Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemistry for diagnosis and prognosis of breast cancer: a review

ABSTRACT Breast cancer is the most prevalent malignant tumor and main oncologic cause of mortality in women. Although most diagnosis of breast pathology is accomplished using hematoxylin and eosin stained sections, some cases require immunohistochemistry for proper evaluation. We investigated the latter cases including distinctions between ductal and lobular carcinoma, in situ and invasive carcinoma, typical ductal hyperplasia and atypical ductal hyperplasia/ductal carcinoma in situ, papillary and spindle cell lesion assessment, metastasis evaluation, and assessment of prognostic and therapy markers. E-cadherin is used to differentiate ductal and lobular carcinoma; 34βE12, CK8, p120 catenin and β-catenin also produce consistent results. Myoepithelial cell (MEC) stains are used to evaluate in situ and invasive carcinoma; calponin, smooth muscle myosin heavy chain and p63 are sensitive/specific markers. 34βE12 and CK5/6 are positive in ductal hyperplasia, which enables its differentiation from atypical ductal hyperplasia and ductal carcinoma in situ. CK 5/6, ER and MEC markers are consistent options for evaluating papillary lesions. Spindle cell lesions can be assessed using β-catenin, SMA, CD34, p63, CKs and hormone receptors. It is important to differentiate primary carcinomas from metastases; the most commonly used markers to identify breast origin include mammaglobin, GCDFP-15, GATA3 and ER, although none of these is completely sensitive or specific. Immunohistochemistry can be used to evaluate central prognostic and predictive factors including molecular subtypes, HER2, hormone receptors, proliferation markers (Ki-67) and lymph-vascular invasion markers including ERG, CD31, CD34, factor VIII and podoplanin. Owing to the complexity of mammary lesions, diagnosis also depends on each particular situation, evaluation of cytological characteristics revealed by immunochemistry and correlation with histological findings.
Multidrug Resistance Regulators MarA, SoxS, Rob, and RamA Repress Flagellar Gene Expression and Motility in Salmonella enterica Serovar Typhimurium

The mar-sox-rob regulon is a large and highly conserved stress response network in the Enterobacteriaceae family. Although it is well characterized in E. coli, the extent of this regulon in related species is unclear. Here, the control of costly flagellar gene expression is connected to the mar-sox-rob regulon of S. Typhimurium, contrasting with the E. coli regulon model. These findings demonstrate the flexibility of the mar-sox-rob regulon to accommodate novel regulatory targets, and they provide evidence for its broader regulatory role within this family of diverse bacteria. ABSTRACT Production of flagella is costly and subject to global multilayered regulation, which is reflected in the hierarchical control of flagellar production in many bacterial species. For Salmonella enterica serovar Typhimurium and its relatives, global regulation of flagellar production primarily occurs through the control of flhDC transcription and mRNA translation. In this study, the roles of the homologous multidrug resistance regulators MarA, SoxS, Rob, and RamA (constituting the mar-sox-rob regulon in S. Typhimurium) in regulating flagellar gene expression were explored. Each of these regulators was found to inhibit flagellar gene expression, production of flagella, and motility. To different degrees, repression via these transcription factors occurred through direct interactions with the flhDC promoter, particularly for MarA and Rob. Additionally, SoxS repressed flagellar gene expression via a posttranscriptional pathway, reducing flhDC translation. The roles of these transcription factors in reducing motility in the presence of salicylic acid were also elucidated, adding a genetic regulatory element to the response of S. Typhimurium to this well-characterized chemorepellent. Integration of flagellar gene expression into the mar-sox-rob regulon in S. Typhimurium contrasts with findings for closely related species such as Escherichia coli, providing an example of plasticity in the mar-sox-rob regulon throughout the Enterobacteriaceae family. IMPORTANCE The mar-sox-rob regulon is a large and highly conserved stress response network in the Enterobacteriaceae family. Although it is well characterized in E. coli, the extent of this regulon in related species is unclear. Here, the control of costly flagellar gene expression is connected to the mar-sox-rob regulon of S. Typhimurium, contrasting with the E. coli regulon model. These findings demonstrate the flexibility of the mar-sox-rob regulon to accommodate novel regulatory targets, and they provide evidence for its broader regulatory role within this family of diverse bacteria.
Pre-exposure prophylaxis uptake and discontinuation among young black men who have sex with men in Atlanta, Georgia: A prospective cohort study.

