Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificial Neural Network Analysis-Based Immune-Related Signatures of Primary Non-Response to Infliximab in Patients With Ulcerative Colitis

Infliximab (IFX) is an effective medication for ulcerative colitis (UC) patients. However, one-third of UC patients show primary non-response (PNR) to IFX. Our study analyzed three Gene Expression Omnibus (GEO) datasets and used the RobustRankAggreg (RRA) algorithm to assist in identifying differentially expressed genes (DEGs) between IFX responders and non-responders. Then, an artificial intelligence (AI) technology, artificial neural network (ANN) analysis, was applied to validate the predictive value of the selected genes. The results showed that the combination of CDX2, CHP2, HSD11B2, RANK, NOX4, and VDR is a good predictor of patients’ response to IFX therapy. The range of repeated overall area under the receiver-operating characteristic curve (AUC) was 0.850 ± 0.103. Moreover, we used an independent GEO dataset to further verify the value of the six DEGs in predicting PNR to IFX, which has a range of overall AUC of 0.759 ± 0.065. Since protein detection did not require fresh tissue and can avoid multiple biopsies, our study tried to discover whether the key information, analyzed by RNA levels, is suitable for protein detection. Therefore, immunohistochemistry (IHC) staining of colonic biopsy tissues from UC patients treated with IFX and a receiver-operating characteristic (ROC) analysis were used to further explore the clinical application value of the six DEGs at the protein level. The IHC staining of colon tissues from UC patients confirmed that VDR and RANK are significantly associated with IFX efficacy. Total IHC scores lower than 5 for VDR and lower than 7 for RANK had an AUC of 0.828 (95% CI: 0.665–0.991, p = 0.013) in predicting PNR to IFX. Collectively, we identified a predictive RNA model for PNR to IFX and explored an immune-related protein model based on the RNA model, including VDR and RANK, as a predictor of IFX non-response, and determined the cutoff value. The result showed a connection between the RNA and protein model, and both two models were available. However, the composite signature of VDR and RANK is more conducive to clinical application, which could be used to guide the preselection of patients who might benefit from pharmacological treatment in the future.
Comparison of Dose and Effectiveness of a Single-Session Ultrasound-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids With Different Sizes

Purpose This study aimed to compare the dose and effectiveness of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids with different sizes and explore the effect of uterine fibroid size on dose, which provided dose evaluation for clinicians in accordance with the size of uterine fibroids. Materials and Methods A total of 1,000 patients with symptomatic uterine fibroids who received a single-session USgHIFU treatment were enrolled in this study. The size of fibroids was divided into seven groups: 3–4 cm, 4–5 cm, 5–6 cm, 6–7 cm, 7–8 cm, 8–9 cm, and 9–11 cm. The dose was expressed on the basis of the energy efficiency factor (EEF) as the energy required for ablation per unit volume of tissue, and the non-perfused volume ratio (NPVR) was used to assess the effect of HIFU ablation. Results The median NPVR of 88.3% (IQR: 80.3%–94.8%) was obtained, and no significant difference was observed among the seven groups. The classification of T2-weighted image signal intensity fibroids in the 4–5 cm group was compared with that in the 6–7 cm and 8–9 cm groups, and the difference was significant (p < 0.05). However, the proportion of T2WI hyperintense signal fibroids had no significant difference among the seven groups (p > 0.05). The median EEF was 3.88 J/mm3, and a significant difference was observed among the seven groups of EEF (p < 0.05). The EEF of groups with a fibroid size less than 6 cm was more than double the EEF of groups with a fibroid size above 6 cm. In addition, the EEF of groups with a fibroid size of 4–5 cm and 3–4 cm was 3–4 times higher than those with a fibroid size above 7 cm (p < 0.05). Conclusions A single-session HIFU ablation for uterine fibroids of 3–11 cm can obtain an NPVR of more than 80%. The EEF decreased with the increase of the size of uterine fibroids. A fibroid size of 6.5 cm was considered as a clinical meaningful point affecting EEF.
Correlation between cyclooxygenase-2 expression and angiogenesis in human breast cancer.

