bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum corrections to the thermodynamics and phase transition of a black hole surrounded by a cavity in the extended phase space
Authors: Feng Zhongwen , Zhou Xia , Zhou Shiqi , Yang Shuzheng
Published: June 2022

In the extended phase space, we investigate the rainbow gravity-corrected thermodynamic phenomena and phase structure of the Schwarzschild black hole surrounded by a spherical cavity. The results show that rainbow gravity has a very significant effect on the thermodynamic phenomena and phase structure of the black hole. It prevents the black hole from total evaporation and leads to a remnant with a limited temperature but no mass. Additionally, we restore the P − V criticality and obtain the critical quantities of the canonical ensemble. When the temperature or pressure is smaller than the critical quantities, the system undergoes two Hawking-Page-like phase transitions and one first-order phase transition, which never occurs in the original case. Remarkably, our findings demonstrate that the thermodynamic behavior and phase transition of the rainbow SC black hole surrounded by a cavity in the extended phase space are analogous to those of the Reissner–Nordström anti-de Sitter black hole. Therefore, rainbow gravity activates the effect of electric charge and cutoff factor in the evolution of the black hole.
Multi-cycling nanoindentation in additively manufactured Inconel 625 before and after laser peening
Authors: Tajyar Ali , Brooks Nicholas , Vaseghi Majid , Hackel Lloyd , Momeni Kasra , Davami Keivan
Published: June 2022

In this research, a room temperature multicycle nanoindentation technique was implemented to evaluate the effects of the laser peening (LP) process on the surface mechanical behavior of additively manufactured (AM) Inconel 625. Repetitive deformation was introduced by loading-unloading during an instrumented nanoindentation test on the as-built (No LP), 1-layer, and 4-layer laser peened (1LP and 4LP) conditions. It was observed that laser-peened specimens had a significantly higher resistance to penetration of the indenter and lower permanent deformation. This is attributed to the pre-existing dislocation density induced by LP in the material which affects the dislocation interactions during the cyclic indentation. Moreover, high levels of compressive stresses, which are greater in the 4LP specimen than the 1LP specimen, lead to more effective improvement of surface fatigue properties. The transition of the material response from elastic-plastic to almost purely elastic in 4LP specimens was initiated much earlier than it did in the No LP, and 1LP specimens. In addition to the surface fatigue properties, hardness and elastic modulus were also evaluated and compared.
A roughness calculation method based on milling topography simulation
Authors: Zhang Lei , Zheng Minli , Zhang Wei , Li Kangning
Published: June 2022

The surface texture and roughness parameters of the workpiece after milling have a greater impact on the performance of the workpiece, so the analysis of the milling topography is particularly important. Firstly, the edge line of the ball end milling cutter was modeled. According to the movement law of the milling process, a complete set of milling topography simulation model was established, and a new influencing factor phase difference is proposed. In addition to the conventional cutting parameters, the model also considers the phase difference and tool inclination. Secondly, through the topography analysis and the calculation of the height of the convex peak H
max, the comparison with the experiment was carried out to further verify the accuracy of the model. Finally, the point cloud data obtained from the topography simulation is processed, the roughness Sa is calculated according to the least square method. and the influence of the phase difference Δφ and the tool inclination β on the milling topography, surface texture and roughness Sa are respectively analyzed. The conclusions obtained provide guidance and reference for industrial parts designers who have specific texture requirements.
Cellular uptake and cytotoxicity of PEGylated gold nanoparticles in C33A cervical cancer cells
Authors: David Shaquan , Patel Devanshi Yogeshkumar , Cardona Sandra M. , Kirby Neil , Mayer Kathryn M
Published: June 2022

Gold nanoparticles (GNPs) have served as an excellent candidate for biomedical applications. GNPs can be conjugated with carboxyl-polyethylene glycol-thiol (PEG) as a stealth coating which prolongs circulation time [Lipka J et al 2010 Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials, 31 , 6574–6581, Janát-Amsbury M et al 2011 Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur. J. Pharm. Biopharm, 77 , 417–423] and increases cellular uptake.[He B et al 2017 Increased cellular uptake of peptide-modified PEGylated gold nanoparticles. Biochem. Biophys. Res. Commun., 494 , 339–345, Soenen S. J et al 2014 , The cellular interactions of PEGylated gold nanoparticles: effect of PEGylation on cellular uptake and cytotoxicity. Part. Part. Syst. Charact., 31 , 794–800, Guo J et al 2016 Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells. Int. J. Pharm., 509 , 16–27. Brandenberger C et al 2010 Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol‐coated gold nanoparticles. Small, 6 , 1669–1678. To examine the biological effects of PEG-coated GNPs, we investigated their cytotoxicity on human cervical cancer C33A cells as compared to citrate-capped GNPs. Our results indicated that PEGylated GNPs markedly induce apoptosis and necrosis causing cell shrinkage and cell membrane asymmetry. 30 nm citrate-capped GNPs were synthesized in aqueous solution using a citrate-reduction method. GNPs were functionalized with PEG (MW = 7500 g mol−1. The GNPs were characterized using scanning electron microscopy (SEM), confirming that the as-synthesized GNPs have a diameter of 30 nm. Dynamic light scattering (DLS) determined that the hydrodynamic diameter of PEGylated GNPs was 78.82 nm, and that of citrate-capped GNPs was 43.82 nm. Zeta potential measurements showed an increase in colloidal stability for PEGylated GNPs as compared to citrate GNPs, with a zeta potential of −33.33 mV observed for citrate-capped GNPs and a zeta potential of −43.38 mV observed for PEGylated GNPs. The PEGylated GNPs were found to effectively induce early and late-stage apoptosis in C33A cells with a significant reduction in total cell viability of 32.3%. Based on the apoptotic activity in C33A cells, PEGylated GNPs may serve as a promising radiosensitizer for cancer treatments.
Geometry, analysis, and morphogenesis: Problems and prospects
Authors: Lewicka Marta , Mahadevan L.
Published: June 2022

