bluuebunny/crossref_metadata_2025 huggingface dataset:
Does prehabilitation before esophagectomy improve postoperative outcomes? A systematic review and meta-analysis
Authors: An Kevin R , Seijas Vanessa , Xu Michael S , Grüßer Linda , Humar Sapna , Moreno Amabelle A , Turk Marvee , Kasanagottu Koushik , Alzghari Talal , Dimagli Arnaldo , Ko Michael A , Villena-Vargas Jonathan , Papatheodorou Stefania , Gaudino Mario F L
Published: November 2023

Esophagectomy for esophageal cancer is associated with high morbidity. It remains unclear whether prehabilitation, a strategy aimed at optimizing patients’ physical and mental functioning prior to surgery, improves postoperative outcomes. A systematic review and meta-analysis was conducted to evaluate the effect of prehabilitation on post-operative outcomes after esophagectomy. Data sources included Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and PEDro, with information from 1 January 2000 to 5 August 2023. The analysis included randomized controlled trials and observational studies that compared prehabilitation interventions to standard care prior to esophagectomy. A random effects model was used to generate a pooled estimate for pairwise meta-analysis, meta-analysis of proportions, and meta-analysis of means. A total of 1803 patients were included with 584 in randomized controlled trials (RCTs) and 1219 in observational studies. In the randomized evidence, there were no significant differences between prehabilitation and control in the odds of postoperative pneumonia (15.0 vs. 18.9%, odds ratio (OR) 1.06 [95% confidence interval (CI): 0.66;1.72]) or pulmonary complications (14 vs. 25.6%, OR 0.68 [95% CI: 0.32;1.45]). In the observational data, there was a reduction in both postoperative pneumonia (22.5 vs. 32.9%, OR 0.48 [95% CI: 0.28;0.83]) and pulmonary complications (26.1 vs. 52.3%, OR 0.35 [95% CI: 0.17;0.75]) with prehabilitation. Hospital and intensive care unit length of stay (days), operative mortality, and severe complications (Clavien-Dindo ≥ 3) did not differ between groups in both the randomized data and observational data. Prehabilitation demonstrated reductions in postoperative pneumonia and pulmonary complications in observational studies, but not RCTs. The overall certainty of these findings is limited by the low quality of the available evidence.
Comprehensive characterization and detection of nut allergens in bakery foods using Q-TOF mass spectrometry and bioinformatics
Authors: Xu Daokun , Huang Haolun , Liu Zhen , Wang Yumei , Liu Qinan , Jiang Xing , Yang Jun , Ling Rui
Published: November 2023

Food allergy is a growing health issue worldwide and the demand for sensitive, robust and high-throughput analytical methods is rising. In recent years, mass spectrometry-based methods have been established for multiple food allergen detection. In the present study, a novel method was developed for the simultaneous detection of almond, cashew, peanut, and walnut allergens in bakery foods using liquid chromatography–mass spectrometry. Proteins unique to these four ingredients were extracted, followed by trypsin digestion, quadrupole time-of-flight (Q-TOF) mass spectrometry and bioinformatics analysis. The raw data were processed by de-novo sequencing module plus PEAKS DB (database search) module of the PEAKS software to screen peptides specific to each nut species. The thermal stability and uniqueness of these candidate peptides were further verified using triple quadrupole mass spectrometry (QQQ-MS) in multiple reaction monitoring (MRM) mode. Each nut species was represented by four peptides, all of which were validated for label-free quantification (LFQ). Calibration curves were constructed with good linearity and correlation coefficient (r2) greater than 0.99. The limits of detection (LODs) were determined to range from 0.11 to 0.31 mg/kg, and were compared with the reference doses proposed by Voluntary Incidental Trace Allergen Labelling (VITAL). The recoveries of the developed method in incurred bakery food matrices ranged from 72.5% to 92.1% with relative standard deviations (RSD) of <5.2%. The detection of undeclared allergens in commercial bakery food samples confirmed the presence of these allergens. In conclusion, this method provides insight into the qualitative and quantitative detection of trace levels of nut allergens in bakery foods.
HPA axis differential flatness and Liouvillian study for higher resiliency investigations
Authors: Nicolau Florentina , Mounier Hugues , Androulakis Ioannis P
Published: November 2023

In this paper, we study several existing quantitative models of the hypothalamic–pituitary–adrenal (HPA) axis from a control systems theory viewpoint, that is, we suppose that we can act on the dynamics of the HPA axis throughout some parameters, which are the system inputs. In particular, we will focus on flatness and Liouvillian properties of the considered control systems of the HPA axis. We first study the minimal three-dimensional model of Bangsgaard and Ottesen (2017, Math. Biosci., 287:24–35) and the semi-mechanistic four-dimensional model of Gupta et al. (2007, Theor. Biol. Medical Model., 4(1):8) which are shown to be flat, and then, we consider the more involved and important model proposed in Rao & Androulakis (2019, Sci. Rep., 9(1):11212; 2020, IFAC-PapersOnLine, 53(2):15858–15863), with seven states, for which we prove that for the nominal values of the parameters involved in the model, flatness no longer holds. The more involved model satisfies however a similar but weaker property than flatness: it is a Liouvillian system.
Asymptotic Stability of 2-Domain Walls for the Landau–Lifshitz–Gilbert Equation in a Nanowire With Dzyaloshinskii–Moriya Interaction
Authors: Côte Raphaël , Ferriere Guillaume
Published: November 2023

