bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing for Alpha in Linear Factor Pricing Models with a Large Number of Securities
Authors: Pesaran M Hashem , Yamagata Takashi
Published: February 2023

This article considers tests of alpha in linear factor pricing models when the number of securities, N, is much larger than the time dimension, T, of the individual return series. We focus on class of tests that are based on Student’s t-tests of individual securities which have a number of advantages over the existing standardized Wald type tests, and propose a test procedure that allows for non-Gaussianity and general forms of weakly cross-correlated errors. It does not require estimation of an invertible error covariance matrix, it is much faster to implement, and is valid even if N is much larger than T. We also show that the proposed test can account for some limited degree of pricing errors allowed under Ross’s arbitrage pricing theory condition. Monte Carlo evidence shows that the proposed test performs remarkably well even when T = 60 and N = 5000. The test is applied to monthly returns on securities in the S&P 500 at the end of each month in real time, using rolling windows of size 60. Statistically significant evidence against Sharpe–Lintner capital asset pricing model and Fama–French three and five factor models are found mainly during the period of Great Recession (2007M12–2009M06).
Preexisting evidence and outcome of phase III trials in gastrointestinal oncology: a systematic review
Authors: Bregni Giacomo , Trevisi Elena , Saúde Conde Rita , Vanhooren Michele , Akin Telli Tugba , Assaf Irene , Hendlisz Alain , Di Maio Massimo , Sclafani Francesco
Published: February 2023

Background

A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of preexisting evidence.

Methods

EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastroesophageal, hepatocellular, biliary tract, pancreatic, small bowel, colorectal, anal, stromal, and neuroendocrine) between January 2000 and June 2020. Trials investigating anticancer drugs for advanced disease, with superiority design and standard treatments as control were eligible. The highest level of preexisting evidence was retrieved from the main study report.

Results

A total of 193 phase III trials were included, and 69 (35.8%) met their primary endpoint. Positivity rates were as follows: gastroesophageal 37%, colorectal 48%, pancreatic 17.1%, hepatocellular 20%, neuroendocrine 75%, and both biliary tract and GIST 60%. No information about preexisting evidence was found for 44 trials (22.8%). For the remaining 149, preexisting evidence consisted of phase II studies in 123 cases (82.6%) and phase I studies in 26 cases (17.4%). The probability of success was 34.1%, 35.8%, and 35.7%, respectively (P = .934). No parameter from prior studies predicted the outcome of phase III trials except β < .2 (P = .048). A numerically increased success rate was observed for phase III trials preceded by positive phase II studies (41.9% vs 18.5%, P = .2).

Conclusions

There does not appear to be an association between level of prior evidence and success of phase III gastrointestinal cancer trials. These data, along with the high phase III failure rate, highlight the need to improve the drug development process in this setting.
Which lottery numbers do players play?
Authors: Hanley James , Cronin Michael
Published: February 2023

The Irish national lottery went through 62 rollovers during 2021 and 2022 before a winner finally claimed the top prize. James Hanley and Michael Cronin use data from four continents to examine what lies behind lottery droughts, and estimate the most, and least, popular numbers being picked
Does it pay to park in front of a fire hydrant?
Authors: Andrade Chris , Auerbach Jonathan , Bacelar Icaro , Lee Hane , Tan Angela , Vazquez Mariana , Ward Owen
Published: February 2023

You’re a New York motorist, running horribly late, and there’s an empty space beckoning right outside your destination. Problem is, it’s in front of a fire hydrant. Should you risk getting a ticket? Take some advice from Chris Andrade, Jonathan Auerbach, Icaro Bacelar, Hane Lee, Angela Tan, Mariana Vazquez, and Owen Ward
Why your data viz needs alt text
Authors: Green Nathan
Published: February 2023

Readers who are blind or visually impaired can miss out on important content if it’s in the form of a plot or diagrams. Nathan Green talks to Mine Dogucu, lecturer in statistics at UCL and co-author of an open access book, on how straightforward it has become to ensure nobody misses out on your data-based story
Morphoanatomy, Histochemistry, and Phytochemistry of Stem and Leaves ofCrateva tapiaL.
Authors: Magalhães Cledson dos Santos , da Silva Flávia Carolina Lins , Randau Karina Perrelli
Published: February 2023

Crateva tapia L. occurs only in Brazil and belongs to the family Capparaceae. This study aimed to characterize the morphoanatomy and histochemistry of stem and leaves, and phytochemical tests of the leaf of C. tapia. Macroscopic characterization was performed with the aid of a pachymeter and a stereomicroscope. Cross-sections of the stem, petiole, petiolule, and leaf blade, as well as paradermal sections of the leaf blade were mounted on microscope slides. Analyzes were carried out with optical microscopy. For histochemical analysis, different reagents were useda ccording to the targeted metabolite. Phytochemical tests of the methanolic extracts of the leaves were performed using thin layer chromatography. Crateva tapia has a stem with a circular cross-section and smooth bark. The leaves are alternate spirally, compound 3-foliolate. The leaf blade is elliptical and has a reticulate dictiodromous nerve. Through anatomical characterization, it was possible to identify a hypostomatic leaf blade with anisocytic, tetracytic, and anomocytic stomata and the presence of secretory canals. Through histochemistry and phytochemical tests, it was possible to observe the presence of different metabolites. Thus, the results obtained in this study contribute to the quality control of C. tapia, a species only found in Brazil, increasing the taxonomic knowledge of the family Capparaceae.
Three-Dimensional Ultrastructural and Volume Analysis of the Redundant Nuclear Envelope of Developing and Matured Sperm in Mice
Authors: Uemura Kei-ichiro , Miyazono Yoshihiro , Hiroshige Tasuku , Ohta Keisuke , Ueda Kosuke , Nishihara Kiyoaki , Nakiri Makoto , Hirashima Shingo , Igawa Tsukasa , Nakamura Kei-ichiro
Published: February 2023