The remarkable range of biological forms in and around us, such as the undulating shape of a leaf or flower in the garden, the coils in our gut, or the folds in our brain, raise a number of questions at the interface of biology, physics, and mathematics. How might these shapes be predicted, and how can they eventually be designed? We review our current understanding of this problem, which brings together analysis, geometry, and mechanics in the description of the morphogenesis of low-dimensional objects. Starting from the view that shape is the consequence of metric frustration in an ambient space, we examine the links between the classical Nash embedding problem and biological morphogenesis. Then, motivated by a range of experimental observations and numerical computations, we revisit known rigorous results on curvature-driven patterning of thin elastic films, especially the asymptotic behaviors of the solutions as the (scaled) thickness becomes vanishingly small and the local curvature can become large. Along the way, we discuss open problems that include those in mathematical modeling and analysis along with questions driven by the allure of being able to tame soft surfaces for applications in science and engineering.
Acceleratingin silicosaturation mutagenesis using compressed sensing
Authors: Schreiber Jacob , Nair Surag , Balsubramani Akshay , Kundaje Anshul
Published: June 2022

Motivation

In silico saturation mutagenesis (ISM) is a popular approach in computational genomics for calculating feature attributions on biological sequences that proceeds by systematically perturbing each position in a sequence and recording the difference in model output. However, this method can be slow because systematically perturbing each position requires performing a number of forward passes proportional to the length of the sequence being examined.

Results

In this work, we propose a modification of ISM that leverages the principles of compressed sensing to require only a constant number of forward passes, regardless of sequence length, when applied to models that contain operations with a limited receptive field, such as convolutions. Our method, named Yuzu, can reduce the time that ISM spends in convolution operations by several orders of magnitude and, consequently, Yuzu can speed up ISM on several commonly used architectures in genomics by over an order of magnitude. Notably, we found that Yuzu provides speedups that increase with the complexity of the convolution operation and the length of the sequence being analyzed, suggesting that Yuzu provides large benefits in realistic settings.

Availability and implementation

We have made this tool available at https://github.com/kundajelab/yuzu.
ZipHiC: a novel Bayesian framework to identify enriched interactions and experimental biases in Hi-C data
Authors: Osuntoki Itunu G , Harrison Andrew , Dai Hongsheng , Bao Yanchun , Zabet Nicolae Radu
Published: June 2022

Motivation

Several computational and statistical methods have been developed to analyze data generated through the 3C-based methods, especially the Hi-C. Most of the existing methods do not account for dependency in Hi-C data.

Results

Here, we present ZipHiC, a novel statistical method to explore Hi-C data focusing on the detection of enriched contacts. ZipHiC implements a Bayesian method based on a hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC) to detect interactions in two-dimensional space based on a Hi-C contact frequency matrix. ZipHiC uses data on the sources of biases related to the contact frequency matrix, allows borrowing information from neighbours using the Potts model and improves computation speed using the ABC model. In addition to outperforming existing tools on both simulated and real data, our model also provides insights into different sources of biases that affects Hi-C data. We show that some datasets display higher biases from DNA accessibility or Transposable Elements content. Furthermore, our analysis in Drosophila melanogaster showed that approximately half of the detected significant interactions connect promoters with other parts of the genome indicating a functional biological role. Finally, we found that the micro-C datasets display higher biases from DNA accessibility compared to a similar Hi-C experiment, but this can be corrected by ZipHiC.

Availability and implementation

The R scripts are available at https://github.com/igosungithub/HMRFHiC.git.

Supplementary information

Supplementary data are available at Bioinformatics online.
Changes in brain activity with tominersen in early-manifest Huntington’s disease
Authors: Hawellek D J , Garces P , Meghdadi A H , Waninger S , Smith A , Manchester M , Schobel S A , Hipp J F
Published: June 2022

It is unknown whether alterations in EEG brain activity caused by Huntington’s disease may be responsive to huntingtin-lowering treatment. We analysed EEG recordings of 46 patients (mean age = 47.02 years; standard deviation = 10.19 years; 18 female) with early-manifest Stage 1 Huntington’s disease receiving the huntingtin-lowering antisense oligonucleotide tominersen for 4 months or receiving placebo as well as 39 healthy volunteers (mean age = 44.48 years; standard deviation = 12.94; 22 female) not receiving treatment. Patients on tominersen showed increased resting-state activity within a 4–8 Hz frequency range compared with patients receiving placebo (cluster-based permutation test, P < 0.05). The responsive frequency range overlapped with EEG activity that was strongly reduced in Huntington’s disease compared with healthy controls (cluster-based permutation test, P < 0.05). The underlying mechanisms of the observed treatment-related increase are unknown and may reflect neural plasticity as a consequence of the molecular pathways impacted by tominersen treatment.

