bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells
Authors: Satoh Kazuki , Kobayashi Yoichi , Fujimaki Kaori , Hayashi Shinko , Ishida Saori , Sugiyama Daisuke , Sato Takahiko , Lim Kyungtaek , Miyamoto Megumi , Kozuma Shiho , Kadokura Michinori , Wakita Kenichi , Hata Masato , Hirahara Kazuki , Amano Masato , Watanabe Ichiro , Okamoto Atsushi , Tuettenberg Andrea , Jonuleit Helmut , Tanemura Atsushi , Maruyama Shoichi , Agatsuma Toshinori , Wada Teiji , Nishikawa Hiroyoshi
Published: June 2021

Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.
Consumer Minimalism
Authors: Wilson Anne V , Bellezza Silvia
Published: June 2021

Minimalism in consumption can be expressed in various forms, such as monochromatic home design, wardrobe capsules, tiny home living, and decluttering. This research offers a unified understanding of the variegated displays of minimalism by establishing a conceptual definition of consumer minimalism and developing the 12-item Minimalist Consumer Scale to measure the construct. Three distinct dimensions of consumer minimalism are identified: number of possessions (reflecting the ownership of few possessions), sparse aesthetic (reflecting the preference for simple and uncomplicated designs), and mindfully curated consumption (reflecting the thoughtful selection of possessions). A series of studies, using samples from a variety of populations (N = 3,735) demonstrates the validity and reliability of the tridimensional Minimalist Consumer Scale, situates the measure conceptually and empirically within a broader nomological network of related constructs (e.g., voluntary simplicity, frugality, green values, materialism), and documents the scale’s ability to predict relevant consumer preferences and behaviors.
Halyomorpha halys (Hemiptera: Pentatomidae) on Kiwifruit in Northern Italy: Phenology, Infestation, and Natural Enemies Assessment
Authors: Francati Santolo , Masetti Antonio , Martinelli Riccardo , Mirandola Daniele , Anteghini Giacomo , Busi Riccardo , Dalmonte Francesco , Spinelli Francesco , Burgio Giovanni , Dindo Maria Luisa
Published: June 2021

The brown marmorated stink bug (BMSB), Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), is an Asian invasive plant-feeding insect and an emerging kiwifruit pest. Knowledge about the BMSB dynamics and damage to kiwifruit outside the bug native range is scarce. This 2-yr study was aimed at describing phenology and infestation dynamics of BMSB in green-fleshed and yellow-fleshed kiwifruits. Natural enemies were investigated as well. Field surveys were performed weekly in two sites in Northern Italy by pheromone-baited traps and visual samplings, from early Spring to mid-Autumn. All BMSB life stages were collected and kept under observation to assess occurrence of parasitoids. A sample of fruit was dissected weekly to detect BMSB feeding injuries. In 2018–2019, BMSB was found throughout the growing season with two generations per year with a large overlapping of all life stages. Pheromone-baited traps and visual samplings gave consistent results and can be both considered effective sampling methods on kiwifruit. Fruit injuries were significantly related to kiwifruit development stage, weekly captures of BMSBs by traps, and cultivar. Several BMSB egg masses were found on kiwifruit leaves. Anastatus bifasciatus Geoffroy (Hymenoptera: Eupelmidae), a native egg parasitoid with Palearctic distribution, emerged from 20.14% of eggs in 2018, but the percent parasitism dropped to 0.47% in 2019. In both years, other natural enemies were found exerting negligible pressure on BMSB populations. The determination of reliable economic thresholds for BMSB on kiwifruit is urgently needed to develop a robust and sustainable integrated pest management (IPM) strategy, and this study provides data towards that direction.
The combined application of the anti-RAS1 and anti-RIM101 2'-OMethylRNA oligomers enhances Candida albicans filamentation control
Authors: Barbosa Ana , Araújo Daniela , Henriques Mariana , Silva Sónia
Published: June 2021

Although antisense oligomers (ASOs) have been successfully utilized to control gene expression, they have been little exploited to control Candida albicans virulence's determinants. Filamentation is an important virulence factor of C. albicans, and RAS1 and RIM101 genes are involved in its regulation. Thus, the main goal of this work was to project ASOs, based on 2'-OMethyl chemical modification, to target RAS1 and RIM101 mRNA and to validate its application either alone or in combination, to reduce Candida filamentation in different human body fluids.

It was verified that both, anti-RAS1 2'OMe and anti-RIM101 2'OMe oligomers, were able to reduce the levels of RAS1 and RIM101 genes’ expression and to significantly reduce C. albicans filamentation. Furthermore, the combined application of anti-RAS1 2'OMe oligomer and anti-RIM101 2'OMe oligomer enhances the control of C. albicans filamentation in artificial saliva and urine.

