Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating Tumor Cells Correlate with Clinicopathological Features and Outcomes in Differentiated Thyroid Cancer

Background/Aims: As biomarkers, circulating tumor cells (CTCs) from solid tumors can predict metastases and prognoses, and help monitor treatment efficacy. However, conventional CellSearch methods have low sensitivity to differentiated thyroid cancer (DTC) CTCs. In this study, for the first time, we used negative enriching (NE) immunofluorescence–in situ hybridization (iFISH) of chromosome 8 to capture and identify CTCs in DTC patients; and investigated how CTCs correlate with clinicopathological factors and prognosis in DTC patients with distant metastases (DM). Methods: In this prospective study, we enrolled 72 patients with DTC before they underwent 131I treatment, and 30 healthy controls (HC). Their CTCs were measured in 7.5 ml peripheral blood using the NE–iFISH technique. CTC was defined by the aneuploidy. Results: We detected CTCs in 62 (86.1%) of the 72 subjects with DTC. The mean number of CTCs in patients with DTC with DM (DM+) was significantly higher than in the HC group (P< 0.001) and DTC patients without DM (DM-; P=0.0016). We found CTCs ≥ 5 was significantly associated with DM+ DTC (P=0.009; sensitivity: 64.3%; specificity: 83.8%); CTCs ≥ 7 was related to poor response to 131I treatment (sensitivity: 73.7 %; specificity: 69.6 %), and was also associated with worse prognosis in DM+ DTC (P< 0.001). Conclusion: We found CTCs ≥ 5 to be a potential predictive index for DM+ DTC; and CTCs ≥7 as a possible indicator of poor response to 131I treatment and worse prognosis in DM+ DTC.
The ARF7 and ARF19 Transcription Factors Positively Regulate PHOSPHATE STARVATION RESPONSE1 in Arabidopsis Roots1

PHOSPHATE STARVATION RESPONSE1, encoding the key regulator of responses to Pi starvation, is the target gene of the transcription factors ARF7 and ARF19 and is positively regulated by auxin signaling in Arabidopsis roots. PHOSPHATE STARVATION RESPONSE1 (PHR1) is a key regulatory component of the response to phosphate (Pi) starvation. However, the regulation of PHR1 in this response remains poorly understood. Here, we report that PHR1 is a target of the transcription factors AUXIN RESPONSE FACTOR7 (ARF7) and ARF19 and is positively regulated by auxin signaling in Arabidopsis (Arabidopsis thaliana) roots. PHR1 expression was induced by exogenous auxin and suppressed by auxin transport inhibitors in Arabidopsis roots. In the PHR1 promoter, three auxin-response elements, which are bound directly by ARF7 and ARF19, were shown to be essential for PHR1 expression. The arf7, arf19, and arf7 arf19 mutants showed down-regulated expression of PHR1 and downstream Pi starvation-induced genes in roots; they also exhibited defective Pi uptake in roots and overaccumulation of anthocyanin in shoots. The induction of lateral root formation in response to low Pi and to exogenous auxin was decreased in the phr1 mutant, whereas the expression of LATERAL ORGAN BOUNDARIES-DOMAIN16 (LBD16) and LBD29 was not changed significantly. PHR1 acted independently of LBD16 and LBD29 in the regulation of lateral root formation in response to low Pi. Under low-Pi conditions, lateral root impairment in the arf7 arf19 mutant was partially rescued by constitutive expression of PHR1, demonstrating that reduced PHR1 expression contributed to the arf7 arf19 phenotype. In addition to PHR1, other genes encoding MYB-CC members also were targets of ARF7 and ARF19. Our work thus reveals a mechanism coordinating auxin signaling and the PHR1 regulon in Arabidopsis responses to Pi deficiency.
Transcription Factor Zhx2 Deficiency Reduces Atherosclerosis and Promotes Macrophage Apoptosis in Mice

Objective— The objective of this study was to determine the basis of resistance to atherosclerosis of inbred mouse strain BALB/cJ. Approach and Results— BALB/cJ mice carry a naturally occurring null mutation of the gene encoding the transcription factor Zhx2, and genetic analyses suggested that this may confer resistance to atherosclerosis. On a hyperlipidemic low-density lipoprotein receptor null background, BALB/cJ mice carrying the mutant allele for Zhx2 exhibited up to a 10-fold reduction in lesion size as compared with an isogenic strain carrying the wild-type allele. Several lines of evidence, including bone marrow transplantation studies, indicate that this effect of Zhx2 is mediated, in part, by monocytes/macrophages although nonbone marrow–derived pathways are clearly involved as well. Both in culture and in atherosclerotic lesions, macrophages from Zhx2 null mice exhibited substantially increased apoptosis. Zhx2 null macrophages were also enriched for M2 markers. Effects of Zhx2 on proliferation and other bone marrow–derived cells, such as lymphocytes, were at most modest. Expression microarray analyses identified >1000 differentially expressed transcripts between Zhx2 wild-type and null macrophages. To identify the global targets of Zhx2, we performed ChIP-seq (chromatin immunoprecipitation sequencing) studies with the macrophage cell line RAW264.7. The ChIP-seq peaks overlapped significantly with gene expression and together suggested roles for transcriptional repression and apoptosis. Conclusions— A mutation of Zhx2 carried in BALB/cJ mice is responsible in large part for its relative resistance to atherosclerosis. Our results indicate that Zhx2 promotes macrophage survival and proinflammatory functions in atherosclerotic lesions, thereby contributing to lesion growth.
Stenotrophomonas maltophilia colonization during allogeneic hematopoietic stem cell transplantation is associated with impaired survival