Hawellek et al. report that patients with Huntington’s disease treated with the huntingtin-lowering antisense oligonucleotide tominersen exhibited increased EEG power in the theta/alpha frequency range. The underlying mechanisms of the observed changes are unknown and may reflect neural plasticity as a consequence of the molecular pathways impacted by tominersen treatment.
China’s Stance on the Normativity of International Climate Change Law: An Interactional Account
Authors: Li Feiyue
Published: June 2022

Existing analytical accounts of China’s interactions with international law are underdeveloped. This article proposes the use of an interactional model to explain the normativity of international law from three perspectives: shared understandings, normative qualities of international law, and the reception of individual countries to these normative qualities. Furthermore, the interactional model is used to explain how conceptions of the normativity of international climate change law are developed in China. It finds that China has accepted the common responsibility system under an enhanced transparency framework, while adhering to the facilitative nature of international commitments to accommodate the needs of developing countries and stringently insisting on obligations of support from developed countries being met. In this, China’s position on the normative qualities of international climate change law is influenced by its international identities, power status, national interests, and domestic understandings of anthropogenic climate change. The interactional account that follows implies that future research on China’s interactions with international law should be cautious of both Western centrism and Chinese exceptionalism and consider both the legitimacy of international law and China’s own domestic context.
Gain-of-function TLR7 and loss-of-function A20 gene variants identify a novel pathway for Mendelian lupus and lupus nephritis
Authors: Villalvazo Priscila , Carriazo Sol , Rojas-Rivera Jorge , Ramos Adrián M , Ortiz Alberto , Perez-Gomez Maria Vanessa
Published: June 2022

Systemic lupus erythematosus (SLE) is a chronic and inflammatory autoimmune disease of unknown origin that may cause kidney disease, i.e. lupus nephritis (LN). Within a wider trend towards an expanding field of genetic causes of kidney disease, two recent reports have emphasized the role of Mendelian autoimmune disorders in causing LN both in children and in young adults. Loss-of-function (LOF) variants of tumor necrosis factor alpha–induced protein 3 (TNFAIP3) and gain of function (GOF) variants of Toll-like receptor 7 (TLR7) cause SLE and LN, respectively. Interestingly, both genes regulate the same signaling route, as A20, the protein encoded by TNFAIP3, inhibits nuclear factor ĸB (NF-ĸB) activation while TLR7 promoted NF-ĸB activation. Moreover, TNFAIP3 and TLR7 variants are relatively frequent, potentially contributing to polygenic risk for LN. Finally, they both may be expressed by kidney cells, potentially contributing to the severity of kidney injury in persons who have already developed autoimmunity. The fact that both genes regulate the same pathway may lead to novel therapeutic approaches targeting the shared molecular pathway.
Larval growth of the polychaete Arenicola marina under different temperature and food conditions: consequences on bioenergetic models
Authors: Broquard Coralie , Lancelot Théo , Lefebvre Sébastien , Courcot Lucie , Gaudron Sylvie M
Published: June 2022

Arenicola marina, a marine benthic polychaete, is widespread on sandy beaches in Europe and considered as an ecosystem engineer despite commonly used as bait by fishermen. Data regarding the bioenergetics of the lugworm larval stages are still incomplete. Trochophore is initially lecithotroph and then becomes planktotroph while growing as metatrochophore on subtidal area, a quite stable daily temperature environment compared with the foreshore, where juveniles and adult live, with daily temperature fluctuating up to 15°C. These discrepancies in temperature ranges may influence the temperature corrections (TCs) that control metabolic rates during the life cycle of A. marina. We carried out laboratory experiments in microcosms by inducing artificial spawning of lugworms, and then undertaken in vitro fertilization to obtain embryos and, finally, to follow, the larval development up to 10 segments with chaetae for 50 days under three temperature conditions (13°C, 15°C and 17°C) and two food conditions (‘fed’ and ‘non-fed’). The first feeding (‘birth’) of A. marina larvae was deciphered anatomically for a size between 450 and 500 μm and described at 17 days post-fertilization for larvae reared at 15°C and 17°C. Using a biphasic model with a von Bertalanffy growth before ‘birth’ and an exponential growth after ‘birth’, among the three temperature treatments, the 15°C condition exhibited the best larval performance. TC based on embryonic and larval metabolic rates gave an Arrhenius temperature of ~6661 K and a higher boundary temperature tolerance range of ~294.5 K. Both temperature values differ from those calculated from TC based mostly on juvenile and adult metabolic rates. We claim to use two sets of Arrhenius temperatures according to the life history stages of A. marina while using Dynamic Energy Budget model. This model was developed initially in order to manage the conservation of the lugworm species.
Pre-pandemic Physical Function and Social Network in Relation to COVID-19-Associated Depressive Burden in Older Adults in Sweden
Authors: Triolo Federico , Saadeh Marguerita , Sjöberg Linnea , Fratiglioni Laura , Welmer Anna-Karin , Calderón-Larrañaga Amaia , Dekhtyar Serhiy
Published: June 2022

Background and Objectives

The coronavirus disease 2019 (COVID-19) pandemic, as well as the measures intended to limit its spread, have likely affected older adults’ depressive burden. Good physical functioning and a rich social network may benefit older adults’ mental health. We examined whether pre-pandemic physical functioning and social network were associated with depressive burden during the first wave of the COVID-19 pandemic in Stockholm, Sweden.