BACKGROUND HIV pre-exposure prophylaxis (PrEP) has great potential to reduce HIV incidence among young black men who have sex with men (YBMSM) but initiation and persistence for this group remain low. We sought to understand the patterns and predictors of PrEP uptake and discontinuation among YBMSM in Atlanta, Georgia. METHODS PrEP was offered to all participants in a prospective cohort of HIV-negative YBMSM aged 18-29. For initiators, time on and off PrEP was recorded. Time to PrEP uptake, first discontinuation, and final discontinuation were assessed with the Kaplan-Meier method, with Cox proportional hazard models used to identify factors associated with uptake and discontinuation. RESULTS After 440 person-years of follow-up, 44% of YBMSM initiated PrEP through the study after a median of 122 days (IQR 44-275). Of PrEP initiators, 69% had a first discontinuation and 40% had a final discontinuation during the study period. The median time to first PrEP discontinuation was 159 days (IQR 97-237). Factors associated with PrEP uptake included higher self-efficacy, sexually transmitted infection, and condomless anal intercourse. Factors associated with discontinuation included younger age, cannabis use, STI, and fewer sex partners. HIV incidence was 5.23/100 person-years (95% CI 3.40-7.23) with lower rate among those who started PrEP (incidence rate ratio 0.39 [95% CI 0.16-0.92]). CONCLUSIONS Persistent PrEP coverage in this cohort of YBMSM was suboptimal and discontinuations common despite additional support services available through the study. Interventions to support PrEP uptake and persistence, especially for younger and substance-using YBMSM, will be necessary to achieve full PrEP effectiveness.
Performance of Two-Stage Cervical Cancer Screening With Primary High-Risk Human Papillomavirus Testing in Women Living With Human Immunodeficiency Virus.

OBJECTIVE To evaluate the performance of cervical cancer screening algorithms for women living with human immunodeficiency virus (HIV), using primary high-risk human papillomavirus (HPV) testing followed by cytology, visual inspection with acetic acid, or colposcopy. METHODS We conducted a prospective cohort study of women living with HIV in Botswana. All participants underwent high-risk HPV testing. Participants with positive high-risk HPV test results underwent cytology, visual inspection with acetic acid, colposcopy, and biopsy. Participants with negative high-risk HPV test results also underwent cytology. Histopathology was the reference standard for determination of preinvasive cervical disease and cervical cancer. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and likelihood ratios (LR) of high-risk HPV-based two-stage screening algorithms were calculated. RESULTS Among 300 women screened, 88 (29%) had a positive high-risk HPV test result, and 29 of the 88 (35%) women who tested positive for high-risk HPV had CIN 2 or higher on histopathology. High-risk HPV followed by colposcopy resulted in a sensitivity of 83%, specificity of 49%, PPV of 47%, LR+ of +1.6, and LR- of -0.4. High-risk HPV followed by visual inspection with acetic acid resulted in a reduced sensitivity of 59%, specificity of 49%, PPV of 39%, LR+ of +1.2, and LR- of -0.8. High-risk HPV testing followed by cytology also resulted in a reduced sensitivity of 62%, specificity of 77%, PPV of 60%, LR+ of +2.7, and LR- of -0.5. Stratification by HPV 16/18/45 did not improve performance of the algorithms. CONCLUSION In a high-risk population with HIV, high-risk HPV testing followed by colposcopy demonstrated the highest sensitivity and PPV in detecting high-grade cervical dysplasia. Allocating resources to colposcopy in resource-limited settings may be more effective than other screening strategies.
Quantitative assessment of three vendor’s metal artifact reduction techniques for CT imaging using a customized phantom

