bluuebunny/crossref_metadata_2025 huggingface dataset:
Description of patient questions received by clinical pharmacists in the Nudge Study
Authors: Marrs Joel C , Orlando Steven T , Saseen Joseph J , Novins-Montague Sylvie , Sandy Lisa Caputo , Waughtal Joy , Glorioso Thomas J , Ho P Michael
Published: June 2023

Purpose

The Nudge Study is a patient level–randomized trial testing different text message medication refill reminders sent to patients assigned to 4 arms: (1) usual care, (2) generic text, (3) optimized text, and (4) optimized text plus chatbot. This report describes the frequency and types of patient questions sent to clinical pharmacists (CPs) following text reminders.

Methods

Patients were enrolled from Denver Health and Hospital Authority (DHHA) and Veterans Affairs Eastern Colorado Health Care System (VA ECHCS) from October 1, 2019, through May 30, 2021. Included patients responded to at least 1 text or interactive voice response (IVR) message. Patients were dichotomized as those who posed at least 1 question to a CP and those who posed no questions.

Results

Of the 6,325 patients enrolled in an intervention arm, 3,323 (52.5%) responded to at least 1 text or IVR message, and among those responding, 305 (9.2%) responded with a pharmacist question. Patient factors associated with submitting a CP question included age (45-74 years), enrollment from DHHA, and receipt of the optimized text or optimized text plus chatbot message versus the generic text. Questions to CP were in the following categories: medication related (48.2%), refill logistics (38.4%), cost (9.2%), and other (17.7%).

Conclusion

In a text messaging intervention focused on medication refills, there were few questions directed to the CP. Patients assigned to receive optimized texts were more likely to have questions. We hypothesize that this may suggest greater patient engagement regarding their condition, resulting in more questions.
Facial Hypertrophy as a Complication of Weight Gain in Autologous Fat Graft Patients: Considerations and Recommendations
Authors: Anderson Lexy , Nguyen Clara Do Tran , Trinh Kathleen , Dorfman Robert , Tandon Vickram , Do Nicholas , Lambros Val , Grotting James , Song David , Delong Michael
Published: June 2023

Fat grafting can restore facial volume for reconstructive and cosmetic indications. Common practice often involves extracting lipoaspirate from the most abundant anatomic location. However, grafted fat retains the phenotypic characteristics of its original location and can undergo exaggerated hypertrophy with patient weight fluctuations. The aim of this study was to systematically assess the literature to summarize the reported effects of postoperative weight gain on facial hypertrophy in patients after facial fat grafting and to determine potentially avoidable factors. A search through PubMed/MEDLINE was conducted on October 4, 2022, to identify relevant articles with appropriate search terms. No lower date limit was applied and all eligible nonanimal clinical articles in English were included for review. Reports were summarized and presented as descriptive statistics. The search generated 714 articles. After abstract and full-text review of the initial set of articles, 6 were included in our analysis. All articles described poor cosmetic outcomes resulting from nonanatomic hypertrophy of the grafted fat. None of the articles reported a thorough methodology for selecting the donor site to minimize fat hypertrophy with potential future weight fluctuations. Grafted facial fat is susceptible to exaggerated hypertrophy as a result of changes in patient weight. Specifically, harvesting lipoaspirate from maximally abundant areas of the body may increase this risk. Individualizing the area of fat donation may attenuate unwanted fat growth and further contribute to increased patient quality of life.

Level of Evidence: 4
Man, or Machine? Artificial Intelligence Language Systems in Plastic Surgery
Authors: Palacios Jose F , Bastidas Nicholas
Published: June 2023

Artificial intelligence (AI) language models are computer programs trained to understand and generate human-like text. The latest AI language models available to the public have impressive language generation capability with immediate applications in both academia and private practice. Plastic surgeons can immediately leverage this technology to more efficiently allocate valuable human capital to higher-yield tasks. This can ultimately translate to higher patient volume, higher research output, and improved patient communication. Commercially available models offer business solutions that should not be ignored by plastic surgeons hoping to establish, optimize, or grow their practices. In this paper, the authors review the current state of AI language systems, discuss potential applications, and explore the risks and limitations of this technology.
Farrerol attenuates glutamate-induced apoptosis in HT22 cells via the Nrf2/heme oxygenase-1 pathway
Authors: Gao Liying , Wang Tong , Zhuoma Dongzhi , Yuan Ruiying , Huang Shan , Li Bin
Published: June 2023

Farrerol is a flavonoid found in plants with a wide range of pharmacological effects, including protection and enhancement of nerve cell function, as well as antioxidant and antibacterial properties, among others. Neurodegenerative diseases are irreversible neurological disorders resulting from the loss of neuronal cells in the brain and spinal cord. In this experiment, we investigated the neuroprotective and antioxidant effects of farrerol on glutamate-induced HT22 cells. Our results showed that farrerol inhibited reactive oxygen species expression, apoptosis, mitochondrial damage, and the activation of caspases 3 and 9 in HT22 cells induced by glutamate. Additionally, farrerol potentially regulated the Nrf2/heme oxygenase-1 (HO-1) signaling pathway, as it attenuated the nuclear translocation of Nrf2 and promoted the expression of HO-1. These findings suggest that farrerol has potential as a new therapeutic option.
Genetic fine-mapping from summary data using a nonlocal prior improves the detection of multiple causal variants
Authors: Karhunen Ville , Launonen Ilkka , Järvelin Marjo-Riitta , Sebert Sylvain , Sillanpää Mikko J
Published: June 2023

Motivation

Genome-wide association studies (GWAS) have been successful in identifying genomic loci associated with complex traits. Genetic fine-mapping aims to detect independent causal variants from the GWAS-identified loci, adjusting for linkage disequilibrium patterns.

