bluuebunny/crossref_metadata_2025 huggingface dataset:
Proton pump Inhibitors and Risk of Enteric Infection in Inflammatory Bowel Disease: A Self-controlled Case Series
Authors: Varma Sanskriti , Trudeau Stephen J , Li Jianhua , Freedberg Daniel E
Published: March 2023

Background

We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD), after adequately accounting for baseline differences between PPI users and nonusers.

Methods

This was a self-controlled case series, with each patient serving as their own control. Ambulatory patients with IBD were included if they were tested for enteric infection by multiplex polymerase chain reaction testing panel (GIPCR) and/or Clostridoides difficile toxin PCR from 2015 to 2019 and received PPIs for some but not all of this period. Rates of enteric infections were compared between the PPI-exposed period vs pre- and post-PPI periods identical in duration to the exposed period. Conditional Poisson regression was used to adjust for time-varying factors.

Results

Two hundred twenty-one IBD patients were included (49% ulcerative colitis, 46% Crohn’s disease, and 5% indeterminate colitis). The median PPI duration was 7 months (interquartile range 4 to 11 months). A total of 25 (11%) patients had a positive GIPCR or C. difficile test in the PPI period, 9 (4%) in the pre-PPI period, and 8 (4%) in the post-PPI period. Observed incidence rates for enteric infections were 2.5, 7.4, and 2.2 per 100 person years for the pre-PPI, PPI, and post-PPI periods, respectively (adjusted incidence rate ratios, 2.8; 95% confidence interval [CI] 1.3-6.0) for PPI vs pre-PPI and 2.9 (95% CI, 1.3-6.4) for PPI vs post-PPI). The adjusted absolute excess risk associated with PPIs was 4.9 infections per 100 person years.

Conclusions

Proton pump inhibitors were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.
Enhancing the nation’s public health information infrastructure: a report from the ACMI symposium
Authors: Dixon Brian E , Staes Catherine , Acharya Jessica , Allen Katie S , Hartsell Joel , Cullen Theresa , Lenert Leslie , Rucker Donald W , Lehmann Harold
Published: March 2023

The COVID-19 pandemic exposed multiple weaknesses in the nation’s public health system. Therefore, the American College of Medical Informatics selected “Rebuilding the Nation's Public Health Informatics Infrastructure” as the theme for its annual symposium. Experts in biomedical informatics and public health discussed strategies to strengthen the US public health information infrastructure through policy, education, research, and development. This article summarizes policy recommendations for the biomedical informatics community postpandemic. First, the nation must perceive the health data infrastructure to be a matter of national security. The nation must further invest significantly more in its health data infrastructure. Investments should include the education and training of the public health workforce as informaticians in this domain are currently limited. Finally, investments should strengthen and expand health data utilities that increasingly play a critical role in exchanging information across public health and healthcare organizations.
Common Cents: Bank Account Structure and Couples’ Relationship Dynamics
Authors: Olson Jenny G , Rick Scott I , Small Deborah A , Finkel Eli J
Published: March 2023

When a romantic relationship becomes serious, partners often confront a foundational decision about how to organize their personal finances: pool money together or keep things separate? In a six-wave longitudinal experiment, we investigated whether randomly assigning engaged or newlywed couples to merge their money in a joint bank account increases relationship quality over time. Whereas couples assigned to keep their money in separate accounts or to a no-intervention condition exhibited the normative decline in relationship quality across the first 2 years of marriage, couples assigned to merge money in a joint account sustained strong relationship quality throughout. The effect of bank account structure on relationship quality is multiply determined. We examine—and find support for—three potential mechanisms using both experimental and correlational methods: merging finances (1) improves how partners feel about how they handle money, (2) promotes financial goal alignment, and (3) sustains communal norm adherence (e.g., responding to each other’s needs without expectations of reciprocity). While prior research has documented a correlation between financial interdependence and relationship quality, our research offers the first experimental evidence that increasing financial interdependence helps newlyweds preserve stronger relationship quality throughout the newlywed period and potentially beyond.
Effects of midgut bacteria inHyphantria cunea(Lepidoptera: Erebidae) on nuclear polyhedrosis virus andBacillus thuringiensis(Bacillales: Bacillaceae)
Authors: Chen Hongjian , Hao Dejun , Chen Changyu , Sun Yuhang , Yu Xiaohang
Published: March 2023