We consider a ferromagnetic nanowire, with an energy functional $E$ with easy-axis in the direction $e_{1}$, and which takes into account the Dzyaloshinskii–Moriya interaction. We consider configurations of the magnetization that are perturbations of two well-separated domain wall and study their evolution under the Landau–Lifshitz–Gilbert flow associated to $E$. Our main result is that, if the two walls have opposite speed, these configurations are asymptotically stable, up to gauges intrinsic to the invariances of the energy $E$. Our analysis builds on the framework developed in [4], taking advantage that it is amenable to space localisation.
Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh, 2011–2014
Authors: Ciszewski Jenna , Taniuchi Mami , Lee Benjamin , Colgate E Ross , Platts-Mills James A , Haque Rashidul , Zaman K , Lopman Benjamin , Petri William A , Kirkpatrick Beth D , Rogawski McQuade Elizabeth T
Published: November 2023

To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = −0.59 log copies per gram of stool; 95% confidence interval [CI], −.99 to −.19). Duration of illness was on average 0.47 days (95% CI, −.23 to 1.17 days) shorter among vaccinated children. Rotarix vaccination reduces shedding burden among breakthrough cases of rotavirus gastroenteritis.

Clinical Trials Registration . NCT01375647.
Prolonged Mpox Disease in People With Advanced HIV: Characterization of Mpox Skin Lesions
Authors: O’Shea Jesse , Zucker Jason , Stampfer Samuel , Cash-Goldwasser Shama , Minhaj Faisal S , Dretler Alexandra , Cheeley Justin , Chaudhuri Shaoli , Gallitano Stephanie M , Gunaratne Shauna , Parkinson Melissa , Epling Brian , Morcock David R , Sereti Irini , Deleage Claire
Published: November 2023

We report 3 complicated and prolonged cases of mpox in people with advanced human immunodeficiency virus (HIV) not on antiretroviral therapy (ART) at mpox diagnosis. Multiple medical countermeasures were used, including prolonged tecovirimat treatment and immune optimization with ART initiation. Immunofluorescence of skin biopsies demonstrated a dense immune infiltrate of predominantly myeloid and CD8+ T cells, with a strong type I interferon local response. RNAscope detected abundant replication of monkeypox virus (MPXV) in epithelial cells and dendritic cells. These data suggest that prolonged mpox in people with advanced HIV may be due to ongoing MPXV replication, warranting aggressive medical countermeasures and immune optimization.
Epitope Mapping of SARS-CoV-2 Spike Antibodies in Vaccinated Kidney Transplant Recipients Reveals Poor Spike Coverage Compared to Healthy Controls
Authors: Karaba Andrew H , Morgenlander William R , Johnston Trevor S , Hage Camille , Pekosz Andrew , Durand Christine M , Segev Dorry L , Robien Mark A , Heeger Peter S , Larsen Christian P , Blankson Joel N , Werbel William A , Larman H Benjamin , Tobian Aaron A R
Published: November 2023

Kidney transplant recipients (KTRs) develop decreased antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population.

Clinical Trials Registration.  NCT04969263.
Tenofovir Douche as HIV Preexposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics (DREAM 01)
Authors: Weld Ethel D , McGowan Ian , Anton Peter , Fuchs Edward J , Ho Ken , Carballo-Dieguez Alex , Rohan Lisa C , Giguere Rebecca , Brand Rhonda , Edick Stacey , Bakshi Rahul P , Parsons Teresa , Manohar Madhuri , Seigel Aaron , Engstrom Jared , Elliott Julie , Jacobson Cindy , Bagia Christina , Wang Lin , Al-khouja Amer , Hartman Douglas J , Bumpus Namandje N , Spiegel Hans M L , Marzinke Mark A , Hendrix Craig W
Published: November 2023

Background

Despite highly effective HIV preexposure prophylaxis (PrEP) options, no options provide on-demand, nonsystemic, behaviorally congruent PrEP that many desire. A tenofovir-medicated rectal douche before receptive anal intercourse may provide this option.

Methods

Three tenofovir rectal douches—220 mg iso-osmolar product A, 660 mg iso-osmolar product B, and 660 mg hypo-osmolar product C—were studied in 21 HIV-negative men who have sex with men. We sampled blood and colorectal tissue to assess safety, acceptability, pharmacokinetics, and pharmacodynamics.

Results

The douches had high acceptability without toxicity. Median plasma tenofovir peak concentrations for all products were several-fold below trough concentrations associated with oral tenofovir disoproxil fumarate (TDF). Median colon tissue mucosal mononuclear cell (MMC) tenofovir-diphosphate concentrations exceeded target concentrations from 1 hour through 3 to 7 days after dosing. For 6–7 days after a single product C dose, MMC tenofovir-diphosphate exceeded concentrations expected with steady-state oral TDF 300 mg on-demand 2-1-1 dosing. Compared to predrug baseline, HIV replication after ex vivo colon tissue HIV challenge demonstrated a concentration-response relationship with 1.9 log10 maximal effect.

Conclusions

All 3 tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF and with lower systemic tenofovir. Tenofovir douches may provide a single-dose, on-demand, behaviorally congruent PrEP option, and warrant continued development.