Research Design and Methods

A telephone assessment of depressive burden using the symptoms of sadness, anxiety, worrying, reduced sleep, and reduced appetite was conducted in May–September 2020 in 930 older adults from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study. Objective measures of gait speed, muscle strength, and balance; and self-reports of social connections and support were collected in 2016–2019. Logistic models were adjusted for sociodemographic, clinical, lifestyle, and pandemic-related factors (loneliness, change in physical and social engagement, and experience of death due to COVID-19).

Results

Only good muscle strength (odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.32–0.85; ref: poor strength, ≥17 s) and rich social support (OR: 0.67; 95% CI: 0.45–0.99; ref: poor support) exhibited an independent association with depressive burden, even after accounting for pandemic-related factors. A combination of good muscle strength and rich social support were associated with the greatest reduction in depressive burden (OR: 0.35; 95% CI: 0.18–0.66; ref: poor social support and poor muscle strength).

Discussion and Implications

Prepandemic social support and muscle strength could supply older adults with resilience against the depressive burden associated with the COVID-19 pandemic.
Sea Snacks from DNA Tracks: Using DNA Metabarcoding to Characterize the Diet of Green Turtles (Chelonia Mydas)
Authors: Sarkis Christine M , Hoenig Brandon D , Seney Erin E , Gaspar Stephanie A , Forsman Anna M
Published: June 2022

Synopsis

The green turtle (Chelonia mydas) is a circumglobal species with a wide dietary breadth that varies among regions and life history stages. Comprehensive understanding of foraging ecology over space and time is critical to inform conservation and management of this species and its habitats. Here, we used DNA metabarcoding to test candidate primer sets with 39 gut content homogenates from stranded green turtles (FL, USA) to identify primer sets that maximize detection of food items and specificity of taxonomic classifications. We tested six existing universal primer sets to detect plants, animals, and eukaryotes more broadly (CO1, 18SV1-V3, 18SV4, rbcL, UPA, ITS). The CO1 and 18SV4 primer sets produced the greatest number of dietary amplicon sequence variants (ASVs) and unique taxonomic classifications, and they were the only primer sets to amplify taxa from all three kingdoms relevant to green turtle diet (Animalia, Chromista, and Plantae). Even though the majority of CO1-derived reads were of host origin (>90%), this primer set still produced the largest number of dietary ASVs classified to species among the six primer sets. However, because the CO1 primer set failed to detect both vascular plants and green algae, we do not recommend the use of this primer set on its own to characterize green turtle diet. Instead, our findings support previous research highlighting the utility of using multiple primer sets, specifically targeting CO1 and the V4 region of the 18S gene, as doing so will provide the most comprehensive understanding of green turtle diet. More generally, our results highlight the importance of primer and loci selection and the need to validate primer sets against the study system of interest. The addition of DNA metabarcoding with optimized primer sets to the sea turtle researcher's toolbox will both increase our understanding of foraging ecology and better inform science-based conservation and ecosystem management.
The likely suspects framework: the need for a life cycle approach for managing Atlantic salmon (Salmo salar) stocks across multiple scales
Authors: Bull C D , Gregory S D , Rivot E , Sheehan T F , Ensing D , Woodward G , Crozier W
Published: June 2022

The ongoing declines in Atlantic salmon populations across its range underscore the need for co-ordinated scientific-based knowledge to support management and decisions for their conservation. Current salmon management actions remain largely focused on addressing bottlenecks to production in the freshwater phase of the life-cycle, whereas the continued declines observed in the recent decades are thought to be driven primarily by constraints on the marine phase. The challenges brought by global warming and other emerging stressors require immediate actions, requiring us to re-think the methods behind stock assessment and forge stronger linkages between data, models and policies to promote more effective management actions. We outline a scientific framework that takes a wider ecosystem view, designed to evaluate holistically a suite of indicators and potential drivers of salmon mortality at key phases of the life cycle. The aims of the proposed “Likely Suspects Framework” are to enhance cross-fertilisation of ideas between assessment processes at the stock-complex scale and stock-specific focused management activities, and to develop new decision support tools to improve management efficiencies and scenario testing. Adopting such an approach provides a new way to catalyse the acquisition and deployment of both existing and new data and models that are urgently needed for assisting the conservation and future stewardship of salmon stocks on both sides of the Atlantic.
Improvement in feed efficiency and reduction in nutrient loading from rainbow trout farms: the role of selective breeding
Authors: Kause Antti , Nousiainen Antti , Koskinen Heikki
Published: June 2022