The ultrastructure of the nuclear envelope (NE) and redundant NE (RNE) of the spermatozoon cannot be observed in detail using conventional electron microscopy. Thus, this study aimed to employ transmission electron microscopy (TEM) and focused ion beam/scanning electron microscopy (FIB/SEM) tomography to fill this research gap. Male mice aged 13 weeks were deeply anesthetized, and the testes and vas deferens were extracted and processed for electron microscopy. In round spermatids, the acrosomal vesicle compressed the nucleus, and the acrosomal center was depressed. The nucleoli concentrated on the contralateral side of the acrosome formation site. In mature spermatozoa, the RNE accumulated in the neck with the residual bodies. The NE pores exhibited a hexagonal pattern. The body surface area and volume of the nuclei of spermatids and spermatozoa in each maturation phase were analyzed using FIB/SEM tomography. The body surface area and volume of the nuclei decreased during spermatid maturation into spermatozoa. The RNE converged at the sperm neck and possessed a honeycomb structure. The method used revealed that the nuclei of spermatids gradually condense as they mature into spermatozoa. This method may be used to analyze small tissues, such as RNE, and detect morphological abnormalities in microtissues, such as spermatozoa.
A Multidisciplinary Approach to Improvements in Perioperative Antibiotic Prophylaxis at a Military Treatment Facility
Authors: Baker Amelia L , McElrath Angela , Giancola Stephanie E , Schumaker Annabel L , Barsoumian Alice E
Published: February 2023

Introduction

Surgical site infections complicate 2%-5% of surgeries. According to the Centers for Disease Control and Prevention, half of all surgical site infections are preventable. Adherence to published recommendations regarding perioperative antibiotic administration decreases the incidence of surgical site infections. Members of the Department of Anesthesia noticed casual observations of inaccurate prescribing of antibiotics at our institution, Brooke Army Medical Center, and approached the Antimicrobial Stewardship Program to collaborate on this issue.

Materials and Methods

A team of anesthesiologists, clinical pharmacists, and infectious disease specialists collaborated with the Department of Surgery to improve this effort as part of a multiyear project from 2018 to 2021. We first assessed adherence to recommended perioperative antibiotic use to establish a baseline and next, noticing gaps, created a project with the goal to improve compliance to >90% across surveyed measures. Our key interventions included educational initiatives, creation of facility-specific guidelines, peer benchmarking, updating order sets, interdisciplinary collaboration, creation of intraoperative reminders and visual aids, and tailored presentations to selected services.

Results

Of 292 charts (2.3% of cases from January to October 2018) reviewed pre-intervention, compliance rates were 84% for antibiotic choice, 92% for dose, 65% for redosing, and 71% for postoperative administration. Of doses, 100% were timed correctly, and thus, this variable was not targeted. Post-intervention, our review of 387 charts (10% of cases from May to November 2020) showed no change in correct antibiotic choice (84%) and statistical improvement to 96% for correct dose, 95% for correct redosing, and 85% for correct postoperative administration (P < .05 for all).

Conclusions

Our multidisciplinary approach of collaboration with multiple departments, creating guidelines and providing feedback, improved compliance with perioperative antibiotic administration recommendations.
Automated classification of Chandra X-ray point sources using machine learning methods
Authors: Kumaran Shivam , Mandal Samir , Bhattacharyya Sudip , Mishra Deepak
Published: February 2023

A large number of unidentified sources found by astronomical surveys and other observations necessitate the use of an automated classification technique based on machine learning (ML) methods. The aim of this paper is to find a suitable automated classifier to identify the point X-ray sources in the Chandra Source Catalogue (CSC) 2.0 in the categories of active galactic nuclei (AGN), X-ray emitting stars, young stellar objects (YSOs), high-mass X-ray binaries (HMXBs), low-mass X-ray binaries (LMXBs), ultra luminous X-ray sources (ULXs), cataclysmic variables (CVs), and pulsars. The catalogue consists of ≈317 000 sources, out of which we select 277 069 point sources based on the quality flags available in CSC 2.0. In order to identify unknown sources of CSC 2.0, we use MW features, such as magnitudes in optical/ultraviolet bands from Gaia-EDR3, Sloan Digital Sky Survey, and GALEX, and magnitudes in infrared bands from 2MASS, WISE, and MIPS-Spitzer, in addition to X-ray features (flux and variability) from CSC 2.0. We find the Light Gradient Boosted Machine, an advanced decision tree-based ML classification algorithm, suitable for our purpose and achieve 93  per  cent precision, 93  per  cent recall score, and 0.91 Mathew’s Correlation coefficient score. With the trained classifier, we identified 54 770 (14 066) sources with more than 3σ (4σ) confidence, out of which there are 32 600 (8574) AGNs, 16,148 (5,166) stars, 5,184 (208) YSOs, 439 (46) HMXBs, 197 (71) LMXBs, 50 (0) ULXs, 89 (1) CVs, and 63 (0) pulsars. This method can also be useful for identifying sources of other catalogues reliably.
Pulsar scintillation studies with LOFAR: II. Dual-frequency scattering study of PSR J0826+2637 with LOFAR and NenuFAR
Authors: Wu Ziwei , Coles William A , Verbiest Joris P W , Ambalappat Krishnakumar Moochickal , Tiburzi Caterina , Grießmeier Jean-Mathias , Main Robert A , Liu Yulan , Kramer Michael , Wucknitz Olaf , Porayko Nataliya , Osłowski Stefan , Nielsen Ann-Sofie Bak , Donner Julian Y , Hoeft Matthias , Brüggen Marcus , Vocks Christian , Dettmar Ralf-Jürgen , Theureau Gilles , Serylak Maciej , Kondratiev Vladislav , McKee James W , Shaifullah Golam M , Kravtsov Ihor P , Zakharenko Vyacheslav V , Ulyanov Oleg , Konovalenko Olexandr O , Zarka Philippe , Cecconi Baptiste , Koopmans Léon V E , Corbel Stéphane
Published: February 2023

