bluuebunny/crossref_metadata_2025 huggingface dataset:
Census of gaseous satellites around local spiral galaxies
Authors: Zhu Jingyao , Putman Mary E
Published: March 2023

We present a search for gas-containing dwarf galaxies as satellite systems around nearby spiral galaxies using 21 cm neutral hydrogen (H i) data from the Arecibo Legacy Fast ALFA (ALFALFA) Survey. We have identified 15 spiral ‘primary’ galaxies in a local volume of 10 Mpc with a range of total masses, and have found 19 gas-containing dwarf satellite candidates within the primaries’ virial volumes (R200) and 46 candidates within 2R200. Our sensitivity using ALFALFA data converts to MH i ≈ 7.4 × 106 M⊙ at 10 Mpc, which includes 13 of the 26 gaseous dwarf galaxies in the Local Group, and the H i properties of our sample are overall similar to these 13. We found 0–3 gaseous satellites per host galaxy within R200 and 0–5 within 2R200, which agrees with the low numbers present for the Milky Way and M31. There is also agreement with the star-forming satellite numbers per host in the deep optical surveys SAGA and ELVES, and the Auriga cosmological simulations. When scaled to R200, the optical surveys do not show a trend of increasing quenched fraction with host mass; there is a slight increase in the total number of gaseous satellites with host mass for our sample. The low numbers of gaseous/star-forming satellites around spiral hosts are consistent with the idea that a universal and effective satellite quenching mechanism, such as ram pressure stripping by the host halo, is likely at play.
Hot accretion flows in low-luminosity active galactic nuclei in NGC 4258 and NGC 7213
Authors: Szanecki Michał , Niedźwiecki Andrzej , Wojaczyński Rafał
Published: March 2023

We study the high energy emission of two active galactic nuclei (AGNs), NGC 4258 and NGC 7213. We directly apply the general-relativistic hot flow model, kerrflow, to the archival BeppoSAX, NuSTAR, and Suzaku observations of these objects. Most of these data sets indicate that about 10–20 per cent of the accretion power is used for the direct heating of electrons; however, we find also indications for significant changes of the electron heating efficiency in some cases. Furthermore, all these X-ray data sets indicate rather strongly magnetized flows, with the magnetic field close to the equipartition with the gas pressure. Comparison of the model prediction with the Fermi/LAT data for NGC 7213 allows us to constrain the content of non-thermal protons to at most 10 per cent.
Evolution of disc and corona in MAXI J1348−630 during the 2019 reflare: NICER and Insight-HXMT view
Authors: Dai Xiaohang , Kong Lingda , Bu Qingcui , Santangelo Andrea , Zhang Shu , Ji Long , Zhang Shuangnan , Yorgancioglu Emre Seyit
Published: March 2023

In this work, using Neutron star Interior Composition Explorer and Insight-Hard X-ray Modulation Telescope observations, we present a study of the broad-band spectral and timing evolution of the source throughout the first reflare, which occurred about 4-month after the major outburst. Our findings suggest that during the reflare, below a critical luminosity Lcrit ∼ 2.5 × 1036 (D/2.2 kpc)2 erg s−1, the scale of the corona shrinks in the radial direction, whereas the inner radius of the disc does not change considerably; however, the inner radius of the disc starts to move inward when the source exceeds the critical luminosity. We conclude that at low luminosity the increase in accretion rate only heats up the inner zone of the accretion disc without the transfer of angular momentum which occurs above a certain luminosity.
Low selenium intake is associated with risk of all-cause mortality in kidney transplant recipients
Authors: Yepes-Calderón Manuela , Kremer Daan , Post Adrian , Sotomayor Camilo G , Seidel Ulrike , Huebbe Patricia , Knobbe Tim J , Lüersen Kai , Eisenga Michele F , Corpeleijn Eva , de Borst Martin H , Navis Gerjan J , Rimbach Gerald , Bakker Stephan J L
Published: March 2023

Background

Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants.

Methods

In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008–11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed.

Results

In 693 KTR (43% men, 52 ± 12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1–23.4) μg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70–3.28); P < .001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized β 0.49, P < .001).