Resource efficiency, the ratio of inputs to outputs, is essential for both the economic and environmental performance of any sector of food production. This study quantified the advancement in the feed conversion ratio (FCR) and reduction in nutrient loading from rainbow trout farming in Finland and the degree to which genetic improvements made by a national breeding program have contributed to this advancement. The study combined two datasets. One included annual records on farm-level performance of commercial rainbow trout farms from 1980 onwards, and the other included individuals across eight generations of the national breeding program. The data from the commercial farms showed that from 1980 onwards, the farm-level feed conversion ratio improved by 53.4%, and the specific nitrogen and phosphorus loading from the farms decreased by over 70%. Hence, to produce 1 kg of fish today, only half of the feed is needed compared to the 1980s. The first generation of the breeding program was established in 1992. The FCR was not directly selected for, and hence, the genetic improvement in the FCR is a correlated genetic change in response to the selection for growth and body composition. Since 1992, the estimated genetic improvement in the FCR has been 1.74% per generation, resulting in a cumulative genetic improvement of 11.6% in eight generations. Genetic improvement in the FCR is estimated to be 32.6% of the total improvement in the FCR observed at farms, implying that genetic improvement is a significant contributor to resource efficiency. The use of genetically improved rainbow trout, instead of the base population of fish, reduces feed costs by 18.3% and total production costs by 7.8% at commercial farms (by −0.266€ per kg of ungutted fish). For phosphorus and nitrogen, it can be assumed that the use of fish material with an improved FCR also leads to 18.3% less nitrogen and phosphorus flowing into an aquatic environment. Such improvements in resource efficiency are win–wins for both industry and the environment—the same amount of seafood can be produced with significantly reduced amounts of raw materials and reduced environmental impact.
Association Between Rotavirus Vaccination and Antibiotic Prescribing Among Commercially Insured US Children, 2007–2018
Authors: Hall Eric W , Tippett Ashley , Fridkin Scott , Anderson Evan J , Lopman Ben , Benkeser David , Baker Julia M
Published: June 2022

Background

Vaccines may play a role in controlling the spread of antibiotic resistance. However, it is unknown if rotavirus vaccination affects antibiotic use in the United States (US).

Methods

Using data from the IBM MarketScan Commercial Database, we conducted a retrospective cohort of US children born between 2007 and 2018 who were continuously enrolled for the first 8 months of life (N = 2 136 136). We followed children through 5 years of age and compared children who completed a full rotavirus vaccination series by 8 months of age to children who had not received any doses of rotavirus vaccination. We evaluated antibiotic prescriptions associated with an acute gastroenteritis (AGE) diagnosis and defined the switching of antibiotics as the prescription of a second, different antibiotic within 28 days. Using a stratified Kaplan-Meier approach, we estimated the cumulative incidence for each study group, adjusted for receipt of pneumococcal conjugate vaccine, provider type, and urban/rural status.

Results

Overall, 0.8% (n = 17 318) of participants received an antibiotic prescription following an AGE diagnosis. The 5-year adjusted relative cumulative incidence of antibiotic prescription following an AGE diagnosis was 0.793 (95% confidence interval [CI], .761–.827) among children with complete rotavirus vaccination compared to children without rotavirus vaccination. Additionally, children with complete vaccination were less likely to switch antibiotics (0.808 [95% CI, .743–.887]). Rotavirus vaccination has averted an estimated 67 045 (95% CI, 53 729–80 664) antibiotic prescriptions nationally among children born between 2007 and 2018.

Conclusions

These results demonstrate that rotavirus vaccines reduce antibiotic prescribing for AGE, which could help reduce the growth of antibiotic resistance.
Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype
Authors: Viswanathan Vignesh , Cao Hongbin , Saiki Julie , Jiang Dadi , Mattingly Aaron , Nambiar Dhanya , Bloomstein Joshua , Li Yang , Jiang Sizun , Chamoli Manish , Sirjani Davud , Kaplan Michael , Holsinger F Christopher , Liang Rachel , Von Eyben Rie , Jiang Haowen , Guan Li , Lagory Edward , Feng Zhiping , Nolan Garry , Ye Jiangbin , Denko Nicholas , Knox Sarah , Rosen Daria-Mochly , Le Quynh-Thu
Published: June 2022

Adult salivary stem/progenitor cells (SSPC) have an intrinsic property to self-renew in order to maintain tissue architecture and homeostasis. Adult salivary glands have been documented to harbor SSPC, which have been shown to play a vital role in the regeneration of the glandular structures postradiation damage. We have previously demonstrated that activation of aldehyde dehydrogenase 3A1 (ALDH3A1) after radiation reduced aldehyde accumulation in SSPC, leading to less apoptosis and improved salivary function. We subsequently found that sustained pharmacological ALDH3A1 activation is critical to enhance regeneration of murine submandibular gland after radiation damage. Further investigation shows that ALDH3A1 function is crucial for SSPC self-renewal and survival even in the absence of radiation stress. Salivary glands from Aldh3a1–/– mice have fewer acinar structures than wildtype mice. ALDH3A1 deletion or pharmacological inhibition in SSPC leads to a decrease in mitochondrial DNA copy number, lower expression of mitochondrial specific genes and proteins, structural abnormalities, lower membrane potential, and reduced cellular respiration. Loss or inhibition of ALDH3A1 also elevates ROS levels, depletes glutathione pool, and accumulates ALDH3A1 substrate 4-hydroxynonenal (4-HNE, a lipid peroxidation product), leading to decreased survival of murine SSPC that can be rescued by treatment with 4-HNE specific carbonyl scavengers. Our data indicate that ALDH3A1 activity protects mitochondrial function and is important for the regeneration activity of SSPC. This knowledge will help to guide our translational strategy of applying ALDH3A1 activators in the clinic to prevent radiation-related hyposalivation in head and neck cancer patients.
Identifying relevant determinants of in-hospital time to diagnosis for ANCA-associated vasculitis patients
Authors: Dirikgil Ebru , Tas Sander W , Verburgh Cornelis A , Soonawala Darius , Hak A Elisabeth , Remmelts Hilde H F , IJpelaar Daphne , Laverman Gozewijn D , Rutgers Abraham , van Laar Jaap M , Moens Hein J Bernelot , Verhoeven Peter M J , Rabelink Ton J , Bos Willem Jan W , Teng Y K Onno
Published: June 2022