Interstellar scattering (ISS) of radio pulsar emission can be used as a probe of the ionized interstellar medium (IISM) and causes corruptions in pulsar timing experiments. Two types of ISS phenomena (intensity scintillation and pulse broadening) are caused by electron density fluctuations on small scales (< 0.01 au). Theory predicts that these are related, and both have been widely employed to study the properties of the IISM. Larger scales (∼1 – 100 au) cause measurable changes in dispersion and these can be correlated with ISS observations to estimate the fluctuation spectrum over a very wide scale range. IISM measurements can often be modelled by a homogeneous power-law spatial spectrum of electron density with the Kolmogorov (−11/3) spectral exponent. Here, we aim to test the validity of using the Kolmogorov exponent with PSR J0826+2637. We do so using observations of intensity scintillation, pulse broadening and dispersion variations across a wide fractional bandwidth (20–180 MHz). We present that the frequency dependence of the intensity scintillation in the high-frequency band matches the expectations of a Kolmogorov spectral exponent, but the pulse broadening in the low-frequency band does not change as rapidly as predicted with this assumption. We show that this behaviour is due to an inhomogeneity in the scattering region, specifically that the scattering is dominated by a region of transverse size ∼40 au. The power spectrum of the electron density, however, maintains the Kolmogorov spectral exponent from spatial scales of 5 × 10−6 au to ∼100 au.
Using X-ray continuum-fitting to estimate the spin of MAXI J1305–704
Authors: Feng Ye , Steiner James F , Ramirez Santiago Ubach , Gou Lijun
Published: February 2023

MAXI J1305–704 is a transient X-ray binary with a black hole primary. It was discovered on 2012 April 9, during its only known outburst. MAXI J1305–704 is also a high inclination low-mass X-ray binary with prominent dip features in its light curves, so we check the full catalogue of 92 Swift/XRT continuous observations of MAXI J1305–704, focusing only on the stable spectra. We select 13 ‘gold’ spectra for which the rms <0.075 and the coronal scattered fraction $f_{\mathrm{sc}} \lesssim 25$ per cent. These ‘gold’ data are optimal thermal-state observations for continuum-fitting modelling, in which the disc extends to the innermost stable circular orbit and is geometrically thin. The black hole spin was unknown for this object before. By utilizing the X-ray continuum fitting method with the relativistic thin disc model kerrbb2 and supplying the known dynamical binary system parameters, we find MAXI J1305–704 has a moderate spin ($a_{*}=0.87_{-0.13}^{+0.07}$) at a 68.3 per cent confidence level. This is the first determination of MAXI J1305–704’s spin.
Strand specificity of ribonucleotide excision repair inEscherichia coli
Authors: Łazowski Krystian , Faraz Mahmood , Vaisman Alexandra , Ashton Nicholas W , Jonczyk Piotr , Fijalkowska Iwona J , Clausen Anders R , Woodgate Roger , Makiela-Dzbenska Karolina
Published: February 2023

In Escherichia coli, replication of both strands of genomic DNA is carried out by a single replicase—DNA polymerase III holoenzyme (pol III HE). However, in certain genetic backgrounds, the low-fidelity TLS polymerase, DNA polymerase V (pol V) gains access to undamaged genomic DNA where it promotes elevated levels of spontaneous mutagenesis preferentially on the lagging strand. We employed active site mutants of pol III (pol IIIα_S759N) and pol V (pol V_Y11A) to analyze ribonucleotide incorporation and removal from the E. coli chromosome on a genome-wide scale under conditions of normal replication, as well as SOS induction. Using a variety of methods tuned to the specific properties of these polymerases (analysis of lacI mutational spectra, lacZ reversion assay, HydEn-seq, alkaline gel electrophoresis), we present evidence that repair of ribonucleotides from both DNA strands in E. coli is unequal. While RNase HII plays a primary role in leading-strand Ribonucleotide Excision Repair (RER), the lagging strand is subject to other repair systems (RNase HI and under conditions of SOS activation also Nucleotide Excision Repair). Importantly, we suggest that RNase HI activity can also influence the repair of single ribonucleotides incorporated by the replicase pol III HE into the lagging strand.
Transcriptional pause extension benefits the stand-by rather than catch-up Rho-dependent termination
Authors: Song Eunho , Hwang Seungha , Munasingha Palinda Ruvan , Seo Yeon-Soo , Kang Jin Young , Kang Changwon , Hohng Sungchul
Published: February 2023

