases with a clinical phenotype of bvFTD but no associated elementary neurologic features was performed, with diagnosis either autopsy-confirmed (n = 57) or supported by CSF evidence of non-Alzheimer pathology (n = 117). Genetic analysis of the 3 most common genes with pathogenic autosomal dominant mutations associated with frontotemporal degeneration was performed in all patients, which identified cases with C9orf72 expansion (n = 28), progranulin (GRN) mutation (n = 12), and microtubule-associated protein tau (MAPT) mutation (n = 10). Cox proportional hazards regressions were used to test for associations between survival and mutation status, sex, age at symptom onset, and education. Results Across all patients with bvFTD, the presence of a disease-associated pathogenic mutation was associated with shortened survival (hazard ratio [HR] 2.164, 95% confidence interval [CI] 1.391, 3.368). In separate models, a GRN mutation (HR 2.423, 95% CI 1.237, 4.744), MAPT mutation (HR 8.056, 95% CI 2.938, 22.092), and C9orf72 expansion (HR 1.832, 95% CI 1.034, 3.244) were each individually associated with shorter survival relative to sporadic bvFTD. A mutation on the MAPT gene results in an earlier age at onset than a C9orf72 expansion or mutation on the GRN gene (p = 0.016). Conclusions Our findings suggest that autosomal dominantly inherited mutations, modulated by age at symptom onset, associate with shorter survival among patients with bvFTD. We suggest that clinical trials and clinical management should consider mutation status and age at onset when evaluating disease progression.
Laser and radiofrequency ablations for benign and malignant thyroid tumors

Abstract A growing body of evidence is being published regarding the safety and efficacy of minimally invasive image-guided ablation techniques. While clinical applications of these techniques are increasing, international societies have started to publish treatment guidelines and to make efforts to standardize both terminology and reporting criteria for image-guided thyroid ablations. Laser ablation and radiofrequency ablation (RFA) are among the most common ablation techniques either for benign and malignant thyroid nodules. Unlike laser ablation and RFA in the treatment of benign thyroid nodules, where safety and efficacy have been widely demonstrated, evidence regarding local tumor control of thyroid malignancies is still limited. However, preliminary results are encouraging and image-guided thermal ablation techniques can be considered a valid alternative to surgery for the treatment of benign thyroid nodules and recurrent thyroid cancers. This review evaluates the basic concept of RFA and laser ablations, their techniques, clinical outcomes, and complications based on the suggestions of several society guidelines. Multidisciplinary collaboration remains critical to identify patients which may benefit from minimally invasive image-guided thermal ablations, especially if surgery or radioiodine therapy are not feasible options.
Relationships between Potentially Toxic Elements in intertidal sediments and their bioaccumulation by benthic invertebrates

The bioaccumulation of Potentially Toxic Elements (PTEs) by benthic invertebrates in estuarine sediments is poorly understood. We sampled and analysed PTEs in sediments and benthic invertebrates from five sites in the Skeena Estuary (British Columbia, Canada), including sites adjacent to an abandoned cannery and a decommissioned papermill. Our aim was to elucidate baseline levels of PTE concentrations at sites that may be recovering from disturbance associated with prior industrial development and identify organisms that could be used to biomonitor the impact of future industrial developments. There was no indication that sediments of the salmon cannery were polluted, but acidic sediments adjacent to the papermill contained elevated concentrations of Cd, Cr, Hg and Pb. Benthic invertebrate community assemblages confirm that sediments have mostly recovered from prior industrial development associated with discharge of papermill sludge. Overall, we did not observe any relationship between PTE concentrations in the sediment and PTE concentrations in invertebrate tissues. However, we did observe a negative relationship between sediment pH and the Biota-Sediment Accumulation Factor (BSAF) of most PTEs for Oregon pill bugs (Gnorimosphaeroma oregonensis). G. oregonensis, observed at all sites, feeds on the fibers associated with the papermill discharge. Thus, G. oregonensis is a useful biomonitors for quantifying the impact of the decommissioned papermill, and are candidate biomonitors for assessing the impact of similar industrial development projects on intertidal ecosystems.
Amyloid-Beta Modulates Low-Threshold Activated Voltage-Gated L-Type Calcium Channels of Arcuate Neuropeptide Y Neurons Leading to Calcium Dysregulation and Hypothalamic Dysfunction

