Miracle-dz/UniFAR-FTUs huggingface dataset:
Building a Better Long-Short Equity Portfolio Executive Summary

Long-short equity (“LSE”) is a classic hedge fund strategy that has historically generated higher risk-adjusted returns with lower volatility than equity markets. It has become a core strategy for many institutional portfolios and currently comprises 25% of the HFRI Index. LSE is also quickly becoming established with mutual fund investors. In this paper, we review the track record for LSE, the intuition and sources of returns underlying the strategy, and its potential as part of a diversified portfolio.
Diagnostic Process Using Endoscopy for Biliary Strictures: A Narrative Review

The diagnostic process for biliary strictures remains challenging in some cases. A broad differential diagnosis exists for indeterminate biliary strictures, including benign or malignant lesions. The diagnosis of indeterminate biliary strictures requires a combination of physical examination, laboratory testing, imaging modalities, and endoscopic procedures. Despite the progress of less invasive imaging modalities such as transabdominal ultrasonography, computed tomography, and magnetic resonance imaging, endoscopy plays an essential role in the accurate diagnosis, including the histological diagnosis. Imaging findings and brush cytology and/or forceps biopsy under fluoroscopic guidance with endoscopic retrograde cholangiopancreatography (ERCP) are widely used as the gold standard for the diagnosis of biliary strictures. However, ERCP cannot provide an intraluminal view of the biliary lesion, and its outcomes are not satisfactory. Recently, peroral cholangioscopy, confocal laser endomicroscopy, endoscopic ultrasound (EUS), and EUS-guided fine-needle aspiration have been reported as useful for indeterminate biliary strictures. Appropriate endoscopic modalities need to be selected according to the patient’s condition, the lesion, and the expertise of the endoscopist. The aim of this review article is to discuss the diagnostic process for indeterminate biliary strictures using endoscopy.
GAKTpore: Stereological Characterisation Methods for Porous Foams in Biomedical Applications

In tissue engineering, scaffolds are a key component that possess a highly elaborate pore structure. Careful characterisation of such porous structures enables the prediction of a variety of large-scale biological responses. In this work, a rapid, efficient, and accurate methodology for 2D bulk porous structure analysis is proposed. The algorithm, “GAKTpore”, creates a morphology map allowing quantification and visualisation of spatial feature variation. The software achieves 99.6% and 99.1% mean accuracy for pore diameter and shape factor identification, respectively. There are two main algorithm novelties within this work: (1) feature-dependant homogeneity map; (2) a new waviness function providing insights into the convexity/concavity of pores, important for understanding the influence on cell adhesion and proliferation. The algorithm is applied to foam structures, providing a full characterisation of a 10 mm diameter SEM micrograph (14,784 × 14,915 px) with 190,249 pores in ~9 min and has elucidated new insights into collagen scaffold formation by relating microstructural formation to the bulk formation environment. This novel porosity characterisation algorithm demonstrates its versatility, where accuracy, repeatability, and time are paramount. Thus, GAKTpore offers enormous potential to optimise and enhance scaffolds within tissue engineering.
Hodgkin Lymphoma—Review on Pathogenesis, Diagnosis, Current and Future Treatment Approaches for Adult Patients

Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which HL has turned from an incurable disease to a neoplasm with an excellent prognosis. First-line treatment with stage-adapted treatment consisting of chemotherapy and/or radiotherapy results in cure rates of approximately 80%. Second-line treatment mostly consists of intensive salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Novel approaches such as antibody drug conjugates and immunomodulatory drugs have shown impressive results in clinical trials in refractory and relapsed HL and are now increasingly implemented in earlier treatment lines. This review gives a comprehensive overview on HL addressing epidemiology, pathophysiology and current treatment options as well as recent developments and perspectives.
Long-Term Outcomes of Stereotactic Radiosurgery for Trigeminal, Facial, and Jugular Foramen Schwannoma in Comparison with Vestibular Schwannoma