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.
Dynamic Changes in Schlemm Canal and Iridocorneal Angle Morphology During Accommodation in Children With Healthy Eyes: A Cross-Sectional Cohort Study.

Purpose The purpose of this study was to explore changes in Schlemm canal (SC), trabecular meshwork (TM), and iridocorneal angle (ICA) morphology during accommodative effort in children and young adults. Methods We acquired anterior segment optical coherence tomography images (AS-OCT) of the ICA and ciliary muscle (CM) of both eyes of 50 children age 4 to 16 years with healthy eyes, at two levels of accommodation: 2.5 and 15 diopters (D). Semiautomated nasal ICA measurements were as follows: angle opening distance at 500/750 μm (AOD-500, -750), trabecular iris space area at 500/750 μm (TISA-500, -750), and trabecular iris angle at 500/750 μm (TIA-500, -750). Manual measurements were as follows: anteroposterior and radial SC diameter (SC-APD, SC-RD), cross-sectional area of SC (SC-CSA) and TM height (TMH), TM length (TML), and TM density (TMD). CM width was measured at 1, 2, and 3 mm from the scleral spur (CM-1, CM-2, CM-3). For each parameter, a three-level random-effects model was fitted to estimate differences between the two levels of accommodation. Results With accommodative effort, SC diameters and CSA increase significantly, as do TM length and iridocorneal angle parameters. With increasing age, SC dimensions reduce. Angle parameters are smaller in eyes with greater spherical equivalent (hypermetropia). Conclusions AS-OCT can be used to visualize dynamic morphologic changes in outflow structures with physiologic accommodation. The increase in SC dimensions with accommodative effort may contribute to the regulation of IOP in children.
Bias in Contraceptive Provision to Young Women Among Private Health Care Providers in South West Nigeria.

CONTEXT Health care providers' biases regarding the provision of contraceptives to adolescent and young adult women may restrict women's access to contraceptive methods. METHODS Two mystery client visits were made to each of 52 private-sector health care facilities and individual providers in South West Nigeria in June 2016. In one visit, the mystery client portrayed an unmarried, nulliparous adolescent, and in the other, the client portrayed a married adult woman with two children. During subsequent in-depth interviews, providers were read vignettes describing hypothetical clients with these same profiles, and were asked how they would interact with each. Descriptive analyses of mystery client interactions were combined with thematic analyses of the interview data. RESULTS In greater proportions of married-profile visits than of unmarried-profile visits, mystery clients reported that providers had asked about past contraceptive use and method preference; the opposite was true in regard to providers' using side effects to dissuade clients from practicing contraception. In in-depth interviews, providers expressed concerns about fertility loss among unmarried women who used hormonal contraceptives. Providers more commonly recommended condoms, emergency contraception and the pill for unmarried clients, and longer-acting methods for married clients. The restriction of methods was typically explained by providers of various backgrounds in terms of protecting younger, unmarried clients from damaging their fertility. CONCLUSIONS Provider bias in the provision of contraceptives to adolescent and young adult women in South West Nigeria may affect quality of care and method choice. Interventions to reduce provider bias should go beyond technical training to address the underlying sociocultural beliefs that lead providers to impose restrictions that are not based on evidence.
Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury

Puerarin is a major active ingredient of the traditional Chinese plant medicine, Radix Puerariae, and commonly used in the treatment of myocardial and cerebral ischemia. However, the effects of puerarin on neuropathic pain are still unclear. In this study, a neuropathic pain animal model was created by partial sciatic nerve ligation. Puerarin (30 or 60 mg/kg) was intraperitoneally injected once a day for 7 days. Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment. Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats, especially at 7 days after model establishment. At 7 days after model establishment, quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed mRNA expression of transient receptor potential vanilloid 1 (Trpv1) and transient receptor potential ankyrin 1 (Trpa1) in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury. These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.
Vessel Wall Enhancement in Unruptured Intracranial Aneurysms: An Indicator for Higher Risk of Rupture? High-Resolution MR Imaging and Correlated Histologic Findings