PURPOSE Cyclooxygenase (COX)-2 is overexpressed in breast cancer and may have a role in regulating tumor growth via effects on angiogenesis, cell proliferation, or apoptosis. This study aimed to derive data from human breast carcinomas to help substantiate or refute these relationships. EXPERIMENTAL DESIGN We performed immunohistochemical analysis of a set of 86 breast tumors for COX-2, estrogen receptor (ER), progesterone receptor (PGR), HER-2, Ki67 (a marker of proliferation), and CD31 (an endothelial cell marker of angiogenesis). RESULTS COX-2 protein expression was detected in 79% of all tumors studied, ER was detected in 79% of all tumors studied, PGR was detected in 73% of all tumors studied, and HER-2 was detected in 16% of all tumors studied. COX-2 protein expression did not significantly correlate with tumor size, grade, axillary lymph node status, or the presence of vascular invasion. A significant negative correlation (P < 0.001) was observed between ER and Ki67. COX-2 expression showed a significant linear correlation with CD31 staining (P < 0.001). No significant correlations were observed between COX-2 and ER, PGR, or HER-2. CONCLUSIONS This study demonstrates a novel relationship between COX-2 expression and the neovasculature of human breast adenocarcinomas. If this is a functional relationship, it provides support for a potential therapeutic role of COX-2 inhibitors in human breast cancer tissue via their antiangiogenic properties.
Autism spectrum disorder in Prader–Willi syndrome: A systematic review

Prader–Willi syndrome (PWS) is a rare genetic disorder that results from lack of expression of paternally‐derived genes on chromosome 15q11‐13; caused by a deletion (DEL), uniparental disomy (UPD), or a rare imprinting center defect. PWS is associated with a distinct behavioral phenotype that in some respects overlaps with autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by restricted or repetitive behaviors (RRBs) and social‐communication impairment. The goal of this review was to (i) review published literature investigating core ASD symptoms in PWS and (ii) provide a prevalence estimate of ASD in PWS. Two independent reviewers searched Medline, CINAHL, PsychINFO, Embase, and Web of Science to find studies that answered the research questions. Individuals with PWS demonstrate significant levels of RRBs and social‐communication impairment, in some reports reaching similar levels to those of non‐PWS ASD comparison groups. Individuals with UPD had more social‐communication impairment than those with DEL. Of 786 PWS participants, 210 (26.7%) were reported as meeting criteria for ASD, either based on clinical diagnosis or by exceeding clinical cut‐points on relevant ASD symptom measures. In studies that distinguished genetic subtypes, rates of ASD were higher in individuals with PWS with UPD (67 of 190; 35.3%) than those with DEL (47 of 254; 18.5%). Published data on the association of PWS and ASD to date are limited to sample means of 8 years of age and older. Further research is needed to identify early markers of ASD in PWS children, to support earlier diagnosis and intervention for this important comorbidity. © 2015 Wiley Periodicals, Inc.
Mortality studies of metalworking fluid exposure in the automobile industry: VI. A case-control study of esophageal cancer.

BACKGROUND Results are reported from a nested case-control study of 60 esophageal cancer deaths among 46,384 automobile manufacturing workers potentially exposed to metalworking fluids (MWF) in machining and grinding operations. METHODS By using incidence-density sampling, controls were selected with a sampling ratio of 20:1 from among co-workers who remained at risk by the age of death of the case, matched on race, gender, plant, and year of birth. Conditional logistic regression was used to evaluate the risk associated with cumulative exposure (mg/m3-years) to each of three types of metalworking fluid (straight, soluble, and synthetic MWF), as well as with years of exposure to selected components of MWF, including nitrosamines, sulfur, biocides, and several metals. RESULTS Esophageal cancer was found to be significantly associated with exposure to both soluble and synthetic MWF in grinding operations. The odds ratios (ORs) for grinding with soluble MWF were elevated at 2.5 or greater in all categories of cumulative exposure, although the exposure-response trend was statistically significant only when exposure was measured as duration. Those with 12 or more years exposure to soluble MWF in grinding operations experienced a 9.3-fold relative risk of esophageal cancer mortality (95% CI = 2.1-42.1). The OR for ever grinding with synthetic MWF was 4.1 (95% CI = 1.1-15.0). Elevated risk was also associated with two agents found in both synthetic and soluble fluids, nitrosamines, and biocides. For exposure to nitrosamines, the OR was 5.4 (95% CI = 1.5-19.9); for biocides the OR was 3.8 (95% CI = 0.8-18.9). However, because the same workers were exposed to grinding with synthetics, nitrosamines and biocides, it was not possible to separate the specific risks associated with these components.
The association between C-reactive protein concentration and depression in later life is due to poor physical health: results from the Health in Men Study (HIMS)

