bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Brexit voting patterns in the British house of commons: an analysis based on Bayesian mixture models with flexible concomitant covariate effects
Authors: Berrettini Marco , Galimberti Giuliano , Ranciati Saverio , Murphy Thomas Brendan
Published: February 2024

The results of some divisions related to Brexit held in the House of Commons are investigated. In particular, a new class of mixture models with concomitant covariates is developed to identify groups of members of parliament with similar voting behaviour. The methodological novelty lies in the flexibility introduced by the use of smooth functions to model the effect of concomitant covariates on the component weights of the mixture. Results show this approach allows to quantify the effect of the age of members of parliament, as well as preferences and competitiveness in the constituencies they represent, on their position towards Brexit.
Whose Anthropocene?: a data-driven look at the prospects for collaboration between natural science, social science, and the humanities
Authors: Santana Carlos , Petrozzo Kathryn , Perkins T J
Published: February 2024

Although the idea of the Anthropocene originated in the earth sciences, there have been increasing calls for questions about the Anthropocene to be addressed by pan-disciplinary groups of researchers from across the natural sciences, social sciences, and humanities. We use data analysis techniques from corpus linguistics to examine academic texts about the Anthropocene from these disciplinary families. We read the data to suggest that barriers to a broadly interdisciplinary study of the Anthropocene are high, but we are also able to identify some areas of common ground that could serve as interdisciplinary bridges.
Preparing Figures for Publication in Microscopy Today
Authors: Maleeff Bev , Levey Gennifer , Price Bob
Published: February 2024

Microscopic and macroscopic images, photographs, and computer-generated graphics are important components of the content published in Microscopy Today. Each type of graphic requires careful attention to its content and composition, that is, how well the image illustrates the facts being described, and its dimensions, resolution, and color balance. This paper is a brief guide to preparing acceptable content for print and digital publication.
Double-mode RR Lyrae stars observed by K2: analysis of high-precision Kepler photometry
Authors: Nemec James M , Linnell Nemec Amanda F , Moskalik Pawel , Molnár László , Plachy Emese , Szabó Róbert , Kolenberg Katrien
Published: February 2024

The results of a Fourier analysis of high-precision Kepler photometry of 75 double-mode RR Lyrae (RRd) stars observed during NASA’s K2 Mission (2014-18) are presented. Seventy-two of the stars are ‘classical’ RRd (cRRd) stars lying along a well-defined curve in the Petersen diagram and showing no evidence of Blazhko modulations. The remaining three stars are ‘anomalous’ RRd (aRRd) stars that lie well below the cRRd curve in the Petersen diagram. These stars have larger fundamental-mode amplitudes than first-overtone amplitudes and exhibit Blazhko variations. Period-amplitude relations for the individual pulsation components of the cRRd stars are examined, as well as correlations involving Fourier phase-difference and amplitude-ratio parameters that characterize the light curves for the two radial modes. A simple statistical model relating the fundamental (P0) and first-overtone (P1) periods to [Fe/H] provides insight into the functional form of the Petersen diagram. A calibration equation for estimating [Fe/H]phot abundances of ‘classical’ RRd stars is derived by inverting the model and using 211 field and 57 globular cluster cRRd stars with spectroscopic metallicities to estimate the model coefficients. The equation is used to obtain [Fe/H]phot for the full sample of 72 K2 cRRd stars and for 2130 cRRd stars observed by the ESA Gaia Mission. Of the 49 K2 cRRd stars that are in the Gaia DR3 catalogue only five were found to be correctly classified, the remainder having been misclassified ‘RRc’ or ‘RRab’.
Probing the small-scale structure of the intergalactic medium with ESPRESSO: spectroscopy of the lensed QSO UM673
Authors: Cristiani Stefano , Cupani Guido , Trost Andrea , D’Odorico Valentina , Guarneri Francesco , Lo Curto Gaspare , Meneghetti Massimo , Di Marcantonio Paolo , Faria João P , González Hernández Jonay I , Lovis Christophe , Martins Carlos J A P , Milaković Dinko , Molaro Paolo , Murphy Michael T , Nunes Nelson J , Pepe Francesco , Rebolo Rafael , Santos Nuno C , Schmidt Tobias M , Sousa Sérgio G , Sozzetti Alessandro , Zapatero Osorio María Rosa
Published: February 2024