Results

We present “FiniMOM” (fine-mapping using a product inverse-moment prior), a novel Bayesian fine-mapping method for summarized genetic associations. For causal effects, the method uses a nonlocal inverse-moment prior, which is a natural prior distribution to model non-null effects in finite samples. A beta-binomial prior is set for the number of causal variants, with a parameterization that can be used to control for potential misspecifications in the linkage disequilibrium reference. The results of simulations studies aimed to mimic a typical GWAS on circulating protein levels show improved credible set coverage and power of the proposed method over current state-of-the-art fine-mapping method SuSiE, especially in the case of multiple causal variants within a locus.

Availability and implementation

https://vkarhune.github.io/finimom/.
Plasmid permissiveness of wastewater microbiomes can be predicted from 16S rRNA sequences by machine learning
Authors: Moradigaravand Danesh , Li Liguan , Dechesne Arnaud , Nesme Joseph , de la Cruz Roberto , Ahmad Huda , Banzhaf Manuel , Sørensen Søren J , Smets Barth F , Kreft Jan-Ulrich
Published: June 2023

Motivation

Wastewater treatment plants (WWTPs) harbor a dense and diverse microbial community. They constantly receive antimicrobial residues and resistant strains, and therefore provide conditions for horizontal gene transfer (HGT) of antimicrobial resistance (AMR) determinants. This facilitates the transmission of clinically important genes between, e.g. enteric and environmental bacteria, and vice versa. Despite the clinical importance, tools for predicting HGT remain underdeveloped.

Results

In this study, we examined to which extent water cycle microbial community composition, as inferred by partial 16S rRNA gene sequences, can predict plasmid permissiveness, i.e. the ability of cells to receive a plasmid through conjugation, based on data from standardized filter mating assays using fluorescent bio-reporter plasmids. We leveraged a range of machine learning models for predicting the permissiveness for each taxon in the community, representing the range of hosts a plasmid is able to transfer to, for three broad host-range resistance IncP plasmids (pKJK5, pB10, and RP4). Our results indicate that the predicted permissiveness from the best performing model (random forest) showed a moderate-to-strong average correlation of 0.49 for pB10 [95% confidence interval (CI): 0.44–0.55], 0.43 for pKJK5 (0.95% CI: 0.41–0.49), and 0.53 for RP4 (0.95% CI: 0.48–0.57) with the experimental permissiveness in the unseen test dataset. Predictive phylogenetic signals occurred despite the broad host-range nature of these plasmids. Our results provide a framework that contributes to the assessment of the risk of AMR pollution in wastewater systems.

Availability and implementation

The predictive tool is available as an application at https://github.com/DaneshMoradigaravand/PlasmidPerm.
Faithfully Describing and Responding to Addiction and Pain: Christian “Homefulness” and Desire
Authors: Swinton John , Yang Emmy
Published: June 2023

This investigation develops in three steps. First, we seek to complexify the opioid crisis in a way that helps us to see how the issues of misguided desire and misplaced attachments are fundamentally important for a theological account of opioid addiction.1 Second, acknowledging the connections between pain and opioid addiction, we explore some of the ways in which our understanding of pain can influence our understanding of and responses to opioid use. Finally, we offer some tentative reflections on the theological and ecclesial dimensions of the opioid crisis which hold the potential to influence the nature of a Christian response to the issues. Having laid out these steps, we argue for the church’s calling, where she complexifies the narratives about the opioid crisis and provides individuals suffering from opioid use “homeful” encounters with God and the community.
Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with chronic kidney disease: meta-analysis of phase 3 randomized controlled trials
Authors: Minutolo Roberto , Liberti Maria Elena , Simeon Vittorio , Sasso Ferdinando C , Borrelli Silvio , De Nicola Luca , Garofalo Carlo
Published: June 2023

Background

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are new therapeutic agents for anaemia in chronic kidney disease (CKD). We evaluated by meta-analysis and meta-regression the efficacy and safety of HIF-PHIs in patients with CKD-related anaemia.

Methods

We selected phase 3 randomized clinical trials (RCTs) comparing HIF-PHIs and erythropoiesis-stimulating agents (ESAs) in dialysis and non-dialysis patients. Efficacy outcomes were the changes from baseline of haemoglobin, iron parameters (hepcidin, serum iron, TIBC, TSAT, ferritin) and intravenous iron dose; as safety outcomes we considered cancer, adjudicated major adverse cardiovascular events (MACE), MACE+ (MACE plus hospitalization for hearth failure or unstable angina or thromboembolic event), thrombotic events (deep vein thrombosis, pulmonary embolism), arterovenous fistula (AVF) thrombosis and death.