ABSTRACT Background C-reactive protein (CRP) is a non-specific marker of inflammation that has been associated with depression and vascular disease, particularly in men. This study aimed to investigate the association between high CRP concentration and depression while taking physical health into account. Method A cross-sectional study of a community-dwelling sample of 5438 men aged 70+. Participants with scores ⩾7 on the 15-item Geriatric Depression Scale (GDS-15) were considered to display clinically significant depressive symptoms. We measured the serum concentration of CRP with a high-sensitivity assay. The assessment of physical co-morbidity included three components: the Charlson weighted index, self-report of major health events on a standardized questionnaire, and the physical component of the 36-item Short-Form Health Survey (SF-36). Other measured factors included age, native language, education, a standardized socio-economic index, smoking, prior or current history of depression treatment, cognitive impairment (Mini-Mental State Examination score <24) and body mass index (BMI). Results Participants with depression (n=340) were older than their controls without depression (age in years: 76·6±4·4 v. 75·4±4·1). Men with CRP concentration >3 mg/l had an increased odds ratio (OR) [1·59, 95% confidence interval (CI) 1·20–2·11] of being depressed compared to men with CRP ⩽3 mg/l. This association became non-significant once we adjusted the analysis for the measures of physical co-morbidity and other confounding factors (OR 1·22, 95% CI 0·86–1·73). Conclusions The physiological mechanisms that lead to the onset and maintenance of depressive symptoms in older men remain to be determined, but CRP concentration is unlikely to play a significant role in that process.
Aminoacyl‐tRNA synthetase gene regulation in Bacillus subtilis: induction, repression and growth‐rate regulation

The thrS gene in Bacillus subtilis is specifically induced by starvation for threonine and is, in addition, autorepressed by the overproduction of its own gene product, the threonyl‐tRNA synthetase. Both methods of regulation employ an antitermination mechanism at a factor‐independent transcription terminator that occurs just upstream of the start codon. The effector of the induction mechanism is thought to be the uncharged tRNAThr, which has been proposed to base pair in two places with the leader mRNA to induce antitermination. Here we show that the autoregulation by synthetase overproduction is likely to utilize a mechanism similar to that characterized for induction by amino acid starvation, that is by altering the levels of tRNA charging in the cell. We also demonstrate that the base pairing interaction at the two proposed contact points between the tRNA and the leader are necessary but not always sufficient for either form of regulation. Finally, we present evidence that the thrS gene is expressed in direct proportion to the growth rate. This method of regulation is also at the level of antitermination but is independent of the interaction of the tRNA with the leader region.
Temporal distribution, localization and metabolism of all-trans-retinol, didehydroretinol and all-trans-retinal during Xenopus development.

Recently, the temporal and spatial distribution patterns of the retinoid receptor ligands 9-cis-retinoic acid and all-trans-retinoic acid were described in Xenopus embryos during early development [Creech Kraft, Schuh, Juchau and Kimelman (1994) Proc. Natl. Acad. Sci. U.S.A. , in the press]. The present study demonstrates the presence and distribution of their likely precursors, all-trans-retinol, didehydroretinol, didehydroretinal and all-trans-retinal, as well as the occurrence of 4-oxo metabolites, in Xenopus embryos. The temporal and spatial distribution patterns of all-trans-retinol, didehydroretinol and all-trans-retinal did not coincide with that observed for 9-cis-retinoic acid but, in certain regards, were similar to the patterns delineated for all-trans-retinoic acid and all-trans-retinoyl beta-glucuronide. Evidence is presented that 9-cis-retinoic acid can be synthesized from both all-trans-retinoic acid and all-trans-retinol in Xenopus embryos, suggesting that the difference between the distributions of 9-cis-retinoic acid and the other retinoids may be caused by selective synthesis and/or protein binding of the 9-cis isomer.
Response to Comment on: Sukumar et al. Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance–Related Endothelial Cell Dysfunction. Diabetes 2013;62:2130–2134