Conclusions

Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.
Challenges and opportunities for modeling coupled human and natural systems
Authors: Li Yan , Sang Shan , Mote Safa , Rivas Jorge , Kalnay Eugenia
Published: March 2023

With the growing recognition of coupled human and natural systems (CHANS), modeling CHANS with two-way feedbacks has become a frontier research area and a critical tool to achieve sustainability. The challenges in CHANS modeling and opportunities to advance its science and application to promote the sustainability of CHANS are discussed in this paper.
Nest traits and major flooding events influence nest survival of Emperor Geese while regional environmental variation linked to climate does not
Authors: Thompson Jordan M , Uher-Koch Brian D , Daniels Bryan L , Schmutz Joel A , Sedinger Benjamin S
Published: March 2023

The reproductive ecology of geese that breed in the Arctic and subarctic is likely susceptible to the effects of climate change, which is projected to alter the environmental conditions of northern latitudes. Nest survival is an important component of productivity in geese; however, the effects of regional environmental conditions on nest survival are not well understood for some species, including the Emperor Goose (Anser canagicus), a species of conservation concern that is endemic to the Bering Sea region. We estimated nest survival and examined how indices of regional environmental conditions, nest traits (nest age, initiation date, and maximum number of eggs in the nest), and researcher disturbance influenced daily survival probability (DSP) of Emperor Goose nests using hierarchical models and 24 years of nest monitoring data (1994–2017) from the Yukon–Kuskokwim Delta (Y–K Delta) in western Alaska. Our results indicate that overall nest survival was generally high (µ = 0.766, 95% CRI: 0.655–0.849) and ranged from 0.327 (95% CRI: 0.176–0.482) in 2013 to 0.905 (95% CRI: 0.839–0.953) in 1995. We found that DSPs of nests were influenced by nest traits, negatively influenced by major tidal flooding events and by researcher disturbance, but were not influenced by regional indices of spring timing, temperature and precipitation during nesting, or fox and vole abundance on the Y–K Delta. However, the number of nests found each year was negatively related to our index of fox abundance, suggesting nests that failed as a result of fox predation may have never been discovered due to our limited nest-searching efforts during egg laying. Our results suggest that regional environmental variation had minimal influence on the nest survival of Emperor Geese, although major flooding events were important. Nevertheless, we suspect that within-year variation in local weather conditions and local abundance of predators and alternative prey may be important and should be considered in future studies.
Multimethod Assessment of Psychosis and Psychotic Phenomena
Authors: Mihura Joni L. , Kleiger James H. , Khadivi Ali
Published: March 2023

This comprehensive chapter examines the nature of the psychosis spectrum from multiple perspectives. Beginning with a definition of psychosis and psychotic phenomena, the chapter summarizes criteria from the fifth edition, text revision, of the Diagnostic and Statistical Manual of Mental Disorders and the 11th revision of the International Classification of Diseases and Related Health Problems and clarifies conceptual, terminological, and cultural issues that help sharpen the understanding of the structural factors, underlying dimensions, developmental issues, and course of psychotic disorders. A central theme concerns the multimethod assessment of symptom dimensions (including the importance of assessing insight), as well as an identification of risk and protective factors that mediate the severity of psychotic symptoms and disorders. Finally, the chapter discusses the restorative nature of interpersonal relationships in the recovery process, with implications for the role that therapeutic assessment can play in working with individuals struggling with psychotic phenomena.
Neuronavigation
Authors: Goetz Stefan M. , Kammer Thomas
Published: March 2023

The relatively high focality of transcranial brain stimulation requires accurate targeting of the fields delivered to the brain in order to stimulate the neural circuits that mediate the intended effect while reducing the unintended exposure of other brain areas. A range of tools support accurate individualized targeting of transcranial stimulation. Since targets are increasingly defined through anatomical, functional, or connectivity imaging, individualized gyrus-precise head models help to identify optimal placement of the stimulation transducers. Neuronavigation systems, such as frameless stereotaxy, can enable accurate delivery of stimulation to these targets. This is achieved by real-time tracking of the stimulation transducer and the subject’s head, and co-registering the head position to a computer model of the head anatomy and other target information. Whereas neuronavigation is currently limited to the spatial positioning of the transducers relative to the brain target, stimulation technologies that introduce functional or neuron-type-specific selectivity will demand novel tools for optimal targeting. As real-time simulation and robot-assisted motion-compensated transducer placement become feasible, technology is trending toward the convergence of computational intervention planning and neuronavigation.
Trans-species microRNA loci in the parasitic plant Cuscuta campestris have a U6-like snRNA promoter
Authors: Hudzik Collin , Maguire Sean , Guan Shengxi , Held Jeremy , Axtell Michael J
Published: March 2023

