Miracle-dz/UniFAR-FTUs huggingface dataset:
Head rotation evoked tinnitus due to superior semicircular canal dehiscence

Abstract Introduction: Superior semicircular canal dehiscence affects the auditory and vestibular systems due to a partial defect in the canal's bony wall. In most cases, sound- and pressure-induced vertigo are present, and are sometimes accompanied by pulse-synchronous tinnitus. Case presentation: We describe a 50-year-old man with superior semicircular canal dehiscence whose only complaints were head rotation induced tinnitus and autophony. Head rotation in the plane of the right semicircular canal with an angular velocity exceeding 600°/second repeatedly induced a ‘cricket’ sound in the patient's right ear. High resolution temporal bone computed tomography changes, and an elevated umbo velocity, supported the diagnosis of superior semicircular canal dehiscence. Conclusion: In addition to pulse-synchronous or continuous tinnitus, head rotation induced tinnitus can be the only presenting symptom of superior semicircular canal dehiscence without vestibular complaints. We suggest that, in our patient, the bony defect of the superior semicircular canal (‘third window’) might have enhanced the flow of inner ear fluid, possibly producing tinnitus.
Multi-wavelength time-resolved optical mammography

A clinical study that has involved more than 150 patients up to now is being performed to test the diagnostic potential of time-resolved transmittance imaging for the detection and characterization of breast lesions. The system routinely operates at 4 wavelengths (683, 785, 913, and 975 nm), thus being sensitive to oxy-, deoxyhemoglobin, water, and lipids. Using a modified instrument operating at 7 wavelengths, images of 43 patients were acquired also at 637 and 656 nm, and proved to offer increased contrast for the detection of malignant lesions.
Serum Neurofilament Light Protein as a Marker for Diffuse Axonal Injury: Results from a Case Series Study.

Diffuse axonal injury (DAI) is an important cause of morbidity in patients with traumatic brain injury (TBI). There is currently no simple and reliable technique for early identification of patients with DAI, or to prognosticate long-term outcome in this patient group. In the present study, we examined acute serum concentrations of neurofilament light (NFL) in nine patients with severe TBI and DAI using a novel ultrasensitive single molecule array (Simoa) assay. The relationships between the NFL concentrations and MRI in the acute stage as well as clinical outcome and magnetic resonance diffusion tensor imaging (MR-DTI) parameters at 12 months were analyzed. We found that the mean NFL concentrations among the patients displayed a 30-fold increase compared with controls, and that NFL completely discriminated between the patients and controls. We also found a relationship between serum NFL and MR-DTI parameters, with higher NFL concentrations in patients with higher trace (R2 = 0.79) and lower fractional anisotropy (FA) (R 2 = 0.83). These results suggest that serum NFL may be a valuable blood biomarker for TBI, reflecting the severity of DAI.
Convergent origination of a Drosophila-like dosage compensation mechanism in a reptile lineage

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (Anolis carolinensis), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that Anolis sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage. The age of this system approximately coincides with the ages of the avian and two mammalian sex chromosomes systems. To compensate for the almost complete Y Chromosome degeneration, X-linked genes have become twofold up-regulated, restoring ancestral expression levels. The highly efficient dosage compensation mechanism of Anolis represents the only vertebrate case identified so far to fully support Ohno's original dosage compensation hypothesis. Further analyses reveal that X up-regulation occurs only in males and is mediated by a male-specific chromatin machinery that leads to global hyperacetylation of histone H4 at lysine 16 specifically on the X Chromosome. The green anole dosage compensation mechanism is highly reminiscent of that of the fruit fly, Drosophila melanogaster. Altogether, our work unveils the convergent emergence of a Drosophila-like dosage compensation mechanism in an ancient reptilian sex chromosome system and highlights that the evolutionary pressures imposed by sex chromosome dosage reductions in different amniotes were resolved in fundamentally different ways.
Musculoskeletal Hydatid Cysts Resembling Tumors: A Report of Five Cases