Results

We included 26 RCTs with 24 387 patients. Random effect meta-analysis of the unstandardized mean difference between HIF-PHIs and ESAs showed a significant change in haemoglobin levels from baseline of 0.10 g/dL (95% CI 0.02 to 0.17). Meta-regression analysis showed a significantly higher haemoglobin change for HIF-PHIs in younger patients and versus short-acting ESA (0.21 g/dL, 95% CI 0.12 to 0.29 versus –0.01, 95% CI –0.09 to 0.07 in studies using long-acting ESA, P < .001). No significant effect on heterogeneity was found for type of HIF-PHIs. In comparison with ESAs, HIF-PHIs induced a significant decline in hepcidin and ferritin and a significant increase in serum iron and TIBC, while TSAT did not change; intravenous iron dose was lower with HIF-PHI (–3.1 mg/week, 95% CI –5.6 to –0.6, P = .020). Rate ratio of cancer (0.93, 95% CI 0.76 to 1.13), MACE (1.00, 95% CI 0.94 to 1.07), MACE+ (1.01, 95% CI 0.95 to 1.06), thrombotic events (1.08, 95% CI 0.84 to 1.38), AVF thrombosis (1.02, 95% CI 0.93 to 1.13) and death (1.02, 95% CI 0.95 to 1.13) did not differ between HIF-PHIs and ESAs.

Conclusions

HIF-PHIs at the doses selected for the comparisons are effective in correcting anaemia in comparison with ESA therapy with a significant impact on iron metabolism without notable difference among various agents. No safety signals emerge with use of HIF-PHIs.
NephroCheck at 10: addressing unmet needs in AKI diagnosis and risk stratification
Authors: Martin-Cleary Catalina , Sanz Ana Belen , Avello Alejandro , Sanchez-Niño Maria Dolores , Ortiz Alberto
Published: June 2023

Despite its name, the current diagnosis of acute kidney injury (AKI) still depends on markers of decreased kidney function and not on markers of injury. This results in a delayed diagnosis: AKI is diagnosed based on serum creatinine criteria only when the severity of injury is enough to decrease glomerular filtration rate. Moreover, by the time AKI is diagnosed, the insult may have already ceased, and even appropriate therapy targeted at the specific insult and its associated pathogenic pathways may no longer be effective. Biomarkers of injury are needed that allow the diagnosis of AKI based on injury criteria. At least three commercially available immunoassays assessing urinary or plasma neutrophil gelatinase-associated lipocalin and urinary tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 ([TIMP2]*[IGFBP7]) (NephroCheck®) have generated promising data regarding prediction and early diagnosis of AKI, although their relative performance may depend on clinical context. Recently, a urinary peptidomics classifier (PeptAKI) was reported to predict AKI better than current biomarkers. Focusing on [TIMP2]*[IGFBP7], the cellular origin of urinary TIMP2 and IGFBP7 remains unclear, especially under the most common predisposing condition for AKI, i.e. chronic kidney disease. We now discuss novel data on the kidney cell expression of TIMP2 and IGFBP7 and its clinical implications.
Aetiology and outcome in hospitalized cardiac arrest patients
Authors: Albert Malin , Herlitz Johan , Rawshani Araz , Forsberg Sune , Ringh Mattias , Hollenberg Jacob , Claesson Andreas , Thuccani Meena , Lundgren Peter , Jonsson Martin , Nordberg Per
Published: June 2023

Aims

To study aetiologies of in-hospital cardiac arrests (IHCAs) and their association with 30-day survival.

Methods and results

Observational study with data from national registries. Specific aetiologies (n = 22) of IHCA patients between April 2018 and December 2020 were categorized into cardiac vs. non-cardiac and six main aetiology categories: myocardial ischemia, other cardiac causes, pulmonary causes, infection, haemorrhage, and other non-cardiac causes. Main endpoints were proportions in each aetiology, 30-day survival, and favourable neurological outcome (Cerebral Performance Category scale 1–2) at discharge. Among, 4320 included IHCA patients (median age 74 years, 63.1% were men), approximate 50% had cardiac causes with a 30-day survival of 48.4% compared to 18.7% among non-cardiac causes (P < 0.001). The proportion in each category were: myocardial ischemia 29.9%, pulmonary 21.4%, other cardiac causes 19.6%, other non-cardiac causes 11.6%, infection 9%, and haemorrhage 8.5%. The odds ratio (OR) for 30-day survival compared to myocardial ischemia for each category were: other cardiac causes OR 1.48 (CI 1.24–1.76); pulmonary causes OR 0.36 (CI 0.3–0.44); infection OR 0.25 (CI 0.18–0.33); haemorrhage OR 0.22 (CI 0.16–0.3); and other non-cardiac causes OR 0.56 (CI 0.45–0.69). IHCA caused by myocardial ischemia had the best favourable neurological outcome while those caused by infection had the lowest OR 0.06 (CI 0.03–0.13).

Conclusion

In this nationwide observational study, aetiologies with cardiac and non-cardiac causes of IHCA were evenly distributed. IHCA caused by myocardial ischemia and other cardiac causes had the strongest associations with 30-day survival and neurological outcome.
Metabolic Responses of Normal Rat Kidneys to a High Salt Intake
Authors: Shimada Satoshi , Hoffmann Brian R , Yang Chun , Kurth Theresa , Greene Andrew S , Liang Mingyu , Dash Ranjan K , Cowley Allen W
Published: June 2023

In this study, novel methods were developed, which allowed continuous (24/7) measurement of arterial blood pressure and renal blood flow in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. Specifically, the study determined the effects of a high salt (HS; 4.0% NaCl) diet upon whole kidney O2 consumption and arterial and renal venous plasma metabolomic profiles of normal Sprague–Dawley rats. A separate group of rats was studied to determine changes in the cortex and outer medulla tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to 4.0% NaCl diet. In addition, targeted mRNA expression analysis of cortical segments was performed. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. A novel finding was the increased expression of glycolysis-related genes in Cx and isolated proximal tubular segments in response to an HS diet, consistent with increased release of pyruvate and lactate from the kidney to the renal venous blood. Data suggests that aerobic glycolysis (eg, Warburg effect) may contribute to energy production under these circumstances. The study provides evidence that kidney metabolism responds to an HS diet enabling enhanced energy production while protecting from oxidative stress and injury.