Small regulatory RNAs can move between organisms and regulate gene expression in the recipient. Whether the trans-species small RNAs being exported are distinguished from the normal endogenous small RNAs of the source organism is not known. The parasitic plant Cuscuta campestris (dodder) produces many microRNAs that specifically accumulate at the host–parasite interface, several of which have trans-species activity. We found that induction of C. campestris interface-induced microRNAs is similar regardless of host species and occurs in C. campestris haustoria produced in the absence of any host. The loci-encoding C. campestris interface-induced microRNAs are distinguished by a common cis-regulatory element. This element is identical to a conserved upstream sequence element (USE) used by plant small nuclear RNA loci. The properties of the interface-induced microRNA primary transcripts strongly suggest that they are produced via U6-like transcription by RNA polymerase III. The USE promotes accumulation of interface-induced miRNAs (IIMs) in a heterologous system. This promoter element distinguishes C. campestris IIM loci from other plant small RNAs. Our data suggest that C. campestris IIMs are produced in a manner distinct from canonical miRNAs. All confirmed C. campestris microRNAs with documented trans-species activity are interface-induced and possess these features. We speculate that RNA polymerase III transcription of IIMs may allow these miRNAs to be exported to hosts.
A dolabralexin-deficient mutant provides insight into specialized diterpenoid metabolism in maize
Authors: Murphy Katherine M , Dowd Tyler , Khalil Ahmed , Char Si Nian , Yang Bing , Endelman Benjamin J , Shih Patrick M , Topp Christopher , Schmelz Eric A , Zerbe Philipp
Published: March 2023

Two major groups of specialized metabolites in maize (Zea mays), termed kauralexins and dolabralexins, serve as known or predicted diterpenoid defenses against pathogens, herbivores, and other environmental stressors. To consider the physiological roles of the recently discovered dolabralexin pathway, we examined dolabralexin structural diversity, tissue-specificity, and stress-elicited production in a defined biosynthetic pathway mutant. Metabolomics analyses support a larger number of dolabralexin pathway products than previously known. We identified dolabradienol as a previously undetected pathway metabolite and characterized its enzymatic production. Transcript and metabolite profiling showed that dolabralexin biosynthesis and accumulation predominantly occur in primary roots and show quantitative variation across genetically diverse inbred lines. Generation and analysis of CRISPR-Cas9-derived loss-of-function Kaurene Synthase-Like 4 (Zmksl4) mutants demonstrated dolabralexin production deficiency, thus supporting ZmKSL4 as the diterpene synthase responsible for the conversion of geranylgeranyl pyrophosphate precursors into dolabradiene and downstream pathway products. Zmksl4 mutants further display altered root-to-shoot ratios and root architecture in response to water deficit. Collectively, these results demonstrate dolabralexin biosynthesis via ZmKSL4 as a committed pathway node biochemically separating kauralexin and dolabralexin metabolism, and suggest an interactive role of maize dolabralexins in plant vigor during abiotic stress.
AWARENESS OF PAEDIATRIC RADIOLOGICAL PROTECTION AND IMAGING PARAMETERS AMONG GROUP OF SRI LANKAN RADIOGRAPHERS
Authors: Satharasinghe Duminda , Niroshan Nithiyananthan , Jeyasugiththan Jeyasingam
Published: March 2023

The present survey evaluated the level of awareness of radiological protection concepts and imaging parameters among Sri Lankan radiographers for the first time. The data were collected using an electronic questionnaire of 22 questions on demographic data, awareness of radiation protection concepts and imaging parameters. Only 84 out of 122 (68.8%) requested radiographers to return the questionnaire. More than 85% had ≥3 years of experience in the radiography field. The average scores for questions on best practices, imaging parameters and radiation protection were 75, 75.8 and 70.2%, respectively, with an overall score of 73.4%. Significant confusion existed on protective shielding, paediatric consenting capability, use of grids and excess X-ray field during paediatric radiography. Although the overall knowledge and awareness of participants on studied concepts were satisfactory, a continuous professional development credit system and implementation of a code of practice are required to improve the quality of radiography practice.
Investigations into hydrogen sulfide-induced suppression of neuronal activityin vivoand calcium dysregulationin vitro
Authors: Kim Dong-Suk , Pessah Isaac N , Santana Cristina M , Purnell Benton S , Li Rui , Buchanan Gordon F , Rumbeiha Wilson K
Published: March 2023