Abstract A metal implant was placed in an acrylic phantom to enable quantitative analysis of the metal artifact reduction techniques used in computed tomography (CT) scanners from three manufacturers. Two titanium rods were placed in a groove in a cylindrical phantom made by acrylic, after which the groove was filled with water. The phantom was scanned using three CT scanners (Toshiba, GE, Siemens) under the abdomen CT setting. CT number accuracy, contrast-to-noise ratio, area of the metal rods in the images, and fraction of affected pixel area of water were measured using ImageJ. Different iterative reconstruction, dual energy, and metal artifact reduction techniques were compared within three vendors. The highest contrast-to-noise ratio of three scanners were 85.7 ± 8.4 (Toshiba), 85.9 ± 11.7 (GE), and 55.0 ± 14.8 (Siemens); and the most correct results of metal area were 157.1 ± 1.4 mm2 (Toshiba), 155.0 ± 1.0 (GE), and 170.6 ± 5.3 (Siemens). The fraction of affected pixel area obtained using single-energy metal artifact reduction of Toshiba scanner was 2.2% ± 0.7%, which is more favorable than 4.1% ± 0.7% obtained using metal artifact reduction software of GE scanner (p = 0.002). Among all quantitative results, the estimations with fraction of affected pixel areas matched the effect of metal artifact reduction in the actual images. Therefore, the single-energy metal artifact reduction technique of Toshiba scanner had a desirable effect. The metal artifact reduction software of GE scanner effectively reduced the effect of metal artifacts; however, it underestimated the size of the metal rods. The monoenergetic and dual energy composition techniques of Siemens scanner could not effectively reduce metal artifacts.
Cell-type-specific analysis of alternative polyadenylation using single-cell transcriptomics data

Abstract Alternative polyadenylation (APA) is emerging as an important layer of gene regulation because the majority of mammalian protein-coding genes contain multiple polyadenylation (pA) sites in their 3′ UTR. By alteration of 3′ UTR length, APA can considerably affect post-transcriptional gene regulation. Yet, our understanding of APA remains rudimentary. Novel single-cell RNA sequencing (scRNA-seq) techniques allow molecular characterization of different cell types to an unprecedented degree. Notably, the most popular scRNA-seq protocols specifically sequence the 3′ end of transcripts. Building on this property, we implemented a method for analysing patterns of APA regulation from such data. Analyzing multiple datasets from diverse tissues, we identified widespread modulation of APA in different cell types resulting in global 3′ UTR shortening/lengthening and enhanced cleavage at intronic pA sites. Our results provide a proof-of-concept demonstration that the huge volume of scRNA-seq data that accumulates in the public domain offers a unique resource for the exploration of APA based on a very broad collection of cell types and biological conditions.
Comparison of sleep and chronotype between senior and undergraduate university students

ABSTRACT The university programs for seniors provide a third age perspective in lifelong learning with classes and recreational facilities, and enable students to share their experiences and knowledge. A good sleep quality promotes better cognitive functioning and serves to protect against age-related cognitive declines. Central nervous system reorganization takes place during sleep, and although the influence of sleep quality on memory is not clear, circadian rhythm disorders affect alertness and individual performance. Physiological change during aging need to be clarified to better understand how university might help students. The aim of the present study was to evaluate for the first time the chronotype, the sleep quality and their relationship in senior university students and to compare them with those of undergraduate students. The Morningness–Eveningness Questionnaire (MEQ) and the Pittsburgh Sleep Quality Index (PSQI) were used. The results indicated that approximately 50% of the participants were good sleepers. This percentage was equal in the senior and undergraduate students. The results showed that undergraduate students tended toward eveningness while senior students tended toward morningness. Among the undergraduate students, evening type chronotypes had a tendency toward higher PSQI scores and this affected their daytime function scores, while it did not in the senior students, in whom worsening sleep quality was associated with disturbances such as going to the bathroom and nocturnal awakening. This information would be useful for designing environmental interventions to optimize sleep/work cycles for decreasing age-associated changes in memory in senior students and for improving the academic achievements of undergraduate students.
Changes in the Substrate Source Reveal Novel Interactions in the Sediment-Derived Methanogenic Microbial Community