Clinical Trials Registration . NCT02750540.
Development and Evaluation of “The Delta Plus-Minus Even Distribution Check”: A Novel Patient-Based Real-Time Quality Control Method for Laboratory Tests
Authors: Hatanaka Noriko , Yamamoto Yoshikazu , Shiozaki Yuya , Kuramura Eiji , Nagai Naoharu , Kondo Akira , Kamioka Mikio
Published: November 2023

Background

Laboratory testing of large sample numbers necessitates high-volume rapid processing, and these test results require immediate validation and a high level of quality assurance. Therefore, real-time quality control including delta checking is an important issue. Delta checking is a process of identifying errors in individual patient results by reviewing differences from previous results of the same patient (Δ value). Under stable analytical conditions, Δ values are equally positively and negatively distributed.

Methods

The previous 20 Δ values from 3 tests (cholesterol, albumin, and urea nitrogen) were analyzed by calculating the R-value: “the positive Δ value ratio minus 0.5.” This method of monitoring optimized R-values is referred to as the even-check method (ECM) and was compared with quality control (QC) testing in terms of error detection.

Results

Bias was observed on 4 of the 120 days for the 3 analytes measured. When QC detected errors, the ECM captured the same systematic errors and more rapidly. In contrast, the ECM did not generate an alarm for the one random error that occurred in QC. While QC did not detect any errors, the percentage of R-values exceeding the acceptable range was under 2%, the number of days generating alarms was between 16 and 21 days, with short alarm periods, and a median number of samples per alarm period between 7 and 9 samples.

Conclusions

The ECM is a practical real-time QC method, controlled by setting R-value conditions, that quickly detects bias values.
Performance assessment of an iterative ensemble smoother with local analysis to assimilate big 4D seismic datasets applied to a complex pre-salt-like benchmark case
Authors: Maschio Célio , Silva Neto Gilson Moura , Davolio Alessandra , Rios Vinicius de Souza , Schiozer Denis José
Published: November 2023

The use of 4D seismic (4DS) (or time-lapse seismic, TLS) in data assimilation (DA) makes the process more complex due to the higher amount of data to be assimilated, requiring more robust methods and better computational resources (processing capacity and memory). The development and application of permanent seismic monitoring technologies have increased in recent years, improving the overall 4D seismic quality in terms of signal resolution and repeatability. However, a massive amount of data is generated from the multiple monitors, making the incorporation of 4DS data in the DA process more complex. Therefore, robust DA methods capable of dealing with huge amount of data effectively and efficiently are essential. This paper aims to assess the performance of an iterative ensemble smoother method, named subspace ensemble randomized maximum likelihood with a local analysis, to assimilate a big dataset. The method was applied in a challenging pre-salt-like benchmark case with eight seismic surveys, one base, and seven monitors. The 4DS data are the impedance ratios (between two consecutive monitors) in 15 seismic horizons, totaling 105 maps to be assimilated. To our best knowledge, this is state of the art in terms of practical applications in DA. It was possible to assimilate all the data simultaneously: the 105 horizons for the 4DS data and the wells’ production and pressure data. The DA was successful in terms of results quality and method performance. We also ran a case assimilating only well data for comparison purposes.
Multiwavelength variability and broad-band SED modelling of BL Lac during a bright flaring period MJD 59000–59943
Authors: Shah Zahir
Published: November 2023

We carried out a detailed temporal and spectral study of the BL Lacertae (BL Lac) by using the long-term Fermi-Large Area Telescope (LAT) and Swift-X-ray Telescope (XRT)/Ultraviolet Optical Telescope (UVOT) observations, during the period MJD 59000–59943. The daily-binned γ-ray light curve displays a maximum flux of $1.74\pm 0.09\times 10^{-5} \,\rm photons\, cm^{-2}\, s^{-1}$ on MJD 59868, which is the highest daily γ-ray flux observed from BL Lac. The γ-ray variability is characterized by power spectral density (PSD), rms–flux relation, and flux distribution study. We find that the power-law model fits the PSD with index ∼1, which suggests a long-memory process at work. The observed rms–flux relation exhibits a linear trend, which indicates that the γ-ray flux distribution follows a lognormal distribution. The skewness/Anderson–Darling test and histogram fit reject the normality of flux distribution, and instead suggest that the flux distribution is a lognormal distribution. The fractional variability amplitude shows that the source is more variable in the X-ray band than in optical/ultraviolet/γ-ray bands. In order to obtain an insight into the underlying physical process, we extracted broad-band spectra from different time periods of the light curve. The broad-band spectra are statistically fitted with the convolved one-zone leptonic model with different forms of the particle energy distribution. We found that spectral energy distribution during different flux states can be reproduced well with the synchrotron, synchrotron self-Compton, and external Compton emissions from a broken power-law electron distribution, ensuring equipartition condition. A comparison between the best-fitting physical parameters shows that the variation in different flux states is mostly related to an increase in the bulk Lorentz factor and spectral hardening of the particle distribution.
Line-of-sight structure of troughs identified in Subaru Hyper Suprime-Cam Year 3 weak lensing mass maps
Authors: Shimasue Takumi , Osato Ken , Oguri Masamune , Shimakawa Rhythm , Nishizawa Atsushi J
Published: November 2023