Hyphantria cunea Drury (Lepidoptera: Erebidae) is a quarantine pest in China that can cause damage to hundreds of plants. As biological control agents, Nuclear Polyhedrosis Virus (NPV) and Bacillus thuringiensis Berliner (Bacillales: Bacillaceae) (Bt) are commonly used to inhibit the prevalence of H. cunea. To investigate the role of midgut bacteria in the infection of NPV and Bt in H. cunea, we performed a series of tests, including isolating the dominant culturable bacteria in the midgut, eliminating intestinal bacteria, and respectively inoculating the dominant strains with NPV and Bt for bioassay. Two dominant bacteria, Klebsiella oxytoca Lautrop (Enterobacterales: Enterobacteriaceae) and Enterococcus mundtii Collins (Lactobacillales: Enterococcaceae), in the midgut of H. cunea were identified, and a strain of H. cunea larvae without intestinal bacteria was successfully established. In the bioassays of entomopathogen infection, K. oxytoca showed significant synergistic effects with both NPV and Bt on the death of H. cunea. In contrast, E. mundtii played antagonistic effects. This phenomenon may be attributed to the differences in the physico-chemical properties of the two gut bacteria and the alkaline environment required for NPV and Bt to infect the host. It is worth noting that the enhanced insecticidal activity of K. oxytoca on NPV and Bt provides a reference for future biological control of H. cunea by intestinal bacteria.
Estimating the efficiency gain of covariate-adjusted analyses in future clinical trials using external data
Authors: Li Xiudi , Li Sijia , Luedtke Alex
Published: March 2023

We present a framework for using existing external data to identify and estimate the relative efficiency of a covariate-adjusted estimator compared to an unadjusted estimator in a future randomized trial. Under conditions, these relative efficiencies approximate the ratio of sample sizes needed to achieve a desired power. We develop semiparametrically efficient estimators of the relative efficiencies for several treatment effect estimands of interest with either fully or partially observed outcomes, allowing for the application of flexible statistical learning tools to estimate the nuisance functions. We propose an analytic Wald-type confidence interval and a double bootstrap scheme for statistical inference. We demonstrate the performance of the proposed methods through simulation studies and apply these methods to estimate the efficiency gain of covariate adjustment in Covid-19 therapeutic trials.
The LMC impact on the kinematics of the Milky Way satellites: clues from the running solar apex
Authors: Makarov Dmitry , Khoperskov Sergey , Makarov Danila , Makarova Lidia , Libeskind Noam , Salomon Jean-Baptiste
Published: March 2023

Dwarf galaxies provide a unique opportunity for studying the evolution of the Milky Way (MW) and the Local Group as a whole. Analysing the running solar apex based on the kinematics of the MW satellites, we discovered an unexpected behaviour of the dipole term of the radial velocity distribution as a function of the Galactocentric distance. The nearby satellites (<100 kpc) have a bulk motion with an amplitude of 140–230 km s−1, while the more distant ones show an isotropic distribution of the radial velocities. Such strong solar apex variations cannot be explained by the net rotation of the satellites, as it would require an enormously high rotation rate (≈970 km s−1). If we exclude the Large and Magellanic Clouds (LMC) and its most closely related members from our sample, this does not suppress the bulk motion of the nearby satellites strongly enough. Nevertheless, we have demonstrated that the observed peculiar kinematics of the MW satellites can be explained by a perturbation caused by the first infall of the LMC. First, we ‘undone’ the effect of the perturbation by integrating the orbits of the MW satellites backwards (forwards) with (without) massive LMC. It appears that the present-day peculiar enhancement of the solar apex in the inner halo is diminished the most in the case of 2 × 1011 M⊙ LMC. Next, in self-consistent high-resolution N-body simulations of the MW–LMC interaction, we found that the solar apex shows the observed behaviour only for the halo particles with substantial angular momentum, comparable to that of the MW satellites.
The mass of our observable Universe
Authors: Gaztañaga Enrique
Published: March 2023

The standard cosmological model Lambda Cold Dark Matter (LCDM) assumes a global expanding space–time of infinite extent around us. But such idea is inconsistent with the observed cosmic acceleration unless we advocate for the existence of a mysterious dark energy (DE) or a cosmological constant (Λ). Here, we argue instead that our Universe has a very large but finite regular mass M, without the need to invoke DE or Λ. A system with a finite mass M has a finite gravitational radius rS = 2GM. When M is contained within rS, this is a black hole (BH). Nothing from inside can escape outside rS, which becomes a boundary for the inside dynamics. In the limit where there is nothing else outside, the inside corresponds then to a local isolated universe. Such boundary condition is equivalent to a Λ term: $\Lambda =3/r_\mathrm{ S}^2$. We can therefore interpret cosmic acceleration as a measurement of the gravitational radius of our Universe, rS, with a mass M ≃ 6 × 1022 M⊙. Such BH Universe is observationally very similar to the LCDM, except for the lack of the largest scale perturbations, which are bounded by rS.
The association of urinary epidermal growth factors with ADPKD disease severity and progression
Authors: Harskamp Laura R , Perez-Gomez Maria Vanessa , Heida Judith E , Engels Gerwin E , van Goor Harry , van den Heuvel Marius C , Streets Andrew J , Ong Albert C M , Ortiz Alberto , Gansevoort Ron T ,   the DIPAK Consortium, Drenth J P H , de Fijter J W , van Gastel M D A , Meijer E , Losekoot M , Peters D J M , Visser F W , Wetzels J , Zietse R
Published: March 2023

Background

The epidermal growth factor receptor (EGFR) pathway is involved in kidney tissue repair and growth. Preclinical interventional data and scarce human data have suggested a role for this pathway in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD), while other data have suggested that its activation is causally linked to repair of damaged kidney tissue. We hypothesize that urinary EGFR ligands, as a reflection of EGFR activity, are associated with kidney function decline in ADPKD in the context of tissue repair following injury, and as the disease progresses as a sign of insufficient repair.

