Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of tumoral and stromal ALDH 1A1 expression in breast invasive duct carcinoma in Egyptian female patients

Background Cancer is considered a stem cell disease. Many stem cell markers are recently well known to have main roles in carcinogenesis and tumor progression. Aldehyde dehydrogenase 1A1 (ALDH1A1) is a stem cell marker that thought to have a role in many cancers. This study aimed to evaluate the expression of ALDH1A1 in different molecular types of breast invasive ductal carcinomas (NOS), and its relation to clinicopathological data. Materials and methods This is a retrospective study carried out on 40 cases of NOS of the breast. The cases were collected from archives of Early Cancer Detection Unit, Benha Faculty of Medicine and Pathology Department, International Medical Center, between the years 2007 and 2013. Previously estrogen receptor, progesterone receptor, Her2/neu and Ki-67 stained slides were reevaluated for each case. Both tumoral and stromal expression of ALDH1A1 was also evaluated for each case. Results A significant positive correlation of ALDH1A1 tumoral expression was observed in patients with age more than 55 years (P<0.05), higher tumor grade (P<0.05), large tumor size (T) (P<0.05), lymph node metastasis (P<0.01), distant metastases, and advanced TNM stage (P<0.05). A significant association of tumoral ALDH1A1 with estrogen receptor and progesterone receptor negativity was noted (P<0.05) while the expression of ALDH1A1 in tumor cells appeared more frequently in Her2/neu-positive cases (P<0.05). Expression of ALDH1A1 in stromal cells correlated inversely with the presence of distant metastasis and advanced tumor stage (P<0.05 for both). Tumoral ALDH1A1 expression showed inverse highly significant correlations (P<0.0001) with patient’s survival. Increased stromal expression of ALDH1A1 showed a significant relation to disease-free survival and overall survival (P<0.05). Tumoral ALDH1A1 expression correlated inversely with the overall survival and disease-free survival of luminal A and luminal B cases (P<0.05 for all). Conclusion ALDH1A1 may have a dual role in NOS progression. Also, ALDH1A1 could be used to predict chemoresistant cases among different molecular subtypes. Induction of stromal ALDH1A1 expression could be a possible therapeutic target in the future to suppress tumor progression.
Myasthenia Gravis and Congenital Myasthenic Syndromes.

PURPOSE OF REVIEW Myasthenia gravis (MG) is an autoimmune neuromuscular disease that causes fluctuating weakness in ocular, bulbar, and limb muscles and can, in 15% of cases, cause myasthenic crisis, a neurologic emergency characterized by respiratory failure. Although infrequent, MG needs to be promptly recognized and treated because the potential for improvement and remission is very high. The diagnosis of MG can be challenging and delayed because of the fluctuating nature of muscle weakness and the overlap of signs and symptoms with other neuromuscular diseases.This article reviews the importance of prompt recognition of the typical signs and symptoms, best tests to confirm the diagnosis, currently available acute and chronic treatment modalities, the role of thymectomy, and the natural history of the disease. Special consideration related to the diagnosis and management in women during pregnancy and in children will also be reviewed. This article also includes an overview of congenital myasthenic syndromes. RECENT FINDINGS Recent significant efforts in standardizing and improving the care of patients with MG have occurred, as well as new momentum in developing new drugs for patients with MG who do not adequately respond to currently available treatments. The number of clinical trials and drugs in development for MG is steadily increasing. Eculizumab has been recently approved by the US Food and Drug Administration (FDA) for adult patients with generalized MG who are acetylcholine receptor-antibody positive, based on the REGAIN (Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis) study, a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. An international, multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone has demonstrated that thymectomy improves clinical outcome in patients with nonthymomatous MG. Clinical care guidelines have been published, and the recommendations for clinical research standards and the Myasthenia Gravis Foundation of America MGFA clinical classification published in 2000 have become widely accepted by the clinical and research community of MG experts. SUMMARY MG is a highly treatable disease with many effective treatment modalities available and with a natural history that continues to improve thanks to better diagnostic tests and effective drugs. The diagnosis and management of patients affected by MG can be highly rewarding for any neurologist as most patients are able to live normal lives if treated appropriately. Nevertheless, future research is needed to address unresolved clinical issues, such as when and how to discontinue immunosuppressive medications in patients in remission, the role and timing of thymectomy in children, and better treatment options for refractory patients.
Cancer-associated fibroblasts in epithelial ovarian carcinoma: relation to clinicopathologic characteristics and microvessel density