The gravitationally lensed quasar J014516.6-094517 at z = 2.719 has been observed with the ESPRESSO instrument at the ESO VLT to obtain high-fidelity spectra of the two images A and B with a resolving power R = 70 000. At the redshifts under investigation (2.1 ≲ z ≲ 2.7), the Lyman forests along the two sightlines are separated by sub-kiloparsec physical distances and exhibit a strong correlation. We find that the two forests are indistinguishable at the present level of signal-to-noise ratio and do not show any global velocity shift, with the cross-correlation peaking at Δv = 12 ± 48 $\rm m~s^{-1}$. The distribution of the difference in velocity of individual Ly α features is compatible with a null average and a mean absolute deviation of 930 $\rm m~s^{-1}$. Significant differences in NH i column density are not detected, putting a limit to the RMS fluctuation in the baryon density on ≲1 proper kpc scales of Δρ/ρ ≲ 3 per cent. On the other hand, metal lines show significant differences both in velocity structure and in column density. A toy model shows that the difference in velocity of the metal features between the two sightlines is compatible with the motions of the baryonic component associated with dark matter haloes of typical mass M ≃ 2 × 1010 M⊙, also compatible with the observed incidence of the metal systems. The present observations confirm the feasibility of the Sandage test of the cosmic redshift drift with high-fidelity spectroscopy of the Lyman forest of distant, bright quasars, but also provide an element of caution about the intrinsic noise associated with the usage of metal features for the same purpose.
Next-generation therapeutics for rare genetic disorders
Authors: Sankar Akhila , Y S Ravi Kumar , Singh Anjali , Roy Riya , Shukla Rashmi , Verma Bhupendra
Published: February 2024

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.
Unraveling the complexity of the senescence-associated secretory phenotype in adamantinomatous craniopharyngioma using multimodal machine learning analysis
Authors: Prince Eric W , Apps John R , Jeang John , Chee Keanu , Medlin Stephen , Jackson Eric M , Dudley Roy , Limbrick David , Naftel Robert , Johnston James , Feldstein Neil , Prolo Laura M , Ginn Kevin , Niazi Toba , Smith Amy , Kilburn Lindsay , Chern Joshua , Leonard Jeffrey , Lam Sandi , Hersh David S , Gonzalez-Meljem Jose Mario , Amani Vladimir , Donson Andrew M , Mitra Siddhartha S , Bandopadhayay Pratiti , Martinez-Barbera Juan Pedro , Hankinson Todd C
Published: February 2024

Background

Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed.

Methods

We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining.

Results

We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells.

Conclusions

A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.
Tumor location and neurocognitive function—Unravelling the association and identifying relevant anatomical substrates in intra-axial brain tumors
Authors: Shah Kanchi , Bhartia Vinayak , Biswas Chandrima , Sahu Arpita , Shetty Prakash M , Singh Vikas , Velayutham Parthiban , Awate Suyash P , Moiyadi Aliasgar V
Published: February 2024

Background

Neurocognitive function is a key outcome indicator of therapy in brain tumors. Understanding the underlying anatomical substrates involved in domain function and the pathophysiological basis of dysfunction can help ameliorate the effects of therapy and tailor directed rehabilitative strategies.

Methods

Hundred adult diffuse gliomas were co-registered onto a common demographic-specific brain template to create tumor localization maps. Voxel-based lesion symptom (VLSM) technique was used to assign an association between individual voxels and neuropsychological dysfunction in various domains (attention and executive function (A & EF), language, memory, visuospatial/constructive abilities, and visuomotor speed). The probability maps thus generated were further co-registered to cortical and subcortical atlases. A permutation-based statistical testing method was used to evaluate the statistically and clinically significant anatomical parcels associated with domain dysfunction and to create heat maps.

Results

Neurocognition was affected in a high proportion of subjects (93%), with A & EF and memory being the most affected domains. Left-sided networks were implicated in patients with A & EF, memory, and language deficits with the perisylvian white matter tracts being the most common across domains. Visuospatial dysfunction was associated with lesions involving the right perisylvian cortical regions, whereas deficits in visuomotor speed were associated with lesions involving primary visual and motor output pathways.

Conclusions

Significant baseline neurocognitive deficits are prevalent in gliomas. These are multidomain and the perisylvian network especially on the left side seems to be very important, being implicated in dysfunction of many domains.
Incidence and survival characteristics of pediatric ganglioglioma from 2004 to 2018, with focus on infratentorial sites
Authors: Chen Yongzhen , Buchanan Paula , Brossier Nicole M , Navalkele Pournima
Published: February 2024

Background

Ganglioglioma (GG) is a slow-growing glioneuronal neoplasm, most frequently seen in the supratentorial location in older children and associated with epilepsy syndromes. GG is rare in the infratentorial location, hence we embarked upon analyzing the National Cancer Institute’s (NCI) Survival, Epidemiology, and End Results (SEER) database to better evaluate GG outcomes by location in comparison to the broader pediatric low-grade glioma (pLGG) population.

Methods

Pediatric patients diagnosed with GG and pLGG from 2004 to 2018 were included in the study. Their demographic, clinical, and survival characteristics were analyzed using SEER*Stat.