Methods

In the present study, we measured the EGFR ligands, EGF and heparin binding-EGF (HB-EGF), in 24-h urine samples of 301 ADPKD patients and 72 age- and sex-matched living kidney donors to dissect the role of the EGFR pathway in ADPKD. During a median follow-up of 2.5 years, the association of urinary EGFR ligand excretion with annual change in estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume in ADPKD patients was analyzed using mixed-models methods, and the expression of three closely related EGFR family receptors in ADPKD kidney tissue was investigated by immunohistochemistry. Additionally, the effect of reducing renal mass (after kidney donation), was assessed to investigate whether urinary EGF matches this reduction and thus reflects the amount of remaining healthy kidney tissue.

Results

At baseline, urinary HB-EGF did not differ between ADPKD patients and healthy controls (P = .6), whereas a lower urinary EGF excretion was observed in ADPKD patients [18.6 (11.8–27.8)] compared with healthy controls [51.0 (34.9–65.4) μg/24 h, P < .001]. Urinary EGF was positively associated with baseline eGFR (R = 0.54, P < .001) and a lower EGF was strongly associated with a more rapid GFR decline, even when adjusted for ADPKD severity markers (β = 1.96, P < .001), whereas HB-EGF was not. Expression of the EGFR, but not other EGFR-related receptors, was observed in renal cysts but was absent in non-ADPKD kidney tissue. Finally, unilateral nephrectomy resulted in a decrease of 46.4 (–63.3 to –17.6) % in urinary EGF excretion, alongside a decrease of 35.2 ± 7.2% in eGFR and 36.8 ± 6.9% in measured GFR (mGFR), whereas maximal mGFR (measured after dopamine induced hyperperfusion) decreased by 46.1 ± 7.8% (all P < .001).

Conclusions

Our data suggest that lower urinary EGF excretion may be a valuable novel predictor for kidney function decline in patients with ADPKD.
Optimizing biomarkers for accurate ependymoma diagnosis, prognostication, and stratification within International Clinical Trials: A BIOMECA study
Authors: Chapman Rebecca J , Ghasemi David R , Andreiuolo Felipe , Zschernack Valentina , Espariat Arnault Tauziede , Buttarelli Francesca R , Giangaspero Felice , Grill Jacques , Haberler Christine , Paine Simon M L , Scott Ian , Jacques Thomas S , Sill Martin , Pfister Stefan , Kilday John-Paul , Leblond Pierre , Massimino Maura , Witt Hendrik , Modena Piergiorgio , Varlet Pascale , Pietsch Torsten , Grundy Richard G , Pajtler Kristian W , Ritzmann Timothy A
Published: March 2023

Background

Accurate identification of brain tumor molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European “Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)” study.

Methods

Across 6 European BIOMECA laboratories, we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via fluorescent in situ hybridization (FISH) and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH.

Results

DNA Methylation profiling classified 65.3% (n = 96/147) of cases as EPN-PFA and 15% (n = 22/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99%–100% across 3 centers). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP—fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-center concordance and low sensitivity and specificity while MIP, MLPA, and DNA methylation-based approaches demonstrated greater accuracy.

Conclusions

We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q, and CDKN2A loss while FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches.
Patients’ Perceptions Regarding the Relevance of Items Contained in the Functional Assessment of Cancer Therapy Kidney Symptom Index-19
Authors: Bergerot Cristiane Decat , Malhotra Jasnoor , Bergerot Paulo , Philip Errol J , Castro Daniela V , Hsu JoAnn , Mota Augusto Cesar de Andrade , Cardoso de Azeredo Andressa , Neto João Nunes de Matos , Hutson Thomas , Grünwald Viktor , Bex Axel , Psutka Sarah P , Rini Brian , Plimack Elizabeth R , Master Viraj , Albiges Laurence , Choueiri Toni K , Pal Sumanta , Powles Thomas
Published: March 2023

Background

There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC.

Methods

This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics.

Results

A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity.