Transcriptional pause is essential for all types of termination. In this single-molecule study on bacterial Rho factor-dependent terminators, we confirm that the three Rho-dependent termination routes operate compatibly together in a single terminator, and discover that their termination efficiencies depend on the terminational pauses in unexpected ways. Evidently, the most abundant route is that Rho binds nascent RNA first and catches up with paused RNA polymerase (RNAP) and this catch-up Rho mediates simultaneous releases of transcript RNA and template DNA from RNAP. The fastest route is that the catch-up Rho effects RNA-only release and leads to 1D recycling of RNAP on DNA. The slowest route is that the RNAP-prebound stand-by Rho facilitates only the simultaneous rather than sequential releases. Among the three routes, only the stand-by Rho's termination efficiency positively correlates with pause duration, contrary to a long-standing speculation, invariably in the absence or presence of NusA/NusG factors, competitor RNAs or a crowding agent. Accordingly, the essential terminational pause does not need to be long for the catch-up Rho's terminations, and long pauses benefit only the stand-by Rho's terminations. Furthermore, the Rho-dependent termination of mgtA and ribB riboswitches is controlled mainly by modulation of the stand-by rather than catch-up termination.
The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase
Authors: Rinaldi Carlo , Pizzul Paolo , Casari Erika , Mangiagalli Marco , Tisi Renata , Longhese Maria Pia
Published: February 2023

DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). NHEJ is induced by the binding to DSBs of the Ku70–Ku80 heterodimer, which acts as a hub for the recruitment of downstream NHEJ components. An important issue in DSB repair is the maintenance of the DSB ends in close proximity, a function that in yeast involves the MRX complex and Sae2. Here, we provide evidence that Ku contributes to keep the DNA ends tethered to each other. The ku70-C85Y mutation, which increases Ku affinity for DNA and its persistence very close to the DSB ends, enhances DSB end-tethering and suppresses the end-tethering defect of sae2Δ cells. Impairing histone removal around DSBs either by eliminating Tel1 kinase activity or nucleosome remodelers enhances Ku persistence at DSBs and DSB bridging, suggesting that Tel1 antagonizes the Ku function in supporting end-tethering by promoting nucleosome removal and possibly Ku sliding inwards. As Ku provides a block to DSB resection, this Tel1 function can be important to regulate the mode by which DSBs are repaired.
Mousepost 2.0, a major expansion of the resource
Authors: Timmermans Steven , Vandewalle Jolien , Libert Claude
Published: February 2023

The Mousepost 1.0 online search tool, launched in 2017, allowed to search for variations in all protein-coding gene sequences of 36 sequenced mouse inbred strains, compared to the reference strain C57BL/6J, which could be linked to strain-specific phenotypes and modifier effects. Because recently these genome sequences have been significantly updated and sequences of 16 extra strains added by the Mouse Genomes Project, a profound update, correction and expansion of the Mousepost 1.0 database has been performed and is reported here. Moreover, we have added a new class of protein disturbing sequence polymorphisms (besides stop codon losses, stop codon gains, small insertions and deletions, and missense mutations), namely start codon mutations. The current version, Mousepost 2.0 (https://mousepost.be), therefore is a significantly updated and invaluable tool available to the community and is described here and foreseen by multiple examples.
Nutritional interventions for the prevention and treatment of cancer therapy-induced oral mucositis: an umbrella review of systematic reviews and meta-analysis
Authors: Amiri Khosroshahi Reza , Talebi Sepide , Zeraattalab-Motlagh Sheida , Imani Hossein , Rashidi Amirabbas , Travica Nikolaj , Mohammadi Hamed
Published: February 2023

Context

To date, the efficacy of nutritional interventions on oral mucositis (OM) in patients with cancer, and the quality of this evidence have not been explored.

Objective

The goal of this umbrella review was to provide a comprehensive evaluation of nutritional interventions for patients with cancer with OM, as well as to assess the quality of this evidence.

Data sources

Meta-analyses were searched for using PubMed, Scopus, and ISI Web of Science databases until December 2021, with no time restrictions.

Data extraction

Meta-analyses of randomized control trials that evaluated the effects of nutritional interventions on the incidence of OM in patients with cancer had inclusion criteria for this umbrella review. Data extraction, quality assessment of meta-analyses, and primary studies were done independently by 2 authors. The Grading of Recommendations Assessment, Development, and Evaluation technique was used to grade the certainty of evidence.

Data analysis

A total of 26 meta-analyses were included in this umbrella review. The results showed that honey, glutamine, and propolis can reduce the incidence of severe OM, based on moderate evidence quality. In addition, zinc supplementation significantly reduced the incidence of OM, regardless of symptom severity; however, low certainty of the evidence was observed. The effects of vitamin E, curcumin, and probiotics on OM were not statistically significant.

Conclusion

This umbrella review shows that honey, glutamine, and propolis can significantly reduce the incidence of severe OM. These findings need to be confirmed with well-designed, longitudinal randomized controlled trials.

