Miracle-dz/UniFAR-FTUs huggingface dataset:
Worrisome Histologic Alterations Following Fine Needle Aspiration of the Thyroid

OBJECTIVE To investigate worrisome histologic alterations following fine needle aspiration (FNA) of the thyroid (WHAFFT). STUDY DESIGN Of 1,890 FNA thyroid cases, 265 underwent surgical excision. The histologic sections of these cases were studied for WHAFFT lesions. Thirty control cases were also studied. RESULTS WHAFFT lesions were present in 38.49% of cases. Acute lesions were seen in 30 and chronic in 72 cases. Control cases did not show WHAFFT lesions. The common lesions were hemorrhage and fibrosis. Worrisome lesions, like nuclear atypia, vascular changes, capsular pseudoinvasion and metaplasia, were present in 32 (12.07%) cases. CONCLUSION Considering the large number of FNAs and reduction in the number of thyroid excisions, the advantages of FNA are manifold as compared to the few diagnostic problems. Misdiagnosis can be avoided with awareness of WHAFFT lesions.
A Review of Cancer in U.S. Hispanic Populations

There are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies. Cancer Prev Res; 5(2); 150–63. ©2012 AACR.
The dual EGFR/HER‐2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN‐38

Members of the human epidermal receptor (HER) family are frequently associated with aggressive disease and poor prognosis in multiple malignancies. Lapatinib is a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and HER‐2. This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN‐38, the active metabolite of irinotecan (CPT‐11), in colon and gastric cancer cell lines. Concentration‐dependent antiproliferative effects of both lapatinib and SN‐38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines (lapatinib range 0.08–11.7 μM; SN‐38 range 3.6–256 nM). Lapatinib potently inhibited the growth of a HER‐2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER‐2 expression. The combination of lapatinib and SN‐38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested. Cotreatment with lapatinib and SN‐38 also resulted in enhanced cell cycle arrest and the induction of apoptosis with subsequent cellular pharmacokinetic analysis demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN‐38 when compared to SN‐38 treatment alone. Finally, the combination of lapatinib and CPT‐11 demonstrated synergistic antitumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity compared to CPT‐11 monotherapy. These results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in the treatment of gastrointestinal carcinomas. © 2009 UICC
Efficient sparse matrix-vector multiplication on x86-based many-core processors

Sparse matrix-vector multiplication (SpMV) is an important kernel in many scientific applications and is known to be memory bandwidth limited. On modern processors with wide SIMD and large numbers of cores, we identify and address several bottlenecks which may limit performance even before memory bandwidth: (a) low SIMD efficiency due to sparsity, (b) overhead due to irregular memory accesses, and (c) load-imbalance due to non-uniform matrix structures. We describe an efficient implementation of SpMV on the IntelR Xeon PhiTM Coprocessor, codenamed Knights Corner (KNC), that addresses the above challenges. Our implementation exploits the salient architectural features of KNC, such as large caches and hardware support for irregular memory accesses. By using a specialized data structure with careful load balancing, we attain performance on average close to 90% of KNC's achievable memory bandwidth on a diverse set of sparse matrices. Furthermore, we demonstrate that our implementation is 3.52x and 1.32x faster, respectively, than the best available implementations on dual IntelR XeonR Processor E5-2680 and the NVIDIA Tesla K20X architecture.
Beamforming Optimization for Physical Layer Security in MISO Wireless Networks

A wireless network of multiple transmitter-user pairs overheard by an eavesdropper, where the transmitters are equipped with multiple antennas, while the users and eavesdropper are equipped with a single antenna, is considered. At different levels of wireless channel knowledge, the problem of interest is beamforming to optimize the users’ quality-of-service (QoS) in terms of their secrecy throughputs or maximize the network's energy efficiency under users’ QoS. All these problems are seen as very difficult optimization problems with many nonconvex constraints and nonlinear equality constraints in beamforming vectors. The paper develops path-following computational procedures of low complexity and rapid convergence for the optimal beamforming solution. Their practicability is demonstrated through numerical examples.
Individual prediction of long‐term outcome in adolescents at ultra‐high risk for psychosis: Applying machine learning techniques to brain imaging data