Conclusion

There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients’ cancer journey.
Regulatory Issues: PMDA – Review of Sakigake Designation Products: Oncolytic Virus Therapy with Delytact Injection (Teserpaturev) for Malignant Glioma
Authors: Maruyama Yoshiaki , Sakurai Akira , Noda Shinichi , Fujiwara Yasuhiro , Okura Narumi , Takagi Toshinori , Asano Junichi , Honda Futaba
Published: March 2023

In June 2021, the Ministry of Health, Labor and Welfare approved Delytact Injection as a regenerative medical product for oncolytic virus therapy. The active substance of Delytact Injection is teserpaturev, a genetically engineered herpes simplex virus type 1 (strain F) in which the α47 gene and both copies of the γ34.5 gene have been deleted and the infected cell protein 6 (ICP6) gene has been inactivated by the insertion of the lacZ gene from Escherichia coli. Delytact Injection, when intratumorally administered to patients with malignant glioma, is expected to exert the following effects: (1) the mutant virus selectively replicates in tumor cells and destroys the infected cells through the replication process, exerting a cytocidal effect, and (2) the administration leads to induction of tumor-responsive T cells, which activates antitumor immunity and thus prolongs the survival of patients with malignant glioma. A Japanese phase II study (Study GD01) was conducted in patients with glioblastoma who had residual or recurrent tumors after radiotherapy with concomitant temozolomide. In Study GD01, however, stable disease continued for an extended period in some patients with glioblastoma. Hence, Delytact Injection is expected to be effective to a certain level. In line with this, Delytact Injection has been approved as an option for the treatment of malignant glioma, with one of the 3 approval conditions including conducting a use-results comparison survey and resubmission of the marketing authorization application within the granted time period of 7 years, under the conditional and time-limited approval scheme described in Article 23–26 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices.
The association between mortality and door-to-antibiotic time: a systematic review and meta-analysis
Authors: Huang Jiao , Yang Jiang-tao , Liu Jing-chen
Published: March 2023

Purpose

Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the association between door-to-antibiotic time (each hour of delay) and mortality in sepsis.

Methods

We searched PubMed and Embase through 10 November 2022 to identity cohort studies that evaluated the adjusted association between door-to-antibiotic time (each hour of delay) and mortality in adult patients with sepsis. The primary outcome was mortality. Analysis was based on inverse-variance weighting using a fixed-effects model. The variances were derived from the logarithms of the reported confidence intervals (CIs) for associations. We estimated the odds ratio, 95% CI, and number needed to treat for the pooled data.

Results

Fifteen cohort studies involving 106 845 patients were included in the meta-analysis. Door-to-antibiotic time (each hour of delay) was associated with increased risk of mortality (odds ratio: 1.07; 95% CI: 1.06–1.08; P < 0.0001; number needed to treat = 91), with high heterogeneity (I2 = 82.2%). The association was robust in sensitivity analyses and consistent in subgroup analyses. No publication bias was found.

Conclusion

In adult patients with sepsis, each hour of delay in antibiotic administration is associated with increased odds of mortality.

Key messages What is already known on this topic Sepsis is a common and lethal syndrome that affects millions of people worldwide. The updated 2018 Surviving Sepsis Campaign guidelines recommended initiating empirical broad-spectrum antibiotic coverage within 1 hour of identification of sepsis and septic shock. Delay in antibiotic administration may increase the risk of mortality in patients with sepsis. What this study adds This meta-analysis evaluates and quantifies the association between door-to-antibiotic time (each hour of delay) and mortality in patients with sepsis. Each hour of delay in antibiotic administration is associated with increased odds of mortality in sepsis. The number needed to treat (NNT) with delayed antibiotic administration for one additional death was 91. How this study might affect research, practice, or policy: More efforts should be made to speed up the diagnosis of sepsis or sepsis shock.
Dopamine multivalent-modified polyaspartic acid for MRI-guided near-infrared photothermal therapy
Authors: Du Liang , Chen Wei , Zhong Jie , Yan Shuang , Yang Chenwu , Pu Yu , Zhu Jiang , Chen Tianwu , Zhang Xiaoming , Wu Changqiang
Published: March 2023

Nanophotothermal agents that provide efficient and precise treatment at tumor sites are attracting increasing attention in biomedicine. In particular, the method combination of nanophotothermal agents and magnetic resonance imaging (MRI) shows great promise for biomedical therapeutic applications. Herein, a simple nanophotothermal agent with dopamine multivalent-modified polyaspartic acid chelated superparamagnetic iron oxide (SPIO) and ferric ion (SPIO@PAsp-DAFe/PEG) was developed for MRI-guided near-infrared photothermal therapy (PTT). SPIO@PAsp-DAFe/PEG was random SPIO nanocluster with good water solubility, had a diameter of 57.8 ± 7.8 nm in dynamic light scattering, negatively charged surface (zeta potential = −11 mV), exhibited good stability and outstanding photothermal conversion efficiency (35.4%) and produced superior magnetic resonance enhanced imaging. In the experiment with tumor-bearing mice, the MRI not only monitored the accumulation of SPIO@PAsp-DAFe/PEG nanocomposites enhanced by near-infrared irradiation after intravenous administration but also determined the appropriate time window for PTT. With the use of MRI-guided near-infrared therapy, the SPIO@PAsp-DAFe/PEG nanocomposites provided excellent therapeutic effects, confirming their great potential as effective MRI/PTT therapeutic agents.
Upside down and the game of C allocation
Authors: Rezaie Negar , D’Andrea Ettore , Scartazza Andrea , Gričar Jožica , Prislan Peter , Calfapietra Carlo , Battistelli Alberto , Moscatello Stefano , Proietti Simona , Matteucci Giorgio
Published: March 2023