Results

This study describes the largest cohort of pediatric GG, including 852 cases from year 2004 to 2018, with focus on infratentorial sites. Patients with brainstem GG or those with subtotally resected disease were identified as having higher risk of death.

Conclusions

Our analysis highlights brainstem GG as a high-risk, poor-prognostic subgroup and elaborates on the incidence and survival characteristic of this lesser-known subgroup.
Hypoxaemia and risk of asphyxia during underground work in artisanal cobalt mines
Authors: Musa Obadia P , Pyana Kitenge J , Carsi Kuhangana T , Verpaele S , Ndala Nyongonyi A , Kayembe Kitenge T , Katoto P d M , Banza Lubaba Nkulu C , Nemery B
Published: February 2024

Background

More than half the cobalt needed for vehicle electrification originates from the southern part of the Democratic Republic of the Congo (DRC), with a substantial part being extracted by artisanal miners.

Aims

To investigate oxygen saturation during underground work among cobalt artisanal miners.

Methods

In a field survey, we measured oxygen saturation (SpO2) and heart rate by pulse oximetry in 86 miners from two underground mines and 24 miners from a surface mine at four different time points: before descent into the mine (T1), at 50 minutes in the mine (T2), upon leaving the shaft (T3), and 10 minutes after having left the mine (T4).

Results

Miners working underground (–36 to –112 meters) were somewhat older (34.8 ± 6.7 years) than those working in the surface mine (32.0 ± 6.5 years), and they worked more hours daily (12.6 ± 1.2 hours) than controls (9.0 ± 0.0 hours). All participants had SpO2 >95% at T1 and T4. At T2, SpO2 dropped below 93% and 80% in 35% and 10% underground miners, respectively; SpO2 was still <93% at T3 in 13%. SpO2 remained stable among surface miners. Later, we showed that underground ambient oxygen levels decreased well below 21% in several pits.

Conclusions

Pulse oximetry revealed relevant hypoxaemia during underground work in a substantial proportion of artisanal miners. Such hypoxaemia without evidence of underlying cardiovascular disease is indicative of low ambient oxygen, due to insufficient mine ventilation. This may cause deaths from asphyxia. The hazards of low ambient oxygen in artisanal mines must be prevented by appropriate technical measures ensuring the supply of sufficient fresh air.
Embodied emissions policies—design options and political mobilization potential
Authors: Jordan Nino David
Published: February 2024

The topic of greenhouse gas emissions embodied in products is gaining in prominence and the possibilities for measuring and verifying them are improving. This provides fertile ground for those who demand that climate policy should address such embodied emissions. There are different design options for policies targeting embodied emissions. Such differences affect which groups can be mobilized in their favour. This paper shows that procurement standards which target intermediate products can mobilize the support of relatively low carbon producers of high carbon materials, while product standards which target final products can mobilize the support of producers of relatively low carbon materials and knowledge-intensive service providers.
Even low levels of tree cover improve dietary quality in West Africa
Authors: den Braber Bowy , Hall Charlotte , Brandt Martin , Reiner Florian , Mugabowindekwe Maurice , Rasmussen Laura Vang
Published: February 2024

Forests are attracting attention as a promising avenue to provide nutritious and “free” food without damaging the environment. Yet, we lack knowledge on the extent to which this holds in areas with sparse tree cover, such as in West Africa. This is largely due to the fact that existing methods are poorly designed to quantify tree cover in drylands. In this study, we estimate how various levels of tree cover across West Africa affect children's (aged 12–59 months) consumption of vitamin A–rich foods. We do so by combining detailed tree cover estimates based on PlanetScope imagery (3 m resolution) with Demographic Health Survey data from >15,000 households. We find that the probability of consuming vitamin A–rich foods increases from 0.45 to 0.53 with an increase in tree cover from the median value of 8.8 to 16.8% (which is the tree cover level at which the predicted probability of consuming vitamin A–rich foods is the highest). Moreover, we observe that the effects of tree cover vary across poverty levels and ecoregions. The poor are more likely than the non-poor to consume vitamin A–rich foods at low levels of tree cover in the lowland forest-savanna ecoregions, whereas the difference between poor and non-poor is less pronounced in the Sahel-Sudan. These results highlight the importance of trees and forests in sustainable food system transformation, even in areas with sparse tree cover.
Gadolinium Concentration Measurement with an Atomic Absorption Spectrophotometer
Authors: Marti Ll , Labarga L
Published: February 2024