We would like to thank Drs. Jandeleit-Dahm and Schmidt (1) for their interesting comments regarding our study examining the role of the Nox2 isoform of NADPH oxidase in insulin resistance–related endothelial cell dysfunction (2). We would also like to congratulate them on their own elegant and comprehensive piece of work examining the role of the Nox isoforms Nox1, Nox2, and Nox4 in the development of advanced type 1 diabetes–related atherosclerosis (3). Based on their findings that Nox1 may be more important in diabetes-related atherosclerosis than other isoforms of NADPH oxidase, the authors raise concerns regarding our conclusions that Nox2 has a critical …
Nucleotide correlation between HAV isolates from human patients and environmental samples

Hepatitis A disease is endemic in Albania even though records from the Medical Authority show outbreaks involving only limited numbers of people. In the city of Laç, 200 people became ill following an outbreak of hepatitis A started on November 2002. The age distribution of the cases shows a peak in the age group 5–9 (43.5%) followed by the age group 10–14 (28%) and the age group 1–4 (18%). No cases were recorded in the age group 0–1. Drinking water and sewage samples were collected, using electropositive cartridges, during the outbreak. Rotavirus was identified by RT‐PCR in two out of five drinking water samples; however, all the samples tested negative for HAV and astrovirus. Rotavirus was also identified in three out of five sewage samples from which four were HAV positive. HAV‐RNA was identified in 28 (62.2%) out of 45 IgM anti‐HAV positive sera collected during the outbreak. Genotype IA was expressed from all the amplified samples. Sequence analysis of the overlapping VP1‐2A region shows 97–99% homology with three Italian strains IT‐SCH‐00, IT‐ZAM‐01, and IT‐CAP‐00 and one Spanish strain (Sa 30/06/95), whereas the phylogenetic tree built from the 168 bp sequence of the VP1‐2A shows four clusters, one including 24 out of 28 RT‐PCR positive sera. Considering the deduced amino acid sequence, only one substitution was identified and reported previously for genotype IB. J. Med. Virol. 75:8–12, 2005. © 2005 Wiley‐Liss, Inc.
Retrospective Comparison of Diabetic Foot Ulcer and Venous Stasis Ulcer Healing Outcome Between a Dermal Repair Scaffold (PriMatrix) and a Bilayered Living Cell Therapy (Apligraf)

OBJECTIVE: The goal of this study was to review clinical experience in treating diabetic and venous stasis wounds with Apligraf or PriMatrix. METHODS: A total of 40 diabetic foot ulcers and 28 venous stasis ulcers were treated with either PriMatrix or Apligraf for number of days open and for number of days for complete healing between the 2 treatments. CONCLUSIONS: Although both treatments were highly effective, the study results of 68 ulcers in 48 patients demonstrated that patients treated with PriMatrix healed faster than patients treated with Apligraf despite larger wound sizes.
p66Shc Is a Negative Regulator of FcεRI-Dependent Signaling in Mast Cells

Aggregation of FcεRI on mast cells activates signaling pathways, resulting in degranulation and cytokine release. Release of mast cell-derived inflammatory mediators is tightly regulated by the interplay of positive and negative signals largely orchestrated by adapter proteins. Among these, the Shc family adapter p52Shc, which couples immunoreceptors to Ras activation, positively regulates FcεRI-dependent signaling. Conversely, p66Shc was shown to uncouple the TCR for the Ras–MAPK pathway and prime T cells to undergo apoptotic death. Loss of p66Shc in mice results in breaking of immunologic tolerance and development of lupus-like autoimmune disease, which includes alopecia among its pathological manifestations. The presence of numerous activated mast cells in alopecic skin areas suggests a role for this adapter in mast cells. In this study, we addressed the involvement of p66Shc in FcεRI-dependent mast cell activation. We showed that p66Shc is expressed in mast cells and that mast cells from p66Shc−/− mice exhibit enhanced responses following Ag stimulation of FcεRI. Furthermore, using RBL-2H3 cell transfectants, we showed that aggregation of FcεRI resulted in the recruitment of a p66Shc–SHIP1 complex to linker for activation of T cells. Collectively, our data identified p66Shc as a negative regulator of mast cell activation.
Is vertical jump height a body size-independent measure of muscle power?