Non-structural carbohydrates (NSCs) represent the primary carbon (C) reserves and play a crucial role in plant functioning and resilience. Indeed, these compounds are involved in the regulation between C supply and demand, and in the maintenance of hydraulic efficiency. Non-structural carbohydrates are stored in parenchyma of woody organs, which is recognized as a proxy for reserve storage capacity of tree. Notwithstanding the importance of NSCs for tree physiology, their long-term regulation and trade-offs against growth were not deeply investigated. This work evaluated the long-term dynamics of mature tree reserves in stem and root, proxied by parenchyma features and focusing on the trade-off and interplay between the resources allocation in radial growth and reserves in stem and coarse root. In a Mediterranean beech forest, NSCs content, stem and root wood anatomy analysis and eddy covariance data were combined. The parenchyma fraction (RAP) of beech root and stem was different, due to differences in axial parenchyma (AP) and narrow ray parenchyma (nRP) fractions. However, these parenchyma components and radial growth showed synchronous inter-annual dynamics between the two organs. In beech stem, positive correlations were found among soluble sugars content and nRP and among starch content and the AP. Positive correlations were found among Net Ecosystem Exchange (NEE) and AP of both organs. In contrast, NEE was negatively correlated to radial growth of root and stem. Our results suggest a different contribution of stem and roots to reserves storage and a putative partitioning in the functional roles of parenchyma components. Moreover, a long-term trade-off of C allocation between growth and reserve pool was evidenced. Indeed, in case of C source reduction, trees preferentially allocate C toward reserves pool. Conversely, in high productivity years, growth represents the major C sink.
Linalool Induces Resistance Against Tobacco Mosaic Virus in Tobacco Plants
Authors: Jiang Yue , Pan Xiaoyu , Li Yiming , Yang Yizhou , Jia Yina , Lei Bin , Feng Juntao , Ma Zhiqing , Liu Xili , Yan He
Published: March 2023

The essential oil of Cinnamomum camphora is the most widely consumed and used spice in the world today. It has therapeutic effects in medicine and has been shown to have good antibacterial and bacteriostatic effects in agriculture. This study found that C. camphora oil significantly induced plant disease resistance activity. Linalool, its main active component, significantly induced plant disease resistance activity (67.49% at a concentration of 800 μg/ml) over the same concentration of the chitosan oligosaccharide positive control but had no direct effect on tobacco mosaic virus (TMV). In this study of its antiviral mechanism, linalool induced hypersensitive reaction (HR); the overexpression of related defense enzymes SOD, CAT, POD, and PAL; and the accumulation of H2O2 and SA content in N. glutinosa. Besides, linalool induced crops resistance against Colletotrichum lagenarium, Botrytis cinerea, Sclerotinia sclerotiorum, and Phytophthora capsica. Taken together, the anti-TMV mechanism of linalool involved the induction of plant disease resistance through activation of a plant immune response mediated by salicylic acid. Linalool-induced plant disease resistance activity has a long duration, broad spectrum, and rich resources; linalool thus has the potential to be developed as a new plant-derived antiviral agent and plant immune activator.
Grafting Tomato to Manage Southern Blight, Prevent Yield Loss, and Increase Crop Value
Authors: Keinath Anthony P. , Hajihassani Abolfazl
Published: March 2023

Southern blight, caused by the soilborne fungus Athelia rolfsii, has increased in frequency and severity in the southern United States since the use of methyl bromide fumigation ceased. The objective of this study was to evaluate three cultivars of sticky nightshade (Solanum sisymbriifolium), previously used as tomato rootstocks because of resistance to root-knot nematode, for resistance to southern blight. Field experiments in infested soil were done in Georgia in 2020 and 2021 and in South Carolina in 2021. Tomato cultivar Roadster was used as the scion. Control treatments included nongrafted ‘Roadster’ in all experiments and self-grafted ‘Roadster’ in Georgia. In all three experiments, all rootstocks significantly reduced incidence of southern blight and increased vigor ratings compared to control treatments (P ≤ 0.007). The rootstocks Maxifort, White Star, and SisSyn II, but not Diamond, significantly increased marketable weight (P ≤ 0.02) and crop value (P < 0.05) compared to control treatments. In South Carolina only, because of greater yields than in Georgia, net returns with Maxifort and White Star were significantly greater than net return with nongrafted ‘Roadster’ (P = 0.004). When the wholesale price for fresh market tomato is ≥$13/box, grafting may be an effective and economical management for southern blight.
Tobamoviruses Show Broad Host Ranges and Little Genetic Diversity Among Four Habitat Types of a Heterogeneous Ecosystem
Authors: Zamfir Adrián D. , Babalola Bisola M. , Fraile Aurora , McLeish Michael J. , García-Arenal Fernando
Published: March 2023