An important focus of studies of individuals at ultra‐high risk (UHR) for psychosis has been to identify biomarkers to predict which individuals will transition to psychosis. However, the majority of individuals will prove to be resilient and go on to experience remission of their symptoms and function well. The aim of this study was to investigate the possibility of using structural MRI measures collected in UHR adolescents at baseline to quantitatively predict their long‐term clinical outcome and level of functioning. We included 64 UHR individuals and 62 typically developing adolescents (12–18 years old at recruitment). At six‐year follow‐up, we determined resilience for 43 UHR individuals. Support Vector Regression analyses were performed to predict long‐term functional and clinical outcome from baseline MRI measures on a continuous scale, instead of the more typical binary classification. This led to predictive correlations of baseline MR measures with level of functioning, and negative and disorganization symptoms. The highest correlation (r = 0.42) was found between baseline subcortical volumes and long‐term level of functioning. In conclusion, our results show that structural MRI data can be used to quantitatively predict long‐term functional and clinical outcome in UHR individuals with medium effect size, suggesting that there may be scope for predicting outcome at the individual level. Moreover, we recommend classifying individual outcome on a continuous scale, enabling the assessment of different functional and clinical scales separately without the need to set a threshold. Hum Brain Mapp 38:704–714, 2017. © 2016 Wiley Periodicals, Inc.
HCV Genotype 6a Escape From and Resistance to Velpatasvir, Pibrentasvir, and Sofosbuvir in Robust Infectious Cell Culture Models.

BACKGROUND & AIMS Chronic liver diseases caused by hepatitis C virus (HCV) genotype 6 are prevalent in Asia, and millions of people require treatment with direct-acting antiviral regimens, such as NS5A inhibitor velpatasvir combined with the NS5B polymerase inhibitor sofosbuvir. We developed infectious cell culture models of HCV genotype 6a infection to study the effects of these inhibitors and the development of resistance. METHODS The consensus sequences of strains HK2 (MG717925) and HK6a (MG717928), originating from serum of patients with chronic HCV infection, were determined by Sanger sequencing of genomes amplified by reverse-transcription polymerase chain reaction. In vitro noninfectious full-length clones of these 6a strains were subsequently adapted in Huh7.5 cells, primarily by using substitutions identified in JFH1-based Core-NS5A and Core-NS5B genotype 6a recombinants. We studied the efficacy of NS5A and NS5B inhibitors in concentration-response assays. We examined the effects of long-term culture of Huh7.5 cells incubated with velpatasvir and sofosbuvir singly or combined following infection with passaged full-length HK2 or HK6a recombinant viruses. Resistance-associated substitutions (RAS) were identified by Sanger and next-generation sequencing, and their effects on viral fitness and in drug susceptibility were determined in reverse-genetic experiments. RESULTS Adapted full-length HCV genotype 6a recombinants HK2cc and HK6acc had fast propagation kinetics and high infectivity titers. Compared with an HCV genotype 1a recombinant, HCV genotype 6a recombinants of strains HK2 and HK6a were equally sensitive to daclatasvir, elbasvir, velpatasvir, pibrentasvir, and sofosbuvir, but less sensitive to ledipasvir, ombitasvir, and dasabuvir. Long-term exposure of HCV genotype 6a-infected Huh7.5 cells with a combination of velpatasvir and sofosbuvir resulted in clearance of the virus, but the virus escaped the effects of single inhibitors via emergence of the RAS L31V in NS5A (conferring resistance to velpatasvir) and S282T in NS5B (conferring resistance to sofosbuvir). Engineered recombinant genotype 6a viruses with single RAS mediated resistance to velpatasvir or sofosbuvir. HCV genotype 6a viruses with RAS NS5A-L31V or NS5B-S282T were however, able to propagate and escape in Huh7.5 cells exposed to the combination of velpatasvir and sofosbuvir. Further, HCV genotype 6a with NS5A-L31V was able to propagate and escape in the presence of pibrentasvir with emergence of NS5A-L28S, conferring a high level of resistance to this inhibitor. CONCLUSIONS Strains of HCV genotype 6a isolated from patients can be adapted to propagate in cultured cells, permitting studies of the complete life cycle for this important genotype. The combination of velpatasvir and sofosbuvir is required to block propagation of original HCV genotype 6a, which quickly becomes resistant to single inhibitors via the rapid emergence and persistence of RAS. These features of HCV genotype 6a could compromise treatment.
Immune effects of relaxation during chemotherapy for ovarian cancer.