We perform the weak lensing mass mapping analysis to identify troughs, which are defined as local minima in the mass map. Since weak lensing probes the projected matter distribution along the line of sight, these troughs can be produced by single or multiple voids projected along the line of sight. To scrutinize the origins of the weak lensing troughs, we systematically investigate the line-of-sight structure of troughs selected from the latest Subaru Hyper Suprime-Cam (HSC) Year 3 weak lensing data covering $433.48 \, \mathrm{deg}^2$. From a curved sky mass map constructed with the HSC data, we identify 15 troughs with the signal-to-noise ratio higher than 5.7 and address their line-of-sight density structure utilizing redshift distributions of two galaxy samples, photometric luminous red galaxies observed by HSC and spectroscopic galaxies detected by Baryon Oscillation Spectroscopic Survey. While most weak lensing signals due to the troughs are explained by multiple voids aligned along the line of sight, we find that two of the 15 troughs potentially originate from single voids at redshift ∼0.3. The single void interpretation appears to be consistent with our three-dimensional mass mapping analysis. We argue that single voids can indeed reproduce observed weak lensing signals at the troughs if these voids are not spherical but are highly elongated along the line-of-sight direction.
The maximum mass of a black hole which can tidally disrupt a star: measuring black hole spins with tidal disruption events
Authors: Mummery Andrew
Published: November 2023

The tidal acceleration experienced by an object at the event horizon of a black hole decreases as one over the square of the black hole’s mass. As such there is a maximum mass at which a black hole can tidally disrupt an object outside of its event horizon and potentially produce observable emission. This maximum mass is known as the ‘Hills mass’, and in full general relativity is a function of both the black hole’s spin a• and the inclination angle of the incoming object’s orbit with respect to the black hole’s spin axis ψ. In this paper, we demonstrate that the Hills mass can be represented by a simple analytical function of a• and ψ, the first general solution of this problem. This general solution is found by utilizing the symmetries of a class of critical Kerr metric orbits known as the innermost bound spherical orbits. Interestingly, at fixed black hole spin the maximum Hills mass can lie at incoming orbital inclinations outside of the black hole’s equatorial plane ψ ≠ π/2. When compared to previous results in the literature this effect can lead to an increase in the maximum Hills mass (at fixed spin) by as much as a factor of $\sqrt{11/5} \simeq 1.48$ for a maximally rotating black hole. We then demonstrate how Bayesian inference, coupled with an estimate of the mass of a black hole in a tidal disruption event, can be used to place conservative constraints on that black hole’s spin. We provide a publicly available code tidalspin which computes these spin distributions.
The nature of very-faint X-ray binaries: near-infrared spectroscopy of 1RXH J173523.7−354013 reveals a giant companion
Authors: Shaw A W , Degenaar N , Maccarone T J , Heinke C O , Wijnands R , van den Eijnden J
Published: November 2023

Very-faint X-ray binaries (VFXBs) are a subclass of black holes and neutron stars in binaries that appear to be accreting at a very low rate. In addition to providing interesting constraints on poorly understood forms of accretion, elucidating the nature of VFXBs is particularly interesting for binary evolution and population modelling. Through near-infrared (NIR) spectroscopy, we here investigate the nature of the bursting neutron star and VFXB 1RXH J173523.7−354013 (J1735), which persistently accretes at an X-ray luminosity of LX ∼ 1034–1035 ergs−1. Our analysis shows that the NIR emission is dominated by that of the companion star, which we find to be a late G or early K-type giant, making this the second neutron star identified as a VFXB found to have a giant companion. We discuss how several of the system properties are difficult to reconcile with a wind-fed symbiotic X-ray binary. We therefore also propose an alternative scenario wherein J1735 is a wide binary system (supported by the discovery of a 7.5 d modulation in the NIR light curves) with a quiescent luminosity of LX ∼ 1034–1035 ergs−1, in which the donor star is overflowing its Roche lobe. This raises the possibility that J1735 may, every century or more, exhibit very long and very bright outbursts during which it reaches accretion rates around the Eddington limit like the neutron star Z sources.
The two-point correlation function covariance with fewer mocks
Authors: Trusov Svyatoslav , Zarrouk Pauline , Cole Shaun , Norberg Peder , Zhao Cheng , Aguilar Jessica Nicole , Ahlen Steven , Brooks David , de la Macorra Axel , Doel Peter , Font-Ribera Andreu , Honscheid Klaus , Kisner Theodore , Landriau Martin , Magneville Christophe , Miquel Ramon , Nie Jundan , Poppett Claire , Schubnell Michael , Tarlé Gregory , Zhou Zhimin
Published: November 2023