Abstract We tested the hypothesis that the performance of rapid movements represents body size-independent indices of muscle power. Physical education students (n = 159) were tested on various vertical jump (jump height and average power calculated from the ground reaction force) and muscle strength tests. When non-normalized data were used, a principal components analysis revealed a complex and inconsistent structure where jump height and muscle power loaded different components, while muscle strength and power partially overlapped. When the indices of muscle strength and power were properly normalized for body size, a simple and consistent structure of principal components supported the hypothesis. Specifically, the recorded height and muscle power calculated from the same jumps loaded the same components, separately for the jumps predominantly based on concentric actions and jumps based on a rapid stretch – shortening cycle of the leg extensors. The finding that the performance of rapid movements assesses the same physical ability as properly normalized tests of muscle power could be important for designing and interpreting the results of batteries of physical performance tests, as well as for understanding some basic principles of human movement performance.
Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers.

OBJECTIVE To evaluate the effects of low-level laser therapy isolated and associated with Calendula officinalis oil in treating diabetic foot ulcers. METHOD An experimental, randomized, controlled, prospective, interventional clinical case study using a quantitative approach. The sample consisted of 32 diabetic patients of both genders. Participants were randomly divided into four groups. Doppler Ultrasound evaluation of the Ankle-Brachial Index, brief pain inventory and analog pain scale were performed at baseline and after 30 days. RESULTS Reduced pain was observed in the Low-level laser therapy and Low-level laser therapy associated with Essential Fatty Acids groups (p<0.01). Regarding the Ankle-Brachial Index and Doppler Ultrasound, all groups remained stable. By analyzing lesion area reduction, Low-level laser therapy associated with Essential fatty acids group showed a significance of p=0.0032, and the Low-level laser therapy group showed p=0.0428. CONCLUSION Low-level laser therapy, performed alone or associated with the Calendula officinalis oil was effective in relieving pain and accelerating the tissue repair process of diabetic foot. OBJETIVO Avaliar os efeitos da Terapia a Laser de Baixa Intensidade isolada e associada ao óleo de Calendula officinalis no reparo de úlceras em pé diabético. MÉTODO Estudo de caso clínico, experimental, controlado, randomizado, prospectivo, intervencional, de caráter quantitativo. A amostra foi composta de 32 pacientes diabéticos, de ambos os gêneros. Os participantes foram distribuídos aleatoriamente em quatro grupos. Ultrassom Doppler, avaliação do Índice Tornozelo-Braquial, Inventário breve de dor e escala de dor analógica foram realizados no início e após 30 dias. RESULTADOS Houve redução da dor nos grupos Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa intensidade associada aos Ácidos Graxos Essenciais, com p<0,01. Quanto ao Índice Tornozelo-Braquial e Ultrassom Doppler, todos os grupos mantiveram-se estáveis. Na análise da redução de área da lesão, o grupo Terapia a Laser de Baixa Intensidade associada aos Ácidos Graxos Essenciais apresentou uma significância p=0,0032, e o grupo Terapia a Laser de Baixa Intensidade, p=0,0428. CONCLUSÃO A Terapia a Laser de Baixa Intensidade, realizada tanto isoladamente quanto associada ao óleo de Calendula officinalis, foi eficaz no alívio da dor e na aceleração do processo de reparo tecidual de pé diabético.
Herbs–Are they Safe Enough? An Overview

Drugs based on herbs have become a common form of therapy as well as for prophylaxis because they are often perceived as being natural and therefore harmless. Today they are one of the hottest trends and most sought after in the field of nutrition or herbal therapeutics. As the use of complementary medicine grows, so does the knowledge that many compounds in common use not only have a significant effect on the body but may also interact with pharmaceuticals and also with other alternative products. Concurrent use of herbs with drugs may mimic, magnify, or oppose the effect of drugs leading to herb-drug interactions. Currently, there is very little information published on herb-herb or herb-drug interactions as compared to the use of herbs which is progressively growing across the world. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs. The article reviews the recent literature on the adverse effects of herbal remedies including the most widely sold herbal medicinal products, like liquorice, garlic, ginger, green tea, and turmeric, etc., and reinforce the safety aspect of herbal products, which are considered to be relatively safe by common people.