Because gadolinium (Gd) has the highest thermal neutron capture cross section, resulting in an 8 MeV gamma cascade upon capture, it has been proposed for dissolution in water Cherenkov detectors to achieve efficient neutron tagging capabilities. Whereas metallic Gd is insoluble in water, several compounds are very easy to dissolve. Gadolinium sulfate, Gd2(SO4)3, has been thoroughly tested and proposed as the best candidate. Accurate measurement of its concentration, free of doubt from impurities in water, is crucial. An atomic absorption spectrophotometer (AAS) is a device that suits this purpose and is widely used to measure the concentration of many elements. In this study, we describe three different approaches to measure Gd sulfate concentrations in water using an AAS: doping samples with potassium and lanthanum, and employing tantalum and tungsten platforms.
Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2 trials
Authors: Cantini Fabrizio , Marchesoni Antonio , Novelli Lucia , Gualberti Giuliana , Marando Francesca , McDearmon-Blondell Erin L , Gao Tianming , McGonagle Dennis , Salvarani Carlo
Published: February 2024

Objectives

To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with PsA from the SELECT-PsA Phase 3 trials.

Methods

Patients with an inadequate response/intolerance to one or more non-biologic DMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0–24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution and protection from enthesitis development through week 56.

Results

Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (–1.7 vs –1.0) and SPARCC index (–3.4 vs –1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in >80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24.

Conclusions

UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis.

Trial registration

ClinicalTrials.gov identifiers: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).
A review of the medicinal uses and biological activity of Piliostigma thonningii (Schum). Milne-Redh.
Authors: Abubakar Ibrahim Babangida , Malami Ibrahim , Muhammad Aliyu , Salihu Shinkafi Tijjani , Shehu Dayyabu , Maduabuchi Aja Patrick
Published: February 2024

Objective

Piliostigma thonningii is a medicinal plant commonly found in Eastern and Western Africa with a potential traditional usage to treat various diseases. Several studies have revealed interesting pharmacological activity of the plant and different phytochemicals were identified. This study critically reviewed the medicinal uses, phytochemistry, and bioactivity of P. thonningii.

Methods

Relevant databases including ISI Web of Knowledge, Science Direct, Scopus, PubMed, and Google Scholar as well as databases for these were searched for information using the keyword P. thonningii and its synonym.

Key findings

P. thonningii is majorly prepared in Africa as a decoction, infusion, maceration, and ointment and administered orally or topically to treat several diseases such as malaria, cancer, hepatitis, diabetes, and others. Pharmacological studies have demonstrated activity including antimalarial, antiviral, antimicrobial, anti-proliferative, and other medicinal properties. Compounds including piliostigmin, C-methyl flavonols, quercetin, and others were among the active components.

Conclusions

The general use of P. thonnigii in various medicinal forms in Africa presents a great opportunity for the development of innovative research toward the production of natural products and nutraceuticals. Nevertheless, additional studies especially in vivo are necessary to further elucidate the mechanism mediating the bioactivities, especially in relation to the medicinal and nutritional uses.
Deep social neuroscience: the promise and peril of using artificial neural networks to study the social brain
Authors: Sievers Beau , Thornton Mark A
Published: February 2024

This review offers an accessible primer to social neuroscientists interested in neural networks. It begins by providing an overview of key concepts in deep learning. It then discusses three ways neural networks can be useful to social neuroscientists: (i) building statistical models to predict behavior from brain activity; (ii) quantifying naturalistic stimuli and social interactions; and (iii) generating cognitive models of social brain function. These applications have the potential to enhance the clinical value of neuroimaging and improve the generalizability of social neuroscience research. We also discuss the significant practical challenges, theoretical limitations and ethical issues faced by deep learning. If the field can successfully navigate these hazards, we believe that artificial neural networks may prove indispensable for the next stage of the field’s development: deep social neuroscience.
Safety, tolerability, and pharmacokinetics of aildenafil citrate tablets, a novel oral PDE5 inhibitor, in healthy Chinese volunteers after multiple-dose administration
Authors: Xie Ran , Jia Bo , Cheng Lu , Zhao Nan , He Xu , Wang Xia , Zhao Xia , Cui Yimin
Published: February 2024

Background

Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate–specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED).

Aim

This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males.

Methods

Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30 and 60 mg.

Outcomes

The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography–tandem mass spectrometry.

Results

Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1 hour and mean terminal half-lives of 2.75 and 3.26 hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30 to 60 mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group.

Clinical Implications

Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1 hour before sexual intercourse in men with ED.

Strengths and Limitations

This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED.

Conclusion

Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30 and 60 mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration.