Metabolomic and transcriptomic analysis of kidneys of Sprague-Dawley rats fed a high salt diet.
Concluding Embryogenesis After Diaspora: Seed Germination in Illicium Parviflorum
Authors: Losada Juan M
Published: June 2023

Synopsis

Albuminous seeds, dispersed with a minimally developed embryo surrounded by nutrient storage tissue, are pervasive across extinct and extant early diverging angiosperm lineages. Typically, seed ontogenic studies have focused on the time between fertilization and seed release, but in albuminous seeds, embryogenesis is incomplete at the time of seed dispersal. Here, I studied the morphological and nutritional relationships between the embryo and the endosperm after seed dispersal in Illicium parviflorum (Austrobaileyales). Seeds of I. parviflorum germinate over a period of three months. Different stages during the germination process were anatomically evaluated using a combination of histochemistry and immunocytochemistry. At dispersal, the seeds of Illicium contain a tiny achlorophyllous embryo with minimal histological differentiation, surrounded by copious amounts of lipo-protein globules stored in the endosperm within cell walls rich in un-esterified pectins. Six weeks later, the embryo expanded and differentiated the vascular tissues before the emergence of the radicle through the seed coat, as the stored lipids and proteins coalesced within cells. Six weeks later, the cotyledons contained starch and complex lipids intracellularly, and accumulated low-esterified pectins in their cell walls. The proteolipid-rich albuminous seeds of Illicium exemplify how woody angiosperms of the Austrobaileyales, Amborellales, and many magnoliids release seeds with high-energy storage compounds that are reprocessed by embryos that complete development during germination. Seedlings of these lineages thrive in the understory of tropical environments, which match with the predicted habitats where angiosperms evolved.
Effect of papillary muscle approximation on acute ovine functional tricuspid regurgitation
Authors: Gaweda Boguslaw , Jaźwiec Tomasz , Gaddam Manikantam , Bush Jared D , MacDougall Brian , Widenka Kazimierz , Timek Tomasz A
Published: June 2023

OBJECTIVES

Ring annuloplasty represents the standard surgical treatment, but offers suboptimal results in patients with severe functional tricuspid regurgitation. Addition of papillary muscles (PMs) approximation may improve clinical outcomes.

METHODS

Eight healthy adult male sheep (56 ± 4 kg) underwent cardiopulmonary bypass and implantation of sonomicrometry crystals on the tricuspid annulus, PM tips and right ventricular (RV) free wall. Papillary muscles approximation sutures were anchored between anterior–posterior and anterior–septal PMs and their loose ends externalized through RV free wall to epicardial tourniquets. After weaning from cardiopulmonary bypass, acute right heart failure and tricuspid regurgitation were induced, and subsequent sequential anterior–posterior and anterior–septal PM approximations were performed. Echocardiographic, haemodynamic and sonomicrometry data were collected.

RESULTS

Tricuspid regurgitation at baseline in eight sheep was none or trace in 3 and mild in 5, and after induction of acute right heart failure increased significantly to moderate in 5, moderately severe in 1 and severe in 2 (P = 0.011). RV pressure increased from 31 [28; 43] to 51 [47; 55] mmHg (P = 0.012). Anterior–posterior PM approximation decreased regurgitation grade to none or trace in 1, mild in 4 and moderate in 3 (P = 0.016) and reduced PM area from 208 [160; 241] to 108 [48; 181] mm2 (P = 0.008), and anterior–posterior PM distance from 18 [16; 20] to 10 [7; 13] mm (P = 0.037). Anterior–septal approximation also significantly reduced PM area but had no effect on regurgitation grade.

CONCLUSIONS

Anterior–posterior but not anterior–septal PM approximation alleviated acute ovine tricuspid regurgitation. Selective PM approximation may offer better control of tricuspid regurgitation.
Estimating conformal capacity using asymptotic matching
Authors: Miyoshi Hiroyuki , Crowdy Darren G
Published: June 2023

Conformal capacity is a mathematical quantity relevant to a wide range of physical and mathematical problems and recently there has been a resurgence of interest in devising new methods for its computation. In this paper we show how ideas from matched asymptotics can be used to derive estimates for conformal capacity. The formulas derived here are explicit, and there is evidence that they provide excellent approximations to the exact capacity values even well outside the expected range of validity.
Dietary alpha-ketoglutarate enhances intestinal immunity by Th17/Treg immune response in piglets after lipopolysaccharide challenge
Authors: Liu Guang M , Lu Jia J , Sun Wei X , Jia Gang , Zhao Hua , Chen Xiao L , Tian Gang , Cai Jing Y , Zhang Rui N , Wang Jing
Published: June 2023