Systematic Review Registration

PROSPERO registration no. CRD42022301010.
SCARECROW-like GRAS protein PES positively regulates petunia floral scent production
Authors: Shor Ekaterina , Ravid Jasmin , Sharon Elad , Skaliter Oded , Masci Tania , Vainstein Alexander
Published: February 2023

Emission of scent volatiles by flowers is important for successful pollination and consequently, reproduction. Petunia (Petunia hybrida) floral scent is formed mainly by volatile products of the phenylpropanoid pathway. We identified and characterized a regulator of petunia scent production: the GRAS protein PHENYLPROPANOID EMISSION-REGULATING SCARECROW-LIKE (PES). Its expression increased in petals during bud development and was highest in open flowers. Overexpression of PES increased the production of floral volatiles, while its suppression resulted in scent reduction. We showed that PES upregulates the expression of genes encoding enzymes of the phenylpropanoid and shikimate pathways in petals, and of the core regulator of volatile biosynthesis ODORANT1 by activating its promoter. PES is an ortholog of Arabidopsis (Arabidopsis thaliana) PHYTOCHROME A SIGNAL TRANSDUCTION 1, involved in physiological responses to far-red (FR) light. Analyses of the effect of nonphotosynthetic irradiation (low-intensity FR light) on petunia floral volatiles revealed FR light as a scent-activating factor. While PHYTOCHROME A regulated scent-related gene expression and floral scent production under FR light, the influence of PES on volatile production was not limited by FR light conditions.
Tetratricopeptide repeat protein SlREC2 positively regulates cold tolerance in tomato
Authors: Zhang Ying , Peng Yinxia , Liu Juan , Yan Jiarong , Zhu Kangyou , Sun Xin , Bu Xin , Wang Xiujie , Ahammed Golam Jalal , Liu Yufeng , Sun Zhouping , Qi Mingfang , Wang Feng , Li Tianlai
Published: February 2023

Cold stress is a key environmental constraint that dramatically affects the growth, productivity, and quality of tomato (Solanum lycopersicum); however, the underlying molecular mechanisms of cold tolerance remain poorly understood. In this study, we identified REDUCED CHLOROPLAST COVERAGE 2 (SlREC2) encoding a tetratricopeptide repeat protein that positively regulates tomato cold tolerance. Disruption of SlREC2 largely reduced abscisic acid (ABA) levels, photoprotection, and the expression of C-REPEAT BINDING FACTOR (CBF)-pathway genes in tomato plants under cold stress. ABA deficiency in the notabilis (not) mutant, which carries a mutation in 9-CIS-EPOXYCAROTENOID DIOXYGENASE 1 (SlNCED1), strongly inhibited the cold tolerance of SlREC2-silenced plants and empty vector control plants and resulted in a similar phenotype. In addition, foliar application of ABA rescued the cold tolerance of SlREC2-silenced plants, which confirms that SlNCED1-mediated ABA accumulation is required for SlREC2-regulated cold tolerance. Strikingly, SlREC2 physically interacted with β-RING CAROTENE HYDROXYLASE 1b (SlBCH1b), a key regulatory enzyme in the xanthophyll cycle. Disruption of SlBCH1b severely impaired photoprotection, ABA accumulation, and CBF-pathway gene expression in tomato plants under cold stress. Taken together, this study reveals that SlREC2 interacts with SlBCH1b to enhance cold tolerance in tomato via integration of SlNCED1-mediated ABA accumulation, photoprotection, and the CBF-pathway, thus providing further genetic knowledge for breeding cold-resistant tomato varieties.
Computational models of dopamine release measured by fast scan cyclic voltammetry in vivo
Authors: Shashaank N , Somayaji Mahalakshmi , Miotto Mattia , Mosharov Eugene V , Makowicz Emily A , Knowles David A , Ruocco Giancarlo , Sulzer David L
Published: February 2023

Dopamine neurotransmission in the striatum is central to many normal and disease functions. Ventral midbrain dopamine neurons exhibit ongoing tonic firing that produces low extrasynaptic levels of dopamine below the detection of conventional extrasynaptic cyclic voltammetry (∼10–20 nanomolar), with superimposed bursts that can saturate the dopamine uptake transporter and produce transient micromolar concentrations. The bursts are known to lead to marked presynaptic plasticity via multiple mechanisms, but analysis methods for these kinetic parameters are limited. To provide a deeper understanding of the mechanics of the modulation of dopamine neurotransmission by physiological, genetic, and pharmacological means, we present three computational models of dopamine release with different levels of spatiotemporal complexity to analyze in vivo fast-scan cyclic voltammetry recordings from the dorsal striatum of mice. The models accurately fit to cyclic voltammetry data and provide estimates of presynaptic dopamine facilitation/depression kinetics and dopamine transporter reuptake kinetics, and we used the models to analyze the role of synuclein proteins in neurotransmission. The models’ results support recent findings linking the presynaptic protein α-synuclein to the short-term facilitation and long-term depression of dopamine release, as well as reveal a new role for β-synuclein and/or γ-synuclein in the long-term regulation of dopamine reuptake.
Transcriptional analysis links B cells and TERT expression to favorable prognosis in head and neck cancer
Authors: Xian Su , Dosset Magalie , Castro Andrea , Carter Hannah , Zanetti Maurizio
Published: February 2023