We present fitcov an approach for accurate estimation of the covariance of two-point correlation functions that requires fewer mocks than the standard mock-based covariance. This can be achieved by dividing a set of mocks into jackknife regions and fitting the correction term first introduced in Mohammad & Percival (2022), such that the mean of the jackknife covariances corresponds to the one from the mocks. This extends the model beyond the shot-noise limited regime, allowing it to be used for denser samples of galaxies. We test the performance of our fitted jackknife approach, both in terms of accuracy and precision, using lognormal mocks with varying densities and approximate EZmocks mimicking the Dark Energy Spectroscopic Instrument LRG and ELG samples in the redshift range of z = [0.8, 1.1]. We find that the Mohammad–Percival correction produces a bias in the two-point correlation function covariance matrix that grows with number density and that our fitted jackknife approach does not. We also study the effect of the covariance on the uncertainty of cosmological parameters by performing a full-shape analysis. We demonstrate that our fitted jackknife approach based on 25 mocks can recover unbiased and as precise cosmological parameters as the ones obtained from a covariance matrix based on 1000 or 1500 mocks, while the Mohammad–Percival correction produces uncertainties that are twice as large. The number of mocks required to obtain an accurate estimation of the covariance for the two-point correlation function is therefore reduced by a factor of 40–60. The fitcov code that accompanies this paper is available at this GitHub repository.
Effects of Combustible Cigarettes and Electronic Nicotine Delivery Systems on the Development and Progression of Chronic Lung Inflammation in Mice
Authors: Kastratovic Nikolina , Markovic Vladimir , Harrell Carl Randall , Arsenijevic Aleksandar , Stojanovic Milica Dimitrijevic , Djonov Valentin , Volarevic Vladislav
Published: November 2023

Introduction

Although detrimental effects of combustible cigarettes (CCs) on the progression of lung inflammatory diseases are well known, changes in electronic nicotine delivery systems (ENDS)-exposed lung-infiltrated immune cells are still unrevealed.

Aims and Methods

The analysis of blood gas parameters, descriptive and quantitative histology of lung tissues, determination of serum cytokines, intracellular staining, and flow cytometry analysis of lung-infiltrated immune cells were used to determine the differences in the extent of lung injury and inflammation between mice from experimental (CC and ENDS-exposed animals) and control groups (Air-exposed mice).

Results

Continuous exposition to either CCs or ENDS induced severe systemic inflammatory response, increased activation of NLRP3 inflammasome in neutrophils and macrophages and enhanced dendritic cell-dependent activation of Th1 and Th17 cells in the lungs. ENDS induced less severe immune response than CCs. Serum concentrations of inflammatory cytokines were significantly lower in the samples of ENDS-exposed mice. Compared to CCs, ENDS recruited lower number of circulating leukocytes in injured lungs and had less capacity to induce CD14/TLR2-dependent activation of NLRP3 inflammasome in lung-infiltrated neutrophils and macrophages. ENDS-primed dendritic cells had reduced capacity for the generation of Th1 and Th17 cell-driven lung inflammation. Accordingly, extensive immune cell-driven lung injury resulted in severe respiratory dysfunction in CCs-exposed mice, while ENDS caused moderate respiratory dysfunction in experimental animals.

Conclusions

Continuous exposition to either CCs or ENDS induced immune cell-driven lung damage in mice. ENDS triggered immune response, which was less potent than inflammatory response elicited by CCs and, therefore, caused less severe lung injury and inflammation.

Implications

This is the first study that compared the effects of CCs and ENDS on lung-infiltrated immune cells. Although both CCs and ENDS elicited systemic inflammatory response, immune cell-driven lung injury and inflammation were less severe in ENDS-exposed than in CC-exposed animals. Continuous exposition to ENDS-sourced aerosols was less harmful for respiratory function of experimental animals than CC-derived smoke.
Occupational injuries in workers of a Spanish bank
Authors: Reinoso-Barbero L , Pardillos L , Romero-Paredes M-C , Díaz-Garrido R , Mendiguren J-M , Gieco A , Gómez-Gallego F
Published: November 2023

Background

In 2017, 69 108 work-related traffic injuries with medical leave were documented, constituting 12% of all occupational injuries (OI) in Spain.

Aims

The aim of this study was to describe OI within a Spanish bank company during 2017.

Methods

A cross-sectional analysis was conducted using the company’s mandatory OI records, presenting data in both absolute (n) and relative (%) frequencies. The chi-square test was employed for comparisons.

Results

Among the company’s 10 399 employees, 176 OI cases were recorded. Most were minor musculoskeletal incidents, with one severe myocardial infarction and one mild anxiety episode. Lower limb injuries were the most prevalent. Injuries of the trunk (P < 0.001), neck (P < 0.05), and upper limbs (P < 0.001) were linked to workplace factors. Approximately 62% of OI occurred outside the workplace and resulted in more extended medical leave (P < 0.01). Traffic-related injuries accounted for 39% of OI cases and caused 49% of days lost due to OI (P < 0.001).

Female gender (P < 0.001) and age over 40 years (P < 0.05) were significantly associated with OI.

Conclusions

In our study, musculoskeletal injuries were the most common, with a single cardiovascular event being the most severe. OI occurring outside the workplace was more frequent and led to longer medical leaves. Notably, traffic-related injuries were especially significant, exceeding official statistics 4-fold.
What can We Know about Unanswerable Questions?
Authors: Raleigh Thomas
Published: November 2023

I present two arguments that aim to establish logical limits on what we can know. More specifically, I argue for two results concerning what we can know about questions that we cannot answer. I also discuss a line of thought, found in the writings of Pierce and of Rescher, in support of the idea that we cannot identify specific scientific questions that will never be answered.
The legal foundation of responsible research assessment: An overview on European Union and Italy
Authors: Peruginelli Ginevra , Pölönen Janne
Published: November 2023