Weight loss is an early manifestation of Alzheimer's disease that can precede the cognitive decline, raising the possibility that amyloid-β (Aβ) disrupts hypothalamic neurons critical for the regulation of body weight. We previously reported that, in young transgenic mice overexpressing mutated amyloid precursor protein (Tg2576), Aβ causes dysfunction in neuropeptide Y (NPY)-expressing hypothalamic arcuate neurons before plaque formation. In this study, we examined whether Aβ causes arcuate NPY neuronal dysfunction by disrupting intracellular Ca2+ homeostasis. Here, we found that the L-type Ca2+ channel blocker nimodipine could hyperpolarize the membrane potential, decrease the spontaneous activity, and reduce the intracellular Ca2+ levels in arcuate NPY neurons from Tg2576 brain slices. In these neurons, there was a shift from high to low voltage-threshold activated L-type Ca2+ currents, resulting in increased Ca2+ influx closer to the resting membrane potential, an effect recapitulated by Aβ1–42 and reversed by nimodipine. These low voltage-threshold activated L-type Ca2+ currents were dependent in part on calcium/calmodulin-dependent protein kinase II and IP3 pathways. Furthermore, the effects on intracellular Ca2+ signaling by both a positive (ghrelin) and negative (leptin) modulator were blunted in these neurons. Nimodipine pretreatment restored the response to ghrelin-mediated feeding in young (3–5 months), but not older (10 months), female Tg2576 mice, suggesting that intracellular Ca2+ dysregulation is only reversible early in Aβ pathology. Collectively, these findings provide evidence for a key role for low-threshold activated voltage gated L-type Ca2+ channels in Aβ-mediated neuronal dysfunction and in the regulation of body weight. SIGNIFICANCE STATEMENT Weight loss is one of the earliest manifestations of Alzheimer's disease (AD), but the underlying cellular mechanisms remain unknown. Disruption of intracellular Ca2+ homeostasis by amyloid-β is hypothesized to be critical for the early neuronal dysfunction driving AD pathogenesis. Here, we demonstrate that amyloid-β causes a shift from high to low voltage-threshold activated L-type Ca2+ currents in arcuate neuropeptide Y neurons. This leads to increased Ca2+ influx closer to the resting membrane potential, resulting in intracellular Ca2+ dyshomeostasis and neuronal dysfunction, an effect reversible by the L-type Ca2+ channel blocker nimodipine early in amyloid-β pathology. These findings highlight a novel mechanism of amyloid-β-mediated neuronal dysfunction through L-type Ca2+ channels and the importance of these channels in the regulation of body weight.
Organ-specific small non-coding RNA responses in domestic (Sudani) ducks experimentally infected with highly pathogenic avian influenza virus (H5N1)

ABSTRACT The duck represents an important reservoir of influenza viruses for transmission to other avian and mammalian hosts, including humans. The increased pathogenicity of the recently emerging clades of highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype in ducks features systemic viral spread and organ-to-organ variation in viral transcription and tissue damage. We previously reported that experimental infection of Sudani ducks (Cairina moschata) with an Egyptian HPAI (H5N1) virus (clade 2.2.1.2) features high viral replication and severe tissue damage in lung, but lower viral replication and only mild histological changes in brain. Little is known about the involvement of miRNA in organ-specific responses to H5N1 viruses in ducks, and involvement of the other classes of small noncoding RNA (sncRNA) has not been investigated so far. Following RNA sequencing, we have annotated the duck sncRNome and compared global expression changes of the four major sncRNA classes (miRNAs, piRNAs, snoRNAs, snRNAs) between duck lung and brain during a 120 h time course of infection with this HPAI strain. We find major organ-specific differences in miRNA, piRNA and snoRNA populations even before infection and substantial reprogramming of all sncRNA classes throughout infection, which was less pronounced in brain. Pathway prediction analysis of miRNA targets revealed enrichment of inflammation-, infection- and apoptosis-related pathways in lung, but enrichment of metabolism-related pathways (including tryptophan metabolism) in brain. Thus, organ-specific differences in sncRNA responses may contribute to differences in viral replication and organ damage in ducks infected with isolates from this emerging HPAI clade, and likely other strains.
Serologic Evidence of Exposure to Highly Pathogenic Avian Influenza H5 Viruses in Migratory Shorebirds, Australia

