Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective, Randomized Clinical Trial Comparing use of Intraoperative Transesophageal Echocardiography to Standard Care during Radical Cystectomy

Purpose: Our prospective, randomized clinical study aims to evaluate the utility of intraoperative transesophageal echocardiography (TEE) in patients undergoing radical cystectomy. Materials and Methods: Eighty patients were randomized to a standard of care group or the intervention group that received continuous intraoperative TEE. Data are presented as means ± standard deviations, median (25th percentile, 75th percentile), or numbers and percentages. Characteristics were compared between groups using independent sample t-tests, Wilcoxon–Mann–Whitney tests or Chi-square tests, as appropriate. All tests were two-sided and P < 0.05 was considered to indicate statistical significance. Results: Both groups had similar preoperative demographic characteristics. There was a significant difference between central line insertion with all insertions in the control group (15%, 6 vs. 0%, 0; P < 0.003). Of all the perioperative complications, 80% occurred in the control group versus 20% in the TEE group, with 21% of controls experiencing a cardiac or pulmonary complication compared to 5% in the TEE group (8 vs. 2, P < 0.04). The control group patients were more likely to have adverse cardiac complications than the TEE group (15%, 6 vs. 3%, 1; P < 0.040). Postoperative cardiac arrhythmia was observed only in the control group (13%, 5 vs. 0%, 0; P <.007). Prolonged intubation was only observed in the control group (10%, 4 vs. 0%, 0; P < 0.017). Conclusion: TEE can be a useful monitoring tool in patients undergoing radical cystectomy, limiting the use of central line insertion and potentially translating into earlier extubation and decreased postoperative cardiac morbidities.
The Clinical Significance of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Patients with Occupational Cholangiocarcinoma

Objective The present study aimed to identify the clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with occupational cholangiocarcinoma. Methods This study included 10 men with occupational cholangiocarcinoma who were former or current workers at a printing company in Osaka, Japan. Of the 10 patients, 2 had 2 main tumors and 1 had 3 main tumors. Twelve FDG-PET imaging findings in the 10 patients could be analyzed. We evaluated the relationships between FDG-PET imaging parameters and clinicopathological findings of occupational cholangiocarcinoma. Results Abnormal FDG uptake was observed in 8 of the 14 main tumors, with maximum standardized uptake values ranging from 2.9 to 11.0, and the sensitivity was 57.1%. Four patients had lymph node metastases, and abnormal marrow uptake was detected in all these patients. Although precancerous lesions, such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) without any invasion, were not detected, abnormal FDG uptake was demonstrated in 2 of 4 patients with IPNB having an associated invasive carcinoma. Conclusions Although FDG-PET may be useful for assessing tumor progression factors, such as lymph node metastasis, it cannot accurately detect precancerous lesions, such as BilIN and IPNB without invasive carcinoma.
Bayesian inference of hub nodes across multiple networks

Hub nodes within biological networks play a pivotal role in determining phenotypes and disease outcomes. In the multiple network setting, we are interested in understanding network similarities and differences across different experimental conditions or subtypes of disease. The majority of proposed approaches for joint modeling of multiple networks focus on the sharing of edges across graphs. Rather than assuming the network similarities are driven by individual edges, we instead focus on the presence of common hub nodes, which are more likely to be preserved across settings. Specifically, we formulate a Bayesian approach to the problem of multiple network inference which allows direct inference on shared and differential hub nodes. The proposed method not only allows a more intuitive interpretation of the resulting networks and clearer guidance on potential targets for treatment, but also improves power for identifying the edges of highly connected nodes. Through simulations, we demonstrate the utility of our method and compare its performance to current popular methods that do not borrow information regarding hub nodes across networks. We illustrate the applicability of our method to inference of co‐expression networks from The Cancer Genome Atlas ovarian carcinoma dataset.
Trends in the Detail of the Stage and Survival Rate in Hypopharyngeal Cancer over 20 Years.