Background Epithelial ovarian carcinoma (EOC) is the leading cause of mortality among all gynecologic cancers. Recent studies have emphasized the role of the tumor microenvironment in tumor progression. Cancer-associated fibroblasts (CAFs) are the most frequent component in the tumor microenvironment, and α-smooth muscle actin (α-SMA) is the most commonly used marker to identify CAF. This study aimed to investigate the potential role of CAFs in the progression of EOC. Furthermore, we analyzed the relation between the presence of CAF in EOC and clinicopathologic characteristics and tumor microvessel density (MVD). Methods Immunohistochemical staining was performed on 75 cases of epithelial ovarian neoplasms using α-SMA (as a marker of CAFs) and CD34 (for assessment of MVD in EOC cases). Results The presence of CAFs, as assessed by α-SMA intensity and percentage of positive stained area, was significantly more prominent in malignant cases, as compared with borderline and benign cases. It was found that abundant CAFs were significantly associated with high-grade tumors, stage III tumors and tumors with vascular invasion and omental metastasis. A significant positive correlation was detected between the presence of CAFs and tumor MVD in EOC. Conclusion CAFs significantly increase from benign through borderline to malignant ovarian neoplasms. CAFs are significantly higher in high-grade tumors, advanced stage tumors and in tumors with vascular invasion or omental metastasis. CAFs are significantly correlated with tumor MVD in EOC. Thus, CAFs may serve as a poor prognostic indicator in patients with EOC.
A study of magnetic resonance imaging-derived cervical spinal cord dimensions in young adult Nigerians: Clinical relevance

INTRODUCTION: Knowledge of cervical cord dimensions is important in making diagnosis of pathological conditions of the spinal cord. This study used magnetic resonance imaging to determine the normal dimensions of the cervical spinal cord in young adult Nigerians and the influence of age and sex on these dimensions. METHODS: A prospective study of 100 healthy asymptomatic individuals (50 males and 50 females) aged 21–40 years was carried out at Memfys Hospital, Enugu, Nigeria. Disc-level axial T1-weighted 0.35T magnetic resonance images of anteroposterior dimensions (APDs) and transverse dimensions (TDs) were obtained from C2/C3 to C7/T1 in millimeters. Approximate cord area (ACA) was calculated as the product of APD and TD. Test of significance for age- and sex-adjusted dimensions was determined. RESULTS: TD increased from C2/3 (12.2 ± 1.0 mm) to peak at C5/6 level (13.4 ± 1.2 mm) before dropping to 11.6 ± 1.4 mm (C7/T1). APD decreased from 8.1 ± 0.6 mm (C2/3) to 6.9 ± 0.7 mm (C7/T1). ACA also increased from 98.7 ± 11.7 mm2 (C2/3) to peak value of 103.3 ± 14.6 mm2 (C5/6), but dropped to 80.0 ± 14.3 mm2 (C7/T1). In general, there was no significant gender-based difference in values of the cord dimensions except in TD at C2/3 (0.036). ANOVA revealed a significant difference in age-adjusted values of TD (0.022) and AP (0.042) at C5/6. Only TD values had significant variability at C5/6 level when individuals in the age group of 36–40 years were compared to those <30 years old. CONCLUSION: TD and ACA give more representative values of cervical spinal cord size and should be utilized clinically in the assessment of these dimensions. The C5/6 has the highest cervical spinal cord dimension. Sex-adjusted dimensions generally did not show statistically significant difference. There is subtle but significant reduction in TD of cervical spinal cord at C5/6 level toward the age of 40 years.
Insulinoma-associated protein 1 reveals an eminent performance for the diagnosis of pulmonary neuroendocrine tumors in cytological materials