Alpha-ketoglutarate (AKG) is important for improving intestinal and systemic immune function. This study aimed to explore whether AKG enhances gut immunity in lipopolysaccharide (LPS)-challenged piglets by modulating the immune-related helper T cells 17 (Th17)/regulatory T cells (Treg) balance pathway. A 2 × 2 factor design was used on 24 pigs, with the major factors being diet (basal diet or 1% AKG diet) and immunological challenge (saline or LPS). Piglets were fed with a basal or AKG diet for 21 d and then received intraperitoneal injection of LPS or saline. The results demonstrated that AKG supplementation enhanced growth performance compared with the control group (P < 0.05). AKG improved the ileal morphological structure (P < 0.01). Finally, AKG supplementation increased interleukin (IL)-10, transforming growth factor beta-1, forkhead box P3, and signal transducer and activator of transcription 5 genes expression whereas decreasing IL-6, IL-8, IL-1β, tumor necrosis factor-α, IL-17, IL-21, signal transducer and activator of transcription 3 and rar-related orphan receptor c genes expression (P < 0.05). These findings suggested that dietary AKG can improve the growth performance of piglets. Meanwhile, dietary AKG can alleviate LPS-induced intestinal inflammation through Th17/Treg immune response signaling pathway.
Establishment and characterization of an immortalized bovine intestinal epithelial cell line
Authors: Meng Sudan , Wang Y uexin , Wang Shuai , Qian Weifeng , Shao Qi , Dou Mengying , Zhao Shujuan , Wang Jianguo , Li Mengyun , An Yongsheng , He Lei , Zhang Cai
Published: June 2023

Primary bovine intestinal epithelial cells (PBIECs) are an important model for studying the molecular and pathogenic mechanisms of diseases affecting the bovine intestine. It is difficult to obtain and grow PBIECs stably, and their short lifespan greatly limits their application. Therefore, the purpose of this study was to create a cell line for exploring the mechanisms of pathogen infection in bovine intestinal epithelial cells in vitro. We isolated and cultured PBIECs and established an immortalized BIEC line by transfecting PBIECs with the pCI-neo-hTERT (human telomerase reverse transcriptase) recombinant plasmid. The immortalized cell line (BIECs-21) retained structure and function similar to that of the PBIECs. The marker proteins characteristic of epithelial cells, cytokeratin 18, occludin, zonula occludens protein 1 (ZO-1), E-cadherin and enterokinase, were all positive in the immortalized cell line, and the cell structure, growth rate, karyotype, serum dependence and contact inhibition were normal. The hTERT gene was successfully transferred into BIECs-21 where it remained stable and was highly expressed. The transport of short-chain fatty acids and glucose uptake by the BIECs-21 was consistent with PBIECs, and we showed that they could be infected with the intestinal parasite, Neospora caninum. The immortalized BIECs-21, which have exceeded 80 passages, were structurally and functionally similar to the primary BIECs and thus provide a valuable research tool for investigating the mechanism of pathogen infection of the bovine intestinal epithelium in vitro.
Meta-Analysis of Publicly Available Clinical and Preclinical Microbiome Data From Studies of Burn Injury
Authors: Horseman Timothy S , Frank Andrew M , Shupp Jeffrey W , Burmeister David M
Published: June 2023

Following burn injury, alterations in host commensal microbiota across body spaces may leave patients susceptible to opportunistic pathogens and serious sequelae such as sepsis. Generally, studies examining the microbiome postburn have had a limited sample size and lack of longitudinal data, which coupled with experimental and analytic variation, impacts overall interpretation. We performed a meta-analysis of publicly available sequencing data from preclinical and clinical burn studies to determine if there were consistent alterations in the microbiome across various anatomical sites and hosts. Ten human and animal 16S rRNA sequencing studies spanning respiratory, urinary, cutaneous, and gastrointestinal microbiomes were included. Taxonomic classification and alpha and beta diversity metrics were analyzed using QIIME2 v2021.8. Alpha diversity was consistently higher in control samples compared to burn-injured samples which were also different based on host and anatomical location; however, phylogenetic evaluation (ie, Faith PD) elucidated more significant differences compared to taxonomic metrics (ie, Shannon entropy). Beta diversity analysis based on weighted UniFrac showed that rodent specimens clustered less closely to humans than pig samples for both rectal and skin sources. Host species and performing institute were found to have a significant impact on community structure. In rectal samples, bacterial composition in pig and human burn samples included Bacteroidetes, Firmicutes, and Proteobacteria, while rodent samples were dominated by Firmicutes. Proteobacteria and Firmicutes increased on burned skin in each host species. Our results suggest that host species and the performing institute strongly influence microbiome structure. Burn-induced alterations in microbiome diversity and taxa exist across hosts, with phylogenetic metrics more valuable than others. Coordinated, multicenter studies, both clinical and preclinical, within the burn community are needed to more completely realize the diagnostic and therapeutic potential of the microbiome for improving outcomes postburn.
Predictors and Impact of Pneumonia on Adverse Outcomes in Inhalation Injury Patients
Authors: Ronkar Nicolas C , Galet Colette , Richey Karen , Foster Kevin , Wibbenmeyer Lucy
Published: June 2023