Highly pathogenic avian influenza (HPAI) H5Nx viruses of the goose/Guangdong/96 lineage continue to cause outbreaks in poultry and wild birds globally. Shorebirds, known reservoirs of avian influenza viruses, migrate from Siberia to Australia along the East-Asian-Australasian Flyway. We examined whether migrating shorebirds spending nonbreeding seasons in Australia were exposed to HPAI H5 viruses. We compared those findings with those for a resident duck species. We screened >1,500 blood samples for nucleoprotein antibodies and tested positive samples for specific antibodies against 7 HPAI H5 virus antigens and 2 low pathogenicity avian influenza H5 virus antigens. We demonstrated the presence of hemagglutinin inhibitory antibodies against HPAI H5 virus clade 2.3. 4.4 in the red-necked stint (Calidris ruficolis). We did not find hemagglutinin inhibitory antibodies in resident Pacific black ducks (Anas superciliosa). Our study highlights the potential role of long-distance migratory shorebirds in intercontinental spread of HPAI H5 viruses.
99mTc-MIBI SPECT/CT imaging had high sensitivity in accurate localization of parathyroids before parathyroidectomy for patients with secondary hyperparathyroidism

Abstract Purpose: Accurate preoperative parathyroid localization is important for successful parathyroidectomy (PTX). The aim of our study was to investigate whether SPECT/CT has enhanced effect in preoperative localization of parathyroids. Methods: In our retrospective cohort study, we evaluated the effects of technetium-99m methoxyisobutylisonitrile-single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) on preoperative parathyroid localization for 645 secondary hyperparathyroidism (SHPT) patients. Among them, 569 successful PTX patients were divided into group A (received 99mTc-MIBI scintigraphy, n = 175) and group B (received 99mTc-MIBI scintigraphy and SPECT/CT imaging, n = 394). Sensitivity, specificity, and consistency of two imaging methods in preoperative localization of parathyroids were compared. Results: Overall sensitivity and consistency were higher in group B, while there was no difference in specificity between the two groups. In group A, the sensitivity of 99mTc-MIBI was 50.00%, 77.11%, 61.76%, and 76.54% in the right upper gland (RU), right lower gland (RL), left upper gland (LU), and left lower gland (LL) subgroups, while the consistency was 52.00%, 76.57%, 61.71%, and 75.43%, respectively. In group B, the sensitivity of 99mTc-MIBI with SPECT/CT was 69.39%, 90.03%, 78.07%, and 84.27%, and the consistency was 69.54%, 88.32%, 78.43%, and 84.26%, respectively. The sensitivity and consistency in lower glands were higher than in upper glands in both groups. Sensitivity for eutopic parathyroid was higher in group B, while there was no difference for ectopic parathyroid. Conclusions: 99mTc-MIBI SPECT/CT can increase the sensitivity and consistency of preoperative localization of eutopic parathyroid glands, and it can accurately locate ectopic parathyroid without sensitivity improvement.
Parcellation‐based tractographic modeling of the dorsal attention network

The dorsal attention network (DAN) is an important mediator of goal‐directed attentional processing. Multiple cortical areas, such as the frontal eye fields, intraparietal sulcus, superior parietal lobule, and visual cortex, have been linked in this processing. However, knowledge of network connectivity has been devoid of structural specificity.
Genetically distinct Group B Streptococcus strains induce varying macrophage cytokine responses