Our work confirms that ASOs are useful tools for research and therapeutic development on the control of candidiasis.
Fundamental relations for the velocity dispersion of stars in the Milky Way
Authors: Sharma Sanjib , Hayden Michael R , Bland-Hawthorn Joss , Stello Dennis , Buder Sven , Zinn Joel C , Kallinger Thomas , Asplund Martin , De Silva Gayandhi M , D’Orazi Valentina , Freeman Ken , Kos Janez , Lewis Geraint F , Lin Jane , Lind Karin , Martell Sarah , Simpson Jeffrey D , Wittenmyer Rob A , Zucker Daniel B , Zwitter Tomaz , Chen Boquan , Cotar Klemen , Esdaile James , Hon Marc , Horner Jonathan , Huber Daniel , Kafle Prajwal R , Khanna Shourya , Ting Yuan-Sen , Nataf David M , Nordlander Thomas , Saadon Mohd Hafiz Mohd , Tepper-Garcia Thor , Tinney C G , Traven Gregor , Watson Fred , Wright Duncan , Wyse Rosemary F G
Published: June 2021

We explore the fundamental relations governing the radial and vertical velocity dispersions of stars in the Milky Way, from combined studies of complementary surveys including GALAH, LAMOST, APOGEE, the NASA Kepler and K2 missions, and Gaia DR2. We find that different stellar samples, even though they target different tracer populations and employ a variety of age estimation techniques, follow the same set of fundamental relations. We provide the clearest evidence to date that, in addition to the well-known dependence on stellar age, the velocity dispersions of stars depend on orbital angular momentum Lz, metallicity, and height above the plane |z|, and are well described by a multiplicatively separable functional form. The dispersions have a power-law dependence on age with exponents of 0.441 ± 0.007 and 0.251 ± 0.006 for σz and σR, respectively, and the power law is valid even for the oldest stars. For the solar neighbourhood stars, the apparent break in the power law for older stars, as seen in previous studies, is due to the anticorrelation of Lz with age. The dispersions decrease with increasing Lz until we reach the Sun’s orbital angular momentum, after which σz increases (implying flaring in the outer disc) while σR flattens. For a given age, the dispersions increase with decreasing metallicity, suggesting that the dispersions increase with birth radius. The dispersions also increase linearly with |z|. The same set of relations that work in the solar neighbourhood also work for stars between 3 < R/kpc < 20. Finally, the high-[α/Fe] stars follow the same relations as the low-[α/Fe] stars.
Frequency analysis of OGLE-IV photometry for classical Cepheids in Galactic fields: non-radial modes and modulations
Authors: Rathour Rajeev Singh , Smolec Radosław , Netzel Henryka
Published: June 2021

We analyse photometry of ∼2000 Galactic Cepheids available in the OGLE Collection of Variable Stars. We analyse both Galactic disc and Galactic bulge fields; stars classified both as single- and multiperiodic. Our goal was to search for additional low-amplitude variability. We extend the sample of multimode radial pulsators by identifying 10 new candidates for double mode and 6 new candidates for triple-mode pulsation. In the first overtone OGLE sample, we found 12 Cepheids with additional periodicity having period ratio $P_{\rm x}/P_{\rm 1O}\in (0.60,\, 0.65)$. These periodicities do not correspond to any other radial mode. While such variables are abundant in the Magellanic Clouds, only one Cepheid of this class was known in the Galaxy before our analysis. Comparing our sample with the Magellanic Cloud Cepheids, we note a systematic shift towards longer pulsation periods for more metal rich Galactic stars. Moreover, in 11 stars we find one more type of additional variability, with characteristic frequencies close to half of that reported in the group with (0.60, 0.65) period ratios. Two out of the above inventory show simultaneous presence of both signals. Most likely, origin of these signals is connected to excitation of non-radial pulsation modes. We report three Cepheids with low-amplitude periodic modulation of pulsation: two stars are single-mode fundamental and first overtone Cepheids and one is a double-mode Cepheid pulsating simultaneously in fundamental and in first overtone modes. Only the former mode is modulated. It is a first detection of periodic modulation of pulsation in this type of double-mode Cepheids.
Finding protoclusters to trace galaxy evolution – I. The finder and its performance
Authors: Wang Kai , Mo H J , Li Cheng , Chen Yangyao
Published: June 2021

We develop a method to identify protoclusters based on dark matter haloes represented by galaxy groups selected from surveys of galaxies at high redshift. We test the performance of this method on haloes in N-body simulations, and find that it can correctly identify more than 85 per cent of the true protoclusters with $\gtrsim 95$ per cent purity and with mass estimates typically within 0.25 dex from their true values. We show how the information provided by the protoclusters can be used to link galaxies in present-day clusters of galaxies with their high-redshift progenitors. Our tests show that the protoclusters identified by our method can recover reliably the progenitor stellar mass distribution of galaxies, thereby providing an avenue to investigate the formation and evolution of present-day galaxy clusters and their member galaxies.
Probing the He ii re-Ionization ERa via Absorbing C iv Historical Yield (HIERACHY) I: A strong outflow from a z ∼ 4.7 quasar
Authors: Yu Xiaodi , Li Jiang-Tao , Qu Zhijie , Roederer Ian U , Bregman Joel N , Fan Xiaohui , Fang Taotao , Johnson Sean D , Wang Feige , Yang Jinyi
Published: June 2021