BACKGROUND Psychological interventions, such as relaxation training, have been applied to strengthen resistance to disease. There is evidence that relaxation can modify immune parameters in healthy populations and in chemotherapy naive cancer patients. METHODS In this study, 22 patients receiving chemotherapy for ovarian cancer were allocated to relaxation training with a clinical psychologist or to a control group. After 2 months' training, blood was sampled 2 days before chemotherapy in the patients' homes, and at the hospital prior to treatment. RESULTS On average, the intervention group showed higher lymphocyte counts, and a tendency to higher white blood cell numbers as compared to the control group. No significant effects were found in proliferative responses to mitogen and natural killer cell activity after intervention. Relaxation training did not modify the magnitude of changes in immune variables between home samples and at the hospital in anticipation of treatment. CONCLUSIONS The study suggests that relaxation training can positively affect immune parameters in cancer patients, even if training is performed during myelosuppressive therapy.
Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects Reversed by Pathogen Clearance

Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation.
Alexithymia, neurovegetative arousal and neuroticism. An experimental study.

BACKGROUND The association between alexithymia and higher sympathetic vegetative reactivity (emotional arousal) is still controversial. METHODS The objective of this study was to examine differences in the electrodermic reactivity (neurovegetative arousal) of alexithymic subjects compared to nonalexithymic subjects. The study was also designed to determine whether alexithymia is linked to neuroticism (negative emotions). The study sample consisted of 56 psychiatric outpatients. The values for the neurovegetative variables (polygraphic computerized registration) were determined under three different experimental conditions: baseline (relaxation) and two conditions of stress (cognitive and visual stimuli). RESULTS Vegetative reactivity, TAS score (Toronto Alexithymia Scale) and other clinical/test variables showed statistically significant differences between the two groups of patients. Alexithymic subjects demonstrated a high and stable level of autonomic reactivity at baseline and under stress, a greater neuroticism and a tendency to internalize emotional responses. CONCLUSIONS The application of the alexithymic concept to the field of somatization represents a reliable instrument of detection, with important therapeutic implications.
Correlation of vitamin D receptor with bronchial asthma in children

This study was designed to investigate the correlation of vitamin D receptor (VDR) gene polymorphism with bronchial asthma in children. Seventy patients admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the first time from April 2015 to May 2017 were selected as observation group. Patients received routine treatment and intervention. Seventy healthy subjects admitted to hospital during the same period were enrolled as the control group. Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism assay; the levels of total serum immunoglobulin E (IgE) in the two groups were determined by electrochemiluminescence immunoassay; lung function levels in patients were measured using PowerCube (Germany) pulmonary function instrument before and after treatment, and the relationship between VDR gene polymorphism and lung function in children with bronchial asthma was analyzed. The difference in comparison of base frequency of rs1544410 locus of VDR gene had no statistical significance between the two groups (P>0.05). The locus CC frequency of rs7975232 of VDR gene in observation group was lower in the observation group than that in the control group (P<0.05); the locus AC and AA frequencies of rs7975232 of VDR gene were higher in the observation group than those in the control group (P<0.05). The level of vitamin D was lower in the observation group than that in the control group (P<0.05); the level of total serum IgE was higher in the observation group than that in the control group (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with bronchial asthma in the observation group were higher after treatment than those before treatment (P<0.05). The correlation research displayed that VDR gene polymorphism was negatively correlated with lung function levels in children with bronchial asthma (P<0.05). The results showed that children with bronchial asthma are often accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with the severity of asthma, so vitamin D should be strengthened to ameliorate the prognosis of children.
An Automated Method for Retinal Arteriovenous Nicking Quantification From Color Fundus Images