Acute exposure to high concentrations of hydrogen sulfide (H2S) leads to sudden death and, if survived, lingering neurological disorders. Clinical signs include seizures, loss of consciousness, and dyspnea. The proximate mechanisms underlying H2S-induced acute toxicity and death have not been clearly elucidated. We investigated electrocerebral, cardiac, and respiratory activity during H2S exposure using electroencephalogram (EEG), electrocardiogram, and plethysmography. H2S suppressed electrocerebral activity and disrupted breathing. Cardiac activity was comparatively less affected. To test whether Ca2+ dysregulation contributes to H2S-induced EEG suppression, we developed an in vitro real-time rapid throughput assay measuring patterns of spontaneous synchronized Ca2+ oscillations in cultured primary cortical neuronal networks loaded with the indicator Fluo-4 using the fluorescent imaging plate reader (FLIPR-Tetra®). Sulfide >5 ppm dysregulated synchronous calcium oscillation (SCO) patterns in a dose-dependent manner. Inhibitors of NMDA and AMPA receptors magnified H2S-induced SCO suppression. Inhibitors of L-type voltage-gated Ca2+ channels and transient receptor potential (TRP) channels prevented H2S-induced SCO suppression. Inhibitors of T-type voltage-gated Ca2+ channels, ryanodine receptors, and sodium channels had no measurable influence on H2S-induced SCO suppression. Exposures to >5 ppm sulfide also suppressed neuronal electrical activity in primary cortical neurons measured by multielectrode array (MEA), an effect alleviated by pretreatment with the nonselective TRP channel inhibitor, 2-aminoethoxydiphenylborate (2-APB). 2-APB also reduced primary cortical neuronal cell death from sulfide exposure. These results improve our understanding of the role of different Ca2+ channels in acute H2S-induced neurotoxicity and identify TRP channel modulators as novel structures with potential therapeutic benefits.
Prevalence of childhood obesity in Brazil: a systematic review
Authors: Santos Fabrício De Paula , Silva Eliane Aparecida Ferraz , Baêta Caroline Lana Veloso , Campos Felipe Sávio , Campos Helton Oliveira
Published: March 2023

The present study aimed to analyze the prevalence of childhood obesity in Brazil and compare it between boys and girls. This systematic review was conducted and reported according to the guidelines outlined in the PRISMA statement. A systematic search of electronic databases, including PubMed, LILACS, and SciELO, was performed in November 2021. Studies that met the following criteria were included: (i) original quantitative studies regardless of their design; (ii) childhood obesity was clearly defined; (iii) prevalence of childhood obesity was reported or it was possible to extract from tables or figures in the text; and (iv) eligible population included children under 12 years of age. A total of 112 articles were included in the systematic review. The prevalence of childhood obesity in Brazil was of 12.2%, being 10.8% in girls and 12.3% in boys. In addition, wide heterogeneity in the childhood obesity prevalence was observed between the states, since it was 2.6% in Pará, while it was 15.8% in Rondônia. Thus, the importance of urgently implementing measures to prevent and treat childhood obesity should be emphasized aiming to reduce obese children and adolescents and future health problems in adult life resulting from this cardiovascular risk factor.
Purifying selection decreases the potential for Bangui orthobunyavirus outbreaks in humans
Authors: Orf Gregory S , Perez Lester J , Meyer Todd V , Luk Ka-Cheung , Forberg Kenn , Rodgers Mary A , Hadji Abbas , James Linda , Mampunza Samuel , Achari Asmeeta , Yu Guixia , Federman Scot , Chiu Charles Y , McArthur Carole A , Cloherty Gavin A , Berg Michael G
Published: March 2023