Host ranges of plant viruses are poorly known, as studies have focused on pathogenic viruses in crops and adjacent wild plants. High-throughput sequencing (HTS) avoids the bias toward plant–virus interactions that result in disease. Here we study the host ranges of tobamoviruses, important pathogens of crops, using HTS analyses of an extensive sample of plant communities in four habitats of a heterogeneous ecosystem. Sequences of 17 virus operational taxonomic units (OTUs) matched references in the Tobamovirus genus, eight had narrow host ranges, and five had wide host ranges. Regardless of host range, the OTU hosts belonged to taxonomically distant families, suggesting no phylogenetic constraints in host use associated with virus adaptation, and that tobamoviruses may be host generalists. The OTUs identified as tobacco mild green mosaic virus (TMGMV), tobacco mosaic virus (TMV), pepper mild mottle virus, and Youcai mosaic virus had the largest realized host ranges that occurred across habitats and exhibited host use unrelated to the degree of human intervention. This result is at odds with assumptions that contact-transmitted viruses would be more abundant in crops than in wild plant communities and could be explained by effective seed-, contact-, or pollinator-mediated transmission or by survival in the soil. TMGMV and TMV had low genetic diversity that was not structured according to habitat or host plant taxonomy, which indicated that phenotypic plasticity allows virus genotypes to infect new hosts with no need for adaptive evolution. Our results underscore the relevance of ecological factors in host range evolution, in addition to the more often studied genetic factors.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Postoperative emergency department visits for pain after outpatient orthopaedic surgery: did rescheduling hydrocodone make a difference?
Authors: Wassef Christina , Frangenberg Alexander , Lee HaEun , Iloani Nwamaka , Bates Christopher M. , Pientka Amanda C. , Pientka William F.
Published: March 2023

Background:

In 2014, the United States Drug Enforcement Agency rescheduled hydrocodone from schedule III to II to mitigate the opiate crisis in America. Hydrocodone has long served as common pain medication after outpatient orthopaedic surgical procedures in the United States. We hypothesize rescheduling of hydrocodone would correlate with an increase in postoperative emergency department visits for pain.

Methods:

We performed a retrospective review of all outpatient orthopaedic procedures and identified all patients who subsequently presented to our emergency department for postoperative pain for the one calendar year prior to and after the rescheduling of hydrocodone.

Results:

We identified 2984 orthopaedic procedures and 3193 emergency department visits for postoperative pain across all surgical specialties. 875 orthopaedic procedures occurred prior to hydrocodone rescheduling with 48 postoperative ED visits for pain (5.4%). 2109 procedures occurred after the rescheduling of hydrocodone with 123 ED visits for pain postoperatively (5.8%). 199 patients presented to the ED for postoperative pain, for a total of 345 visits. The median postoperative time to emergency room visit for the pre-rescheduling group was 6.5 days versus 4.0 days post-rescheduling.

Conclusions:

We identified statistically significant differences in postoperative medication and prescribed amounts. We identified no difference in the proportion of patients that went to the emergency room by timeframe relative to hydrocodone rescheduling, nor did we identify a difference between samples in terms of gender, race, insurance status, and comorbid conditions. Increased restriction on hydrocodone prescribing did not increase emergency department visits for pain after outpatient orthopaedic surgery.

Level of Evidence:

Therapeutic III.
Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study
Authors: Peronnet Estelle , Blein Sophie , Venet Fabienne , Cerrato Elisabeth , Fleurie Aurore , Llitjos Jean-François , Kreitmann Louis , Terraz Gabriel , Conti Filippo , Gossez Morgane , Rimmelé Thomas , Textoris Julien , Lukaszewicz Anne-Claire , Brengel-Pesce Karen , Monneret Guillaume ,   for the REAnimation Low Immune Status Marker (REALISM) Study Group
Published: March 2023

OBJECTIVES:

There is a crucial unmet need for biomarker-guided diagnostic and prognostic enrichment in clinical trials evaluating immune modulating therapies in critically ill patients. Low monocyte expression of human leukocyte antigen-DR (mHLA-DR), considered as a reference surrogate to identify immunosuppressed patients, has been proposed for patient stratification in immunostimulation approaches. However, its widespread use in clinic has been somewhat hampered by technical constraints inherent to flow cytometry technology. The objective of the present study was to evaluate the ability of a prototype multiplex polymerase chain reaction tool (immune profiling panel [IPP]) to identify immunosuppressed ICU patients characterized by a low mHLA-DR expression.