Objectives

Diagnosing patients with ANCA-associated vasculitis (AAV) can be challenging owing to its rarity and complexity. Diagnostic delay can have severe consequences, such as chronic organ damage or even death. Given that few studies have addressed diagnostic pathways to identify opportunities to improve, we performed a clinical audit to evaluate the diagnostic phase.

Methods

This retrospective, observational study of electronic medical records data in hospitals focused on diagnostic procedures during the first assessment until diagnosis.

Results

We included 230 AAV patients from nine hospitals. First assessments were mainly performed by a specialist in internal medicine (52%), pulmonology (14%), ENT (13%) or rheumatology (10%). The overall median time to diagnosis was 13 [interquartile range: 2–49] days, and in patients primarily examined by a specialist in internal medicine it was 6 [1–25] days, rheumatology 14 [4–45] days, pulmonology 15 [5–70] days and ENT 57 [16–176] days (P = 0.004). Twenty-two of 31 (71%) patients primarily assessed by a specialist in ENT had non-generalized disease, of whom 14 (64%) had ENT-limited activity. Two hundred and nineteen biopsies were performed in 187 patients (81%). Histopathological support for AAV was observed in 86% of kidney biopsies, 64% of lung biopsies and 34% of ENT biopsies.

Conclusion

In The Netherlands, AAV is diagnosed and managed predominantly by internal medicine specialists. Diagnostic delay was associated with non-generalized disease and ENT involvement at presentation. Additionally, ENT biopsies had a low diagnostic yield, in contrast to kidney and lung biopsies. Awareness of this should lead to more frequent consideration of AAV and early referral for a multidisciplinary approach when AAV is suspected.
Expert Review: Prevention of Obstetrical Venous Thromboembolism
Authors: Friedman A. , D’Alton M.
Published: June 2022

(Am J Obstet Gynecol. 2021;225:228–236)

Approximately 9% to 10% of maternal deaths are related to thrombotic pulmonary embolism. The American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), the American College of Chest Physicians (ACCP), the American Society of Hematology, the National Partnership for Maternal Safety, and the Society for Maternal-Fetal Medicine have all published dissimilar recommendations for obstetrical venous thromboembolism (VTE) prophylaxis. Several additional studies have concluded mechanical prophylaxis alone was ineffective during childbirth and during recovery and sequential compression devices were only in use 17% to 21% of the time. While the use of mechanical prophylaxis has become more common, the mortality rate for VTE has not decreased. The United Kingdom implemented guidelines in 2004 for low–molecular-weight heparin prophylaxis and has shown a 40% reduction in maternal deaths from VTE. However, cost, lack of evidence, and safety concerns are included in the argument against heparin prophylaxis. This review focuses on guidelines for heparin prophylaxis during antepartum hospitalizations and following cesarean deliveries (CD).
The Effect of Structured Delivery Preparation Education On Birth Preference
Authors: Til A. , Bostanci M.
Published: June 2022

(Int J Gynecol Obstet. 2021;154:459–465)

The global rates of cesarean delivery (CD) have increased significantly, from 6.7% in 1990 to 31% in 2010-2011. In some countries the CD rate was as high as 53.1% in 2017. In Turkey the CD rate rose from 21.2% in 2003, to 36.7% in 2008, to 48.1% in 2013. Although CD is vital to prevent maternal or fetal mortality in some situations, the side effects include longer recovery time, uterine infection, blood clots, postpartum hemorrhage, and increased risks in future pregnancies. In an effort to decrease unnecessary CD, an interventional study was performed between February 2018 and May 2018 in Denizli, Turkey to see if delivery education on normal vaginal delivery (NVD) would influence delivery method.
Associations of Thrombocytopenia, Transaminase Elevations, and Transfusion With Laboratory Coagulation Tests in Women With Preeclampsia: A Cross-sectional Study
Authors: Combs D.J. , Gray K.J. , Schulman S. , Bateman B.T.
Published: June 2022

(Int J Obstet Anesth. 2021;46:102972)