Telomerase reverse transcriptase (TERT) is a conserved self-tumor antigen overexpressed in ∼85% of tumor cells and is immunogenic in cancer patients. The effect of TERT expression on the regulation of intratumor adaptive immunity has not yet been investigated. We used RNA sequencing data from The Cancer Genome Atlas (TCGA) in 11 solid tumor types to investigate potential interactions between TERT expression, and B and T cell infiltrate in the tumor microenvironment. We found a positive correlation between TERT expression, B and T cells in four cancer types with the strongest association in head and neck squamous cell carcinoma (HSNCC). In HNSCC a Bhigh/TERThigh signature was associated with improved progression-free survival (PFS) (P = 0.0048). This effect was independent of HPV status and not shared in comparable analysis by other conserved tumor antigens (NYESO1, MUC1, MAGE, and CEA). Bhigh/TERThigh HNSCC tumors also harbored evidence of tertiary lymphoid structure (TLS) such as signatures for germinal center (GC) and switched memory B cells, central memory CD4 and effector memory CD8 T cells. Bhigh/TERThigh HNSCC tumors also showed an up-regulation of genes and pathways related to B and T cell activation, proliferation, migration, and cytotoxicity, while factors associated with immunosuppression and cancer cell invasiveness were down-regulated. In summary, our study uncovers a new association between high TERT expression and high B cell infiltrate in HNSCC, suggesting a potential benefit from therapeutic strategies that invigorate intratumor TERT-mediated T-B cooperation.
FDG-PET/CT discriminates between patients with and without lymphomas in primary Sjögren’s syndrome
Authors: van Ginkel Martha S , Arends Suzanne , van der Vegt Bert , Nijland Marcel , Spijkervet Fred K L , Vissink Arjan , Kroese Frans G M , Glaudemans Andor W J M , Bootsma Hendrika
Published: February 2023

Objectives

To assess the usefulness of [18F]-fluorodeoxyglucose (FDG)-PET/CT (i) to discriminate between primary SS (pSS) patients with and without lymphomas and (ii) to evaluate systemic disease activity in pSS.

Methods

ACR-EULAR-positive pSS patients who underwent FDG-PET/CT were included. Scans were visually evaluated and quantitative analysis was performed by measuring standardized uptake values (SUV) of salivary and lacrimal glands and systemic regions. Receiver operating characteristic curve analyses were performed to find SUV cut-off values to discriminate between lymphoma and non-lymphoma.

Results

Of the 70 included patients, 26 were diagnosed with a pSS-associated lymphoma, mostly of the mucosa-associated lymphoid tissue type (23/26). Lymphoma patients showed higher FDG uptake in the parotid and submandibular glands, and more frequently showed presence of nodular lung lesions, compared with non-lymphoma patients. The accuracy of the maximum SUV (SUVmax) in the parotid and submandibular gland to predict lymphoma diagnosis was good, with optimal cut-off points of 3.1 and 2.9. After combining these three visual and quantitative findings (nodular lung lesions, parotid SUVmax > 3.1 and submandibular SUVmax > 2.9), sensitivity was 92% when at least one of the three features were present, and specificity was 91% in case at least two features were present. Furthermore, FDG-PET/CT was able to detect systemic manifestations in pSS patients, mostly involving lymph nodes, entheses and lungs.

Conclusions

FDG-PET/CT can assist in excluding pSS-associated lymphomas in patients without PET abnormalities, possibly leading to a decrease of invasive biopsies in suspected lymphoma patients. Furthermore, FDG-PET/CT is able to detect systemic manifestations in pSS and can guide to the best biopsy location.
Expertise and the Public History of Sexuality ‘Second Opinion’ Submission for the Proposed Special Issue, ‘Sexpertise: Sexual Knowledge and the Public in the Nineteenth and Twentieth Centuries’, Edited by Hannah Charnock, Sarah L. Jones, Ben Mechen.
Authors: Grove Jen
Published: February 2023

How does the history of sexuality function as a form of ‘expertise’ when engaging with those outside of academia? What other types of expertise are at play in doing the public history of sexuality? This essay focuses on engagement with young people via museums and historical artefact collections within a UK context to explore the value of expertise from a range of sectors and from non-professional ‘publics’ and communities. It suggests that the context of UK Higher Education presents particular challenges and opportunities for professional historians doing the public history of sexuality and the way in which they can productively negotiate diverse forms of expertise.
Percutaneous Curved Vertebroplasty Versus Unipedicular Approach Vertebroplasty for Acute Osteoporotic Vertebral Compression Fractures
Authors: Lv Zhendong , Chen Zehao , Chen Hao , Wang Jieying , Han Yingchao , Li Xinfeng , Shen Hongxing , Zhang Yuhui
Published: February 2023

Study Design.

Prospective randomized controlled trial.

Objective.

To clarify whether percutaneous curved vertebroplasty (PCVP) is superior to conventional unipedicular approach vertebroplasty (UVP) in patients with acute osteoporotic vertebral compression fractures (OVCFs).

Summary of Background Data.

Unilateral curved vertebroplasty devices were designed and applied to provide better control of cement placement, which may be superior to traditional UVP for the treatment of acute OVCFs.

Materials and Methods.

Patients with single-level OVCFs of <6 weeks duration and visual analog scale (VAS) of back pain 5 or more were randomly allocated to undergo PCVP or UVP and were followed up for 1 year. The primary outcome was overall VAS scores for back pain during 12 months of follow-up. The secondary outcomes were scores on the Oswestry disability index at each postprocedure clinic visit. Radiographic (cement distribution) and surgical data (operation time, fluoroscopy frequency, and cement volume) were assessed. Complications and adverse events were recorded.

Results.

No statistical difference was found between the PCVP and UVP groups with respect to VAS and Oswestry disability index scores at any follow-up time point. Operative time, fluoroscopy frequency, and cement leakage were similar in both groups, while the PCVP techniques had a larger injection of polymethylmethacrylate (5.5 ± 1.4 vs. 4.2 ± 1.0 mL) and a greater dispersion pattern of cement (P < 0.001). Post hoc observations found that the analgesic effect was positively correlated with the symmetry of bone cement distribution, but not with the surgical method. Two serious adverse events occurred in the vertebroplasty group: one stress ulcer and one allergic reaction.