Outflows from supermassive black holes (SMBHs) play an important role in the co-evolution of themselves, their host galaxies, and the larger scale environments. Such outflows are often characterized by emission and absorption lines in various bands and in a wide velocity range blueshifted from the systematic redshift of the host quasar. In this paper, we report a strong broad line region (BLR) outflow from the z ≈ 4.7 quasar BR 1202-0725 based on the high-resolution optical spectrum taken with the Magellan Inamori Kyocera Echelle (MIKE) spectrograph installed on the 6.5 m Magellan/Clay telescope, obtained from the ‘Probing the He ii re-Ionization ERa via Absorbing C iv Historical Yield’ (HIERACHY) project. This rest-frame ultraviolet (UV) spectrum is characterized by a few significantly blueshifted broad emission lines from high ions; the most significant one is the C iv line at a velocity of $\sim -6500$ km s−1 relative to the H α emission line, which is among the highest velocity BLR outflows in observed quasars at z > 4. The measured properties of UV emission lines from different ions, except for O i and Ly α, also follow a clear trend that higher ions tend to be broader and outflow at higher average velocities. There are multiple C iv and Si iv absorbing components identified on the blue wings of the corresponding emission lines, which may be produced by either the outflow or the intervening absorbers.
Evidence for Fe Kα line and soft X-ray lag in NGC 7456 ultraluminous X-ray source-1
Authors: Mondal Samaresh , Różańska Agata , De Marco Barbara , Markowitz Alex
Published: June 2021

We report the first detection of an Fe Kα line and soft X-ray lag in the ultraluminous X-ray (ULX) source NGC 7456 ULX-1. The XMM–Newton spectra show the presence of the 6.4 keV Fe line at 2.6σ confidence and an upper limit on the FWHM of 32900 km s−1. Assuming that the line arises by reflection from a Keplerian disk, it must originate beyond 85rg from the compact object. As a result of Fourier timing analysis, we found that the soft X-ray photons lag behind the hard X-ray photons with a ∼1300 s delay. The covariance spectra indicate that the hard spectral component is responsible for the correlated variability and the soft X-ray lag. This is the second ULX in which an Fe Kα line is found, the fifth with a soft X-ray lag, and the first with both features detected.
Epigenetic effect of the mycotoxin fumonisin B1 on DNA methylation
Authors: Sugiyama Kei-ichi , Kinoshita Mawo , Furusawa Hiroko , Sato Kaoru , Honma Masamitsu
Published: June 2021

Mycotoxin fumonisin B1 (FB1) is a secondary metabolite that is produced by certain Fusarium species. Although numerous studies demonstrate toxic and carcinogenic effects of FB1, the underlying mechanisms have not been fully elucidated. In this study, we evaluated the epigenetic effects of FB1 for the first time using FLO assays, which detect epigenetic changes that affect the flocculation gene (FLO1) promoter activity in budding yeast. FLO assays showed increased reporter activities of the FLO1 promoter in the presence of 10 and 20 µM FB1. FB1 (20 µM) treatments also promoted flocculation. In subsequent in vitro methylation assays of a bacterial DNA methyltransferase (DNMT), FB1 treatments increased DNMT activities. Moreover, global DNA methylation was significantly increased in HEK293 cells treated with 100 µM FB1. Taken together, these results suggest that FB1 exposure leads to unique epigenetic alterations due to increased DNMT activities and demonstrate that FB1 may be an important risk factor for epigenetic dysfunction-associated human diseases including cancer.
Osteoprotegerin predicts cardiovascular events in patients treated with haemodialysis
Authors: Wu Ping-Hsun , Glerup Rie Io , Svensson My Hanna Sofia , Eriksson Niclas , Christensen Jeppe Hagstrup , Linde Torbjörn , Ljunggren Östen , Fellström Bengt
Published: June 2021

Background

Disturbances in bone mineral metabolism are associated with increased mortality and cardiovascular events (CVEs). However, the association between bone-associated protein biomarkers, mortality and CVEs independent of cytokine activation remains unknown. This study aimed to investigate bone-associated protein biomarkers and the association with inflammatory cytokines and cardiovascular (CV) outcomes.

Methods

This prospective study enrolled haemodialysis patients in Denmark between December 2010 and March 2011. Using a proximity extension proteomics assay, nine bone-associated proteins were examined: cathepsin D (CTSD), cathepsin L1 (CTSL1), dickkopf-related protein 1, fibroblast growth factor 23, leptin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor 2 (TRAIL-R2). The importance of the bone-associated protein markers was evaluated by a random forest (RF) algorithm. The association between bone-associated proteins with all-cause death, CV death and CVEs was analysed in multivariable Cox models adjusted for age, gender, comorbidities, laboratory data and dialysis duration.

Results

We enrolled 331 patients [63.7% men; mean age, 65 years (standard deviation 14.6)] in a prospective cohort study with 5 years of follow-up. When adjusting for confounders, CTSL1 remained associated with all-cause death and four biomarkers were associated with CVEs. However, the association between bone markers and the outcomes was attenuated after adjusting for inflammatory proteins and only OPG remained associated with CVEs in the adjusted model. Evaluating the importance of bone markers by RF, OPG was the most important marker related to CVEs. OPG also improved the prediction of CVEs in integrated discrimination improvement and net reclassification improvement analyses.

Conclusions

OPG, a well-known bone biomarker, was associated with CVEs independent of cytokine activity. In contrast, the association between CVEs and the remaining three bone-associated proteins (TRAIL-R2, CTSD and CTSL1) was affected by cytokine inflammation activity.
Barriers and facilitators to influenza and pneumococcal vaccine hesitancy in rheumatoid arthritis: a qualitative study
Authors: Colmegna Inés , Valerio Valeria , Gosselin-Boucher Vincent , Lacoste Guillaume , Labbe Sara , Lavoie Kim L , Hazel Elizabeth , Ward Brian , Hudson Marie , Peláez Sandra
Published: June 2021

Objectives

Immunization is an essential component of RA care. Nevertheless, vaccine coverage in RA is suboptimal. Contextual, individual and vaccine-related factors influence vaccine acceptance. However, barriers and facilitators of vaccination in RA are not well defined. The aim of this study was to assess perspectives of RA patients and healthcare professionals (HCPs) involved in RA care of barriers and facilitators regarding influenza and pneumococcal vaccines.