BACKGROUND AND PURPOSE: Recent studies have suggested that wall enhancement of unruptured intracranial aneurysms in high-resolution MR imaging might serve as an imaging biomarker for higher risk of rupture. Histologic studies have revealed a possible association among inflammatory processes, degeneration, and destabilization of the aneurysm wall preceding rupture. Understanding the histologic condition underlying aneurysm wall enhancement could be an important step toward assessing the value of this method for risk stratification. We present our observations of aneurysm wall enhancement in MR vessel wall imaging and underlying histologic changes. MATERIALS AND METHODS: We reviewed records of patients with an unruptured middle cerebral artery aneurysm who underwent MR vessel wall imaging before aneurysm clipping. Contrast enhancement of the aneurysm wall was dichotomized into either none/faint or strong. Histologic analysis included myeloperoxidase stain for detection of inflammatory cell invasion and CD34 stain for assessment of neovascularization and vasa vasorum. RESULTS: Thirteen aneurysms were included. Five aneurysms showed strong wall enhancement. Among these, myeloperoxidase staining revealed inflammatory cell infiltration in 4. Three showed neovascularization. In 2 aneurysms, vasa vasorum were present. Seven aneurysms did not show wall enhancement; 1 had only mild enhancement. None of these bore evidence of inflammatory cell invasion or neovascularization, and they all lacked vasa vasorum. CONCLUSIONS: Wall enhancement in MR vessel wall imaging is associated with inflammatory cell invasion, neovascularization, and the presence of vasa vasorum. Enhancement does not occur when histologic signs of inflammation are absent. Our results support the hypothesis that MR vessel wall imaging could provide valuable information for risk stratification.
0.005% Preservative-Free Latanoprost Induces Dry Eye-Like Ocular Surface Damage via Promotion of Inflammation in Mice.

Purpose To investigate the side effects of preservative-free 0.005% latanoprost on the murine ocular surface. Methods We applied 0.005% latanoprost or vehicle in mice in two patterns for 14 to 28 days. Tear production was measured by phenol red cotton test, and corneal epithelial barrier function was assessed by Oregon-green-dextran (OGD) staining. Periodic acid-Schiff (PAS) staining was used to quantify conjunctival goblet cells (GCs). The expression of matrix metalloproteinase (MMP)-3 and -9, occludin-1 and zonula occludens (ZO)-1 in corneal epithelium was assessed by immunofluorescent staining and/or quantitative real-time PCR (qRT-PCR). Inflammation in conjunctiva was assessed by activation of P38 and NF-κB, infiltration of CD4+ T cells, and production inflammatory cytokines including TNF-α, IL-1β, IFN-γ, IL-17A, and IL-13. Apoptosis in ocular surface was assessed by TUNEL and immunofluorescent staining for activated caspase-3 and -8. Cell viability assay was performed in human corneal epithelial cells. Results Topical latanoprost treatment decreased tear production, induced conjunctival GC loss, disrupted the corneal epithelial barrier, and promoted cell apoptosis in the ocular surface. Topical latanoprost treatment increased the expression of MMP-3 and -9, and decreased the expression of ZO-1 and occludin-1 in the corneal epithelium. Topical application of latanoprost promoted activation of P38-NF-κB signaling and production of TNF-α and IL-1β in conjunctiva. Topical application of latanoprost increased CD4+ T cells infiltration, with increased production of IFN-γ and IL-17A and decreased production of IL-13 in conjunctiva. Conclusion 0.005% latanoprost induced dry eye-like ocular surface damage via promotion of inflammation in mice.
Direct Reprogramming of Fibroblasts Into Smooth Muscle-Like Cells With Defined Transcription Factors—Brief Report

Objective— To identify the transcription factors that could contribute to direct reprogramming of fibroblasts toward smooth muscle cell fate. Approach and Results— We screened various combinations of transcription factors, including Myocd (myocardin), Mef2C (myocyte enhancer factor 2C), Mef2B (myocyte enhancer factor 2B), Mkl1 (MKL [megakaryoblastic leukemia]/Myocd-like 1), Gata4 (GATA-binding protein 4), Gata5 (GATA-binding protein 5), Gata6 (GATA-binding protein 6), Ets1 (E26 avian leukemia oncogene 1, 5’ domain), and their corresponding carboxyterminal fusions to the transactivation domain of MyoD (myogenic differentiation 1)—indicated by *—for their effects on reprogramming mouse embryonic fibroblasts and human adult dermal fibroblasts to the smooth muscle cell fate as determined by the expression of specific markers. The combination of 3 transcription factors, Myocd (or Myocd*) with Mef2C (or Mef2C*) and Gata6, was the most efficient in enhancing the expression of smooth muscle marker genes and decreasing fibroblast gene expression. Additionally, the derived induced smooth muscle-like cells showed a contractile phenotype in response to carbachol. Conclusions— Combination of Myocd and Gata6 with Mef2C* (MG2*) could sufficiently and efficiently direct differentiation of mouse embryonic and human dermal fibroblasts into induced smooth muscle-like cells, thus opening new opportunities for disease modeling, tissue engineering, and personalized medicine.
Cardiotocography and beyond: a review of one-dimensional Doppler ultrasound application in fetal monitoring