Background Although cytological interpretation of classic pulmonary neuroendocrine tumors (NETs) is straightforward, their identification remains a diagnostic challenge in daily practice, especially if cytomorphological features are unclear. The currently used immunostaining panel has some limitations. insulinoma-associated protein 1 (INSM1) is a transcription factor that is reported in different NETs. The aim of the current study was to identify INSM1 expression in cytological materials of lung NETs, to compare its performance with that of the currently used markers and to compare the expression in primary and corresponding metastatic NETs. Materials and methods This retrospective study included 40 cytological samples of primary pulmonary NETs and nine metastatic extrapulmonary materials of the same patients as well as 20 samples of non-NETs (control group). Image-guided fine-needle aspiration was performed. Cell block sections were stained for INSM1, synaptophysin, CD56, and chromogranin A. For all markers, at least 1% positive cells were considered positive. Diffuse/strong positive was reported if at least 50% of the cells were detected at low power magnification. Focal/weak positivity was defined if less than 50% of tumor cells were positive but not easily identified at low power. Results INSM1 was positive in 92.5% (37/40). The sensitivity for small-cell lung carcinoma, large-cell neuroendocrine carcinoma, and carcinoid was 92.6, 91.7, and 100%, respectively. No significant statistical difference was identified regarding expression in various NET subtypes (P>0.05). INSM1 was negative in all non-NETs. The INSM1 sensitivity was similar to CD56 sensitivity but more than that of synaptophysin and chromogranin. The INSM1 specificity was higher than those of CD56 and chromogranin A and equal to synaptophysin. The INSN1 sensitivity was similar to the sensitivity of the combined conventional markers as a group with a superior specificity. INSM1 staining in the nine metastatic NETs was matched up to their primary tumors. Conclusion INSM1 combined high sensitivity, specificity, and accuracy when compared with the currently used markers. Nuclear INSM1 expression is easier and faster to interpret than the cytoplasmic or membranous expression of the other markers. It should be used in neuroendocrine marker panels. INSM1 staining was retained in all metastatic sites.
Myotonic Muscular Dystrophies.

PURPOSE OF REVIEW This article describes the clinical features, pathogenesis, prevalence, diagnosis, and management of myotonic dystrophy type 1 and myotonic dystrophy type 2. RECENT FINDINGS The prevalence of myotonic dystrophy type 1 is better understood than the prevalence of myotonic dystrophy type 2, and new evidence indicates that the risk of cancer is increased in patients with the myotonic dystrophies. In addition, descriptions of the clinical symptoms and relative risks of comorbidities such as cardiac arrhythmias associated with myotonic dystrophy type 1 have been improved. SUMMARY Myotonic dystrophy type 1 and myotonic dystrophy type 2 are both characterized by progressive muscle weakness, early-onset cataracts, and myotonia. However, both disorders have multisystem manifestations that require a comprehensive management plan. While no disease-modifying therapies have yet been identified, advances in therapeutic development have a promising future.
Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer’s Disease: A Resting-State fMRI Study

The hippocampus is generally reported as one of the regions most impacted by Alzheimer’s disease (AD) and is closely associated with memory function and orientation. Undirected functional connectivity (FC) alterations occur in patients with mild cognitive impairment (MCI) and AD, and these alterations have been the subject of many studies. However, abnormal patterns of directed FC remain poorly understood. In this study, to identify changes in directed FC between the hippocampus and other brain regions, Granger causality analysis (GCA) based on voxels was applied to resting-state functional magnetic resonance imaging (rs-fMRI) data from 29 AD, 65 MCI, and 30 normal control (NC) subjects. The results showed significant differences in the patterns of directed FC among the three groups. There were fewer brain regions showing changes in directed FC with the hippocampus in the MCI group than the NC group, and these regions were mainly located in the temporal lobe, frontal lobe, and cingulate cortex. However, regarding the abnormalities in directed FC in the AD group, the number of affected voxels was greater, the size of the clusters was larger, and the distribution was wider. Most of the abnormal connections were unidirectional and showed hemispheric asymmetry. In addition, we also investigated the correlations between the abnormal directional FCs and cognitive and clinical measurement scores in the three groups and found that some of them were significantly correlated. This study revealed abnormalities in the transmission and reception of information in the hippocampus of MCI and AD patients and offer insight into the neurophysiological mechanisms underlying MCI and AD.
Cell Intrinsic Deregulated ß-Catenin Signaling Promotes Expansion of Bone Marrow Derived Connective Tissue Type Mast Cells, Systemic Inflammation, and Colon Cancer