Inhalation injury (II) is the third mortality prognostic factor for burn injury following age and burn size. II can lead to pulmonary complications such as pneumonia and acute respiratory distress syndrome (ARDS); all of which have been hypothesized to increase morbidity and mortality in II. Herein, we aimed to identify variables associated with the risk of developing pneumonia and to determine the impact of pneumonia on selected II outcomes. De-identified data from the Prospective Inhalation Study titled Inhalation Injury Scoring System to Predict Inhalation Injury Severity (ISIS) were used. II was confirmed by fiberoptic bronchoscopy. Demographics, injury, and hospital course information were recorded. P < .05 was considered significant. One hundred subjects were included. On univariate analysis, pneumonia was associated with burn severity, race, and receipt of colloid during the first 24 hours. Patients who developed pneumonia spent more time on a ventilator, had longer hospitalizations (LOS) and were more likely to need a tracheostomy. On multivariate analysis, total number of ventilator days was associated with pneumonia (Odd ratio (OR) = 1.122 [1.048–1.200], P = .001). Both pneumonia and receipt of colloid were predictive of increased ventilator days (OR = 2.545 [1.363–4.753], P < .001 and OR = 2.809 [1.548–5.098], P < .001, respectively). Pneumonia was not an independent predictor of LOS, ARDS, or mortality. Pneumonia remains a high-risk complication associated with two times more ventilator days in II. Future research should focus on prevention of pneumonia and the relationship between colloid fluids and pneumonia and early ventilator liberation in II patients.
Radiation dose, schedule, and novel systemic targets for radio-immunotherapy combinations
Authors: Karapetyan Lilit , Iheagwara Uzoma K , Olson Adam C , Chmura Steven J , Skinner Heath K , Luke Jason J
Published: June 2023

Immunotherapy combinations are being investigated to expand the benefit of immune checkpoint blockade across many cancer types. Radiation combinations, in particular using stereotactic body radiotherapy, are of keen interest because of underlying mechanistic rationale, safety, and availability as a standard of care in certain cancers. In addition to direct tumor cytotoxicity, radiation therapy has immunomodulatory effects such as induction of immunogenic cell death, enhancement of antigen presentation, and expansion of the T-cell receptor repertoire as well as recruitment and increased activity of tumor-specific effector CD8+ cells. Combinations of radiation with cytokines and/or chemokines and anti-programmed death 1 and anticytotoxic T-lymphocyte antigen 4 therapies have demonstrated safety and feasibility, as well as the potential to improve long-term outcomes and possibly induce out of irradiated field or abscopal responses. Novel immunoradiotherapy combinations represent a promising therapeutic approach to overcome radioresistance and further enhance systemic immunotherapy. Potential benefits include reversing CD8+ T-cell exhaustion, inhibiting myeloid-derived suppressor cells, and reversing M2 macrophage polarization as well as decreasing levels of colony-stimulating factor-1 and transforming growth factor-β. Here, we discuss current data and mechanistic rationale for combining novel immunotherapy agents with radiation therapy.
Simulation of unconfined seepage in soil–rock mixture slope by virtual element method
Authors: Sun Yinghao , Yi Qi , Wang Jiao , Sun Guanhua , Lin Shan
Published: June 2023

The virtual element method (VEM) is commonly used in engineering due to its ability to solve arbitrary node meshes. In this study, we propose a method to determine the free surface of the unconfined seepage problem in soil–rock mixtures slope using the advantages of the VEM. By cutting meshes in the iteration, our method overcomes the limitation of fixed mesh in solving the free surface, and the numerical tests confirm the accuracy of the proposed method in predicting the location of the seepage surface. Moreover, the results demonstrate that the presence of rock blocks significantly impacts the unconfined seepage behavior of soil–rock mixtures slope, revealing the importance of considering rock blocks in the analysis of such systems.
Variations in pollinator-mediated selection of floral traits across flowering times
Authors: Cha Yong-Peng , Zhang Jie , Ma Yin-Mei , Tong Zhao-Li , Wu Yun , Luo Lun , Li Qing-Jun
Published: June 2023

Spatiotemporal variations in plant–pollinator interactions drive floral evolution and shape the diversity of flowers in angiosperms. However, the potential role of plant–pollinator interactions in driving floral differentiation across flowering times within a population has not been documented. In this study, we aimed to quantify the variations in pollinator-mediated selection of floral traits across different flowering times of Primula sikkimensis (an entomophilous plant) in two natural populations. The results demonstrated that plants were shorter and produced fewer flowers with larger sizes in the early flowering time than in the late flowering time. In early flowering time, pollinator types were fewer and visitation frequency was lower than in late flowering time, resulting in lower female fitness. Pollinator-mediated selection of floral traits varied with flowering time, and more floral traits received pollinator-mediated selection during early flowering time. These results highlight that temporal variation in plant–pollinator interactions may have a potential role in driving floral diversification within the population.
A complex presentation and successful management of fistulizing perianal Crohn’s disease extending to the mid-back
Authors: Vazquez Christopher , Kodia Karishma , Giri Bhuwan , Paluvoi Nivedh
Published: June 2023

Fistulizing perianal disease is a debilitating complication present in nearly half of all patients diagnosed with Crohn’s disease. The majority of anal fistulas arising in these patients are complex. Treatment can be challenging with therapy often requiring both medical and surgical interventions with differing levels of symptomatic relief. Fecal diversion is an option after medical and surgical modalities have been exhausted but demonstrates limited efficacy. Complex perianal fistulizing Crohn’s disease is inherently morbid and can be difficult to manage. We present a case of a young male with Crohn’s, severe malnutrition and multiple perianal abscess with extensive fistula tracts up to his back; a planned fecal diversion was instituted to control sepsis and allow for wound healing and optimize medical therapy.
Treatment of talus osteochondral defects with arthroscopy debridement and bone marrow concentrate: a 6-month follow-up case report study
Authors: Mitev Konstantin
Published: June 2023