Methods

Eight focus groups (four with RA patients and four with HCPs) and eight semi-structured open-ended individual interviews with vaccine-hesitant RA patients were conducted. Data were audio recorded, transcribed verbatim and imported to MAXQDA software. Analysis using the framework of vaccine hesitancy proposed by the Strategic Advisory Group of Experts on Immunization was conducted.

Results

RA patients and HCPs reported common and specific barriers and facilitators to influenza vaccination that included contextual, individual and/or group and vaccine- and/or vaccination-specific factors. A key contextual influence on vaccination was patients’ perception of the media, pharmaceutical industry, authorities, scientists and the medical community at large. Among the individual-related influences, experiences with vaccination, knowledge/awareness and beliefs about health and disease prevention were considered to impact vaccine acceptance. Vaccine-related factors including concerns about vaccine side effects such as RA flares, the safety of new formulations, the mechanism of action, access to vaccines and costs associated with vaccination were identified as actionable barriers.

Conclusion

Acknowledging RA patients’ perceived barriers to influenza and pneumococcal vaccination and implementing specific strategies to address them might increase vaccination coverage in this population.
Maternal sensitivity and infant neural response to touch: an fNIRS study
Authors: Mateus Vera , Osório Ana , Miguel Helga O , Cruz Sara , Sampaio Adriana
Published: June 2021

The mother’s attunement to her infant’s emotional needs influences her use of touching behaviors during mother–infant interactions. Moreover, maternal touch appears to modulate infants’ physiological responses to affective touch. However, little is known about the impact of maternal sensitivity on infants’ touch processing at a brain level. This study explored the association between maternal sensitivity when infants (N = 24) were 7 months old and their patterns of cortical activation to touch at 12 months. Brain activation was measured using functional near-infrared spectroscopy. Changes in oxy-hemoglobin (HbO2) and deoxy-hemoglobin (HHb) concentrations were measured in the left somatosensory cortex and right temporal cortex while infants received two types of tactile stimulation—affective and discriminative touch. Results showed that a lower maternal sensitivity was associated with a higher HbO2 response for discriminative touch over the temporal region. Additionally, infants of less sensitive mothers tended to present a higher response in HbO2 for affective touch over the somatosensory region. These findings suggest that less sensitive interactions might result in a lower exposure to maternal touch, which can be further related to infants’ neural processing of touch.
Paraquat but not diquat induces TGF-β expression and thus activates calcium-NFAT axis for epithelial–mesenchymal transition
Authors: Yang Wenyu , Ma Xinrun , Zhu Yong , Meng Xiaoxiao , Tian Rui , Yang Zhengfeng
Published: June 2021

Paraquat (PQ) and diquat (DQ), two highly efficient herbicides sharing similar chemical backbone, both induce reactive oxygen species and are highly toxic to humans and livestock, however, PQ but not DQ poisoning result in pulmonary fibrosis, the leading cause of high mortality rate in patients suffering PQ toxicity. Understanding the unique mechanism of PQ different from DQ therefore would provide potential strategies to reduce PQ-induced pulmonary fibrosis. Here, we identified that PQ but not DQ continuously upregulates TGF-β expression in alveolar type II (AT II) cells. Importantly, such high expression of TGF-β increases cytosolic calcium levels and further promotes the activation of calcineurin-NFAT axis. TGF-β mainly activates NFATc1 and NFATc2, but not NFATc3 or NFATc4. Administration of the inhibitors targeting cytosolic calcium or calcineurin largely reverses PQ-induced epithelial–mesenchymal transition (EMT), whereas DQ has little effects on activation of NFAT and EMT. Ultimately, PQ poisoned patients exhibit significantly reduced blood calcium levels compared to DQ poisoning, possibly via the large usage of calcium by AT II cells. All in all, we found a vicious cycle that the upregulated TGF-β in PQ-induced EMT further aggravates EMT via promotion of the calcium–calcineurin axis, which could be potential drug targets for treating PQ-induced pulmonary fibrosis.
A Core Outcome Set for Research in Patients on Extracorporeal Membrane Oxygenation
Authors: Hodgson Carol L. , Fulcher Bentley , Mariajoseph Frederick P. , Burrell Aidan J. C. , Pellegrino Vincent , Brodie Daniel , Fan Eddy
Published: June 2021

OBJECTIVES:

A core set of outcomes have been identified and published, which are essential to include in all clinical research evaluating the use of extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events. The purpose of this international modified Delphi study was to determine which measurement tools and the timing of measurement should be selected for the core outcome set for research evaluating patients receiving extracorporeal membrane oxygenation.

DESIGN:

This was a two-round international, multidisciplinary web-based, modified Delphi study.

PATIENTS:

Participants were identified from the International Extracorporeal Membrane Oxygenation Network and the Extracorporeal Life Support Organization, including consumers, multidisciplinary clinicians, researchers and industry partners.