Preeclampsia is associated with increased incidence of thrombocytopenia (TCP) and coagulopathy, causing concern about obstetric hemorrhage [postpartum hemorrhage (PPH)] and spinal-epidural hematoma with neuraxial procedures. In the absence of other contraindications, a patient with a platelet count >70×109/L and normal platelet function should be a candidate for a neuraxial procedure. Coagulation testing is not routine in preeclamptic women. Previous data and guidelines on the relationship between coagulation testing and risk of complications from neuraxial procedures are inconsistent. This study aimed to better understand the use of coagulation testing in patients with preeclampsia.
Clinical Profiles of Placenta Accreta Spectrum: The PACCRETA Population-based Study
Authors: Kayem G. , Seco A. , Beucher G. , Dupont C. , Branger B. , Creen Herbert C. , Huissoud C. , Freeson J. , Winer N. , Langer B. , Rozenberg P. , Morel O. , Bonnet M.P. , Perrotin F. , Azria E. , Carbillon L. , Chiesa C. , Raynal P. , Rudigoz R.C. , Dreyfus M. , Vendittelli F. , Patrier S. , Deneuz-Tharaux C. , Sentilhes L.
Published: June 2022

(BJOG. 2021;128:1646–1655)

Placenta accreta occurs when a placenta attaches too deeply into the uterine wall. Placenta increta and percreta are more severe forms where the placenta embeds further into the uterine myometrium or grows through the uterus to other nearby organs. All three of these conditions are included in placenta accreta spectrum or PAS. The major complications of PAS include the placenta not being able to normally deliver leading to heavy bleeding and potential hysterectomy. PAS is a major cause of maternal mortality and morbidity and occurs in 1.7 to 4.6 per 10,000 deliveries. Due to the rise in cesarean deliveries (CD) the rate of PAS has been reported as high as 90 per 10,000 in recent years.
Hyperbaric Prilocaine Versus Hyperbaric Bupivacaine for Spinal Anesthesia in Women Undergoing Elective Cesarean Section: A Comparative Rrandomized Double-blind Study
Authors: Chapron K. , Sleth J.C. , Capdevila X. , Bringuier S. , Dadure C.
Published: June 2022

(Anaesthesia. 2021;76:777–784. [Epub January 11, 2021])

Spinal anesthesia is the standard technique for patients undergoing cesarean delivery (CD). Bupivacaine has been a mainstay for spinal anesthesia for decades due to its minimal onset time and extended duration of motor and sensory block. There are disadvantages, however, such as some effect variability between patients. Prilocaine is a newer local anesthetic and is expected to provide a shorter duration of motor block. The aim of this study is to compare the motor block durations of hyperbaric prilocaine and bupivacaine when used for spinal anesthesia in patients undergoing elective CD.
Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial
Authors: Czarnetzki C. , Albrecht E. , Masouyé P. , Baeriswyl M. , Poncet A. , Robin M. , Kern C. , Tramèr M.R.
Published: June 2022

(Anesth Analg. 2021;133:1540–1549)

Succinylcholine is the muscle relaxant commonly chosen for rapid sequence induction, despite many adverse effects. Rocuronium bromide, 1.0 to 1.2 mg/kg, can also be used for rapid sequence induction with an onset time comparable to that of succinylcholine, but prolonged recovery time. The onset time of rocuronium may be shortened using magnesium sulfate. This superiority study compared the use of intravenous pretreatment of magnesium sulfate followed by a dose of rocuronium with the use of succinylcholine in terms of intubation conditions.
Analgesia After Cesarean Delivery in the United States 2008-2018: A Retrospective Cohort Study
Authors: Reed S.E. , Tan H.S. , Fuller M.E. , Krishnamoorthy V. , Ohnuma T. , Raghunathan K. , Habib A.F.
Published: June 2022

(Anesth Analg. 2021;133:1550–1558)

Multimodal, opioid-sparing analgesia is currently recommended for postcesarean pain management in the United States. These regimens combine neuraxial morphine, scheduled nonsteroidal anti-inflammatory drugs (NSAIDs) and scheduled acetaminophen. Recent studies have supported the use of scheduled acetaminophen plus opioids on an as-needed basis rather than acetaminophen-opioid combination drugs. This study aimed to investigate analgesia following cesarean delivery under neuraxial anesthesia in the United States and examine variations in analgesic regimens over time and between institutions.
Critical Tracheal Stenosis From Adenoid Cystic Carcinoma During Pregnancy: Case Report
Authors: Pino R.M. , Riley L.E.
Published: June 2022

(J Clin Anesth. 2021;77:110620)

The complication of full-term pregnancy by malignancy occurs in an estimated 0.1% of cases. Adenoid cystic carcinoma (ACC) is itself a rare cancer of the head and neck, amounting to just 0.2% of tracheal tumors. As an aggressive carcinoma, ACC produces critical symptoms including airway obstruction often preceded initially by coughing, stridor, dyspnea, and hemoptysis. This case report advances the literature with documentation of the most extensive ACC during pregnancy with advancing tracheal stenosis reported to date, and critical methods by which a difficult airway was managed during cesarean delivery (CD).
CE: An Evidence-Based Yoga Practice for Hospitalized Adults on Medical–Psychiatric Units
Authors: Dossett Angela , Smith Anne , Gingerich Marcia K. , Cullen Laura
Published: June 2022

Background:

Yoga-based treatments, which are recognized by the National Institutes of Health's National Center for Complementary and Integrative Health as a form of complementary and alternative medicine, have proven to be beneficial for people with various psychiatric disorders, including depression, anxiety, posttraumatic stress disorder, and attention deficit–hyperactivity disorder, as well as schizophrenia and other psychotic disorders.