Clinical Trial Registration

CTR20192473 (http://www.chinadrugtrials.org.cn).
Effects of electrolyte supplementation on performance and physiological responses of preconditioning beef calves
Authors: Ferreira Matheus F L , Hernandez Gracia P , Santos Aline C R , Bohnert David , Upah Nathan , Ranches Juliana
Published: February 2024

The objective of this study was to evaluate the effects of electrolyte solution supplementation on the performance and physiological responses of beef calves during a 45-d preconditioning phase. Forty Angus × Hereford steers (230.4 ± 4.8 kg body weight [BW]) were sorted into 20 pens (2 steers/pen) following weaning (day 0). Treatments were randomly assigned to pens: (1) control: access to water only and (2) electrolyte: access to water and electrolyte solution supplementation (10% of total daily water intake) from days 1 to 14. Calf BW and blood samples were collected on days 0, 1, 3, 7, 14, 21, and 44 of the study. Blood samples were analyzed for sodium, potassium, albumin, haptoglobin, ceruloplasmin, and cortisol. All variables were analyzed using the MIXED procedure of SAS. Electrolyte solution consumption was estimated at 0.70 kg/calf daily (SEM ± 0.21). Calves assigned to the Electrolyte treatment had greater water and total liquid intake than control (P < 0.05). No effects of treatment were observed on ADG or BW (P > 0.05). Effects of day (P < 0.004), but not treatment or treatment × day were observed for sodium, potassium, albumin, cortisol, ceruloplasmin, and haptoglobin. Electrolyte solution supplementation during the preconditioning period did not improve performance nor influenced stress-related markers, however improved liquid intake.
Genomic surveillance and evolutionary dynamics of type 2 porcine reproductive and respiratory syndrome virus in China spanning the African swine fever outbreak
Authors: Wu Zhiyong , Chang Tong , Wang Decheng , Zhang Hongliang , Liu Haizhou , Huang Xinyi , Tian Zhijun , Tian Xiaoxiao , Liu Di , An Tongqing , Yan Yi
Published: February 2024

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a serious threat to the pig industry in China. Our previous study demonstrated that PRRSV persists with local circulations and overseas imports in China and has formed a relatively stable epidemic pattern. However, the sudden African swine fever (ASF) outbreak in 2018 caused serious damage to China’s pig industry structure, which resulted in about 40 per cent of pigs being slaughtered. The pig yields recovered by the end of 2019. Thus, whether the ASF outbreak reframed PRRSV evolution with changes in pig populations and further posed new threats to the pig industry becomes a matter of concern. For this purpose, we conducted genomic surveillance and recombination, NSP2 polymorphism, population dynamics, and geographical spread analysis of PRRSV-2, which is dominant in China. The results showed that the prevalence of ASF had no significant effects on genetic diversities like lineage composition, recombination patterns, and NSP2 insertion and deletion patterns but was likely to lead to changes in PRRSV-2 recombination frequency. As for circulation of the two major sub-lineages of Lineage 1, there was no apparent transmission of NADC30-like among provinces, while NADC34-like had obvious signs of inter-provincial transmission and foreign importation during the ASF epidemic. In addition, two suspected vaccine recombinant epidemic strains suggest a slight safety issue of vaccine use. Herein, the interference of ASF to the PRRSV-2 evolutionary pattern was evaluated and vaccine safety was analyzed, in order to monitor the potential threat of PRRSV-2 to China’s pig industry in the post-epidemic era of ASF.
Endothelium‐mediated regulation of platelet activation: Involvement of multiple protein kinases
Authors: Provenzale Isabella , Solari Fiorella A. , Schönichen Claudia , Brouns Sanne L. N. , Fernández Delia I. , Kuijpers Marijke J. E. , van der Meijden Paola E. J. , Gibbins Jonathan M. , Sickmann Albert , Jones Chris , Heemskerk Johan W. M.
Published: February 2024

The endothelial regulation of platelet activity is incompletely understood. Here we describe novel approaches to find molecular pathways implicated on the platelet–endothelium interaction. Using high‐shear whole‐blood microfluidics, employing coagulant or non‐coagulant conditions at physiological temperature, we observed that the presence of human umbilical vein endothelial cells (HUVEC) strongly suppressed platelet adhesion and activation, via the collagen receptor glycoprotein VI (GPVI) and the PAR receptors for thrombin. Real‐time monitoring of the cytosolic Ca2+ rises in the platelets indicated no major improvement of inhibition by prostacyclin or nitric oxide. Similarly under stasis, exposure of isolated platelets to HUVEC reduced the Ca2+ responses by collagen‐related peptide (CRP‐XL, GPVI agonist) and thrombin (PAR agonist). We then analyzed the label‐free phosphoproteome of platelets (three donors), exposed to HUVEC, CRP‐XL, and/or thrombin. High‐resolution mass spectrometry gave 5463 phosphopeptides, corresponding to 1472 proteins, with good correlation between biological and technical replicates (R > .86). Stringent filtering steps revealed 26 regulatory pathways (Reactome) and 143 regulated kinase substrates (PhosphoSitePlus), giving a set of protein phosphorylation sites that was differentially (44) or similarly (110) regulated by HUVEC or agonist exposure. The differential regulation was confirmed by stable‐isotope analysis of platelets from two additional donors. Substrate analysis indicated major roles of poorly studied protein kinase classes (MAPK, CDK, DYRK, STK, PKC members). Collectively, these results reveal a resetting of the protein phosphorylation profile in platelets exposed to endothelium or to conventional agonists and to endothelium‐promoted activity of a multi‐kinase network, beyond classical prostacyclin and nitric oxide actors, that may contribute to platelet inhibition.
Histone deacetylase 6 deficiency protects the liver against ischemia/reperfusion injury by activating PI3K/AKT/mTOR signaling
Authors: Pan Jie , Yu Qiwen , Song Yaodong , Cui Zongchao , He Qianqian , Cui Mengwei , Mei Chaopeng , Cui Huning , Wang Haifeng , Li Huihui , Chen Sanyang
Published: February 2024