Although challenges in treatment of musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding the musculoskeletal HC lesions resembling tumor is scarce. This paper presented 5 patients (3 males, 2 females) with a mean age of 41.6 years with tumor‐like lesions of HC. Three of them had left ilium and acetabulum involvement, one involved left femur, and one involved left thigh muscle compartments. Pain was the main symptom and was seen in all patients. Clinical examination, radiologic evaluation, and histologic analysis were performed for diagnosis. Patients were treated through different surgical options, including simple debridement, bone cement filling with or without internal fixation, hip arthrodesis, reconstruction using hemipelvic replantation with femoral prosthesis and distal femur endoprosthetic replacement. After surgery, the operation region was washed by 20% hypertonic saline, and debridement was performed carefully without contamination. All patients received albendazole treatment. Cases were followed up 1 to 9 years for the recurrence. Walking difficulty and pain were the main symptoms during the follow‐up. One patient was symptom‐free. A reoccurrence in the perioperative soft tissue was detected in only one patient and control visits with antihelmintic treatment were recommended. We would like to emphasize that HC should be kept in mind for the differential diagnosis of the cystic or tumoral lesions of the musculoskeletal system, particularly in the endemic regions. Prompt diagnosis is of paramount importance for preventing destruction and complications.
Targeted genome fragmentation with CRISPR/Cas9 enables fast and efficient enrichment of small genomic regions and ultra-accurate sequencing with low DNA input (CRISPR-DS)

Next-generation sequencing methods suffer from low recovery, uneven coverage, and false mutations. DNA fragmentation by sonication is a major contributor to these problems because it produces randomly sized fragments, PCR amplification bias, and end artifacts. In addition, oligonucleotide-based hybridization capture, a common target enrichment method, has limited efficiency for small genomic regions, contributing to low recovery. This becomes a critical problem in clinical applications, which value cost-effective approaches focused on the sequencing of small gene panels. To address these issues, we developed a targeted genome fragmentation approach based on CRISPR/Cas9 digestion that produces DNA fragments of similar length. These fragments can be enriched by a simple size selection, resulting in targeted enrichment of up to approximately 49,000-fold. Additionally, homogenous length fragments significantly reduce PCR amplification bias and maximize read usability. We combined this novel target enrichment approach with Duplex Sequencing, which uses double-strand molecular tagging to correct for sequencing errors. The approach, termed CRISPR-DS, enables efficient target enrichment of small genomic regions, even coverage, ultra-accurate sequencing, and reduced DNA input. As proof of principle, we applied CRISPR-DS to the sequencing of the exonic regions of TP53 and performed side-by-side comparisons with standard Duplex Sequencing. CRISPR-DS detected previously reported pathogenic TP53 mutations present as low as 0.1% in peritoneal fluid of women with ovarian cancer, while using 10- to 100-fold less DNA than standard Duplex Sequencing. Whether used as standalone enrichment or coupled with high-accuracy sequencing methods, CRISPR-based fragmentation offers a simple solution for fast and efficient small target enrichment.
Natural History of Headache Five Years after Traumatic Brain Injury (P3.294)

Objective: Describe the natural history of headache (HA) in individuals with moderate to severe traumatic brain injury (TBI) prior to and over the first five years after injury. Background: HA is the most frequently reported symptom following TBI. However, little is known about how HAs after TBI change over time, nor their impact on daily functioning. Design/Methods: Prospective enrollment and follow up at 3, 6, 12 and 60 months post injury of 316 individuals admitted to inpatient rehabilitation with mostly moderate to severe TBI. HA history, prevalence, frequency, pain, impact, and classification of new or worse HA (compared to pre-injury) were examined. Results: Individuals were 72[percnt] male, 73[percnt] Caucasian, 55[percnt] injured in motor vehicle crashes, with an average age of 42. Pre-injury HA was reported in 17[percnt] of individuals. New or worse HA prevalence was high and remained so over time with 41[percnt] at baseline, 39[percnt] at 3 months, 35[percnt] at 6 months, 34[percnt] at 1 year, and 35[percnt] at 5 years. Average headache pain (on 0 to 10 scale) remained high over time ranging from 6.2 at baseline to 5.7 at 5 years post injury. HA had substantial impact on daily life across all time points. Having HA several days per week or daily was common with up to 37[percnt] at 5 years post injury continuing to experience frequent headache. In addition, over 75[percnt] report HA symptoms consistent with a diagnosis of migraine or probable migraine over the five years post injury. Conclusions: HA is a substantial problem after TBI with a large portion of individuals reporting frequent HA with significant long-term impact. Results suggest that ongoing assessment and treatment of HA after TBI is needed as HA remains a problem 5 years post injury. Disclosure: Dr. Stacey has nothing to disclose. Dr. Lucas has received personal compensation for activities with Allergan, Zogenix, Allozyne, Kineta, Wadsworth Foundation, Biogen, and Genzyme as a speaker and/or an advisor. Dr. Temkin has nothing to disclose. Dr. Dikmen has nothing to disclose. Dr. Bell has nothing to disclose. Dr. Hoffman has nothing to disclose.
Protein phosphatase 2A is essential to maintain active Wnt signaling and its Aβ tumor suppressor subunit is not expressed in colon cancer cells