Methanogenesis occurs in many natural environments and is used in biotechnology for biogas production. The efficiency of methane production depends on the microbiome structure that determines interspecies electron transfer. In this research, the microbial community retrieved from mining subsidence reservoir sediment was used to establish enrichment cultures on media containing different carbon sources (tryptone, yeast extract, acetate, CO2/H2). The microbiome composition and methane production rate of the cultures were screened as a function of the substrate and transition stage. The relationships between the microorganisms involved in methane formation were the major focus of this study. Methanogenic consortia were identified by next generation sequencing (NGS) and functional genes connected with organic matter transformation were predicted using the PICRUSt approach and annotated in the KEGG. The methane production rate (exceeding 12.8 mg CH4 L−1 d−1) was highest in the culture grown with tryptone, yeast extract, and CO2/H2. The analysis of communities that developed on various carbon sources casts new light on the ecophysiology of the recently described bacterial phylum Caldiserica and methanogenic Archaea representing the genera Methanomassiliicoccus and Methanothrix. Furthermore, it is hypothesized that representatives of Caldiserica may support hydrogenotrophic methanogenesis.
The Effect of Preoperative Symptom Duration on Postoperative Outcomes After Minimally Invasive Transforaminal Lumbar Interbody Fusion

Study Design: Retrospective. Object: This study aims to examine whether the time spanning from symptom onset to surgical intervention has an effect on postoperative clinical improvement in patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Summary of Background Data: Evidence is limited regarding the influence of preoperative symptom duration on patient-reported outcomes (PROs). Methods: Patients undergoing a primary, single-level minimally invasive transforaminal lumbar interbody fusion were retrospectively reviewed and stratified according to preoperative symptom duration (<12 mo and ≥12 mo). Differences in PROs, including Oswestry Disability Index (ODI), 12-Item Short-Form Physical Component Score (SF-12 PCS), Visual Analogue Scale (VAS) back pain, and VAS leg pain, at each postoperative timepoint and were compared between duration of symptoms (DOS) cohorts using linear regression. Achievement of minimal clinically important difference (MCID) for PROs was compared using χ2 analysis. Results: A total of 248 patients were included: 96 had a DOS <12 months and 152 had a DOS >12 months. When comparing PROs preoperatively, the shorter DOS cohort had significantly worse ODI, VAS leg pain, and SF-12 PCS compared with patients with longer DOS. However, there was no preoperative difference in VAS back pain between cohorts. Postoperatively, there were no significant differences in improvement of PROs throughout the 12-month timepoint. The shorter DOS cohort had a comparable number of patients achieving MCID for ODI, VAS back pain, VAS leg pain, and SF-12 PCS relative to the longer DOS cohort. Conclusions: In our study, patients with DOS <12 months exhibited significantly worse ODI and VAS leg pain scores at the time of surgery compared with patients with longer DOS. However, these patients demonstrated similar clinical improvement postoperatively regardless of preoperative symptom duration. These findings suggest that delayed surgical intervention may not lead to impaired functional recovery in patients with degenerative lumbar disease.
Exploring Inflammatory Mediators in Fetal and Maternal Compartments During Human Parturition.

OBJECTIVE To examine inflammatory mediators in three fetomaternal biological compartments to inform theory related to the fetal and maternal inflammatory contributions to parturition at term and preterm. METHODS We conducted a cross-sectional study of amniotic fluid, cord blood, and maternal plasma from women with singleton pregnancies. Women had one of four conditions: term labor (n=11), term not in labor (n=13), spontaneous preterm birth with intact membranes (preterm birth; n=13), or preterm prelabor rupture of membranes (PROM; n=8). We measured two damage-associated molecular pattern markers (high-mobility group box-1 [HMGB1] and uric acid) and two acute phase response markers (interleukin [IL]-6 and C-reactive protein [CRP]) using enzyme-linked immunosorbent assay. The distribution of each analyte within amniotic fluid, cord blood, and maternal plasma across the four conditions (term not in labor, term labor, preterm birth, and preterm PROM) were calculated. To explore whether there were distributional differences in each analyte across each of the four labor conditions, we used a nonparametric Kruskal-Wallis test. For analytes that differed across groups, we further compared distributions by labor group (term labor vs term not in labor, and preterm PROM vs preterm birth). RESULTS Fetal compartments (amniotic fluid and cord blood) showed higher HMGB1 in term labor vs term not in labor and preterm PROM vs preterm birth. Amniotic fluid IL-6, cord blood CRP and cord blood uric acid were higher in term vs term not in labor. Cord blood uric acid was higher in preterm PROM vs preterm birth. Only maternal plasma IL-6 was higher in term labor vs term not in labor. CONCLUSION Accumulation of HMGB1 and an overall increase in inflammation observed on the fetal side, but not the maternal side, may be signals of parturition. Understanding fetal-derived proparturition inflammatory signals at term and preterm, especially in preterm PROM, might provide fetal-specific biomarkers and identify underlying mechanisms and targets for interventions to reduce the risk of preterm birth and preterm PROM.
Adolescent and Parent Experiences of Acceptance and Commitment Therapy for Pediatric Chronic Pain: An Interpretative Phenomenological Analysis