MEASUREMENTS:

Measurement tools and the timing of measurement were identified from a systematic review of the literature and clinical trials registrations. The primary outcome was the percentage of respondents who completed each survey and indicated that a measurement tool as well as the timing of the measurement should “always” be included in a core outcome set.

MAIN RESULTS:

Participant response rates were 46 of 65 (71%) and 40 of 46 (87%) for rounds one and two, respectively, with participants representing, researchers, consumers, and industry partners from 15 countries over five continents. Seven measurement tools were identified for the core outcome set of patients on extracorporeal membrane oxygenation.

CONCLUSIONS:

This study has identified appropriate measurement instruments and the timing of measurement to include in the core outcome set for research evaluating patients receiving extracorporeal membrane oxygenation. This was an important final step to standardize and synthesize research efforts internationally.
Transient Cardiac Injury in Adolescents Receiving the BNT162b2 mRNA COVID-19 Vaccine
Authors: Snapiri Ori , Rosenberg Danziger Chen , Shirman Nina , Weissbach Avichai , Lowenthal Alexander , Ayalon Itay , Adam Dganit , Yarden-Bilavsky Havatzelet , Bilavsky Efraim
Published: June 2021

Background:

Vaccines are paramount in the effort to end the coronavirus disease 2019 global epidemic. BNT162b2 is approved for the vaccination of adolescents over 16 years of age. Systemic adverse events were scarce though the pretested cohort of this age group was relatively small. The aim of the current study is to raise awareness for potential adverse reactions.

Methods:

This is a case series of patients diagnosed with perimyocarditis following vaccination. Patients were compiled from 3 pediatric medical centers in Israel through a network of pediatricians and data regarding those cases was collected. In addition, incidence of perimyocarditis during the vaccination period was compared with previous years.

Results:

All patients were males 16–18 years old, of Jewish descent, who presented with chest pain that began 1–3 days following vaccination (mean, 2.1 days). In 6 of the 7 patients, symptoms began following the 2nd dose and in 1 patient following the 1st dose. All cases were mild and none required cardiovascular or respiratory support. The incidence of perimyocarditis during the vaccination period was elevated in comparison to previous years.

Conclusions:

This case series describes a time association between coronavirus disease 2019 vaccine and perimyocarditis in adolescents. All cases were mild, although only long-term follow-up can reveal the true impact of this cardiac injury. While it seems that the incidence of perimyocarditis during the vaccination campaign period is increased, a more comprehensive data collection on a wider scale should be done. We hope this report will serve as a reminder to report events and allow for analysis of potential adverse reactions.
Crisaborole prevents infiltration of neutrophils to suppress itch in a mouse model of atopic dermatitis
Authors: Sakai Kent , Sanders Kristen M. , Pavlenko Darya , Lozada Taisa , Akiyama Tasuku
Published: June 2021

The phosphodiesterase-4 inhibitor crisaborole exerts an antipruritic effect and is effective for the treatment of mild-to-moderate atopic dermatitis. However, the mechanisms underlying the antipruritic effect of crisaborole are not completely understood. In this study, we tested whether crisaborole affects spontaneous itch-related behavior as well as neutrophil infiltration and epidermal nerve fiber density (ENFD) in the ovalbumin (OVA)-induced mouse model of atopic dermatitis. OVA treatment resulted in atopic-like skin lesions and spontaneous scratching, which was significantly inhibited by crisaborole treatment. OVA treatment significantly increased neutrophil infiltration and nonpeptidergic ENFD compared with vehicle-treated mice. Crisaborole significantly inhibited neutrophil infiltration without a significant effect on nonpeptidergic ENFD. In a cytokine array, crisaborole significantly decreased neutrophil chemokines, such as CXCL1, CXCL2, and CXCL5. Crisaborole may inhibit atopic dermatitis itch through inhibition of neutrophil infiltration and chemokine expression.
Comparison of effective corneal refractive centration to the visual axis: LASIK vs SMILE, a contralateral eye digitized comparison of the postoperative result
Authors: Vingopoulos Filippos , Zisimopoulos Athanasios , Kanellopoulos Anastasios John
Published: June 2021

Purpose:

To define and compare the centration of the ablation effect in laser in situ keratomileusis (LASIK) with the corresponding effect in small-incision lenticule extraction (SMILE), in myopic laser vision correction to possibly explain the refractive performance differences noted between the two procedures in a contralateral eye study.

Setting:

Private ambulatory eye surgery unit.

Design:

Prospective randomized contralateral eye study.

Methods:

In 22 consecutive patients (44 eyes), 1 eye was prospectively randomized to undergo myopic topography-guided LASIK treatment and the contralateral eye to undergo SMILE; digital image analysis of the achieved centration to the aimed corneal vertex was assessed for both procedures on perioperative Scheimpflug tangential curvature maps, using a proprietary digitized methodology.

Results:

The radial displacement measured in micrometers in the above treated 44 eyes, between the attempted centration point on the corneal vertex vs the center of the measured effective anterior corneal curvature flattening was on average 130 ± 62 mm in the 22 eyes of LASIK group and 313 ± 144 mm in the 22 contralateral eyes of the SMILE group (P < .001).