Mast cells constitutively express ß-catenin and expand in solid tumors such as colon and skin cancer. However, the role of ß-catenin signaling in mast cells and the cause or effect of mast cell expansion and tumor growth has yet to be established. In earlier studies we used mast cell depletion and protease staining approaches, to provide evidence for a causative role of mast cells in small bowel polyposis, and related specific phenotypes and distributions of tumor infiltrating mast cells to stages of tumor growth. Here we report that, stabilization of ß-catenin expands mast cells to promote high incidence of colon polyposis and infrequent small bowel polyps and skin cancer. Expression of a dominant acting ß-catenin in mast cells (5CreCAT) stimulated maturation and expression of granule stored proteases. Both mucosal and connective tissue type mast cells accumulated in colonic small bowel polyps independent of gender, and mice developed chronic systemic inflammation with splenomegaly. Reconstitution of polyposis-prone mice with bone marrow from 5CreCAT mice resulted in focal expansion of connective tissue like mast cells, which are normally rare in benign polyps and characteristically expand during adenoma-to-carcinoma transition. Our findings highlight a hitherto unknown contribution of ß-catenin signaling in mast cells to their maturation and to increased risk of colon cancer.
A Review of Microsoft Academic Services for Science of Science Studies

Since the relaunch of Microsoft Academic Services (MAS) 4 years ago, scholarly communications have undergone dramatic changes: more ideas are being exchanged online, more authors are sharing their data, and more software tools used to make discoveries and reproduce the results are being distributed openly. The sheer amount of information available is overwhelming for individual humans to keep up and digest. In the meantime, artificial intelligence (AI) technologies have made great strides and the cost of computing has plummeted to the extent that it has become practical to employ intelligent agents to comprehensively collect and analyze scholarly communications. MAS is one such effort and this paper describes its recent progresses since the last disclosure. As there are plenty of independent studies affirming the effectiveness of MAS, this paper focuses on the use of three key AI technologies that underlies its prowess in capturing scholarly communications with adequate quality and broad coverage: (1) natural language understanding in extracting factoids from individual articles at the web scale, (2) knowledge assisted inference and reasoning in assembling the factoids into a knowledge graph, and (3) a reinforcement learning approach to assessing scholarly importance for entities participating in scholarly communications, called the saliency, that serves both as an analytic and a predictive metric in MAS. These elements enhance the capabilities of MAS in supporting the studies of science of science based on the GOTO principle, i.e., good and open data with transparent and objective methodologies. The current direction of development and how to access the regularly updated data and tools from MAS, including the knowledge graph, a REST API and a website, are also described.
Very Low Efficiency of Direct Reprogramming of Astrocytes Into Neurons in the Brains of Young and Aged Mice After Cerebral Ischemia

After cerebral ischemia, the ratio between astroglial cells and neurons in the neurovascular unit is disrupted in the perilesional area. We hypothesized that restoring the balance within the neurovascular unit may lead to an improved neurorestoration after focal ischemia. Recently, an innovative technology has been invented to efficiently convert proliferating astroglial cells into neurons in the injured young brain. However, the conversion efficacy of this technology has not been explored in the post-stroke brains of the aged rodents. To this end, we used a retroviral delivery system encoding the transcription factor Ngn2 alone or in combination with the antiapoptotic factor Bcl-2 to target proliferating astrocytes in the neocortex of young and aged mice after cerebral ischemia. Successful direct in vivo reprogramming of reactive glia into neuroblasts and mature neurons was assessed by cellular phenotyping. We found that the conversion efficacy of proliferating astrocytes into neurons after cerebral ischemia in young and aged mice is disappointingly low, most likely because the therapeutic vectors carrying the conversion gene are engulfed by phagocytes shortly after intracortical administration. We conclude that other viral vectors and combinations of transcription factors should be employed to improve the efficacy of glia-to-neuron conversion after stroke in young and aged rodents.
Yes-Associated Protein 1 Plays Major Roles in Pancreatic Stellate Cell Activation and Fibroinflammatory Responses