During the past decade, responsible research assessment (RRA) has become a major science policy goal to advance responsible research and innovation and open science. Starting with the DORA declaration in 2012, common understanding of the needs and demands of RRA has been shaped by a growing number of initiatives, culminating in a European Commission supported Agreement on reforming research assessment published in July 2022. In this paper, we outline and investigate the normative framework for RRA, ranging from binding legal norms (hard law), rules of conduct which, in principle, have no legally binding force but which nevertheless may have practical effects’ (soft law) to self-regulation in supranational (the European Union) and one national (Italy) context. As shown by our analysis of hard and soft legal sources for RRA, apart from constitutional and legal provisions regarding freedom of research, autonomy of universities and non-discrimination and gender equality, the legal foundation for RRA rests mainly on soft law and policy norms. In the discussion we relate the normative framework for RRA to research integrity guidelines and consider the challenges of ensuring coherent RRA implementation across countries and research funding and performing institutions. We conclude that self-regulation and soft law are good starting points and may pave the way for hard law down the line: this can be seen as the optimum mix of regulatory mechanisms to mainstream RRAs.
Spontaneous Brain Activity Alterations in First-Episode Psychosis: A Meta-analysis of Functional Magnetic Resonance Imaging Studies
Authors: Cattarinussi Giulia , Grimaldi David Antonio , Sambataro Fabio
Published: November 2023

Background and Hypothesis

Several studies have shown that spontaneous brain activity, including the total and fractional amplitude of low-frequency fluctuations (LFF) and regional homogeneity (ReHo), is altered in psychosis. Nonetheless, neuroimaging results show a high heterogeneity. For this reason, we gathered the extant literature on spontaneous brain activity in first-episode psychosis (FEP), where the effects of long-term treatment and chronic disease are minimal.

Study Design

A systematic research was conducted on PubMed, Scopus, and Web of Science to identify studies exploring spontaneous brain activity and local connectivity in FEP estimated using functional magnetic resonance imaging. 20 LFF and 15 ReHo studies were included. Coordinate-Based Activation Likelihood Estimation Meta-Analyses stratified by brain measures, age (adolescent vs adult), and drug-naïve status were performed to identify spatially-convergent alterations in spontaneous brain activity in FEP.

Study Results

We found a significant increase in LFF in FEP compared to healthy controls (HC) in the right striatum and in ReHo in the left striatum. When pooling together all studies on LFF and ReHo, spontaneous brain activity was increased in the bilateral striatum and superior and middle frontal gyri and decreased in the right precentral gyrus and the right inferior frontal gyrus compared to HC. These results were also replicated in the adult and drug-naïve samples.

Conclusions

Abnormalities in the frontostriatal circuit are present in early psychosis independently of treatment status. Our findings support the view that altered frontostriatal can represent a core neural alteration of the disorder and could be a target of treatment.
Toll‐interacting protein inhibits transforming growth factor beta signaling in mouse lung fibroblasts
Authors: Chow Yu‐Hua , López‐Martínez Cecilia , Liles W. Conrad , Altemeier William A. , Gharib Sina A. , Hung Chi F.
Published: November 2023

Variations in the Toll‐interacting protein (TOLLIP) gene have been identified in genome‐wide association studies to correlate with risk of disease, mortality, and response to N‐acetylcysteine therapy in idiopathic pulmonary fibrosis. Although TOLLIP is known to modulate innate immune responses, its relevance in organ fibrogenesis remains unknown. Prior work in the literature suggests TOLLIP dampens transforming growth factor beta (TGFβ) signaling in human cell lines. In this study, we examined the role of TOLLIP in mouse lung fibroblast (MLF) responses to TGFβ and in the bleomycin model of experimental lung fibrosis using Tollip−/− mice. We hypothesize that if TOLLIP negatively regulates TGFβ signaling, then Tollip−/− mouse lung fibroblasts (MLFs) would have enhanced response to TGFβ treatment, and Tollip−/− mice would develop increased fibrosis following bleomycin challenge. Primary MLFs were stimulated with TGFβ (1 ng/mL) for 24 h. RNA was obtained to assess global transcriptional responses by RNA‐seq and markers of myofibroblast transition by qPCR. Functional assessment of TGFβ‐stimulated MLFs included cell migration by scratch assay, cell proliferation, and matrix invasion through Matrigel. In the in vivo model of lung fibrosis, Tollip−/− mice and wild‐type (WT) littermates were administered bleomycin intratracheally and assessed for fibrosis. We further examined TGFβ signaling in vivo after bleomycin injury by SMAD2, ERK1/2, and TGFβR1 Western blot. In response to TGFβ treatment, both WT and Tollip−/− MLFs exhibited global transcriptional changes consistent with myofibroblast differentiation. However, Tollip−/− MLFs showed greater number of differentially expressed genes compared to WT MLFs and greater upregulation of Acta2 by qPCR. Functionally, Tollip−/− MLFs also exhibited increased migration and Matrigel invasiveness compared to WT. We found evidence of enhanced TGFβ signaling in Tollip−/− through SMAD2 in vitro and in vivo. Tollip−/− mice experienced lower survival using a standard weight‐adjusted dosing without evidence of differences in fibrosis at Day 21. With adjustment of dosing for sex, no differences were observed in fibrosis at Day 21. However, Tollip−/− mice had greater weight loss and increased bronchoalveolar lavage fluid total protein during early resolution at Day 14 compared to WT without evidence of differences in acute lung injury at Day 7, suggesting impaired resolution of lung injury.
20-year Radiographic Outcomes Following Single Level Cervical Disc Arthroplasty
Authors: Foley David P. , Sasso Willa R. , Ye Jason Y. , Vinayek Sheetal , Smucker Joseph D. , McCarthy Michael H. , Boody Barrett S. , Sasso Rick C.
Published: November 2023

Study Design.