Conclusions:

In this contralateral eye study, topography-guided myopic LASIK was found to achieve significantly better effective centration compared with myopic SMILE, in regard to digitally measured decentration of the effective refractive change achieved in the anterior corneal curvature from the corneal vertex. This may explain the previously reported superior visual outcomes in the LASIK group eyes when compared with the contralateral SMILE group eyes.
Color LED reflection topography: validation of equivalent keratometry reading for IOL power calculation in eyes with previous corneal myopic refractive surgery
Authors: Fernández-Rosés Joaquim , Lamarca José , Hoffer Kenneth J. , Beltrán-Saiz Antonio , Barraquer Rafael I. , Savini Giacomo
Published: June 2021

Purpose:

To compare the accuracy of the equivalent keratometry reading (EKR) from a color LED corneal topographer (Cassini) with that of other no-history formulas for intraocular lens (IOL) power calculation in eyes with previous myopic excimer laser surgery.

Setting:

Centro de Oftalmología Barraquer, Barcelona, Spain.

Design:

Retrospective case series.

Methods:

The refractive outcomes of the Cassini EKR entered into the Haigis formula were compared with those of the Barrett True-K, Haigis-L, and Shammas-PL formulas and the Triple-S method combined with the Haigis formula. Optimized lens constants for virgin eyes were used. The mean prediction error (PE), the median absolute error (MedAE), and the percentage of eyes with a PE within ±0.25 diopter (D), ±0.50 D, ±0.75 D, and ±1.00 D were calculated.

Results:

The study comprised 37 patients (37 eyes). The Haigis-L, Shammas-PL, and Barrett True-K no-history methods produced a myopic mean PE that was significantly different from zero (P < .001, P < .001 and P = .004, respectively), whereas the mean PEs of Cassini EKR and the Triple-S combined with the Haigis formula were not different from zero (P > .05). Repeated-measures analysis of variance disclosed a significant difference among the PE of all methods (P < .0001). The MedAE of the Cassini EKR, Barrett True-K, Haigis-L, Shammas-PL, and Triple-S was, respectively, 0.34 D, 0.34 D, 0.49 D, 0.48 D, and 0.31 D (P = .0026).

Conclusions:

The performance of the combination of standard Haigis formula with Cassini EKR was comparable to other no-history formulas in eyes with previous myopic excimer laser surgery.
Cognitive therapy, mindfulness-based stress reduction, and behavior therapy for the treatment of chronic pain: randomized controlled trial
Authors: Burns John W. , Jensen Mark P. , Thorn Beverly , Lillis Teresa A. , Carmody James , Newman Andrea K. , Keefe Francis
Published: June 2021

Trials of cognitive therapy (CT), mindfulness-based stress reduction (MBSR), and behavior therapy (BT) suggest that all 3 treatments produce reductions in pain and improvements in physical function, mood, and sleep disturbance in people with chronic pain conditions. Fewer studies have compared the relative efficacies of these treatments. In this randomized controlled study, we compared CT, MBSR, BT, and treatment as usual (TAU) in a sample of people with chronic low back pain (N = 521). Eight individual sessions were administered with weekly assessments of outcomes. Consistent with the prior work, we found that CT, MBSR, and BT produced similar pretreatment to posttreatment effects on all outcomes and revealed similar levels of maintenance of treatment gains at 6-month follow-up. All 3 active treatments produced greater improvements than TAU. Weekly assessments allowed us to assess rates of change; ie, how quickly a given treatment produced significant differences, compared with TAU, on a given outcome. The 3 treatments differed significantly from TAU on average by session 6, and this rate of treatment effect was consistent across all treatments. Results suggest the possibility that the specific techniques included in CT, MBSR, and BT may be less important for producing benefits than people participating in any techniques rooted in these evidence-based psychosocial treatments for chronic pain.
Pain by mistake: investigating a link between error-related negativity and pain avoidance behavior
Authors: Traxler Juliane , von Leupoldt Andreas , Vlaeyen Johan W.S.
Published: June 2021

Pain can be considered as a signal of “bodily error”: errors put organisms at danger and activate behavioral defensive systems. If the error is of physical nature, pain is the warning signal that motivates protective action such as avoidance behavior to safeguard our body's integrity. Interestingly, an important component of neural error processing, the error-related negativity (ERN), has been found to be related to avoidance in anxiety disorders. The present study is the first to extend these findings to pain and investigate the relationship between ERN and pain-related avoidance behavior. It was hypothesized that individuals with larger ERN amplitudes would show more pain-related avoidance behavior and would be more persistent in their avoidance despite changes in the environment. Fifty-three healthy individuals performed the Eriksen flanker task during which their brain activity on correct and erroneous motor responses was recorded by means of high-density electroencephalography. Avoidance behavior was assessed with an arm reaching task using the HapticMaster robot arm. The results showed that, in contrast to our hypothesis, avoidance was not related to ERN amplitudes. Surprisingly, persons with elevated ERN amplitudes showed low levels of avoidance specifically during early acquisition trials. In contrast to earlier findings in anxiety disorders, individuals with elevated ERN amplitudes did not engage in more pain-related avoidance behavior. In fact, the opposite pattern was found at the start of acquisition: individuals with higher compared with lower ERN amplitudes were slower in learning to avoid pain. Replications and future studies on the relationship between ERN and avoidance behavior are needed.
The causal-effect of bed rest and post-dural puncture headache in patients receiving diagnostic lumbar puncture: A prospective cohort study
Authors: Tai Chien-Shu , Wu Shang-Liang , Lin Shao-Yu , Liang Ying , Wang Shuu-Jiun , Chen Shih-Pin
Published: June 2021

Background:

Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture. Patients who received lumbar puncture were previously suggested to remain in bed for a certain time to prevent PDPH; however, this concept was challenged by recent studies. We aimed to investigate whether ambulation instead of resting supine following lumbar puncture could increase the risk of PDPH.