Simple Summary Intracranial schwannomas are benign intracranial neoplasms. Vestibular schwannomas (VS) account for 90% of intracranial schwannomas; whereas the other cranial nerve schwannomas, such as trigeminal (TS), facial (FS), and jugular foramen schwannoma (JFS), account for 10% of all cases. Stereotactic radiosurgery (SRS) is a minimally invasive treatment for small to medium VS and known to provide excellent long-term tumor control; however, there remains a paucity of evidence regarding SRS for TS, FS, and JFS due to the rarity of these tumors. We investigated the radiosurgical outcomes of these non-vestibular schwannomas and compared them to those of VS through matched cohort analysis. Abstract Stereotactic radiosurgery (SRS) is known to provide excellent tumor control with functional preservation for vestibular schwannomas (VS), but its efficacy in the other major intracranial schwannomas including trigeminal (TS), facial (FS), and jugular foramen schwannomas (JFS) has not been established yet due to their rarity. We retrospectively analyzed data of 514 consecutive patients who had intracranial schwannomas (460 VS, 22 TS, 7 FS, and 25 JFS) and underwent SRS. The 5- and 10-year tumor control rates were 97% and 94% for VS, 100% and 100% for TS, 80% and 80% for FS, and 100% and 80% for JFS. Radiation-induced complications included one hydrocephalus for TS (4.5%), no cases for FS (0%), and one hydrocephalus and one lower palsy for JFS (8.0%). Through matched cohort analysis between patients with VS and each of the non-VS, we found no statistical difference in tumor control and radiation-induced adverse events. SRS seems to provide long-term tumor control with functional preservation for TS, FS and JFS and the efficacies are similar to VS.
Impact of a Mortality Prediction Rule for Organizing and Guiding Antimicrobial Stewardship Program Activities

Abstract Background Antimicrobial stewardship program (ASP) surveillance at our hospital is supplemented by an internally developed surveillance database. In 2013, the database incorporated a validated, internally developed, prediction rule for patient mortality within 30 days of hospital admission. This study describes the impact of an expanded ASP review in patients at the highest risk for mortality. Methods This retrospective, quasi-experimental study analyzed adults who received antimicrobials with the highest mortality risk score. Study periods were defined as 2011–Q3 2013 (historical group) and Q4 2013–2018 (intervention group). Primary and secondary outcomes were assessed for confounders and analyzed using both unadjusted and propensity score weighted analyses. Interrupted time-series analyses also analyzed key outcomes. Results A total of 3282 and 5456 patients were included in the historical and intervention groups, respectively. There were significant reductions in median antimicrobial duration (5 vs 4 days; P < .001), antimicrobial days of therapy (8 vs 7; P < .001), antimicrobial cost ($96 vs $85; P = .003), length of stay (LOS) (6 vs 5 days; P < .001), intensive care unit (ICU) LOS (3 vs 2 days; P < .001), total hospital cost ($10 946 vs $9119; P < .001), healthcare facility-onset vancomycin-resistant Enterococcus (HO-VRE) incidence (1.3% vs 0.3%; P ≤ .001), and HO-VRE infections (0.6% vs 0.2%; P = .018) in the intervention cohort. Conclusions Reductions in antimicrobial use, hospital and ICU LOS, HO-VRE, HO-VRE infections, and costs were associated with incorporation of a novel mortality prediction rule to guide ASP surveillance and intervention.
Persistent Uncontrolled Asthma: Long-Term Impact on Physical Activity and Body Composition

Rationale Asthma, obesity and physical activity (PA) are interrelated. However, longitudinal data with objective PA measures and direct assessment of body composition are still lacking. Objective To study the impact of symptom control on PA and body composition. Methods In a longitudinal cohort study of the German Center for Lung Research, we assessed the body composition of 233 asthma patients and 84 healthy controls using bioelectrical impedance analysis. PA (ie average daily steps and time of at least moderate activity, steps/min) was measured by accelerometry for one week. Asthma control was assessed by ACT score, ACQ-5 score and history of severe exacerbations. After two years of follow-up, we studied changes in physical activity and body composition in relation to asthma control. Results Patients with uncontrolled asthma had increased fat mass and decreased muscle mass compared to patients with controlled asthma or healthy controls. Both fat mass and muscle mass correlated better with asthma control than the body mass index (BMI). In multivariate regressions adjusted for age and sex, asthma control and physical activity were independent predictors of body composition (R2 = 0.61, p < 0.001). Persistent uncontrolled asthma patients (n=64) had lower physical activity at both baseline (6614 steps/118 min) and follow-up (6195/115). Despite having stable BMI, they also had significant muscle loss (−1.2%, −0.88 kg, p<0.01) and fat accumulation (+1%, +1.1 kg, p<0.01). By contrast, temporarily uncontrolled or controlled asthma patients had higher physical activity at baseline (8670/156) and follow -up (9058/153) with almost unchanged body composition. Conclusion Persistent uncontrolled asthma is associated with sustained physical inactivity and adverse changes in body composition that might be overlooked by relying solely on BMI. Physical activity is an independent predictor of body composition and reliable long-term marker of symptom control.
The Role of circRNAs in Human Papillomavirus (HPV)-Associated Cancers