Canonical Wnt signaling is altered in most cases of colorectal cancer. Experimental evidence indicates that protein phosphatase 2A (PP2A) may play either positive or negative roles in Wnt signaling but its precise in vivo functions remain elusive. In this work, using colon cultured cell lines we showed that basal PP2A activity is markedly reduced in malignant cells compared to non‐malignant counterparts. We found that whereas normal or cancer cells displaying not altered Wnt signaling express mRNAs coding for PP2A‐A scaffold α and β isoforms, cancer cells which have altered Wnt signaling do not express the Aβ isoform mRNA. Remarkably, we found that the Aβ protein levels are lost in all colon cancer cells, and in patients' tumor biopsies. In addition, all cancer cells exhibit higher levels of RalA activity, compared to non‐malignant cells. Rescue experiments to restore Aβ expression in malignant RKO cells, diminished the RalGTPase activation and cell proliferation, indicating that the Aβ isoform acts as tumor suppressor in colon cancer cells. Reciprocal co‐immunoprecipitation and immunofluorescence studies showed that the PP2A‐C and ‐Aα subunits, expressed in all colon cells, interact in vivo with β‐catenin only in malignant cells. Selective inhibition of PP2A did not significantly affect cellular apoptosis but induced dose‐dependent negative effects in β‐catenin‐mediated transcriptional activity and in cell proliferation of malignant cells, indicating that the residual PP2A activity found in malignant cells, mediated by –C and Aα core subunits, is essential to maintain active Wnt signaling and cell proliferation in colon cancer cells. © 2014 Wiley Periodicals, Inc.
Effects of sleep deprivation and aging on long-term and remote memory in mice

Sleep deprivation (SD) following hippocampus-dependent learning in young mice impairs memory when tested the following day. Here, we examined the effects of SD on remote memory in both young and aged mice. In young mice, we found that memory is still impaired 1 mo after training. SD also impaired memory in aged mice 1 d after training, but, by a month after training, sleep-deprived and control aged animals performed similarly, primarily due to remote memory decay in the control aged animals. Gene expression analysis supported the finding that SD has similar effects on the hippocampus in young and aged mice.
Inhibition of glycogen synthase kinase-3β enhances cognitive recovery after stroke: the role of TAK1

Memory deficits are common among stroke survivors. Identifying neuroprotective agents that can prevent memory impairment or improve memory recovery is a vital area of research. Glycogen synthase kinase-3β (GSK-3β) is involved in several essential intracellular signaling pathways. Unlike many other kinases, GSK-3β is active only when dephosphorylated and activation promotes inflammation and apoptosis. In contrast, increased phosphorylation leads to reduced GSK-3β (pGSK-3β) activity. GSK-3β inhibition has beneficial effects on memory in other disease models. GSK-3β regulates both the 5′AMP-activated kinase (AMPK) and transforming growth factor-β-activated kinase (TAK1) pathways. In this work, we examined the effect of GSK-3β inhibition, both independently, in conjunction with a TAK inhibitor, and in AMPK-α2 deficient mice, after stroke to investigate mechanistic interactions between these pathways. GSK-3β inhibition was neuroprotective and ameliorated stroke-induced cognitive impairments. This was independent of AMPK signaling as the protective effects of GSK-3β inhibition were seen in AMPK deficient mice. However, GSK-3β inhibition provided no additive protection in mice treated with a TAK inhibitor suggesting that TAK1 is an upstream regulator of GSK-3β. Targeting GSK-3β could be a novel therapeutic strategy for post-stroke cognitive deficits.
Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

miR-132 and miR-212 are structurally related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same noncoding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/-212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/-212 double-knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/-212 double-knockout line to explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/-212 deletion increased the expression of 1138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/-212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that these two genes may function in a complex, nonredundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/-212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders.
Surfactant and the Adult Respiratory Distress Syndrome