Pediatric chronic pain is common and can be related to reduced functioning in many domains for the young person and their parents. Existing psychological treatments such as Acceptance and Commitment Therapy (ACT) have shown to be effective, but improvements are needed. Qualitative approaches can help improve our understanding of treatment processes and outcomes. The aim of the present qualitative interview study was to explore the lived experiences of young people and parents who had participated in ACT for pediatric chronic pain. Four young persons and four parents were interviewed, and data was analyzed using Interpretative Phenomenological Analysis (IPA). Three themes were generated, each comprising two subthemes: (1) ‘Warning system’, which included experiences from being offered this psychological intervention, and the alternative explanations provided for pain; (2) ‘Change and challenges’, which suggested the importance of the values-based work, and of individual adaptation; and (3) ’A common language’ in which the interaction with others and new ways to communicate around the pain experience were described. Findings highlight the importance of pain education, formulating and acting in line with personal values, and communication around the pain experience, as well as the need for developmental and individual adaptations of interventions.
Comparison of PD-L1 Expression Status between Pure-Solid Versus Part-Solid Lung Adenocarcinomas

Although lung adenocarcinomas (LADs) with ground-glass opacity (GGO; part-solid tumors) have been shown to differ from those without GGO (pure-solid tumors) in clinicopathological features and prognoses, whether programmed death ligand-1 (PD-L1) protein expression differs between these two tumor types is unclear. This study included 124 patients with clinical T1a–c LAD who received pulmonary resections during 2007–2009. The E1L3N antibody was used to stain for PD-L1 in primary LAD specimens. The specimens were considered PD-L1+ if ≥1% of tumor cells showed membrane staining, and were classified as having a high PD-L1+ tumor proportion score (TPS) if ≥50% of the tumor cells did so. Among the 124 patients, 45 had part-solid tumors and 79 had pure-solid tumors. These two groups did not significantly differ in terms of clinical factors. However, the rates for PD-L1 positivity (4% vs. 25%, p < 0.01) and high PD-L1+ TPS (2% vs. 16%, p = 0.02) were significantly higher in the pure-solid tumors. The multivariate analyses (logistic regression model) showed that the odds ratios for PD-L1 positivity and high PD-L1+ TPS in pure-solid LADs were 5.9 (95% CI; 1.2–29.7) and 8.0 (95% CI; 1.0–63.8), respectively. In conclusion, LADs with GGO were correlated with a lower incidence of PD-L1 expression than pure-solid tumors.
Molecular characterization and diagnostic criteria of renal cell carcinoma with emphasis on liquid biopsies

ABSTRACT Introduction: Over the past 6 years, important genomic and transcriptomic studies performed on RCC reported a comprehensive molecular description of RCC pathogenic alterations. Such molecular findings pave the way for an integrated classification, based on histopathology aspects and molecular alterations in order to personalize the clinical management of RCC. Areas covered: The aim of this review is to evaluate the current knowledge and the potential value of liquid biopsy in RCC. Studies on presence and analysis of circulating tumor DNA (ctDNA), circulating RNA, specific microRNA, long non-coding RNA, and circulating tumor cells are reported for each phase of disease, from the diagnostic setting to the localized disease and, lastly, in the metastatic stage. Expert opinion: Advantages of liquid biopsies compared to serial tissue sampling are numerous. However, some limitations must be addressed before considering liquid biopsy as a noninvasive biomarker of clinical utility. The suboptimal sensitivity depends on the assessment technique and genetic platforms used, the tumor organ, the tumor stage, tumor heterogeneity, and clonality. The rate of discordance with tumor tissue genotyping may depends on temporal heterogeneity, spatial heterogeneity, and/or assay error (false-negative or false-positive genotyping).