Group B Streptococcus (GBS) is an opportunistic pathogen that causes preterm birth and neonatal disease. Although GBS is known to exhibit vast diversity in virulence across strains, the mechanisms of GBS-associated pathogenesis are incompletely understood. We hypothesized that GBS strains of different genotypes would vary in their ability to elicit host inflammatory responses, and that strains associated with neonatal disease would induce different cytokine profiles than those associated with colonization. Using a multiplexed, antibody-based protein detection array, we found that production of a discrete number of inflammatory mediators by THP-1 macrophage-like cells was universally induced in response to challenge with each of five genetically distinct GBS isolates, while other responses appeared to be strain-specific. Key array responses were validated by ELISA using the initial five strains as well as ten additional strains with distinct genotypic and phenotypic characteristics. Interestingly, IL-6 was significantly elevated following infection with neonatal infection-associated sequence type (ST)-17 strains and among strains possessing capsule (cps) type III. Significant differences in production of IL1-β, IL-10 and MCP-2 were also identified across STs and cps types. These data support our hypothesis and suggest that unique host innate immune responses reflect strain-specific differences in virulence across GBS isolates. Such data might inform the development of improved diagnostic or prognostic strategies against invasive GBS infections.
Recent advances in amniote palaeocolour reconstruction and a framework for future research

Preserved melanin pigments have been discovered in fossilised integumentary appendages of several amniote lineages (fishes, frogs, snakes, marine reptiles, non‐avialan dinosaurs, birds, and mammals) excavated from lagerstätten across the globe. Melanisation is a leading factor in organic integument preservation in these fossils. Melanin in extant vertebrates is typically stored in rod‐ to sphere‐shaped, lysosome‐derived, membrane‐bound vesicles called melanosomes. Black, dark brown, and grey colours are produced by eumelanin, and reddish‐brown colours are produced by phaeomelanin. Specific morphotypes and nanostructural arrangements of melanosomes and their relation to the keratin matrix in integumentary appendages create the so‐called 'structural colours'. Reconstruction of colour patterns in ancient animals has opened an exciting new avenue for studying their life, behaviour and ecology. Modern relationships between the shape, arrangement, and size of avian melanosomes, melanin chemistry, and feather colour have been applied to reconstruct the hues and colour patterns of isolated feathers and plumages of the dinosaurs Anchiornis, Sinosauropteryx, and Microraptor in seminal papers that initiated the field of palaeocolour reconstruction. Since then, further research has identified countershading camouflage patterns, and informed subsequent predictions on the ecology and behaviour of these extinct animals. However, palaeocolour reconstruction remains a nascent field, and current approaches have considerable potential for further refinement, standardisation, and expansion. This includes detailed study of non‐melanic pigments that might be preserved in fossilised integuments. A common issue among existing palaeocolour studies is the lack of contextualisation of different lines of evidence and the wide variety of techniques currently employed. To that end, this review focused on fossil amniotes: (i) produces an overarching framework that appropriately reconstructs palaeocolour by accounting for the chemical signatures of various pigments, morphology and local arrangement of pigment‐bearing vesicles, pigment concentration, macroscopic colour patterns, and taphonomy; (ii) provides background context for the evolution of colour‐producing mechanisms; and (iii) encourages future efforts in palaeocolour reconstructions particularly of less‐studied groups such as non‐dinosaur archosaurs and non‐archosaur amniotes.
Atrophic Changes and Diffusion Abnormalities of Affected Trigeminal Nerves in Trigeminal Neuralgia Using 7-T MRI

Background: Magnetic resonance imaging (MRI) has been widely used for visualizing trigeminal nerves in trigeminal neuralgia. Objective: To assess atrophy and diffusion abnormalities of affected trigeminal nerves in trigeminal neuralgia with 7-T MRI. Methods: In this prospective study, 14 patients (mean age 49 years; range 31–64 years) with trigeminal neuralgia underwent 7-T MRI. We measured trigeminal nerve volumes along their course through the pontocerebellar cistern. We also evaluated fractional anisotropy (FA) and quantitative anisotropy (QA) values within cisternal segment and pontine nuclei of the affected-side and unaffected-side trigeminal nerves, using diffusion tensor imaging (DTI). Associations between DTI metrics and Barrow Neurological Institute (BNI) pain scores were examined. Results: The volumes were significantly smaller for the affected trigeminal nerves (33.83 ± 23.12 mm3) than for the unaffected ones (47.76 ± 32.48 mm3; p = 0.008). Cisternal segment FA and QA values were significantly lower in affected trigeminal nerves than in unaffected ones. However, DTI measurements in the pontine nuclei revealed no significant differences between affected-side and unaffected-side trigeminal nerves. No DTI metrics significantly correlated with BNI pain scores. Conclusion: Our results suggest that 7-T MRI allows identifications of atrophy and diffusion abnormalities of trigeminal nerves in trigeminal neuralgia.
The Contested Whiteness of Arab Identity in the United States: Implications for Health Disparities Research.