Prospective randomized controlled trial.

Objective.

Compare range of motion (ROM) and adjacent segment degeneration (ASD) following cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) at 20-year follow-up.

Summary of Background Data.

ACDF is the standard of treatment for single-level cervical disc degeneration causing radiculopathy. CDA is claimed to reduce shear strain and adjacent-level ROM changes hypothesized to hasten ASD with ACDF.

Methods.

This study collected data on 47 patients randomized to ACDF or CDA. Lateral cervical spine radiographs were evaluated preoperatively, postoperatively, and at 20-years for alignment, ROM, ASD, and heterotopic ossification.

Results.

Eighty-two percent (18/22) of CDA patients and 84% (21/25) of ACDF patients followed up at 20 years. At 20 years, total cervical (C2-C7) ROM was statistically different between the CDA and fusion groups (47.8° vs. 33.4°, P=0.005). Total cervical ROM was not significantly different between preoperative and 20-year periods following CDA (45.6° vs. 47.4°, P=0.772) or ACDF (40.6° vs. 33.0°, P=0.192). Differences in postoperative and 20-year index-level ROM following CDA were not significant (10.1° vs. 10.2°, P=0.952). Final ASD grading was statistically lower following CDA versus ACDF at both adjacent levels (P<0.005). Twenty-year adjacent level ossification development was increased following ACDF versus CDA (P<0.001). Polyethylene mean thickness decreased from 9.4 mm immediately postoperatively to 9.1 mm at 20-year follow up (P=0.013). Differences in adjacent level ROM from preoperative to 20-year follow-up in both the ACDF and CDA groups did not meet statistical significance (P>0.05).

Conclusions.

CDA maintains index-level and total cervical ROM at very long-term follow-up. Total cervical ROM was higher at 20 years in CDA relative to ACDF. CDA results in lower rates of adjacent segment degeneration and adjacent level ossification development than ACDF.
Acute heart failure following pazopanib treatment: a literature review featuring two case reports
Authors: Kertmen Neyran , Kavgaci Gozde , Yildirim Hasan Cagri , Dizdar Omer
Published: November 2023

Tyrosine kinase inhibitors (TKIs) have transformed cancer treatment but are associated with cardiovascular toxicity, including heart failure. This review examines the cardiotoxicity of pazopanib, a VEGFR-TKI, through two case reports and explores potential mechanisms. The importance of vigilant clinical monitoring to prevent cardiac dysfunction in cancer patients receiving pazopanib is emphasized. We present two cases of acute heart failure following pazopanib treatment. Case 1 involves a comorbidity-free, 62-year-old woman with metastatic renal cell carcinoma who experienced irreversible heart failure. In case 2, a 40-year-old woman with a history of anthracycline-containing chemotherapy developed reversible left ventricular systolic dysfunction following pazopanib discontinuation. Both patients received appropriate management for their heart failure symptoms. Case 1’s condition rapidly deteriorated, leading to her unfortunate demise 3 months after starting pazopanib. In contrast, case 2’s cardiac function improved after discontinuing pazopanib. The advent of TKIs has revolutionized cancer treatment, but their association with cardiovascular toxicity necessitates meticulous monitoring of patients. The cases presented here highlight the importance of recognizing and managing cardiotoxicity, particularly in patients without prior cardiovascular risk factors. Understanding the underlying mechanisms and risk factors for TKI-induced heart failure is crucial to optimize patient care and treatment outcomes. Oncologists should be vigilant in identifying clinical symptoms and closely monitoring cardiac function throughout TKI therapy.
Squamous Cell Carcinoma in Situ Achieves Tumor Clearance in More Mohs Stages Than Invasive Squamous Cell Carcinoma
Authors: Kim Yesul , Khan Amaal H. , Papachristou Charalampos , Decker Ashley , Lawrence Naomi
Published: November 2023

BACKGROUND

Squamous cell carcinoma in situ (SCCIS) has more subclinical lateral extension than invasive squamous cell carcinomas (SCC).

OBJECTIVE

To determine whether it takes a greater number of Mohs stages for clearance of SCCIS compared with SCC and whether the difference in final defect size and clinical size is larger in SCCIS than SCC.

METHODS

All Mohs micrographic surgery cases of SCCIS and SCC performed between January 2011 and December 2021 were identified. Number of Mohs stages were recorded and difference in final defect size and initial clinical size were calculated for SCCIS and SCC.

RESULTS

4,363 cases were included, 1,066 SCCIS and 3,297 invasive SCC. The initial clinical size, final defect size, and the size difference were similar between SCCIS and SCC groups. However, SCCIS underwent more Mohs stages to achieve tumor clearance than invasive SCCs (1.5 ± 0.7 vs 1.4 ± 0.7 respectively, p < .001). In fact, 71% of SCCs were cleared after 1 Mohs stage compared with 61.1% of SCCIS.