Conclusions.

Although PCVP achieved more symmetrical cement distribution, which seemed to be associated with a greater analgesic effect, PCVP did not result in significantly greater pain relief than a UVP in the 12 months after treatment.
SUBRETINAL LIPID GLOBULES AN EARLY BIOMARKER OF MACULAR NEOVASCULARIZATION IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION
Authors: Fragiotta Serena , Parravano Mariacristina , Costanzo Eliana , De Geronimo Daniele , Varano Monica , Fernández-Avellaneda Pedro , Freund K. Bailey
Published: February 2023

Purpose:

To explore the association between subretinal lipid globules (SLGs) detected in eyes with intermediate age-related macular degeneration with the presence of nonexudative macular neovascularization.

Methods:

This was a retrospective analysis of 113 consecutive patients with bilateral intermediate age-related macular degeneration (226 eyes) followed for a least 6 months. All eyes underwent multimodal imaging with fundus autofluorescence, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Subretinal lipid globules were identified on spectral-domain optical coherence tomography as round hyporeflective lesions measuring 31 to 157 µm located between the ellipsoid zone and the retinal pigment epithelium/Bruch membrane complex. Nonexudative macular neovascularization was detected with optical coherence tomography angiography. The features of NE-MNV lesions detected in eyes with SLGs were compared with those in eyes without SLGs.

Results:

Subretinal lipid globules were identified in 15 eyes of which 14 eyes (93.3%) demonstrated NE-MNV on optical coherence tomography angiography. In the remaining 98 eyes without SLGs, 18 (18.4%) displayed NE-AMD on optical coherence tomography angiography. The macular neovascularization area was larger in the SLG subgroup (+0.38 vs. +0.21 mm2, P = 0.008) and showed faster horizontal growth (+727 µm, CI 95% 250.4, 1,205.4) than MNV in eyes without SLGs (+64.9 µm, CI 95%, 24.3, 154) on optical coherence tomography B-scans. After a mean of 11.6 months, the conversion rate to exudative MNV was similar between eyes with SLGs and those without SLGs [8/26 (38.5%) versus 3/13 (27.3%), P = 0.56)].

Conclusion:

The detection of SLGs in eyes with intermediate age-related macular degeneration was strongly correlated with the presence of NE-MNV. Although these MNV lesions were larger and grew faster than NE-MNV detected in eyes lacking SLGs, the rates of conversion to exudative MNV appeared similar.
Current insights in ICU nutrition: tailored nutrition
Authors: Hermans Anoek Jacqueline Hubertine , Laarhuis Babette Irene , Kouw Imre Willemijn Kehinde , van Zanten Arthur Raymond Hubert
Published: February 2023

Purpose of review

To summarize recent research on critical care nutrition focusing on the optimal composition, timing, and monitoring of enteral feeding strategies for (post)-ICU patients. We provide new insights on energy and protein recommendations, feeding intolerance, and describe nutritional practices for coronavirus disease 2019 ICU patients.

Recent findings

The use of indirect calorimetry to establish individual energy requirements for ICU patients is considered the gold standard. The limited research on optimal feeding targets in the early phase of critical illness suggests avoiding overfeeding. Protein provision based upon the absolute lean body mass is rational. Therefore, body composition measurements should be considered. Body impedance analysis and muscle ultrasound seem reliable, affordable, and accessible methods to assess body composition at the bedside. There is inadequate evidence to change our practice of continuous enteral feeding into intermittent feeding. Finally, severe acute respiratory syndrome coronavirus 2 patients are prone to underfeeding due to hypermetabolism and should be closely monitored.

Nutritional therapy should be adapted to the patient's characteristics, diagnosis, and state of metabolism during ICU stay and convalescence. A personalized nutrition plan may prevent harmful over- or underfeeding and attenuate muscle loss. Despite novel insights, more research is warranted into tailored nutrition strategies during critical illness and convalescence.
In-silico studies of inhibitory compounds against protease enzymes of SARS-CoV-2
Authors: Khan Saba , Nasrullah  , Hussain Abrar , Asif Muhammad , Sattar Fouzia Abdul , Audhal Fayyaz Ahmed , Qadir Muhammad Imran , Hamdard Muhammad Hamid
Published: February 2023

In December 2019, a COVID-19 outbreak caused by SARS-CoV-2 raised worldwide health concerns. In this case, molecular docking and drug repurposing computational approaches were engaged to check the efficiency of plant-based inhibitory compounds against SARS-CoV-2 main protease enzyme and papain-like protease enzyme. Twenty phytochemical inhibitory compounds were collected. Then these compounds were screened based on Lipinski’s rule. As a result of this screening eleven compounds were further selected. Quantitative structure–activity relationships analysis was done before molecular docking to check especially the antiviral activity of inhibitory compounds. Docking validation of these compounds was checked by using online server Database of Useful Decoys: Enhanced. Binding affinity value, and pharmacokinetic properties of Aloin compound indicated that it can be used against main protease enzyme of SARS-CoV-2. So, it makes it a promising compound to follow further in cell and biochemical-based assays to explore its potential use against COVID-19.
The neuroprotective effect of electro-acupuncture on cognitive recovery for patients with mild traumatic brain injury: A randomized controlled clinical trial
Authors: Jia Haokun , Chen Yonghan , Wang Yi , Jia Linwei , Tian Yaohui , Jiang Hao
Published: February 2023

Background:

Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. Consciousness disorder is a common complication after TBI while there is still no effective treatment currently. The aim of this study was to investigate the protective effect of electro-acupuncture (EA) on cognitive recovery for patients with mild TBI.