In response to the Institute on Minority Health and Health Disparities' (NIMHD) new health disparities research framework, we call on the National Institutes of Health (NIH) to acknowledge Arabs in the United States as a health disparity population. Arab classification as White leads to their cultural invisibility and perpetuates a cycle of undocumented health disparities.We provide examples of how this contested identity reinforces challenges associated with identifying this population and contributes to enactments of structural violence and undocumented health disparities. Decades of research with Arabs in the United States provides consistent evidence that their health does not fit the health profile of White Americans and that Arabs do not benefit from Whiteness and White privilege associated with their White racial categorization. On the contrary, Arabs in the United States experience discrimination and health disparities that require urgent attention; this can be achieved only by identifying the population with a racial category other than White.We conclude with recommendations to NIH and NIMHD to revise their definition of health disparity populations to include Arabs in the United States. (Am J Public Health. Published online ahead of print September 19, 2019: e1-e4. doi:10.2105/AJPH.2019.305285).
Brain anatomical correlates of fatigue in multiple sclerosis

Fatigue is one of the most debilitating symptoms in patients with multiple sclerosis (MS). Despite its clinical significance, the aetiology and pathophysiology of MS-related fatigue are not well understood. Current evidence and understanding of the neuroanatomical underpinnings of MS-related fatigue are reviewed in this article. The aims of this paper are to (1) review the findings of previous structural neuroimaging studies on MS-related fatigue and summarize consistent findings regarding brain circuitry associated with fatigue in MS, (2) contextualize these findings with the neurochemistry of the relevant circuits and (3) discuss future perspectives with regard to impact on fatigue management of MS patients and methodological challenges towards improved understanding of fatigue pathogenesis. The detailed understanding of the neuroanatomical underpinnings of fatigue might contribute to the identification of novel treatment targets and factors determining treatment resistance to drugs used in current clinical practice.
Evaluation of haematopoietic stem cell transplantation in patients diagnosed with cutaneous T‐cell lymphoma at a tertiary care centre: should we avoid chemotherapy in conditioning regimes?

Advanced stage mycosis fungoides (MF) and Sézary syndrome (SS) account for ~30% of patients with cutaneous T-cell lymphomas (CTCL). The prognosis is poor with a median survival of 36 months.1 Treatments rarely result in durable remissions and recent management guidelines recommend allogeneic haematopoietic stem cell transplant (HSCT) for eligible patients as the best chance of improved survival.
Treatment of Recalcitrant Maxillary Sinusitis With Endoscopic Modified Medial Maxillectomy: A Systematic Review of Safety and Efficacy

Background Endoscopic sinus surgery is an effective treatment option for patients with chronic rhinosinusitis (CRS), although approximately 20% of patients fail to improve with standard surgical procedures. Expanded procedures such as the endoscopic modified medial maxillectomy (EMMM) have been described in management of refractory maxillary sinusitis. Objective This study aims to review the current literature on the safety and efficacy of the EMMM for treatment of refractory maxillary sinusitis. Methods A literature search was performed of PubMed, Ovid, and Cochrane databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. English-language articles evaluating the EMMM procedure on patients with recalcitrant maxillary sinusitis were included. Full-text articles were obtained and evaluated by 2 reviewers independently, with a third reviewer for mediation of disagreements. Results Six studies met eligibility criteria and were included into the study, with follow-up ranging from 12 to 82.8 months. Two studies contained Level 2 evidence and 4 studies contained Level 4 evidence. EMMM was found to be effective in CRS and cystic fibrosis-related CRS (0% and 9.1% revision rate, respectively). Symptom resolution was noted 60% to 80% of patients. Four studies reported complications, with a total of 4 complications out of 211 patients. Conclusions There are no high-quality Level 1 studies evaluating the efficacy and safety of the EMMM procedure. Level 2 to Level 4 studies indicate that this procedure is relatively safe with a low complication rate and symptom resolution in up to 80% of patients with recalcitrant maxillary sinusitis.