DESIGN:

Retrospective observational cohort study.

SETTING:

Adult ICU in a University Hospital, Lyon, France.

PATIENTS:

Critically ill patients with various etiologies enrolled in the REAnimation Low Immune Status Marker study (NCT02638779).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

mHLA-DR and IPP data were obtained from 1,731 blood samples collected from critically ill patients with various etiologies and healthy volunteers. A partial least square regression model combining the expression levels of IPP markers was trained and used for the identification of samples from patients presenting with evidence of immunosuppression, defined here as mHLADR less than 8,000 antibodies bound per cell (AB/C). The IPP gene set had an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI 0.83–0.89) for the identification of immunosuppressed patients. In addition, when applied to the 123 patients still in the ICU at days 5–7 after admission, IPP similarly enriched the number of patients with ICU-acquired infections in the immunosuppressed group (26%), in comparison with low mHLA-DR (22%).

CONCLUSIONS:

This study reports on the potential of the IPP gene set to identify ICU patients presenting with mHLA-DR less than 8,000 AB/C. Upon further optimization and validation, this molecular tool may help in the stratification of patients that could benefit from immunostimulation in the context of personalized medicine.
Efficacy and safety of low-dose aspirin on preventing transplant renal artery stenosis: a prospective randomized controlled trial
Authors: Tian Xiangyong , Ji Bingqing , Niu Xiaoge , Duan Wenjing , Wu Xiaoqiang , Cao Guanghui , Zhang Chan , Zhao Jingge , Wang Zhiwei , Gu Yue , Cao Huixia , Qin Tao , Shao Fengmin , Yan Tianzhong
Published: March 2023

Background:

Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.

Methods:

After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People's Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment (n = 178), or a control group with only standard treatment (n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS).

Results:

In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate (P < 0.001), cholesterol (P = 0.028), and low-density lipoprotein cholesterol (P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference.

Conclusion:

Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS without significant adverse effects.

Trial Registration:

Clinicaltrials.gov, NCT04260828.
A Hypothesis-Generating Prospective Longitudinal Study to Assess the Relative Contribution of Common Respiratory Viruses to Severe Lower Respiratory Infections in Young Children
Authors: Ben-Shimol Shalom , Ramilo Octavio , Leber Amy L. , van der Beek Bart Adriaan , Everhart Kathy , Mertz Sara , Mejias Asuncion , Dagan Ron
Published: March 2023

Background:

Respiratory viruses such as respiratory syncytial virus (RSV), influenza, parainfluenza and human metapneumovirus are well-established etiologies of acute lower respiratory tract infections (ALRIs; LRI-viruses). In contrast, adenovirus (AdV), rhinovirus/enterovirus (RV/EV) and seasonal human coronaviruses (CoV), collectively termed AdV/RV/CoV, are detected both in healthy children and children with ALRI.

Methods:

The methods include a prospective longitudinal case–control study, assessing the prevalence of LRI-viruses versus AdV/RV/CoV in ALRI [community-acquired alveolar pneumonia (CAAP) and bronchiolitis] during hospitalization (visit 1), 7–14 days (visit 2) and 28–35 days (visit 3) in 2–17-month-old children. Controls were 2–27-month-old children hospitalized for elective surgery during the same respiratory seasons.

Results:

We enrolled 99 infants (37 CAAP, 38 bronchiolitis and 24 controls) and obtained 211 nasopharyngeal swabs. Overall, 163 (77%) had greater than or equal to 1 viruses detected; RV/EV (n = 94; 45%) and RSV (n = 71; 34%) were the most frequently detected viruses. In CAAP, the overall LRI-virus prevalence was 78.4%, 32.4% and 5.4% in visits 1, 2 and 3, respectively; the respective rates in bronchiolitis were 73.7%, 34.5% and 8.0%. In controls, no LRI-viruses were detected. In contrast, the overall AdV/RV/CoV prevalence was high among controls (70.8%) and similar among CAAP (48.6%, 40.5% and 40.5%) and bronchiolitis (47.4, 58.6% and 64.0%) across visits.

Conclusions:

Among ALRI cases, LRI-viruses dominated during the acute disease, with prevalence declining within 28–35 days, suggesting their causative role. In contrast, AdV/RV/CoV prevalence was similar during all 3 visits and in controls, suggesting that carriage of these viruses is common during the viral respiratory season. The current study is relatively small and of short duration; however, the findings are supported by other recent studies.
Gender-Affirming Care and Comprehensive Sexuality Education
Authors:   International Association of Forensic Nurses
Published: March 2023