Methods:

A total of 83 patients with initial Glasgow coma scale score higher than 12 points were assigned into this study. Then patients were randomly divided into 2 groups: EA group and control group (group C). Patients in group EA received EA treatment at Neiguan and Shuigou for 2 weeks. At 0 minute before EA treatment (T1), 0 minute after EA treatment (T2), and 8 weeks after EA treatment (T3), level of neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), hypoxia inducible factor-1α (HIF-1α), and malondialdehyde were tested by enzyme-linked immunosorbent assay. The score of Montreal Cognitive Function Assessment (MoCA) and mini-mental state examination (MMSE) as well as cerebral oxygen saturation (rSO2) were detected at the same time.

Results:

Compared with the baseline at T1, the level of NSE, GFAP, HIF-1α, MDA, and rSO2 decreased, and the score of MoCA and MMSE increased in the 2 groups were significantly increased at T2–3 (P < .05). Compared with group C, the level of NSE, GFAP, HIF-1α, MDA, and rSO2 decreased, and the score of MoCA and MMSE increased were significantly increased at T2–3 in group EA; the difference were statistically significant (P < .05).

Conclusions:

EA treatment could improve the cognitive recovery for patients with mild TBI and the potential mechanism may be related to improving cerebral hypoxia and alleviating brain injury.
Exposure to occupational risk factors is associated with the severity and progression of chronic obstructive pulmonary disease
Authors: Chen Yao , Peng Cong , Zhang Hua , Cai Yu , Yuan Rui , Song Pingping , Zhang Chunling , Yan Yongjian
Published: February 2023

Chronic obstructive pulmonary disease (COPD) results from a complex interaction between genes and the environment, and occupational exposures are an underappreciated risk factor. Until now, little research attention has been paid to the potential impact of occupational risk factor exposure on the COPD in China. The aim of this retrospective study was to analyze the role of occupational risk factor exposure on the severity and progression of COPD for exploring new prevention strategies for this disease. This study adopted a random cluster-sampling method. Five grade-A tertiary hospitals that met the inclusion criteria were selected as the survey sites, and patients with COPD hospitalized in these hospitals from January 1, 2019, to December 31, 2019, were selected as the research subjects. Data of the patients diagnosed with COPD met the Global Initiative for Chronic Obstructive Lung Disease (2019) criteria and were collected from the computerized medical record databases. Among 4082 investigated COPD patients, 1063 (26%) were found to have occupational risk factor exposure history. The top 3 industries with a large COPD case number and a history of occupational risk factor exposure ranked in the order of agriculture (including farming, forestry, animal husbandry, and fishery), manufacturing, and mining. Further multivariate logistic regression analysis indicated that when setting a low exposure level as a reference, medium and high exposure levels were correlated with the severity of COPD (odds ratio values were 2.837 and 6.201, respectively, P < .05). Linear regression analysis showed that cumulative exposure to occupational risk factors was negatively correlated with the forced expiratory volume in 1-second percentage of COPD patients, with a correlation coefficient of 0.68. Our results indicated that occupational risk factor exposure levels were related to the severity of COPD significantly. The incubation period of COPD in the exposure group was significantly shorter than that in the non-exposure group. To prevent worked-related COPD, special attention and control efforts should be taken to reduce the level of occupational risk factors such as organic dust, irritating chemicals, etc in the work environments, especially in the industries of agriculture, forestry, animal husbandry and fishery, manufacturing, and mining.
Advances in Genetic Editing of the Human Embryo
Authors: Astarăstoae Vasile , Ioan Beatrice Gabriela , Rogozea Liliana M. , Hanganu Bianca
Published: February 2023

Background:

Genetic engineering has allowed a major development of research in this field, with specialists attempting to edit the human genome, after the successful editing of the genomes of plants and animals. However, human gene editing technologies are at the center of ethical debates around the world.

Areas of Uncertainty:

Ethical concerns about genetic editing of the human embryo raise several issues that can be viewed through the prism of optimism and reluctance leading to a number of recommendations regarding the acceptance of what may soon become a reality.

Data Sources:

A literature search was conducted through PubMed, MEDLINE, Plus, Scopus, and Web of Science (2015–2022) using combinations of keywords, including: human genome or gene editing plus ethics.

Ethics and Therapeutic Advances:

Gene therapy is seen by researchers as a way to solve congenital diseases, multifactorial diseases in general or specific diseases such as cystic fibrosis, muscular dystrophy, or can increase resistance to HIV infection. Genome editing technologies, germline gene editing, clustered regularly interspaced short palindromic repeats gene editing technology, technologies such as zinc finger nucleases are not only advanced gene therapies that require solving technical problems, but also techniques that require complex and complete analysis of ethical problems. Genetic engineering raises many ethical concerns such as: safety concerns especially the risk of off-target effects; autonomy of the individual—with the limitation of the future generations to consent for an intervention over their genome; social justice—keeping in mind the costs of the procedures and their availability to the general population. Discussions can go further from questions such as “How can we do this?” to questions such as “Should we do this?” or “Is society ready to accept this technology and is it able to manage it rationally?”

Conclusions:

The ethics of biomedical research should be based on global dialogue, on the involvement of experts and the public, to achieve a broad social consensus. The fundamental review of the ethics of genetics is a desire and an opportunity of the current period.