Simple Summary Circular RNAs (circRNAs), a new class of non-coding RNAs, are aberrantly expressed in several cancer types. It has been shown that circRNAs are involved in tumorigenesis and cancer progression, as well as in drug resistance. Some circRNAs are useful markers of diagnosis and prognosis. In this review, we examined the role of circRNAs in HPV-associated cancers, highlighting their importance as biomarkers in the diagnosis, prognosis, and therapy of anogenital and oropharyngeal and oral cancers. Abstract Circular RNAs (circRNAs) are a new class of “non-coding RNAs” that originate from non-sequential back-splicing of exons and/or introns of precursor messenger RNAs (pre-mRNAs). These molecules are generally produced at low levels in a cell-type-specific manner in mammalian tissues, but due to their circular conformation they are unaffected by the cell mRNA decay machinery. circRNAs can sponge multiple microRNAs or RNA-binding proteins and play a crucial role in the regulation of gene expression and protein translation. Many circRNAs have been shown to be aberrantly expressed in several cancer types, and to sustain specific oncogenic processes. Particularly, in virus-associated malignancies such as human papillomavirus (HPV)-associated anogenital carcinoma and oropharyngeal and oral cancers, circRNAs have been shown to be involved in tumorigenesis and cancer progression, as well as in drug resistance, and some are useful diagnostic and prognostic markers. HPV-derived circRNAs, encompassing the HPV E7 oncogene, have been shown to be expressed and to serve as transcript for synthesis of the E7 oncoprotein, thus reinforcing the virus oncogenic activity in HPV-associated cancers. In this review, we summarize research advances in the biogenesis of cell and viral circRNAs, their features and functions in the pathophysiology of HPV-associated tumors, and their importance as diagnostic, prognostic, and therapeutic targets in anogenital and oropharyngeal and oral cancers.
The Roadmap of Colorectal Cancer Screening

Simple Summary Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. Fecal occult blood test screening reduces incidence and mortality. However, the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of CRC screening globally and the most recent approaches aimed at improving accuracy and participation in CRC screening, while also considering the need for gender and age differentiation. New fecal tests and markers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel markers, such as circulating mRNA, micro-RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods or arrays and sequencing assays that identify candidate biomarkers in blood samples. Abstract Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.
Self-Sensing Well Cement

Chemical reactions with reservoir fluids and geology related in-situ stress changes may cause damages to cement sealing material in plugged and abandoned oil, gas and CO2 wells. To avoid leakages, a legitimate monitoring technique is needed that could allow for early warning in case such damages occur. In this paper, we test the utility of oil and gas well cement with a conductive filler in sensing stress changes. To this end, we have measured the resistance response of Portland G—oil and gas well cement with carbon nanofibers (CNF) to axial load during uniaxial compressive strength test. Simultaneously, the microseismicity data were collected. The resistance of the nanocomposite was measured using two-point method in the direction of loading. The resistance changes were correlated with acoustic emission events. A total of four different material response regions were distinguished and the resistivity and acoustic emission changes in these regions were described. Our results suggest that the two complementary methods, i.e., acoustic emission and resistance measurements, can be used for sensing stress state in materials including well cement/CNF composites. The results suggest that the well cement/CNF composites can be a good candidate material to be used as a transducer sensing changes in stress state in, e.g., well plugs up to material failure.
A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market

In vitro pharmacokinetic studies were conducted on enantiomer pairs of twelve valinate or tert-leucinate indole and indazole-3-carboxamide synthetic cannabinoid receptor agonists (SCRAs) detected on the illicit drug market to investigate their physicochemical parameters and structure-metabolism relationships (SMRs). Experimentally derived Log D7.4 ranged from 2.81 (AB-FUBINACA) to 4.95 (MDMB-4en-PINACA) and all SCRAs tested were highly protein bound, ranging from 88.9 ± 0.49% ((R)-4F-MDMB-BINACA) to 99.5 ± 0.08% ((S)-MDMB-FUBINACA). Most tested SCRAs were cleared rapidly in vitro in pooled human liver microsomes (pHLM) and pooled cryopreserved human hepatocytes (pHHeps). Intrinsic clearance (CLint) ranged from 13.7 ± 4.06 ((R)-AB-FUBINACA) to 2944 ± 95.9 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHLM, and from 110 ± 34.5 ((S)-AB-FUBINACA) to 3216 ± 607 mL min−1 kg−1 ((S)-AMB-FUBINACA) in pHHeps. Predicted Human in vivo hepatic clearance (CLH) ranged from 0.34 ± 0.09 ((S)-AB-FUBINACA) to 17.79 ± 0.20 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHLM and 1.39 ± 0.27 ((S)-MDMB-FUBINACA) to 18.25 ± 0.12 mL min−1 kg−1 ((S)-5F-AMB-PINACA) in pHHeps. Valinate and tert-leucinate indole and indazole-3-carboxamide SCRAs are often rapidly metabolised in vitro but are highly protein bound in vivo and therefore predicted in vivo CLH is much slower than CLint. This is likely to give rise to longer detection windows of these substances and their metabolites in urine, possibly as a result of accumulation of parent drug in lipid-rich tissues, with redistribution into the circulatory system and subsequent metabolism.
A New Hybrid Sensitive PANI/SWCNT/Ferrocene-Based Layer for a Wearable CO Sensor