Methods:

The study used a prospective cohort design, applying convenience sampling among patients who received diagnostic lumbar puncture between January and September 2018 in the neurology ward of a tertiary medical center. The patients who fulfilled the inclusion criteria were informed that the current practice suggests lying supine for 6 to 8 hours after lumbar puncture, but they were allowed to either follow the suggestion or ambulate by their wills. The timing of bed rest was recorded, in addition to other possible risk factors of PDPH. The study endpoint is the presence or absence of PDPH within 48 hours of lumbar puncture.

Results:

A total of 137 patients who received lumbar puncture were enrolled, including 103 with bed rest following lumbar puncture and 34 without. There was no difference in demographics between the two groups. PDPH was found in 21 patients, with a total follow-up period of 5959 person-hours and an incidence density of 0.35%. There was no significant difference between the incidence of PDPH between the two groups (non-bed rest group 5.9% vs bed rest group 18.4%; p = 0.078), nor was incidence density (non-bed rest group 0.13% vs bed rest group 0.43%, p = 0.113). The results remained the same after adjusting for age.

Conclusion:

Bed rest following lumbar puncture does not prevent PDPH, and even leads to a marginally increased risk of PDPH. Amendment to the current practice guideline post-lumbar puncture care might be needed to improve patient care.
Health care costs associated with primary care physicians versus nurse practitioners and physician assistants
Authors: Rajan Suja S. , Akeroyd Julia M. , Ahmed Sarah T. , Ramsey David J. , Ballantyne Christie M. , Petersen Laura A. , Virani Salim S.
Published: June 2021

Background:

Significant primary care provider (PCP) shortage exists in the United States. Expanding the scope of practice for nurse practitioners (NPs) and physician assistants (PAs) can help alleviate this shortage. The Department of Veterans' Affairs (VA) has been a pioneer in expanding the role of NPs and PAs in primary caregiving.

Purpose:

This study evaluated the health care costs associated with VA patients cared for by NPs and PAs versus primary care physicians (physicians).

Methods:

A retrospective data analysis using two separate cohorts of VA patients, one with diabetes and the other with cardiovascular disease (CVD), was performed. The associations between PCP type and health care costs were analyzed using ordinary least square regressions with logarithmically transformed costs.

Results:

The analyses estimated 12% to 13% (US dollars [USD] 2,626) and 4% to 5% (USD 924) higher costs for patients assigned to physicians as compared with those assigned to NPs and PAs, after adjusting for baseline patient sociodemographics and disease burden, in the diabetes and CVD cohort, respectively. Given the average patient population size of a VA medical center, these cost differences amount to a total difference of USD 14 million/year per center and USD 5 million/year per center for diabetic and CVD patients, respectively.

Implications for practice:

This study highlights the potential cost savings associated with primary caregiving by NPs and PAs. In light of the PCP shortage, the study supports increased involvement of NPs and PAs in primary caregiving. Future studies examining the reasons for these cost differences by provider type are required to provide more scientific evidence for regulatory decision making in this area.
Rates of revascularization and PCI:CABG ratio: a new indicator predicting in-hospital mortality in acute coronary syndromes
Authors: Klein Lloyd W. , Abugroun Ashraf , Daoud Hussein
Published: June 2021

Objective

The principal trend in acute coronary syndrome (ACS) is increasing utilization of percutaneous coronary interventions (PCI) and declining coronary artery bypass graft surgery (CABG) utilization. This study was designed to evaluate whether higher PCI:CABG ratios lead to higher in-hospital PCI or CABG mortality.

Methods

The National Readmission Database for years 2016 was queried for all hospitalized ACS patients who underwent coronary revascularization during their admission. The study population was derived from 355 US hospitals and included 103 021 patients. Hospitals were grouped based on their PCI:CABG ratio into low, intermediate, and high ratio quartiles with a median [interquartile ranges (IQR)] PCI:CABG ratio of 2.9 (2.5–3.2), 5.0 (4.3–5.9) and 8.9 (7.8–10.3), respectively multivariable logistic regression with adjustment for age, demographics and comorbidities were used to identify CABG:PCI ratio related risk for in-hospital CABG and PCI mortality.

Results

Higher PCI:CABG ratios correlated with an increased CABG mortality. There was a median (IQR) mortality of 2.5% (1.6–4.3) in the low ratio quartile; 3.1% (1.9–5.3) in the intermediate quartiles; and 5.3% (3.2–9.1) in the high ratio quartile (P < 0.001). On multivariate analysis, the PCI:CABG ratio was associated with an increased risk for CABG mortality with an adjusted odds ratio of 1.38 (95% CI, 1.14–1.67, P < 0.001) and 2.17 (95% CI, 1.70–2.80, P < 0.001) for hospitals with intermediate and high PCI:CABG ratios, respectively. There was no significant association between PCI:CABG ratio and PCI mortality.