Purpose:

The purpose of this evidence-based practice (EBP) project was to offer structured yoga sessions as a means of providing stress relief, promoting relaxation, reducing anxiety, and improving quality of care among male and female adult patients (ages 18 years and older) hospitalized in a locked medical–psychiatric unit within an academic medical center for treatment of both acute medical and acute psychiatric conditions.

Practice change and implementation:

The Iowa Model and Implementation Strategies for EBP provided the guiding framework for this pilot project. Patients were offered once weekly, 30-to-60-minute yoga sessions for 12 weeks and were screened for their ability to participate by the nurse–yoga instructor and the interprofessional team. Using a Precision Implementation Approach, a data-driven selection of strategies from the implementation framework promoted the adoption and sustainability of the practice change, which were further advanced through interprofessional reinforcement of yoga practice and internal reporting.

Results:

Patient feedback was sought before and after yoga sessions. Thirty-nine patients responded to the pre-yoga questionnaire and 38 patients responded to the post-yoga questionnaire. Patients reported improved mood after yoga, with 23% (nine of 39) reporting feelings of calm and relaxation pre-yoga compared with 76% (29 of 38) post-yoga, and 41% (16 of 39) reporting feelings of anxiety pre-yoga compared with just 5% (two of 38) post-yoga.

Conclusion:

Yoga sessions provided by a nurse certified in yoga instruction improved patients' mood and sense of well-being. Instructional materials and videos were created to promote sustained use. The EBP of providing yoga sessions grew from a pilot program to a sustained change with more widespread use. In addition to patients hospitalized on medical–psychiatric units, the health system expanded the sessions to include inpatients on behavioral health units.
Research With Women Who Use Drugs: Applying a Trauma-informed Framework
Authors: Robinson Kaye , Ickowicz Sarah
Published: June 2022

Women who use drugs (WWUD) experience high rates of trauma. The complex impacts of trauma can act as a barrier to accessing substance use and harm reduction services, and to participation and representation within substance use research. Trauma-informed practice is an evidence-based approach for improved clinical care among WWUD, the principles of which can be applied to substance use research. Many researchers are integrating trauma-informed approaches across research settings, yet these principles are often not referenced specifically within publications, and there is a lack of comprehensive guidance regarding integration of trauma-informed methods across different research designs and methodologies. This commentary describes and discusses the merits of applying the 4 principles of trauma-informed practice – trauma awareness, safety and trustworthiness, choice collaboration and connection, and strengths-based and skills building – to promote safety and inclusion of WWUD in substance use research.
Does Nasal Screening for Methicillin-Resistant Staphylococcus aureus (MRSA) Prevent Deep Surgical Site Infections for Elective Cervical Spinal Fusion?
Authors: Xiong Grace X. , Greene Nattaly E. , Hershman Stuart H. , Fogel Harold A. , Schwab Joseph H. , Bono Christopher M. , Tobert Daniel G.
Published: June 2022

Study Design:

Retrospective cohort study.

Objective:

The objective of this study was to determine the relationship between nasal methicillin-resistant Staphylococcus aureus (MRSA) testing and surgical site infection (SSI) rates in the setting of primary posterior cervical instrumented spine surgery.

Summary of Background Data:

Preoperative MRSA screening and decolonization has demonstrated success for some orthopedic subspecialties in prevention of SSIs. Spine surgery, however, has seen varied results, potentially secondary to the anatomic and surgical heterogeneity of the patients included in prior studies. Given that prior research has demonstrated greater propensity for gram positive SSIs in the cervical spine, we sought to investigate if MRSA screening would be more impactful in the cervical spine.

Materials and Methods:

Adult patients undergoing primary instrumented posterior cervical procedures from January 2015 to December 2019 were reviewed for MRSA testing <90 days before surgery, preoperative mupirocin, perioperative antibiotics, and SSI defined as operative incision and drainage (I&D) <90 days after surgery. Logistic regression modeling used SSI as the primary outcome, MRSA screening as primary predictor, and clinical and demographic factors as covariates.

Results:

This study included 668 patients, of whom MRSA testing was performed in 212 patients (31.7%) and 6 (2.8%) were colonized with MRSA. Twelve patients (1.8%) underwent an I&D. On adjusted analysis, preoperative MRSA testing was not associated with postoperative I&D risk. Perioperative vancomycin similarly had no association with postoperative I&D risk. Notably, 6 patients (50%) grew methicillin sensitive Staphylococcus aureus from intraoperative cultures, with no cases of MRSA.

Conclusions:

There was no association between preoperative nasal MRSA screening and SSIs in primary posterior cervical instrumented procedures, nor was there any association between vancomycin or infection rate. Furthermore, there was a preponderance of gram positive infections but none caused by MRSA. Given these findings, the considerable cost and effort associated with MRSA testing in the setting of primary posterior cervical instrumentation may not be justified. Further research should investigate if higher-risk scenarios demonstrate greater utility of preoperative testing.