Liver transplantation (LT) is the only effective method to treat end‐stage liver disease. Hepatic ischemia‐reperfusion injury (IRI) continues to limit the prognosis of patients receiving LT. Histone deacetylase 6 (HDAC6) is a unique HDAC member involved in inflammation and apoptosis. However, its role and mechanism in hepatic IRI have not yet been reported. We examined HDAC6 levels in liver tissue from LT patients, mice challenged with liver IRI, and hepatocytes subjected to hypoxia/reoxygenation (H/R). In addition, HDAC6 global‐knockout (HDAC6‐KO) mice, adeno‐associated virus‐mediated liver‐specific HDAC6 overexpressing (HDAC6‐LTG) mice, and their corresponding controls were used to construct hepatic IRI models. Hepatic histology, inflammatory responses, and apoptosis were detected to assess liver injury. The molecular mechanisms of HDAC6 in hepatic IRI were explored in vivo and in vitro. Moreover, the HDAC6‐selective inhibitor tubastatin A was used to detect the therapeutic effect of HDAC6 on liver IRI. Together, our results showed that HDAC6 expression was significantly upregulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Compared with control mice, HDAC6 deficiency mitigated liver IRI by inhibiting inflammatory responses and apoptosis, whereas HDAC6‐LTG mice displayed the opposite phenotype. Further molecular experiments show that HDAC6 bound to and deacetylated AKT and HDAC6 deficiency improved liver IRI by activating PI3K/AKT/mTOR signaling. In conclusion, HDAC6 is a key mediator of hepatic IRI that functions to promote inflammation and apoptosis via PI3K/AKT/mTOR signaling. Targeting hepatic HDAC6 inhibition may be a promising approach to attenuate liver IRI.
Building a Trauma-Informed Community: Applying Community Building Circles to an Academic Health Research Setting
Authors: Shetty Neha , Pierson Elizabeth , Manders Khamera B. , Sun YiLing , Masciantonio Elizabeth , Sinko Laura
Published: February 2024

Problem

Within health science disciplines, power dynamics exist that can not only perpetuate harm but also foster feelings of powerlessness and disengagement. Although diversity, equity, and inclusion approaches have been prioritized by many institutions to improve student and staff recruitment, few effective structures exist to promote the retention, support, and inclusion of these individuals.

Approach

Restorative justice circles facilitate a collaborative and personal exercise that welcomes the input of all members, thus acting as a catalyst toward broader and more deeply rooted culture changes and conflict resolution. Restorative justice circles can be applied to strengthen academic learning environments by building community and creating intentional dialog spaces to promote accountability and belonging. The Phoenix Gender-based Violence Lab is an interdisciplinary health research lab composed of diverse researchers who meet monthly for a restorative justice–inspired community-building circle and discussion. The lab members participated in community-building circles from August 2021 to August 2022 during which circle facilitators aimed to prioritize safety, trustworthiness, and transparency and provide collaboration opportunities.

Outcomes

All 10 research team members consented to an anonymous evaluation survey to share their perspectives about incorporating this approach into lab time. Research team members expressed many benefits of circle discussions, including mitigated power dynamics (n = 5), increased lab cohesion (n = 9), improved research processes (n = 6), and enhanced honesty and accountability (n = 4).