Background: Hypopharyngeal cancer frequently presents at an advanced stage and has one of the worst prognosis among the head and neck cancers. Recently, superficial hypopharyngeal cancers with a good prognosis have been detected with a novel endoscopic technique, such as narrow band imaging. Objectives: To evaluate trends in the detail of the stage and survival rate in hypopharyngeal cancer over 20 years. Patients and methods: Between 1993 and 2012, 722 patients with hypopharyngeal cancer treated at the Osaka Medical Center for Cancer and Cardiovascular Disease were studied retrospectively. The 20-year period was subdivided into 5-year periods; Period A (1993-1997, n=101), Period B (1998-2002, n=123), Period C (2003-2007, n=196) and Period D (2008-2012, n=302). The patients at Stage I-II were divided into superficial cancer as Stage I-IIs and invasive cancer as Stage I-IIi. In every period, a transition of the staging and overall survival rate were compared. Results: The 5-year overall survival in Period A, B, C and D were 34%, 39%, 54% and 60%, respectively. The patients at Stage III-IV in Period A, B, C and D comprised 32%, 36%, 47% and 54%, respectively. Both survival rates improved significantly from Period B to C. The ratio of Stage 0 and Stage I-IIs increased significantly from Period C to D. Whereas the 5-year overall survival rates of Stage 0 and Stage I-IIs were similar (80% vs 88%), the 5-year overall survival of Stage I-IIi was significantly poor. Excluding Stage 0 and Stage I-IIs, the 5-year overall survival had little change from Period C to D. Conclusion: The reason for the improvement in hypopharyngeal cancer prognosis was the prognostic improvement of advanced cancer from Period B to C, and an increase in superficial cancer from Period C to D.
Role of Poly Adenosine Diphosphate Ribose Polymerase Inhibitors in Advanced Stage Ovarian Cancer

Ovarian cancer is one of the leading causes of death from gynecologic cancers. In this present era of cancer treatment, therapeutic options for patients with advanced or recurrent ovarian cancer are limited. The present standard of care treatment for advanced ovarian cancer is a platinum-based doublet chemotherapy (paclitaxel and carboplatin with or without bevacizumab) after a maximum attempt of surgical cytoreduction. However, there are no promising options for the management of patients with ovarian cancer refractory to the platinum-based chemotherapy. Therefore, newer, safe, and more effective treatment modalities are required for patients with advanced or recurrent ovarian cancer. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have shown an impressive safety profile and anti-tumor efficacy in patients with breast cancer 1 and 2 (BRCA1 and BRCA2) gene-mutated ovarian cancer who were previously treated with the standard of care chemotherapy. We have done a detailed review of the literature to emphasize the role of PARP inhibitors in the treatment of advanced or relapsed ovarian cancer.
Gene Modification of Transforming Growth Factor β (TGF-β) and Interleukin 10 (IL-10) in Suppressing Mt Sonicate Induced Osteoclast Formation and Bone Absorption

Background Osteoarticular tuberculosis is an osteolytic lesion caused by Mycobacterium tuberculosis (MTB). Inflammatory factors such as TNF-α play a critical role in anti-tuberculosis immunity by regulating osteoblast and osteoclast functions. Both TGF-β and IL-10 have immune suppression effects to downregulate secretion and release of inflammatory factors, such as TNF-α, that play roles in regulating osteoblast and osteoclast functions. This study thus investigated the effects of osteoclast with modified TGF-β and IL-10 gene expression on MTB-induced osteoclast formation and bone absorption. Material/Methods Bone marrow mononuclear cells were induced to differentiate into osteoblasts and osteoclasts in vitro to generate a co-culture system. MTB powder lysed by ultrasound (Mt sonicate) were added in gradients to observe osteoblast formation and osteoclast absorption. Cell apoptosis was measured by flow cytometry, while ELISA was used assess TNF-α, TGF-β, and IL-10. Viral vectors carrying TGF-β or IL-10 gene were used to transfect osteoclasts, followed by ELISA assay. Bone absorption and osteoblast apoptosis were compared among groups. Results Mt sonicate significantly facilitated osteoclast formation and bone formation. It upregulated contents of TNF-α, TGF-β, and IL-10, induced osteoblast apoptosis, enhanced RANKL expression in osteoblasts, and decreased OPG expression. Overexpression of TGF-β and/or IL-10 significantly decreased its upregulation effect on TNF-α by Mt sonicate, and hindered Mt sonicate-induced osteoblast apoptosis, osteoclast formation, and bone absorption. Conclusions Overexpression of TGF-β and IL-10 significantly inhibits TMB-induced TNF-α synthesis and release, suppresses osteoblast apoptosis, and hinders osteoclast formation and bone absorption.
Reduced Postburn Hypertrophic Scarring and Improved Physical Recovery With Yearlong Administration of Oxandrolone and Propranolol

Background: Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for 1 year restores growth in children with large burns. Here, we investigated whether the combined administration of OxProp for 1 year would reduce scarring and improve quality of life compared with control. Study Design: Children with large burns (n = 480) were enrolled into this institutional review board-approved study; patients were randomized to control (n = 226) or administration of OxProp (n = 126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained. Results: Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (P < 0.05) occurred in OxProp-treated scars. With OxProp, scar severity was attenuated and pliability increased (both P < 0.05). Analyses of patient-reported outcomes showed improved general and emotional health within the OxProp-treated group (P < 0.05). Conclusions: Here, we have shown improvements in objective and subjective measures of scarring and an increase in overall patient-reported physical function. The combined administration of OxProp for up to a year after burn injury should be considered for the reduction of postburn scarring and improvement of long-term psychosocial outcomes in children with massive burns.
Lafora Disease: A Ubiquitination-Related Pathology

Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogen-like (polyglucosan) inclusions, named Lafora bodies (LBs). LD is caused by mutations in the EPM2A gene, encoding the dual phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Laforin and malin form a functional complex that is involved in the regulation of glycogen synthesis. Thus, in the absence of a functional complex glycogen accumulates in LBs. In addition, it has been suggested that the laforin-malin complex participates in alternative physiological pathways, such as intracellular protein degradation, oxidative stress, and the endoplasmic reticulum unfolded protein response. In this work we review the possible cellular functions of laforin and malin with a special focus on their role in the ubiquitination of specific substrates. We also discuss here the pathological consequences of defects in laforin or malin functions, as well as the therapeutic strategies that are being explored for LD.
Lateral lumbar interbody fusion in the elderly: a 10-year experience.

OBJECTIVEElderly patients, often presenting with multiple medical comorbidities, are touted to be at an increased risk of peri- and postoperative complications following spine surgery. Various minimally invasive surgical techniques have been developed and employed to treat an array of spinal conditions while minimizing complications. Lateral lumbar interbody fusion (LLIF) is one such approach. The authors describe clinical outcomes in patients over the age of 70 years following stand-alone LLIF.METHODSA retrospective query of a prospectively maintained database was performed for patients over the age of 70 years who underwent stand-alone LLIF. Patients with posterior segmental fixation and/or fusion were excluded. The preoperative and postoperative values for the Oswestry Disability Index (ODI) were analyzed to compare outcomes after intervention. Femoral neck t-scores were acquired from bone density scans and correlated with the incidence of graft subsidence.RESULTSAmong the study cohort of 55 patients, the median age at the time of surgery was 74 years (range 70-87 years). Seventeen patients had at least 3 medical comorbidities at surgery. Twenty-three patients underwent a 1-level, 14 a 2-level, and 18 patients a 3-level or greater stand-alone lateral fusion. The median estimated blood loss was 25 ml (range 5-280 ml). No statistically significant relationship was detected between volume of blood loss and the number of operative levels. The median length of hospital stay was 2 days (range 1-4 days). No statistically significant relationship was observed between the length of hospital stay and age at the time of surgery. There was one intraoperative death secondary to cardiac arrest, with a mortality rate of 1.8%. One patient developed a transient femoral nerve injury. Five patients with symptomatic graft subsidence subsequently underwent posterior instrumentation. A lower femoral neck t-score < -1.0 correlated with a higher incidence of graft subsidence (p = 0.006). The mean ODI score 1 year postoperatively of 31.1 was significantly (p = 0.003) less than the mean preoperative ODI score of 46.2. CONCLUSIONSStand-alone LLIF can be safely and effectively performed in the elderly population. Careful evaluation of preoperative bone density parameters should be employed to minimize risk of subsidence and need for additional surgery. Despite an association with increased comorbidities, age alone should not be a deterrent when considering stand-alone LLIF in the elderly population.
High-Throughput Approaches onto Uncover (Epi)Genomic Architecture of Type 2 Diabetes

Type 2 diabetes (T2D) is a complex disorder that is caused by a combination of genetic, epigenetic, and environmental factors. High-throughput approaches have opened a new avenue toward a better understanding of the molecular bases of T2D. A genome-wide association studies (GWASs) identified a group of the most common susceptibility genes for T2D (i.e., TCF7L2, PPARG, KCNJ1, HNF1A, PTPN1, and CDKAL1) and illuminated novel disease-causing pathways. Next-generation sequencing (NGS)-based techniques have shed light on rare-coding genetic variants that account for an appreciable fraction of T2D heritability (KCNQ1 and ADRA2A) and population risk of T2D (SLC16A11, TPCN2, PAM, and CCND2). Moreover, single-cell sequencing of human pancreatic islets identified gene signatures that are exclusive to α-cells (GCG, IRX2, and IGFBP2) and β-cells (INS, ADCYAP1, INS-IGF2, and MAFA). Ongoing epigenome-wide association studies (EWASs) have progressively defined links between epigenetic markers and the transcriptional activity of T2D target genes. Differentially methylated regions were found in TCF7L2, THADA, KCNQ1, TXNIP, SOCS3, SREBF1, and KLF14 loci that are related to T2D. Additionally, chromatin state maps in pancreatic islets were provided and several non-coding RNAs (ncRNA) that are key to T2D pathogenesis were identified (i.e., miR-375). The present review summarizes major progress that has been made in mapping the (epi)genomic landscape of T2D within the last few years.
Start a fire, kill the bug: The role of platelets in inflammation and infection

Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation. In this review we summarize the current knowledge about how platelets interact with the innate immune system during inflammation and infection and highlight recent advances in the field.
Site of Metastases as Prognostic Factors in Unselected Population of Stage IV Non-Small Cell Lung Cancer