Retinal arteriovenous (AV) nicking is one of the prominent and significant microvascular abnormalities. It is characterized by the decrease in the venular caliber at both sides of an artery-vein crossing. Recent research suggests that retinal AV nicking is a strong predictor of eye diseases such as branch retinal vein occlusion and cardiovascular diseases such as stroke. In this study, we present a novel method for objective and quantitative AV nicking assessment. From the input retinal image, the vascular network is first extracted using the multiscale line detection method. The crossover point detection method is then performed to localize all AV crossing locations. At each detected crossover point, the four vessel segments, two associated with the artery and two associated with the vein, are identified and two venular segments are then recognized through the artery-vein classification method. The vessel widths along the two venular segments are measured and analyzed to compute the AV nicking severity of that crossover. The proposed method was validated on 47 high-resolution retinal images obtained from two population-based studies. The experimental results indicate a strong correlation between the computed AV nicking values and the expert grading with a Spearman correlation coefficient of 0.70. Sensitivity was 77% and specificity was 92% (Kappa κ = 0.70) when comparing AV nicking detected using the proposed method to that detected using a manual grading method, performed by trained photographic graders.
Insight into the Molecular Mechanism of the Transcriptional Regulation of amtB Operon in Streptomyces coelicolor

In Streptomyces coelicolor, amtB transcription is promptly regulated by the global nitrogen regulator GlnR. Although the GlnR binding cis-element has been characterized in amtB promoter, consisting of three GlnR boxes of a3-b3, a1-b1, and a2-b2, its role in GlnR-mediated transcriptional regulation remains unclear. Here, we showed that GlnR had different binding affinity against each pair of GlnR binding sites in amtB promoter (i.e., a3-b3, a1-b1, and a2-b2 sites), and GlnR was able to bind a3-b3 and a1-b1, respectively, but not a2-b2 alone. Consistently, a2 was not a typical GlnR binding site and further experiments showed that a2 was non-essential for GlnR-mediated binding in vitro and transcriptional regulation in vivo. To uncover the physiological role of the three GlnR boxes, we then mutated the wild-type amtB promoter to a typical GlnR-binding motif containing two GlnR boxes (a3-b3–a2-b2), and found although the transcription of the mutated promoter could still be activated by GlnR, its increasing rate was less than that of the wild-type. Based on these findings, one could conclude that the three GlnR boxes assisted GlnR in more promptly activating amtB transcription in response to nitrogen limitation, facilitating bacterial growth under nitrogen stresses.
Performance impact and interplay of SSD parallelism through advanced commands, allocation strategy and data granularity

With the development of the NAND-Flash technology, NAND-Flash based Solid-State Disk (SSD) has been attracting a great deal of attention from both industry and academia. While a range of SSD research topics, from interface techniques to buffer management and Flash Translation Layer (FTL), from performance to endurance and energy efficiency, have been extensively studied in the literature, the SSD being studied was by and large treated as a grey or black box in that many of the internal features such as advanced commands, physical-page allocation schemes and data granularity are hidden or assumed away. We argue that, based on our experimental study, it is these internal features and their interplay that will help provide the missing but significant insights to designing high-performance and high-endurance SSDs. In this paper, we use our highly accurate and multi-tiered SSD simulator, called SSDsim, to analyze several key internal SSD factors to characterize their performance impacts, interplay and parallelisms for the purpose of performance and endurance en-hancement of SSDs. From the results of our experiments, we found that: (1) larger pages tend to have significantly negative impact on SSD performance under many workloads; (2) different physical-page allocation schemes have different deployment en-vironments, where an optimal allocation scheme can be found for each workload; (3) although advanced commands provided by flash manufacturers can improve performance in some cases, they may jeopardize the SSD performance and endurance when used inappropriately; (4) since the parallelisms of SSD can be classified into four levels, namely, channel-level, chip-level, die-level and plane-level, the priority order of SSD parallelism, resulting from the strong interplay among physical-page allocation schemes and advanced commands, can have a very significant impact on SSD performance and endurance.