Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucose-related arterial stiffness and carotid artery remodeling: a study in normal subjects and type 2 diabetes patients.

CONTEXT Hyperglycemia is associated with a higher carotid intima-media thickness (IMT); however, it is not established whether this increase reflects early atherosclerotic changes or adaptive remodeling responding to hyperglycemia-induced alteration in mechanical properties of the arterial wall. OBJECTIVE The aims of this study were to compare carotid geometry and circumferential wall stress between patients with type 2 diabetes mellitus (T2DM) and healthy controls and to evaluate the associations between chronic glucose exposure and measures of arterial structure and function. DESIGN AND SETTING This was a case-control and cross-sectional study within institutional practice. PARTICIPANTS PARTICIPANTS included 133 T2DM patients free of cardiovascular complications and 133 healthy controls with normal glucose metabolism, matched for sex, age, and body mass index. MAIN OUTCOME MEASURES Common carotid artery (CCA) IMT, luminal diameter, wave speed, and local pulse pressure (PP) were evaluated. RESULTS As compared with controls, T2DM patients had higher (P < .0001) CCA IMT (640 ± 81 vs 709 ± 118 μm), luminal diameter (6.12 ± 0.67 vs 6.69 ± 0.56 mm), and brachial PP (47 ± 7 vs 57 ± 12 mm Hg), whereas luminal radius to IMT ratio (4.8 ± 0.7 vs 4.8 ± 0.8, P = .57) and circumferential wall stress (49.0 ± 8.3 vs 50.6 ± 10.3 kPa, P = .26) were comparable between the 2 groups. In T2DM patients, glycosylated hemoglobin was independently related to CCA wave speed and local PP, but not to IMT that was determined by age, local PP, and luminal diameter. CONCLUSIONS This study suggests that the increase in IMT associated with a higher glucose exposure might reflect adaptive remodeling counteracting an increase in pulsatile strain and preventing increase in circumferential wall stress caused by luminal enlargement of stiff arteries.
Genetic predisposition to papillary thyroid carcinoma: involvement of FOXE1, TSHR, and a novel lincRNA gene, PTCSC2.

CONTEXT By genome-wide association studies, the risk allele [A] of SNP rs965513 predisposes strongly to papillary thyroid carcinoma (PTC). It is located in a gene-poor region of 9q22, some 60 kb from the FOXE1 gene. The underlying mechanisms remain to be discovered. OBJECTIVE Our objective was to identify novel transcripts in the 9q22 locus and correlate gene expression levels with the genotypes of rs965513. DESIGN We performed 3' and 5' rapid amplification of cDNA ends and RT-PCR to detect novel transcripts. One novel transcript was forcibly expressed in a cell line followed by gene expression array analysis. We genotyped rs965513 from PTC patients and measured gene expression levels by real-time RT-PCR in unaffected thyroid tissue and matched tumor. SETTING This was a laboratory-based study using cells from clinical tissue samples and a cancer cell line. MAIN OUTCOME MEASURES We detected previously uncharacterized transcripts and evaluated the gene expression levels and the correlation with the risk allele of rs965513, age, gender, chronic lymphocyte thyroiditis (CLT), and TSH levels. RESULTS We found a novel long intergenic noncoding RNA gene and named it papillary thyroid cancer susceptibility candidate 2 (PTCSC2). Transcripts of PTCSC2 are down-regulated in PTC tumors. The risk allele [A] of rs965513 was significantly associated with low expression of unspliced PTCSC2, FOXE1, and TSHR in unaffected thyroid tissue. We also observed a significant association of age and CLT with PTCSC2 unspliced transcript levels. The correlation between the rs965513 genotype and the PTCSC2 unspliced transcript levels remained significant after adjusting for age, gender, and CLT. Forced expression of PTCSC2 in the BCPAP cell line affected the expression of a subset of noncoding and coding transcripts with enrichment of genes functionally involved in cell cycle and cancer. CONCLUSIONS Our data suggest a role for PTCSC2, FOXE1, and TSHR in the predisposition to PTC.
Prospective study of effectiveness of ultrasound-guided radiofrequency ablation versus control group in patients affected by benign thyroid nodules.