Conclusions

The programmatic PCI:CABG ratio is a valid indicator of optimal case selection. The PCI:CABG ratio correlates with in-hospital mortality in ACS.
The Affordable Care Act and Health Care Access and Utilization Among White, Asian, and Latino Immigrants in California
Authors: Chu Jun , Ortega Alexander N. , Park Sungchul , Vargas-Bustamante Arturo , Roby Dylan H.
Published: June 2021

Objective:

The objective of this study was to examine changes in health care access and utilization for White, Asian, and Latino immigrants associated with the implementation of the Patient Protection and Affordable Care Act (ACA) in California.

Study Design:

Using the 2011–2013 and 2015–2017 California Health Interview Survey, we examined changes in 2 health care access and 2 utilization measures among 3 immigrant racial/ethnic groups. We estimated the unadjusted and adjusted percentage point changes in the pre-ACA and post-ACA periods. Adjusted estimates were obtained using linear probability models controlling for predisposing, enabling, and need factors.

Results:

After the ACA was nationally implemented in 2014, rates of insurance increased for non-Latino (NL) White, NL Asian, and Latino immigrant groups in California. Latino immigrants had the largest increase in insurance coverage (14.3 percentage points), followed by NL Asian immigrants (9.9 percentage points) and NL White immigrants (9.2 percentage points). Despite benefitting from the largest increase in insurance coverage, the proportion of insured Latino immigrants was still lower than that of NL White and NL Asian immigrants. Latino immigrants reported a small but significant decrease in the usual source of care (−2.8 percentage points) and an increase in emergency department utilization (2.9 percentage points) after the ACA. No significant changes were found after the ACA in health care access and utilization among NL White and NL Asian immigrants.

Conclusions:

Insurance coverage increased significantly for these 3 immigrant groups after the ACA. While Latino immigrants had the largest gain in insurance coverage, the proportion of Latino immigrants with insurance remained the lowest among the 3 immigrant racial/ethnic groups.
Baseline 18F-FDG PET textural features as predictors of response to chemotherapy in diffuse large B-cell lymphoma
Authors: Coskun Nazim , Okudan Berna , Uncu Dogan , Kitapci Mehmet Tevfik
Published: June 2021

Purpose

We sought to investigate the performance of radiomics analysis on baseline 18F-FDG PET/CT for predicting response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL).

Material and methods

Forty-five patients who received first-line rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy for DLBCL were included in the study. Radiomics features and standard uptake value (SUV)-based measurements were extracted from baseline PET images for a total of 147 lesions. The selection of the most relevant features was made using the recursive feature elimination algorithm. A machine-learning model was trained using the logistic regression classifier with cross-validation to predict treatment response. The independent predictors of incomplete response were evaluated with multivariable regression analysis.

Results

A total of 14 textural features were selected by the recursive elimination algorithm, achieving a feature-to-lesion ratio of 1:10. The accuracy and area under the receiver operating characteristic curve of the model for predicting incomplete response were 0.87 and 0.81, respectively. Multivariable analysis revealed that SUVmax and gray level co-occurrence matrix dissimilarity were independent predictors of lesions with incomplete response to first-line R-CHOP chemotherapy.

Conclusion

Increased textural heterogeneity in baseline PET images was found to be associated with incomplete response in DLBCL.
The set point: weight destiny established before adulthood?
Authors: Rose Kelsey L. , Evans E. Whitney , Sonneville Kendrin R. , Richmond Tracy
Published: June 2021

Purpose of review

Although the set point is one of the best understood weight defense mechanisms, how and when a set point is established and what causes its disruption are not well understood. The purpose of this review is to address these gaps in the literature by exploring studies on the establishment of the set point theory and the underlying metabolic processes that support its existence.

Recent findings

Research suggests that weight loss achieved through restricted energy intake and increased energy expenditure is difficult to maintain and is often followed by greater weight gain over time. It is hypothesized that such weight gain is driven by an individual's set point, a weight range in which the body seeks to remain by adjusting metabolism (e.g. by moderating energy expenditure based on energy intake in times of diet or energy fluctuation). Similar to adults, weight loss in adolescence results in decreased resting metabolic rate (RMR), and that the RMR remains suppressed even with weight restoration.

Recommending weight loss in youth results in metabolic adaptations to restore weight and weight inclusive approaches may be more appropriate to protect their health and wellbeing.
Mycobacterium tuberculosis in solid organ transplant donors and recipients
Authors: Malinis Maricar , Koff Alan
Published: June 2021

Purpose of review

Due to impaired immune response, solid organ transplant (SOT) recipients are susceptible to tuberculosis (TB) and its subsequent morbidity and mortality. Current prevention strategies, diagnostic and treatment approach to TB infection in donors and recipients were reviewed in this article.

Recent findings

Screening of latent tuberculosis infection (LTBI) in donors and recipients is the cornerstone of TB-preventive strategy in recipients and requires an assessment of TB risk factors, TB-specific immunity testing, and radiographic evaluation. Interferon-gamma release assay has superseded the tuberculin skin test in LTBI evaluation despite its recognized limitations. LTBI treatment should be offered to transplant candidates and living donors before transplantation and donation, respectively. Diagnosis of TB disease can be challenging because of nonspecific clinical presentation in the recipient and is limited by the sensitivity of current diagnostics. The approach to LTBI and TB disease treatment is similar to the general population, but can be challenging because of potential drug interactions and toxicities.

The appropriate evaluation of donors and recipients for TB can mitigate posttransplant TB disease. Current approaches to diagnosis and treatment parallels that of immunocompetent hosts. Future research evaluating existing and novel diagnostics and treatment in transplant recipients is needed.