Every year, an estimated 246 million children are subject to some form of gender-based violence, including mistreatment, bullying, psychological abuse, and sexual harassment. Lesbian, gay, bisexual, transgender, two-spirit, or questioning youth are at a heightened risk of experiencing violence and have unique health, educational, and social needs. Fostering an atmosphere of support and acceptance can help alleviate many of these negative outcomes.
Significance of anatomical resection and resection margin status in patients with HBV-related hepatocellular carcinoma and microvascular invasion: a multicenter propensity score-matched study
Authors: Zhang Xiu-Ping , Xu Shuai , Lin Zhao-Yi , Gao Qing-Lun , Wang Kang , Chen Zi-Li , Yan Mao-Lin , Zhang Fan , Tang Yu-Fu , Zhao Zhi-Ming , Li Cheng-Gang , Lau Wan Yee , Cheng Shu-Qun , Hu Ming-Gen , Liu Rong
Published: March 2023

Background:

Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for patients with hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of anatomical resection (AR) versus nonanatomical resection (NAR) combined with resection margin (RM) (narrow RM <1 cm vs. wide RM ≥1 cm) on long-term prognosis in hepatitis B virus-related HCC patients with MVI.

Materials and methods:

Data from multicenters on HCC patients with MVI who underwent hepatectomy was analyzed retrospectively. Propensity score matching analysis was performed in these patients.

Results:

The 1965 enrolled patients were divided into four groups: AR with wide RM (n=715), AR with narrow RM (n=387), NAR with wide RM (n=568), and NAR with narrow RM (n=295). Narrow RM (P<0.001) and NAR (P<0.001) were independent risk factors for both overall survival and recurrence-free survival in these patients based on multivariate analyses. For patients in both the AR and NAR groups, wide RM resulted in significantly lower operative margin recurrence rates than those patients in the narrow RM groups after propensity score matching (P=0.002 and 0.001). Patients in the AR with wide RM group had significantly the best median overall survival (78.9 vs. 51.5 vs. 48.0 vs. 36.7 months, P<0.001) and recurrence-free survival (23.6 vs. 14.8 vs. 17.8 vs. 9.0 months, P<0.001) than those in the AR with narrow RM, NAR with wide RM or with narrow RM groups, respectively.

Conclusions:

If technically feasible and safe, AR combined with wide RM should be the recommended therapeutic strategy for HCC patients who are estimated preoperatively with a high risk of MVI.
Leveraging a nationwide infection surveillance program to implement a colorectal surgical site infection reduction bundle: a pragmatic, prospective, and multicenter cohort study
Authors: Badia Josep M. , Arroyo-Garcia Nares , Vázquez Ana , Almendral Alexander , Gomila-Grange Aina , Fraccalvieri Domenico , Parés David , Abad-Torrent Ana , Pascual Marta , Solís-Peña Alejandro , Puig-Asensio Mireia , Pera Miguel , Gudiol Francesc , Limón Enric , Pujol Miquel ,   Members of the VINCat Colorectal Surveillance Team,   on behalf of VINCat Program*
Published: March 2023

Background:

Bundled interventions usually reduce surgical site infection (SSI) when implemented at single hospitals, but the feasibility of their implementation at the nationwide level and their clinical results are not well established.

Materials and Methods:

Pragmatic interventional study to analyze the implementation and outcomes of a colorectal surgery care bundle within a nationwide quality improvement program. The bundle consisted of antibiotic prophylaxis, oral antibiotic prophylaxis (OAP), mechanical bowel preparation, laparoscopy, normothermia, and a wound retractor. Control group (CG) and Intervention group (IG) were compared. Overall SSI, superficial (S-SSI), deep (D-SSI), and organ/space (O/S-SSI) rates were analyzed. Secondary endpoints included microbiology, 30-day mortality, and length of hospital stay.

Results:

A total of 37 849 procedures were included, 19 655 in the CG and 18 194 in the IG. In all, 5462 SSIs (14.43%) were detected: 1767 S-SSI (4.67%), 847 D-SSI (2.24%), and 2838 O/S-SSI (7.5%). Overall SSI fell from 18.38% (CG) to 10.17% (IG), odds ratio (OR) of 0.503 [0.473–0.524]. O/S-SSI rates were 9.15% (CG) and 5.72% (IG), OR of 0.602 [0.556–0.652]. The overall SSI rate was 16.71% when no measure was applied and 6.23% when all six were used. Bundle implementation reduced the probability of overall SSI (OR: 0.331; CI95: 0.242–0.453), and also O/S-SSI rate (OR: 0.643; CI95: 0.416–0.919). In the univariate analysis, all measures except normothermia were associated with a reduction in overall SSI, while only laparoscopy, OAP, and mechanical bowel preparation were related to a decrease in O/S-SSI. Laparoscopy, wound retractor, and OAP decreased overall SSI and O/S-SSI in the multivariate analysis.

Conclusions:

In this cohort study, the application of a specific care bundle within a nationwide nosocomial infection surveillance system proved feasible and resulted in a significant reduction in overall and O/S-SSI rates in the elective colon and rectal surgery. The OR for SSI fell between 1.5 and 3 times after the implementation of the bundle.