Talus osteochondral defects are a common cause of ankle pain and disability, and require prompt and effective treatment to prevent further damage and improve function. While surgical interventions, such as arthroscopy debridement and bone marrow concentrate therapy, have been used separately to treat these injuries, their combination may offer synergistic benefits. A 28-year-old male patient presented with a history of ankle pain and difficulty with weight-bearing activities. Post-operatively, the patient reported significant improvement in pain and function.
Extending donor criteria: successful lung transplantation post ex vivo back table donor pulmonary artery thrombolysis
Authors: Jacob Samuel , Garg Pankaj , Ahmed Magdy El-Sayed , Makey Ian A
Published: June 2023

Pulmonary embolization in donor lungs is a common finding and found in up to 38% of cases. To expand the pool of organs, transplant centers now utilize lungs, from increased risk donors, that may have pulmonary embolic disease. Modalities of clearing pulmonary artery embolisms are critical to reduce the prevalence of primary graft dysfunction post transplantation. There have been anecdotal cases of pulmonary embolectomy pre and post organ procurement or in vivo and ex vivo thrombolytic therapy performed in donors with massive pulmonary emboli. We report for the first time therapeutic ex vivo thrombolysis on the back table without Ex Vivo Lung Perfusion (EVLP), followed by successful transplantation.
Effect of hypoandrogenism on expression of transient receptor potential vanilloid channels in rat penile corpus cavernosum and erectile function
Authors: Liu Gang , Liu Jing , Kong Xiangjun , Xiong Wen-ju , Jiang Rui
Published: June 2023

Background

Hypoandrogenism is a cause of erectile dysfunction (ED). Vascular smooth muscle cell contraction and relaxation are regulated by TRPV1–4 channels. However, the influence of hypoandrogenism on TRPV1–4 and its relationship with erectile function remain unclear.

Aim

To reveal whether hypoandrogenism affects erectile function by influencing TRPV1–4 expression in the corpus cavernosum of rats.

Methods

Male Sprague-Dawley rats (N = 36) aged 8 weeks were assigned to 6 groups at random (n = 6): sham operation, castrated, castrated + testosterone replacement, sham operation + transfection, castrated + transfection, and castrated + empty transfection. Four weeks after castration, 20 μL of lentiviral vector (1 × 108 TU/mL) carrying the TRPV4 gene was injected into the penile cavernous tissue of the transfection groups. One week after transfection, the maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP) and the content of TRPV1–4, phosphorylated eNOS (p-eNOS)/eNOS, and nitric oxide (NO) in penile cavernous tissue of each group were measured.

Outcomes

Under low androgen conditions, TRPV4 expression in endothelial cells in the rat penile cavernosum was sharply reduced, resulting in a decrease in p-eNOS/eNOS and NO content, which could inhibit erectile function.

Results

In rat penile cavernous tissue, TRPV1–4 was expressed in the cell membranes of endothelial cells and smooth muscle cells. The ICPmax/MAP and the content of TRPV4, p-eNOS/eNOS, and NO end product nitrite level in rat penile cavernous tissue was markedly reduced in the castrated group as compared with the sham group (P < .05). The ICPmax/MAP and the content of TRPV4, p-eNOS/eNOS, and NO end product nitrite level in rat penile cavernous tissue were markedly improved in the castrated + transfection group vs the castrated group (P < .01).

Clinical Implications

Upregulation of TRPV4 expression in penile cavernosum tissue might be a viable therapeutic for ED caused by hypoandrogenism.

Strengths and Limitations

The specific mechanism of TRPV4 in ED needs to be further verified by androgen receptor or TRPV4 gene knockout experiments.

Conclusion

Hypoandrogenism may cause ED by reducing the expression of TRPV4 in rat penile cavernous tissue. Upregulation of TRPV4 expression in penile cavernous tissue can increase the ratio of p-eNOS/eNOS and NO levels and ameliorate the erectile function of castrated rats.
Inferring the astrophysical population of gravitational wave sources in the presence of noise transients
Authors: Heinzel Jack , Talbot Colm , Ashton Gregory , Vitale Salvatore
Published: June 2023

The global network of interferometric gravitational wave (GW) observatories (LIGO, Virgo, KAGRA) has detected and characterized nearly 100 mergers of binary compact objects. However, many more real GWs are lurking sub-threshold, which need to be sifted from terrestrial-origin noise triggers (known as glitches). Because glitches are not due to astrophysical phenomena, inference on the glitch under the assumption it has an astrophysical source (e.g. binary black hole coalescence) results in source parameters that are inconsistent with what is known about the astrophysical population. In this work, we show how one can extract unbiased population constraints from a catalogue of both real GW events and glitch contaminants by performing Bayesian inference on their source populations simultaneously. In this paper, we assume glitches come from a specific class with a well-characterized effective population (blip glitches). We also calculate posteriors on the probability of each event in the catalogue belonging to the astrophysical or glitch class, and obtain posteriors on the number of astrophysical events in the catalogue, finding it to be consistent with the actual number of events included.
Lunar collision rate with primordial black holes
Authors: Caplan M E , Johnston J , Santarelli A D
Published: June 2023