The adult respiratory distress syndrome (ARDS) is an acute, diffuse lung injury that results in impaired gas exchange, loss of lung compliance, and noncardiogenic edema. ARDS can either be a consequence of a direct lung insult or else a manifestation of a systemic inflammatory process (Table 1). At present, management of ARDS is primarily supportive and mortality remains 50 to 80% despite significant advances in medical technology over the last two decades. The role of surfactant in the pathophysiology of ARDS appears complex and is not completely understood. Indeed, different lung injuries may affect surfactant function in different ways, thus making generalizations about surfactant and ARDS difficult. Nevertheless, the remainder of this article will attempt to review: (1) Surface-active properties of lungs with ARDS; (2) mechanisms for derangement of these properties, (3) abnormal lung defenses associated with surfactant dysfunction in ARDS; (4) surfactant preparations available for replacement therapy and dosing considerations; (5) replacement therapy in animal models of ARDS; and (6) replacement therapy in human ARDS.
Dietary advice combined with a salicylate, mineral and vitamin supplement (CV247) has some tumour static properties: a phase II study

Purpose – This pilot study seeks to evaluate whether dietary intervention combined with an oral formulation of sodium salicylate, mineral and vitamin supplements (CV247) altered the rate of progression in patients with malignant disease.Design/methodology/approach – A total of 37 patients were recruited from March 2001 to November 2001 and ran to September 2004. All patients had progressive malignancy at trial entry (def: at least two consecutive increases in tumour markers >10 per cent or radiological progression). Patients, were recommended a diet rich in fresh fruit, vegetables, low in saturated fats, salt and man‐made chemical supplements such as colours and preservatives together with oral CV247 (sodium salicylate, copper gluconate, manganese gluconate and ascorbic acid). Dietary compliance was monitored, from a subgroup, by monthly interviews with the trial dietitian recorded on a linear analogue scale. Quality of life was measured by monthly completion of a Rotterdam symptom check‐list questionnair.
Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH. METHODS We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically. RESULTS Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (odds ratios = 1.1-2.0; P < .01). A higher proportion of subjects with ≥5% weight loss had NASH resolution (51 of 88 [58%]) and a 2-point reduction in NAS (72 of 88 [82%]) than subjects who lost <5% of their weight (P < .001). All patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%-10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions ≥10%. CONCLUSIONS A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses ≥10%.
Loss of Infliximab Into Feces Is Associated With Lack of Response to Therapy in Patients With Severe Ulcerative Colitis.

BACKGROUND & AIMS It is not clear why some patients with ulcerative colitis (UC) do not respond to treatment with anti-tumor necrosis factor (TNF) agents, such as infliximab. It could be that some patients have high level of inflammation, with large quantities of TNF to be neutralized by the drug. We investigated whether loss of anti-TNF agents through ulcerated intestinal mucosa reduces the efficacy of these drugs in patients with severe UC. METHODS We collected fecal samples from 30 consecutive patients with moderate to severely active UC during the first 2 weeks of infliximab therapy at the University of Amsterdam hospital. Infliximab concentrations were measured in serum and supernatants of fecal samples using an enzyme-linked immunosorbent assay (Sanquin Biologicals Laboratory, Amsterdam, The Netherlands). Clinical and endoscopic responses were assessed 2 and 8 weeks and 3 months after treatment began. RESULTS Infliximab was detected in 129 of 195 fecal samples (66%); the highest concentrations were measured in the first days after the first infusion. Patients that were clinical nonresponders at week 2 had significantly higher fecal concentrations of infliximab after the first day of treatment than patients with clinical responses (median concentration, 5.01 μg/mL in nonresponders vs 0.54 μg/mL in responders; P = .0047). We did not observe a correlation between fecal and serum concentrations of infliximab. CONCLUSIONS Infliximab is lost into stools of patients with UC. High fecal concentrations of infliximab in the first days after therapy begins are associated with primary nonresponse. Additional studies are needed to determine how therapeutic antibodies are lost through the intestinal mucosa and how this process affects treatment response. Clinical trial ID: NL41310.018. 12.