CONTEXT Ultrasound-guided radiofrequency ablation (RFA) of solid thyroid nodules (TNs) is a minimally invasive procedure that may induce a volume reduction of symptomatic solid benign TNs. OBJECTIVE The aim of the study was to evaluate the effectiveness and safety of RFA in debulking benign TNs. DESIGN AND PATIENTS Eighty-four consecutive patients with symptomatic and cytologically benign solid nodules were randomly assigned to either a single RFA session (group A; n = 42) or follow-up (group B; n = 42) at our center. Entry criteria were a solid thyroid nodule or predominantly solid (with a fluid component ≤ 30% of the volume), normal thyroid function, no autoimmunity, and no previous thyroid gland treatment. Three subgroups were formed according to the baseline volume of nodules: small (≤ 12 mL), medium (from 12 to 30 mL), or large (>30 mL). METHODS In group A RFA was performed in a single session with the moving-shot technique. Volume and local symptom changes were evaluated 1 and 6 months after RFA. RESULTS In group A, the volume decreased from 24.5. 5 ± 19.6 to 8.6 ± 9.5 6 months after RFA (P = .001). The greatest volume reduction was in small nodules. The pressure symptom score improved only in medium and large nodules (P < .001), whereas the cosmetic score improved in all treated patients (P < .001). The rate of thyroid volumetric reduction was not statistically different between solid and predominantly solid nodules. Only one patient experienced permanent right paramedian vocal cord palsy with inspiratory stridor without dysphonia. In group B, nodule volume remained unchanged, whereas the symptom score was worse at the 6-month evaluation (P = .01). CONCLUSIONS RFA is effective in reducing thyroid nodule volume. The best reduction rate was observed in small TNs. The thyroid volumetric reduction does not change according to the sonographic features. The mean treatment duration was longer in larger TNs.
Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment.

CONTEXT Growth hormone (GH) secretion is reduced in obesity, despite normal serum insulin-like growth factor I (IGF-1) levels, but the association between obesity and the GH signaling is unknown. Furthermore, SIRT1, an nicotinamide adenine dinucleotide-dependent protein deacetylase, reduces hepatic IGF-1 production in mice via blunting of GH-induced STAT5 signaling. OBJECTIVE To study GH signaling in muscle and fat in obese subjects and the interaction with concomitant administration of the putative SIRT1 activator resveratrol, and to assess the effects of inhibiting or knocking down SIRT1 on GH regulated genes in vitro. DESIGN AND PARTICIPANTS Twenty-four obese males were examined in a randomized, double blinded, parallel-group study with resveratrol or placebo treatment for 5 weeks followed by a GH bolus. Muscle and fat biopsies were collected before and after GH. Body composition was assessed by DEXA and MRI. MAIN OUTCOME MEASURE (1) Effect of body composition and age on GH-stimulated STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat. (2) The impact of resveratrol treatment on GH activity. (3) Impact of inhibiting or knocking down SIRT1 on effects of GH in vitro. RESULTS Significant GH-induced STAT5b phosphorylation in muscle and fat in obese subjects was recorded together with increased CISH and SOCS2 mRNA. GH-induced STAT5b phosphorylation in muscle correlated positively with age [r = 0.53, p < 0.01], but not with body composition. Resveratrol administration had no impact on body composition, serum IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect GH signaling in vitro. CONCLUSION (1) GH induced STAT5b phosphorylation is detectable in muscle and fat in adult males with simple obesity, but is not determined by body composition. (2) Resveratrol supplementation does not impact circulating IGF-1 levels or GH signaling in human muscle and fat. (3) Our data speak against a major impact of SIRT1on GH action in human subjects.
Establishment and characterization of novel human primary and metastatic anaplastic thyroid cancer cell lines and their genomic evolution over a year as a primagraft.