One-dimensional Doppler ultrasound (1D-DUS) provides a low-cost and simple method for acquiring a rich signal for use in cardiovascular screening. However, despite the use of 1D-DUS in cardiotocography (CTG) for decades, there are still challenges that limit the effectiveness of its users in reducing fetal and neonatal morbidities and mortalities. This is partly due to the noisy, transient, complex and nonstationary nature of the 1D-DUS signals. Current challenges also include lack of efficient signal quality metrics, insufficient signal processing techniques for extraction of fetal heart rate and other vital parameters with adequate temporal resolution, and lack of appropriate clinical decision support for CTG and Doppler interpretation. Moreover, the almost complete lack of open research in both hardware and software in this field, as well as commercial pressures to market the much more expensive and difficult to use Doppler imaging devices, has hampered innovation. This paper reviews the basics of fetal cardiac function, 1D-DUS signal generation and processing, its application in fetal monitoring and assessment of fetal development and wellbeing. It also provides recommendations for future development of signal processing and modeling approaches, to improve the application of 1D-DUS in fetal monitoring, as well as the need for annotated open databases.
Palliative care in the emergency department: A systematic literature qualitative review and thematic synthesis

Background: Despite a fast-paced environment, the emergency clinician has a duty to meet the palliative patient’s needs. Despite suggested models and interventions, this remains challenging in practice. Aim: To raise awareness of these challenges by exploring the experience of palliative care patients and their families and informal carers attending the emergency department, and of the clinicians caring for them. Design: Qualitative systematic literature review and thematic synthesis. Search terms related to the population (palliative care patients, family carers, clinicians), exposure (the emergency department) and outcome (experience). The search was international but restricted to English and used a qualitative filter. Title, abstracts and, where retrieved, full texts were reviewed independently by two reviewers against predefined inclusion criteria arbitrated by a third reviewer. Studies were appraised for quality but not excluded on that basis. Data sources: MEDLINE [1946-], Embase[1947-], CINAHL [1981-] and PsycINFO [1987-] with a bibliography search. Results: 19 papers of 16 studies were included from Australia (n = 5), the United Kingdom (n = 5), and United States (n = 9) representing 482 clinical staff involved in the emergency department (doctors, nurses, paramedics, social workers, technicians), 61 patients and 36 carers. Nine descriptive themes formed three analytic themes: ‘Environment and Purpose’, ‘Systems of Care and Interdisciplinary Working’ and ‘Education and Training’. Conclusion: In the included studies, provision of emergency palliative care is a necessary purpose of the emergency department. Failure to recognise this, gain the necessary skills or change to systems better suited to its delivery perpetuates poor implementation of palliative care in this environment.
Subclinical Hypothyroidism Impact on the Characteristics of Patients with Polycystic Ovary Syndrome. A Meta-Analysis of Observational Studies

Background/Aims: Definitive polycystic ovary syndrome (PCOS) diagnosis should exclude thyroid dysfunctions. The purpose of the study is to examine the impact of subclinical hypothyroidism on the characteristics of PCOS patients. Methods: A meta-analysis of the published observational studies was conducted. Medline, Scopus, and Cochrane database search was performed to identify the studies that compared euthyroid PCOS and subclinical hypothyroidism (SCH)-PCOS patients. A total of 9 studies were selected, totalizing the inclusion of 1,537 euthyroid PCOS and 301 SCH-PCOS. The data were expressed as raw mean difference and standard error, using the random-effects model. Heterogeneity among studies was examined using the Cochran’s test (Q) and I2 statistics. Results: Anthropometrical parameters were similar in both groups. Total cholesterol (TC) and triglyceride (TG) were higher in SCH-PCOS (p = 0.036 and p = 0.012). High-density lipoprotein cholesterol was lower in the SCH-PCOS group (p = 0.018). Fasting glucose was lower in euthyroid PCOS (p = 0.022). All androgen levels were similar in both group (p > 0.05 for all). Conclusion: TC, TG and fasting glucose were higher in SCH-PCOS patients. Because of the heterogeneity among studies, some summarized results should be interpreted with caution. Consistent data for future studies addressing PCOS diagnosis are provided.