Next Steps

Circle practice has shown promising results within the Phoenix Gender-based Violence Lab, indicating that other academic and medical settings should consider its potential to enhance group dynamics, foster accountability, and cultivate deeper collaboration and appreciation among group members. Further investigation of circle practice in diverse medical and academic settings is needed to fully comprehend the range of outcomes resulting from this intervention and whether they align with the fundamental principles of restorative justice.
The Effectiveness of Adjuvant PD-1 Inhibitors in Patients With Surgically Resected Stage III/IV Acral Melanoma
Authors: Arak Haci , Erkiliç Suna , Yaslikaya Şendağ , Eylemer Mocan Eda , Aktaş Gökmen , Özdemir Melek , Semiz Hüseyin Salih , kiliçkap Saadettin , Özalp Faruk Recep , Sever Özlem Nuray , Akdağ Goncagül , Ağaoğlu Ahmet Burak , Özçelik Melike , Sari Murat , Arcagök Murat , Anik Hicran , Yayla Şaziye Burçak , Sever Nadiye , Açar Fatma Pinar , Bayrakçi İsmail , Turhal Serdar , Ayhan Murat , Kuş Tülay ,   Turkish Oncology Group Study
Published: February 2024

Our aim was to assess the efficacy of adjuvant programmed cell death protein-1 (PD-1) inhibitors and compare the other adjuvant treatments in patients with surgically resected stage III or IV acral melanoma. This study is a multicenter, retrospective analysis. We included 114 patients with stage III or IV acral malignant melanoma who underwent surgery within the past 10 years. We analyzed the effect of adjuvant programmed cell death protein-1 inhibitors on disease-free survival (DFS). The mean follow-up was 40 months, during which 69 (59.5%) patients experienced recurrence. Among the participants, 64 (56.1%) received systemic adjuvant therapy. Specifically, 48.4% received anti–PD-1 therapy, 29.7% received interferon, 14.1% received tezozolomide, and 7.8% received B-Raf proto-oncogene/mitogen-activated protein kinase inhibitors. Patients who received adjuvant therapy had a median DFS of 24 (10.9–37.2) months, whereas those who did not receive adjuvant therapy had a median DFS of 15 (9.8–20.2) months. Multivariate analysis for DFS revealed that the receipt of adjuvant therapy and lymph node metastasis stage were independent significant parameters (P = 0.021, P = 0.018, respectively). No statistically significant difference was observed for DFS between programmed cell death protein-1 inhibitor treatment and other adjuvant treatments. Regarding overall survival (OS), patients who received adjuvant treatment had a median OS of 71 (30.4–111.7) months, whereas those who did not receive adjuvant treatment had a median OS of 38 (16.7–59.3; P = 0.023) months. In addition, there were no significant differences in OS observed between various adjuvant treatment agents (P = 0.122). In our study, we have shown that adjuvant therapy had a positive effect on both DFS and OS in patients with stages III–IV acral melanoma who underwent curative intent surgery. Notably, we found no significant differences between anti–PD-1 therapy and other adjuvant therapies.
Room for Improvement: The Impact of Guideline-Recommended Extended Thromboprophylaxis in Patients Undergoing Abdominal Surgery for Colorectal and Anal Cancer at a Tertiary Referral Center
Authors: Broccard Sacha P. , Edwards Michael A. , Brennan Emily R. , Spaulding Aaron C. , DeLeon Michelle , Mishra Nitin , Casler John D. , Colibaseanu Dorin T.
Published: February 2024

BACKGROUND:

Venous thromboembolism occurs in approximately 2% of patients undergoing abdominal and pelvic surgery for cancers of the colon, rectum, and anus, and is considered preventable. The American Society of Colon and Rectal Surgeons recommends extended prophylaxis in high-risk patients, but there is low adherence to the guidelines.

OBJECTIVE:

This study aims to analyze the impact of venous thromboembolism risk-guided prophylaxis in patients undergoing elective abdominal and pelvic surgeries for colorectal and anal cancers from 2016 to 2021.

DESIGN:

This was a retrospective analysis.

SETTING:

The study was conducted at a multisite tertiary referral academic healthcare system.

PATIENTS:

Patients who underwent elective abdominal or pelvic surgery for colon, rectal or anal cancer.

MAIN OUTCOME MEASURES:

Receipt of Caprini-guided venous thromboembolism prophylaxis, 90 days postoperative rate of deep vein thrombosis, pulmonary embolism, venous thromboembolism, and bleeding events.

RESULTS:

A total of 3,504 patients underwent elective operations, of which 2,224 (63%) received appropriate thromboprophylaxis in the inpatient setting. In the post-discharged cohort of 2,769 patients, only 2% received appropriate thromboprophylaxis in which no thromboembolic events were observed. In the group receiving inappropriate thromboprophylaxis, at 90 days post-discharge, the deep vein thrombosis, pulmonary embolism, and venous thromboembolism rates were 0.60%, 0.40%, and 0.88%, respectively. Postoperative bleeding was not different between the two groups.

LIMITATIONS:

Limitations to our study include its retrospective nature, use of aggregated electronic medical records, and single healthcare system experience.