CONTEXT Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth. OBJECTIVE The aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies. DESIGN We established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC, which was serially xeno-transplanted for more than 1 year in NOD scid gamma mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes, and somatic mutations using RNA array, SNP Chip, and whole exome sequencing. RESULTS Mice carrying sc (OGK-P and OGK-M) tumors developed splenomegaly and neutrophilia with high expression of cytokines including CSF1, CSF2, CSF3, IL-1β, and IL-6. Levels of HIF-1α and its targeted genes were also elevated in these tumors. The treatment of tumor carrying mice with Bevacizumab effectively decreased tumor growth, macrophage infiltration, and peripheral WBCs. SNP chip analysis showed homozygous deletion of exons 3-22 of the PARD3 gene in the cells. Forced expression of PARD3 decreased cell proliferation, motility, and invasiveness, restores cell-cell contacts and enhanced cell adhesion. Next generation exome sequencing identified the somatic changes present in the primary, metastatic, and primagraft tumors demonstrating evolution of the mutational signature over the year of passage in vivo. CONCLUSION To our knowledge, we established the first paired human primary and metastatic ATC cell lines offering unique possibilities for comparative functional investigations in vitro and in vivo. Our exome sequencing also identified novel mutations, as well as clonal evolution in both the metastasis and primagraft.
Low testosterone concentration and atherosclerotic disease markers in male patients with type 2 diabetes.

BACKGROUND Low total T is associated with an increased risk of atherosclerotic complications. However, the magnitude of this association in middle-aged patients with type 2 diabetes (T2D) has not been determined. MATERIALS AND METHODS This cross-sectional study evaluated atherosclerotic disease markers in T2D patients with normal and low plasma total T. A total of 115 male patients, aged younger than 70 years, without a history of cardiovascular events, and with normal [≥ 3.5 ng/mL (≥ 12.1 nmol/L), n = 79] or low [< 3.5 ng/mL (≤ 12.1 nmol/L), n = 36] total T underwent the measurement of highly sensitive C-reactive protein, carotid artery carotid intima-media thickness (IMT), and atherosclerotic plaque by high-resolution B-mode ultrasound and to asses endothelial function by brachial artery flow-mediated dilation. RESULTS Carotid IMT was negatively correlated with total T concentration (r = -0.39, P < .0001). Compared with subjects with normal T, a higher proportion of patients with low total T had carotid IMT of 0.1 cm or greater [80% vs 39%, odds ratio (OR) 6.41; 95% CI 2.5-16.4, P < . 0001], atherosclerotic plaques (68.5% vs 44.8%, OR 2.60, 95% CI 1.12-6.03, P < .0001); endothelial dysfunction (80.5% vs 42.3%, OR 5.77, 95% CI 2.77-14.77, P < .003), and higher highly sensitive C-reactive protein levels (2.74 ± 5.82 vs 0.89 ± 0.88 mg/L, P < .0001). Similar results were found when free T was considered. Multiple logistic regression analyses adjusted for age, diabetes mellitus duration, hemoglobin A1c, lipids, treatment effect, and body mass index reported that a low total T level was independently associated with greater IMT [OR 8.43 (95% CI 2.5-25.8)] and endothelial dysfunction [OR 5.21 (95% CI 1.73-15.66)] but not with the presence of atherosclerotic plaques (OR 1.77, 95% CI 0.66-4.74). CONCLUSIONS Low T is associated with more advanced atherosclerotic disease markers in middle-aged patients with T2D.
Determinants of altered sleep-wake rhythmicity in patients treated for nonfunctioning pituitary macroadenomas.