Background: Yes-associated protein 1 (YAP), a transcriptional co-activator and major effector of the Hippo pathway, regulates cell differentiation and morphology in many cell types and supports aberrant tumor growth. Recent studies showed that YAP is expressed in pancreas tissues in pancreatic ductal adenocarcinoma (PDAC) patients and experimental models of PDAC, with YAP largely found in cancer cells and pancreatic stellate cells (PaSC) in the stroma. Methods and Results: We studied here the role of YAP in the activated phenotype of PaSC. We found that YAP is expressed at low levels in normal mouse pancreas, but protein levels significantly increased after pancreas inflammatory damage induced by repeated cerulein administration in wild-type mice or upon initiation of neoplastic transformation of the pancreas parenchyma in Ptf1-Cre;LSL-KrasG12D/+ (KC) mice. In these animal models, YAP upregulation occurred in parallel with activation and proliferation of PaSC. Consistent with these findings, we found robust YAP expression in culture-activated mouse and human PaSC but not in quiescent, freshly isolated cells. Fully activated PaSC isolated from KC mice or PDAC patient tissues exhibited robust nuclear YAP suggesting YAP transcriptional activity. Agents that induce quiescence such as the Bromodomain and Extra-Terminal (BET) inhibitor iBET151 and the p38 MAPK inhibitor SB203580 reduced YAP levels in PaSC. Stimulation of PaSC with the potent mitogen PDGF elicited marked YAP Ser127 phosphorylation. However, unexpectedly, this effect did not diminish YAP nuclear localization, suggesting that YAP phosphorylation at this site does not govern YAP cellular localization in PaSC. siRNA-mediated knockdown of YAP reduced PDGF-induced PaSC expansion in culture and blunted the persistent activation of Akt and ERK elicited by PDGF stimulation, supporting a role for YAP in PDGF-induced cell growth. YAP knockdown also blunted fibroinflammatory gene expression responses both in unstimulated and transforming growth factor beta 1 (TGFβ1)-stimulated PaSC. Conclusion: Our data suggest a central role for YAP in sustaining the activated phenotype and fibroinflammatory responses in PaSC. Moreover, our findings indicate that a complex crosstalk between YAP, TGFβ1, and PDGF pathways regulates PaSC activity and growth.
Excessive Daytime Sleepiness in Tension-Type Headache: A Population Study

Excessive daytime sleepiness (EDS) is a prevalent sleep-related complaint across the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. However, the association between EDS and TTH is currently scarce. In the present study, we investigated the impact of EDS on the prevalence and clinical presentation of TTH. We utilized data from the Korean Headache-Sleep Study, a national survey that sought to identify headache and sleep characteristics in Korean adults. Participants with an Epworth sleepiness scale score greater or equal to 11 were considered as having EDS. Of the 2,695 participants enrolled, 570 (21.2%) and 313 (11.6%) had TTH and EDS, respectively. EDS was highly prevalent in individuals with chronic tension-type headache (CTTH) than in those without headache (35.7 vs. 9.4%, p < 0.001). The prevalence of EDS in episodic tension-type headache (ETTH) individuals with a headache frequency <1 per month (8.3%, p = 0.511) and ETTH individuals with a headache frequency of 1–14 per month (13.5%, p = 0.054) was not significantly different from that in individuals without headache (9.4%). TTH participants with EDS had a higher headache frequency per month (4.3 ± 8.1 vs. 1.7 ± 4.2, p = 0.013), more severe headache intensity (Visual Analog Scale, 5.0 [3.0–6.0] vs. 4.0 [3.0–6.0], p = 0.008), a higher impact of headache (Headache Impact Test-6 score, 47.1 ± 7.3 vs. 43.5 ± 7.6, p < 0.001), and a higher prevalence of depression (12.7 vs. 3.2%, p < 0.001) than TTH participants without EDS. Consequently, CTTH is associated with higher EDS prevalence compared to ETTH and without headache. Moreover, TTH with EDS had more severe TTH symptoms compared to TTH without EDS.