CONCLUSION:

Most patients in our healthcare system undergoing abdominal or pelvic surgery for cancers of the colon, rectum, and anus were discharged without appropriate Caprini-guided VTE prophylaxis. Risk-guided prophylaxis was associated with decreased rates of in-hospital and discharged venous thromboembolism without an increase in bleeding complications. See Video Abstract.
Current Treatment and Immunomodulation Strategies in Acute Myocarditis
Authors: Ferone Emma , Segev Amitai , Tempo Erika , Gentile Piero , Elsanhoury Ahmed , Baggio Chiara , Artico Jessica , Bhatti Prashan , Scott Paul , Bobbio Emanuele , Merlo Marco , Ameri Pietro , Sinagra Gianfranco , Tschöpe Carsten , Bromage Daniel , Cannata Antonio
Published: February 2024

Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.
Surgical Outcome After Treatment of Radiation-Induced Scleral Necrosis in Patients With Uveal Melanoma
Authors: Jabbarli Leyla , Biewald Eva , Guberina Maja , Le Guin Claudia H.D. , Thomasen Henning , Fiorentzis Miltiadis , Sokolenko Ekaterina , Flühs Dirk , Bornfeld Norbert , Stuschke Martin , Bechrakis Nikolaos E. , Rating Philipp
Published: February 2024

Purpose:

Surgical repair might be required in patients with uveal melanoma (UM) that develop advanced forms of radiation-induced scleral necrosis (RISN). In this monocentric long-term observational study, we aimed at analyzing the treatment outcome after RISN surgery.

Methods:

All consecutive cases with UM who underwent surgical intervention for RISN between 1999 and 2020 were included. Achievement of the tectonic stability and evaluation of incidence and the risk factors for a repetitive patch surgery (RPS) were the main endpoints.

Results:

The final analysis included 57 patients (mean age: 58.7 years; 63.2% female patients), where 55 individuals underwent a patch grafting, and 2 cases were treated with conjunctival reconstructive surgery. The mean follow-up time after grafting was 38.5 months (0.03–221.1 months). Tectonic stability was achieved in 56 (98.3%) patients. Scleral graft (38/55, 69.1%) was the most frequent patching material, followed by Tutopatch (7/55, 12.7%), corneal graft (7/55, 12.7%), dura graft (2/55, 3.6%), and fascia lata (FL) graft (1/55, 1.8%). Eleven patients (20%) underwent RPS after the mean time of 12.9 months (0.3–50.3 months). In the final multivariate Cox regression analysis, the use of Tutopatch (5/7; 71.4%, adjusted hazard ratio = 4.66, P = 0.044) and RISN progression after patch grafting (9/11; 81.8%, adjusted hazard ratio = 9.67, P = 0.008) were independent risk factors for RPS.

Conclusions:

RISN surgery maintains long-term tectonic stability in most of the cases underwent surgical repair for RISN after brachytherapy for UM. Depending on graft material and, particularly, further RISN progression, an RPS might be necessary in certain cases.
Long-Term Outcomes of 6-Week Treatment of Lotilaner Ophthalmic Solution, 0.25%, for Demodex Blepharitis: A Noninterventional Extension Study
Authors: Sadri Ehsan , Paauw James D. , Ciolino Joseph B. , Nijm Lisa , Simmons Blake , Meyer John , Gaddie Ian Benjamin , Berdy Gregg J. , Holdbrook Mark , Baba Stephanie N. , Jalalat Parisa , Yeu Elizabeth
Published: February 2024

Purpose:

The aim of this study was to evaluate the long-term outcomes of lotilaner ophthalmic solution, 0.25%, in the treatment of Demodex blepharitis.

Methods:

This observational, extension study included patients with Demodex blepharitis (N = 239) who completed the Saturn-1 study and presented for the day 180 visit. All participants were assessed at days 180 and 365 after the initiation of 6-week treatment with the study drug or its vehicle.

Results:

The proportion of patients with 0 to 2 collarettes (grade 0) was significantly higher in the study group (N = 128 patients) than in the control group (N = 111 patients) (39.8% vs. 2.7% at day 180 and 23.5% vs. 2.9% at day 365; P < 0.0001). Similarly, the proportion of patients with ≤10 collarettes (collarette grade 0–1) in the study group was significantly higher than in the control group (70.3% vs. 18.0% at day 180 and 62.6% vs. 21.9% at day 365; P < 0.0001). In the study group, erythema continued to improve even after completion of the 6-week lotilaner treatment. No serious ocular adverse events were observed in the study group, and there was 1 treatment-related ocular adverse event in the study group, which was considered mild.

Conclusions:

After 6-week treatment with lotilaner ophthalmic solution, 0.25%, for Demodex blepharitis, no long-term concerns were observed during 1 year of follow-up. A high proportion of patients with 0 to 2 collarettes (grade 0) or ≤10 collarettes (collarette grade of 0 or 1) was observed throughout 1 year of follow-up, indicating that the efficacy of lotilaner ophthalmic solution, 0.25%, against Demodex blepharitis may last well after completion of therapy.