CONTEXT AND OBJECTIVE In a cohort of 17 patients treated for nonfunctioning pituitary macroadenoma (NFMA), we observed alterations in polysomnographic sleep characteristics and actigraphic sleep-wake rhythmicity, and subjective fatigue, daytime somnolence, and low sleep quality. We aimed to confirm the actigraphic data in a larger scale cohort of NFMA patients, powered to address risk factors for altered rhythmicity, including the effects of hydrocortisone replacement. METHODS Sleep-wake rhythmicity in treated NFMA patients was measured using actigraphy for 7 days, and subjective sleep quality and quality of life (QoL) with validated questionnaires. To assess the influence of hydrocortisone dependency, we additionally studied patients with Addison's disease (AD). The results were compared with matched healthy controls. RESULTS We included 69 NFMA patients in long-term remission after trans-sphenoidal surgery on stable replacement therapy for hypopituitarism, 21 AD patients, and 58 controls. NFMA patients reported severely impaired QoL, sleep quality, and increased daytime sleepiness. The day-night dichotomy of activity was fragmented, with decreased daytime activity and a tendency for increased nighttime activity. Preoperative visual field defects (VFD) were associated with this fragmentation, and vasopressin deficiency with decreased sleep efficiency, independent of age, hypopituitarism, or radiotherapy. AD patients showed similar decreases in daytime functioning, but normal subjective and objective sleep, and no daytime sleepiness. CONCLUSION NFMA patients suffer from altered sleep-wake rhythmicity. Hydrocortisone dependency may explain part of the decreased daytime functioning, but the independent influence of VFD and differences between AD and NFMA patients point towards a role for dysfunction of the adjacent suprachiasmatic nucleus (SCN).
Radioactive Iodine Therapy Did Not Significantly Increase the Incidence and Recurrence of Subsequent Breast Cancer.

CONTEXT Previous studies on the extent to which radioactive iodine (RAI) therapy for thyroid cancer increases the risk of subsequently developing breast cancer have given conflicting results. OBJECTIVE This study aimed to evaluate the effect of RAI treatment on breast cancer development and recurrence among female patients with primary thyroid cancer. DESIGN This was a retrospective cohort study. The risk of subsequent breast cancer associated with RAI and its dose in hazard ratios (HRs) with 95% confidential intervals (CIs) were calculated using time-dependent Cox proportional hazard models. PATIENTS A total of 6150 patients with thyroid cancer enrolled between 1973 and 2009 were followed until December 2012. Of these, 3631 (59.0%) received RAI therapy. During the follow-up period, 99 primary breast cancers were diagnosed. MAIN OUTCOME MEASURE Risk of breast cancer development according to RAI therapy and RAI dose during treatment for primary thyroid cancer. RESULTS RAI therapy did not significantly increase the incidence of subsequent breast cancer among female patients (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.22-1.06) when a 2-year latency period was accounted for. High-dose RAI (≥120 mCi) was associated with a reduced incidence of subsequent breast cancer (HR, 0.17; 95% CI, 0.05-0.62) in the cohort with a 2-year latency period. CONCLUSIONS The long-term follow-up results of this study suggest that RAI treatment for patients with thyroid cancer may not increase the risk or recurrence of breast cancer.
The Physiology of the Cerebral Circulation.

This monograph succeeds in providing a useful panoramic review of the experimental studies in the field. The first chapter refers to some aspects of the anatomy of the cerebral blood vessels. The relation between neurons and blood vessels is discussed only briefly, and the problem of the blood-brain barrier was not considered. The second chapter includes a review of capillary density and oxygen transport in the brain, which data extend from the classical papers by Krogh (1918) to the modern findings of Lubbers (1968). In the third chapter, a good review of the innervation of the cerebral vessels may be found. The following chapters form the main bulk of the book. Chapter 4 studies the hemodynamics of the cerebral circulation; it gives a good idea of the subject, although the reference to the effects of posture, tilting, and acceleration is too brief. Chapter 5 has an excellent review of the
A review: Radiographic iodinated contrast media-induced thyroid dysfunction.

CONTEXT Thyroid hormone production is dependent on adequate iodine intake. Excess iodine is generally well-tolerated, but thyroid dysfunction can occur in susceptible individuals after excess iodine exposure. Radiological iodinated contrast media represent an increasingly common source of excess iodine. OBJECTIVE This review will discuss the thyroidal response after acute exposure to excess iodine; contrast iodine-induced thyroid dysfunction; risks of iodine-induced thyroid dysfunction in vulnerable populations, such as the fetus, neonate, and patients with impaired renal function; and recommendations for the assessment and treatment of contrast iodine-induced thyroid dysfunction. METHODS Data for this review were identified by searching PubMed, Google Scholar, and references from relevant articles from 1948 to 2014. CONCLUSIONS With the increase in the use of computed tomography scans in the United States, there is increasing risk of contrast-induced thyroid dysfunction. Patients at risk of developing iodine-induced thyroid dysfunction should be closely monitored after receiving iodinated contrast media and should be treated as needed.
Assessment of Articular Fragment Displacement in Acetabular Fractures: A Comparison of Computerized Tomography and Plain Radiographs