A recent letter studied cratering during collisions between rocky bodies and primordial black holes. Hydrodynamic simulations in that work showed that ejecta blankets from these collisions are steeper because the black holes completely penetrate the target, potentially making these craters distinguishable from traditional point-like impactors. This may allow us to use lunar craters to constrain primordial black holes in the asteroid-mass window, about 1017–1019 g. In this work, we calculate the lunar dark matter flux from the Galactic halo and several models for a dark disc. We consider several effects that may enhance the dark matter flux, such as gravitational focusing on the Solar system and historical modulations due to the Solar system’s galactic orbit. We find that non-detection of novel craters on the Moon can constrain relativistic compact MACHO dark matter up to 1017 g at 95 per cent confidence, motivating a detailed search through lunar surface scans. In addition, we show that fluxes near Earth from dark discs may be significantly enhanced by gravitational focusing and that the relative velocity between the disc and the Sun can result in annual modulations out of phase with the annual modulations from the halo.
Physical conditions and extension of the coronal line region in IC 5063
Authors: Fonseca-Faria M A , Rodríguez-Ardila A , Contini M , Dahmer-Hahn L G , Morganti R
Published: June 2023

We study the ionized and highly ionized gas phases in the Seyfert 2 galaxy IC 5063 by means of the Very Large Telescope (VLT)/Multi-Unit Spectroscopic Explorer (MUSE) integral field spectroscopy. Our analysis allowed us to detect a high-ionization gas outflow traced by the coronal lines [Fe vii] λ6087 and [Fe x] λ6375. Both emissions are found to be extended. The former up to 1.2 kpc and 700 pc north-west (NW) and south-east (SE) from the nucleus, respectively. The latter reaches 700 pc NW of the nucleus. This is the first time that [Fe x] emission is observed at such distances from the central engine in an active galactic nucleus. The [Fe vii] λ6087 emission peaks at the nucleus, with two secondary peaks at the position of the NW and SE radio lobes. The gas kinematics is complex, with the coronal emission displaying split line profiles along the radio jet and line widths of several hundred km s−1. Velocity shifts of up to 600 km s−1 in excess of the systemic velocity of the galaxy are found very close to the radio lobes and along the jet propagation. The extended coronal gas is characterized by temperatures reaching 20 000 K and electron densities >102 cm−3, with the larger values associated with the regions of larger turbulence, likely due to the passage of the radio jet. This hypothesis is supported by photoionization models that combine the effects of the central engine and shocks. Our work highlights the strong relationship between extended coronal emission and the radio jet, with the former suitably tracing the latter, which in the case of IC 5063, propagates very close to the galaxy disc.
Thermonuclear type-I X-ray bursts and burst oscillations from the eclipsing AMXP swift J1749.4–2807
Authors: Albayati A C , Bult P , Altamirano D , Chenevez J , Guillot S , Güver T , Jaisawal G K , Malacaria C , Mancuso G C , Marino A , Ng M , Sanna A , Strohmayer T E
Published: June 2023

Swift J1749.4-2807 is the only known eclipsing accreting millisecond X-ray pulsar. In this paper, we report on seven thermonuclear (Type-I) X-ray bursts observed by NICER during its 2021 outburst. The first six bursts show slow rises and long decays, indicative of mixed H/He fuel, whereas the last burst shows fast rise and decay, suggesting He-rich fuel. Time-resolved spectroscopy of the bursts revealed typical phenomenology (i.e. an increase in blackbody temperature during the burst rise, and steady decrease in the decay), however, they required a variable NH. We found that the values of NH during the bursts were roughly double those found in the fits of the persistent emission prior to each burst. We interpret this change in absorption as evidence of burst–disc interaction, which we observe due to the high inclination of the system. We searched for burst oscillations during each burst and detected a signal in the first burst at the known spin frequency of the neutron star (517.92 Hz). This is the first time burst oscillations have been detected from Swift J1749.4-2807. We further find that each X-ray burst occurs on top of an elevated persistent count rate. We performed time-resolved spectroscopy on the combined data of the bursts with sufficient statistics (i.e. the clearest examples of this phenomenon) and found that the blackbody parameters evolve to hotter temperatures closer to the onset of the bursts. We interpret this as a consequence of an unusual marginally stable burning process similar to that seen through mHz QPOs.
Microquasar Cyg X-3 – a unique jet-wind neutrino factory?
Authors: Koljonen Karri I I , Satalecka Konstancja , Lindfors Elina J , Liodakis Ioannis
Published: June 2023

The origin of astrophysical neutrinos is one of the most debated topics today. Perhaps the most robust evidence of neutrino counterpart comes from supermassive black holes in active galactic nuclei associated with strongly collimated outflows, or jets, that can accelerate particles to relativistic energies and produce neutrinos through hadronic interactions. Similar outflows can also be found from X-ray binaries, or ‘microquasars’, that consist of a neutron star or a stellar-mass black hole accreting matter from a non-degenerate companion star. In some cases, these systems can accelerate particles up to GeV energies implying an efficient acceleration mechanism in their jets. Neutrino production in microquasar jets can be expected with suitable conditions and a hadronic particle population. Microquasar Cyg X-3 is a unique, short orbital period X-ray binary hosting a Wolf–Rayet companion star with a strong stellar wind. The interaction of the dense stellar wind with a relativistic jet leads to particle collisions followed by high-energy gamma-ray and potentially neutrino emission. Here, using the 10-yr neutrino candidate sample of the IceCube neutrino observatory, we find that the events with the highest spatial association with Cyg X-3 occur during short-lived high-energy gamma-ray flaring periods indicating the possible astrophysical nature of these events.