Background Advanced stage non-small cell lung cancer (NSCLC) is a heterogenous disease, yet, with the exception of targeted therapies, most guidelines recommended uniform treatment irrespective of tumor burden or sites of metastases and this may explain, in part, the wide range of responses to same lines of therapy. Aim of work In this work we tried to explore the effect of metastatic sites in on overall survival (OS), in an unselected group of Non-small cell lung cancer patients who received different treatments line. Methods A retrospective analysis was performed on patients with stage IV NSCLC who received systemic treatment at UAB Cancer Center (NCI designated comprehensive cancer center) between 2002 to 2012. The details of sites of metastases, systemic therapy and overall survival were recorded for each patient. Result In 409 patients who received systemic treatment, there was statistically significant lower OS in those presenting with liver metastases (p<0.001), adrenal metastases (p=0.011) and metastases to abdominal lymph nodes (p=0.014). There was no statistically significance difference in OS in patient presenting with pleural metastases or effusion (p=0.908), metastases to heart or pericardium (p=0.654), metastases to bone (p=0.281), brain (p=0.717) or skin and subcutaneous tissue (p=0.642). Conclusion Intra-abdominal metastases confer a particularly poor prognosis in stage IV NSCLC treated with systemic therapy and may identify patients in whom aggressive treatment beyond first line therapy is not appropriate.
An Atypical Case of Silent Aortic Dissection in a Peritoneal Dialysis Patient: A Case Report and Review of Literature

Patient: Male, 55 Final Diagnosis: Type-A aortic dissection Symptoms: Exertional dyspnea • orthopnea Medication: — Clinical Procedure: Emergent surgical repair with mesh implant Specialty: Cardiology Objective: Unusual clinical course Background: Aortic dissection presents with acute chest or back pain and is associated with high mortality. We present a case of aortic dissection with an atypical presentation in a peritoneal dialysis patient, and the challenges met with peritoneal dialysis. Case Report: A 53-year-old African American male presented with progressively worsening exertional dyspnea and orthopnea for 3 days without any history of chest pain. His chest x-ray showed mild pulmonary edema. He was admitted with a diagnosis of heart failure. Bedside echocardiogram revealed severe aortic regurgitation and concern for possible aortic dissection. Computed tomography of chest with contrast showed Stanford type-A aortic dissection extending from the aortic valve to the level of the left subclavian artery. Emergent surgery was performed. Postoperatively, the patient was managed in surgical and trauma intensive care unit to keep the blood pressure in the desired range. Initially, he was started on continuous veno-venous hemodialysis and later on transitioned to intermittent hemodialysis. He was switched back to peritoneal dialysis after 6 weeks of surgery. Conclusions: Atypical presentation of a silent aortic dissection without chest pain in the setting of renal failure and other comorbidities emphasizes that dialysis patients are different from the general population. Sometimes the management needs to be modified from the conventional ways to achieve the high level of success.
Fallback Variable History NNLMs: Efficient NNLMs by precomputation and stochastic training

This paper presents a new method to reduce the computational cost when using Neural Networks as Language Models, during recognition, in some particular scenarios. It is based on a Neural Network that considers input contexts of different length in order to ease the use of a fallback mechanism together with the precomputation of softmax normalization constants for these inputs. The proposed approach is empirically validated, showing their capability to emulate lower order N-grams with a single Neural Network. A machine translation task shows that the proposed model constitutes a good solution to the normalization cost of the output softmax layer of Neural Networks, for some practical cases, without a significant impact in performance while improving the system speed.
Review of the Content and Quality of Mobile Applications About Alzheimer’s Disease and Related Dementias

This study reviewed the content of mobile applications (apps) providing Alzheimer’s disease or related dementias (ADRD) information and assessed quality of the apps. Characteristics, content, and technical aspects of 36 apps in the U.S. Google Play Store and App Store were coded, and quality of the apps was evaluated using the Mobile Application Rating Scale. Caregiving (62.1%) and disease management (55.6%) content was frequently provided. Few apps had an app community (8.3%) or a reminder function (8.3%). Overall, quality of the apps was acceptable; apps by health care–related developers had higher quality scores than those by non-health care–related developers. This analysis showed that ADRD-related apps provide a range of content and have potential to benefit caregivers, individuals with ADRD, health care providers, and the general public. Collaboration of ADRD experts and technology experts is needed to provide evidence-based information using effective technical functions that make apps to meet users’ needs.
Exploring the features of a collaborative connected classroom

This article considers the various dichotomies between types of mathematical understanding. It concludes that whilst the different categorisation is useful, it is the interplay and connections between these types of understanding that is more beneficial to student learning. Theories are drawn from a wide literature base to consider what this might look like in the secondary mathematics classroom and we propose the Collaborative Connected Classroom Model.