Objectives Quantitatively evaluate plain radiographs, relative to computed tomography (CT) scans, for assessment of articular fragment displacement (step and gap) in displaced acetabular fractures and in canine osteotomized acetabular specimens. Design Retrospective evaluation of a consecutive series of CT scans and plain radiographs of patients with displaced acetabular fractures and canine acetabulae osteotomized to represent acetabular fractures with displacement. Setting Level I trauma center. Patients/Participants Computed tomography scans and plain radiographic images of 62 consecutive patients with displaced acetabular fractures were reviewed; 20 patients met the inclusion criteria regarding location, fracture pattern, availability of plain radiographs and CT scans, and the position of the femoral head at the time of radiographic assessment. The hemipelvi of five adult mongrels underwent osteotomy of the acetabulum and similar radiographic evaluation. Intervention Three independent reviewers measured step and gap deformity on plain radiographs and CT scans utilizing a standardized measurement technique. Main Outcome Measurements Sensitivity and specificity of plain radiographs for detecting step and gap displacement (2 mm and 4 mm) relative to CT scans were determined. Intraclass correlation coefficient and intraobserver reliability was also calculated. For the canine specimens, sensitivities of each imaging method were determined relative to actual fragment displacement measurements. Results In the clinical images, when compared to CT, plain radiographs showed poor sensitivity at detecting step deformity (sensitivity = 25%). When analyzed by fracture type, plain radiographs were particularly poor at detecting step deformities in fractures involving a single column of the acetabulum (sensitivity = 0%). Excellent intraobserver and intraclass reliability existed among the three reviewers. Computed tomography scans were considerably more accurate in measuring step and gap displacement relative to actual measurements than plain radiographs in the canine specimens. Conclusions 1) Plain radiographs showed poor sensitivity for the detection of step and gap deformities in patients with acetabular fractures and in osteotomized canine specimens, relative to CT scans; 2) differences between CT and plain radiographs in both specimen types were greatest with the most clinically relevant deformity—i.e., step; and 3) CT scans are essential and should continue to be used in conjunction with plain radiographs in the preoperative evaluation of displaced acetabular fractures and perhaps should be considered in the postoperative assessment of fracture reduction.
Pheochromocytoma and paraganglioma in cyanotic congenital heart disease.

CONTEXT Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL). OBJECTIVE The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL. DESIGN/SETTING/PARTICIPANTS We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000-2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes. RESULTS In study 1, we identified 20 PHEO-PGL cases, of which 18 had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1-57 y). Cases were young at diagnosis (median 31.5 y, range 15-57 y) and 7 of 18 had multiple tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of such syndromes. In study 2, hospitalized CCHD patients had an increased likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6-13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD had no increased risk (odds ratio 0.9, P = .48). CONCLUSIONS There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to hypoxic stress, common genetic or developmental factors, or some combination requires further investigation.
LUPUS ERYTHEMATOSUS: SOME OBSERVATIONS ON ITS ETIOLOGY

I bring up for your consideration advisedly a time-worn subject like lupus erythematosus, a subject which has come up for discussion at almost every dermatologic congress during the last half century, because I am old enough in dermatology to have seen the question of its causation pass through a variety of phases, to have had a somewhat extensive experience in dealing with this disease, and to find in the contemplation of its etiology an indication of the newer paths along which progress is likely to be made in the elucidation of a number of baffling problems which at present cloud the dermatologic horizon. With the various types of this dermatitis and the histologic characteristics which underlie them, I am not here concerned, as they are so familiar as to require no reiteration, but with the etiology it is a different matter, as at present it is largely a matter of