Developing a sensing layer with high electroactive properties is an important aspect for proper functionality of a wearable sensor. The polymeric nanocomposite material obtained by a simple electropolymerization on gold interdigitated electrodes (IDEs) can be optimized to have suitable conductive properties to be used with direct current (DC) measurements. A new layer based on polyaniline:poly(4-styrenesulfonate) (PANI:PSS)/single-walled carbon nanotubes (SWCNT)/ferrocene (Fc) was electrosynthesized and deposed on interdigital transducers (IDT) and was characterized in detail using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoemission spectroscopy (XPS), and X-ray diffraction (XRD). The sensor characteristics of the material towards carbon monoxide (CO) in the concentration range of 10–300 ppm were examined, showing a minimal relative humidity interference of only 1% and an increase of sensitivity with the increase of CO concentration. Humidity interference could be controlled by the number of CV cycles when a compact layer was formed and the addition of Fc played an important role in the decrease of humidity. The results for CO detection can be substantially improved by optimizing the number of deposition cycles and enhancing the Fc concentration. The material was developed for selective detection of CO in real environmental conditions and shows good potential for use in a wearable sensor.
Specialized Pro-Resolving Mediators and the Lymphatic System

Diminished lymphatic function and abnormal morphology are common in chronic inflammatory diseases. Recent studies are investigating whether it is possible to target chronic inflammation by promoting resolution of inflammation, in order to enhance lymphatic function and attenuate disease. Resolution of inflammation is an active process regulated by bioactive lipids known as specialized pro-resolving mediators (SPMs). SPMs can modulate leukocyte migration and function, alter cytokine/chemokine release, modify autophagy, among other immune-related activities. Here, we summarize the role of the lymphatics in resolution of inflammation and lymphatic impairment in chronic inflammatory diseases. Furthermore, we discuss the current literature describing the connection between SPMs and the lymphatics, and the possibility of targeting the lymphatics with innovative SPM therapy to promote resolution of inflammation and mitigate disease.
Baseline Hedgehog Pathway Activation and Increase of Plasma Wnt1 Protein Are Associated with Resistance to Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer

Simple Summary Wnt and Hedgehog (Hh) pathways are associated with stemness profile and with resistance to anti-tumor therapies. Pre-clinical data have suggested a role of these pathways in resistance to immune checkpoint inhibitors (ICIs). Here we evaluated the expression and levels of Shh and Wnt molecules both in plasma and tumor samples in a prospective cohort of 63 consecutive NSCLC patients treated with ICIs. We found that baseline Hh activation as assessed by nuclear staining of Gli1 was associated with poor outcome and high primary resistance rate. Increase of plasma Wnt1 during treatment was associated with resistance to ICIs. This is the first study to our knowledge to find an association between the Hh and Wnt pathways and resistance to ICIs in advanced NSCLC patients. We believe that these results are important to understand the molecular mechanisms associated with resistance to ICIs, and ultimately to improve future treatment strategies. Abstract Hedgehog (Hh) and Wingless-type (Wnt) pathways are associated with resistance to immune checkpoint inhibitors (ICIs) in preclinical studies. This study aimed to assess the association between expression and activation levels of Wnt and Sonic Hedgehog (Shh) pathways and resistance to ICIs in advanced NSCLC patients treated with ICI. Hh and Wnt pathways activation was assessed by immunohistochemistry (Gli1 and beta-catenin) on corresponding tumor tissues, and by plasma concentrations of Shh and Wnt (Wnt1, Wnt2 and Wnt3) at ICI introduction and at the first clinical evaluation. Sixty-three patients were included, with 36 patients (57.1%) with available tissue. Response rate was lower in Gli1+ NSCLC (20.0%) compared to Gli1 negative (Gli-) NSCLC (55.6%) (p = 0.015). Rate of primary resistance was 69.8%, vs. 31.2%, respectively (p = 0.04), and median progression-free survival (PFS) was 1.9 months (interquartile range (IQR) 1.2–5.7) vs. 6.1 months (1.6–26.0), respectively (p = 0.08). Median PFS and overall survival were shorter in case of increase of Wnt1 concentration during ICI treatment compared to other patients: 3.9 months vs. 11.2 months (p = 0.008), and 15.3 months vs. not reached (p = 0.003). In conclusion, baseline activation of Hh pathway and increase of Wnt1 concentrations during ICI treatment were associated with poor outcome in NSCLC patients treated with ICIs.