CONCLUSION

These findings support that SCCIS has more subclinical lateral extension and therefore is appropriate for Mohs surgery.
Clinical Guidance for Dosing and Monitoring Oral Antihormonal Drugs in Patients with Breast Cancer After Roux-en-Y Gastric Bypass
Authors: Kingma Jurjen S. , Peeters Niels W.L. , Knibbe Catherijne A.J. , Agterof Mariette J. , Derksen Wouter J.M. , Burgers Desirée M.T. , van den Broek Marcel P.H.
Published: November 2023

Obesity is associated with an increased risk of cancers, such as breast cancer. Roux-en-Y gastric bypass (RYGB) is a common surgical intervention used to induce weight loss, reduce comorbidities, and improve overall survival. Due to alterations in the gastrointestinal tract, RYGB is associated with changes in oral drug disposition, which can affect treatment outcomes. Oral antihormonal agents were monitored in 9 patients who previously underwent RYGB. The results of therapeutic drug monitoring and estradiol concentrations were analyzed, and a review of the relevant literature was performed. As only 1 of the 6 patients prescribed tamoxifen achieved a therapeutic endoxifen concentration with the standard dose of 20 mg/d, a higher starting dose of 40 mg/d was recommended to increase the probability of attaining a therapeutic plasma concentration. All patients with decreased CYP2D6 metabolic activity could not achieve therapeutic plasma concentrations; therefore, CYP2D6 genotyping was recommended before the initiation of tamoxifen therapy to identify patients who should be switched to aromatase inhibitors. Anastrozole and letrozole exposure in patients who underwent RYGB patients appeared sufficient, with no dose adjustment required. However, until more data become available, monitoring aromatase inhibitor efficacy is recommended. Monitoring the drug concentrations is a viable option; however, only indicative data on therapeutic drug monitoring are available. Therefore, estradiol concentrations should be measured.
Therapeutic Drug Monitoring to Optimize Risperidone Treatment in Children with Autism Spectrum Disorder
Authors: Hermans Rebecca A. , Storm Alaya E.M. , Kloosterboer Sanne M. , Hillegers Manon H.J. , Koch Birgit C.P. , Dierckx Bram , de Winter Brenda C.M.
Published: November 2023

Background:

Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population. In addition, the effect of therapeutic drug monitoring (TDM) on treatment optimization was simulated.

Methods:

In a retrospective cohort (n = 24 children), the target window for risperidone leading to the least increase in body mass index z-scores while retaining effectiveness as measured by the irritability subscale of the Aberrant Behavior Checklist was determined using receiver operating curve analysis. This target range was used to simulate the effect of TDM using a population PK model implemented in the software platform InsightRX. Dosing advice was based on plasma trough concentrations and the dose administered at 12 weeks to simulate whether more children would be on target at 24 weeks after the start of treatment.

Results:

A risperidone sum trough target range of 3.5–7.0 mcg/L would minimize increase in body mass index z-score and optimize effectiveness. Dosing advice using TDM and a population PK model would lead to a larger proportion of children achieving the target concentration range (62.5% versus 16.7%).

Conclusions:

TDM may be a useful tool for optimizing risperidone treatment in children and adolescents with autism spectrum disorder.
Advances in Contact Lens Care Solutions: PVP-I Disinfectant and HAD Wetting Agents From Japan
Authors: Itokawa Takashi , Yamasaki Katsuhide , Suzuki Takashi , Koh Shizuka
Published: November 2023

Half of the individuals who wear contact lenses use reusable lenses that require proper care. Improper contact lens (CL) care and using inadequate disinfecting solutions can lead to lens contamination, CL-related microbial keratitis, and Acanthamoeba keratitis. Oxidative disinfecting solutions, such as hydrogen peroxide, show higher efficacy than multipurpose solutions. Povidone–iodine (PVP-I), an oxidative disinfectant used in ophthalmic surgery, has been proven to be safe and effective. The PVP-I system, a CL disinfecting solution developed in Japan, has demonstrated excellent antimicrobial and antiviral properties. Although CL discomfort does not have a risk of ocular disorders with poor visual prognosis, such as keratitis, CL discomfort can still lead to lens dropout and thus needs to be addressed. To mitigate CL discomfort, it is essential to use disinfecting solutions containing surfactants and wetting agents that improve wettability of the lens surface. A CL solution containing hyaluronic acid derivatives (HADs) as wetting agents that permanently adhere to the lens surface to improve wettability of the lens surface was developed in Japan. There is potential for HAD to be integrated into various solutions. This article reviews the efficacy of novel PVP-I–based disinfecting solution and HAD wetting agents.
Bowman Layer Marking for Correct Placement of Corneal Allogeneic Intrastromal Ring Segments
Authors: Jacob Soosan , Agarwal Amar , Awwad Shady , Parker Jack , Mimouni Michael , J Sambath
Published: November 2023

Corneal allogeneic intrastromal ring segments (CAIRS) refer to the placement of allogeneic rings and segments in intrastromal channels within the cornea. Currently, a deepithelialized donor cornea is used as the allogeneic source for CAIRS and the cut ring is turned sideways and implanted so that the thickness can be varied by varying the distance between the concentric trephine blades. In addition, to obtain a greater effect, CAIRSs are preferred to be implanted with the Bowman layer (BL) facing the corneal apex and posterior stroma facing limbally. Being flexible tissue, it is, however, important to prevent twisting and to maintain correct orientation. We describe a simple technique of marking the BL with a gentian violet surgical marker to simplify CAIRS insertion. BL marking allows easy visibility of twists and helps identify improper orientation, thus allowing correct insertion of CAIRS.