Pathogens carried by insects, such as bunyaviruses, are frequently transmitted into human populations and cause diseases. Knowing which spillover events represent a public health threat remains a challenge. Metagenomic next-generation sequencing (mNGS) can support infectious disease diagnostics by enabling the detection of any pathogen from clinical specimens. mNGS was performed on blood samples to identify potential viral coinfections in human immunodeficiency virus (HIV)-positive individuals from Kinshasa, the Democratic Republic of the Congo (DRC), participating in an HIV diversity cohort study. Time-resolved phylogenetics and molecular assay development assisted in viral characterization. The nearly complete genome of a novel orthobunyavirus related to Nyangole virus, a virus previously identified in neighboring Uganda, was assembled from a hepatitis B virus–positive patient. A quantitative polymerase chain reaction assay was designed and used to screen >2,500 plasma samples from Cameroon, the DRC, and Uganda, failing to identify any additional cases. The recent sequencing of a US Center for Disease Control Arbovirus Reference Collection revealed that this same virus, now named Bangui virus, was first isolated in 1970 from an individual in the Central African Republic. Time-scaled phylogenetic analyses of Bangui with the related Anopheles and Tanga serogroup complexes indicate that this virus emerged nearly 10,000 years ago. Pervasive and episodic models further suggest that this virus is under purifying selection and that only distant common ancestors were subject to positive selection events. This study represents only the second identification of a Bangui virus infection in over 50 years. The presumed rarity of Bangui virus infections in humans can be explained by its constraint to an avian host and insect vector, precluding efficient transmission into the human population. Our results demonstrate that molecular phylogenetic analyses can provide insights into the threat posed by novel or re-emergent viruses identified by mNGS.
CDK6 activity in a recurring convergent kinase network motif
Authors: Gangemi Christina G , Sabapathy Rahkesh T. , Janovjak Harald
Published: March 2023

In humans, more than 500 kinases phosphorylate ~15% of all proteins in an emerging phosphorylation network. Convergent local interaction motifs, in which ≥two kinases phosphorylate the same substrate, underlie feedback loops and signal amplification events but have not been systematically analyzed. Here, we first report a network‐wide computational analysis of convergent kinase‐substrate relationships (cKSRs). In experimentally validated phosphorylation sites, we find that cKSRs are common and involve >80% of all human kinases and >24% of all substrates. We show that cKSRs occur over a wide range of stoichiometries, in many instances harnessing co‐expressed kinases from family subgroups. We then experimentally demonstrate for the prototypical convergent CDK4/6 kinase pair how multiple inputs phosphorylate the tumor suppressor retinoblastoma protein (RB) and thereby hamper in situ analysis of the individual kinases. We hypothesize that overexpression of one kinase combined with a CDK4/6 inhibitor can dissect convergence. In breast cancer cells expressing high levels of CDK4, we confirm this hypothesis and develop a high‐throughput compatible assay that quantifies genetically modified CDK6 variants and inhibitors. Collectively, our work reveals the occurrence, topology, and experimental dissection of convergent interactions toward a deeper understanding of kinase networks and functions.
Knowledge, Judgment, and Skills in Reproductive Health Care and Abortion Are Essential to the Practice of Obstetrics and Gynecology
Authors: Shivraj Pooja , Chadha Rajat , Novak Amanda R. , Dynis Deana N. , Ramin Susan M. , Macones George A. , Wendel George D.
Published: March 2023

A social contract exists between medicine and society. In fulfilling the social contract to our patients and society, physicians have an obligation to provide the evidence-based care that patients want and need. What do the data regarding knowledge, judgment, and skills required to practice obstetrics and gynecology show? Obstetrics and gynecology job task analyses assess the importance of knowledge, judgment, and skills through surveys asking practicing physicians about the criticality and frequency of a variety of task statements to create an importance score. Excerpts from a 2018 practice analysis survey clearly indicate that reproductive health care and abortion are important components of the knowledge, judgment, and skills to practice obstetrics and gynecology in the United States. These standards help to assure the knowledge, judgment, and skills of current and future generations of ob-gyns, so their patients and the public can be provided the comprehensive reproductive health care they want and need. It is sometimes important to restate principles and standards that have become ingrained in thoughts and practices that guide physicians and serve to protect our patients. This concept is important now, as our country, health care professionals, and patients examine the future of reproductive health care, including abortion.
Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause
Authors: Neal-Perry Genevieve , Cano Antonio , Lederman Samuel , Nappi Rossella E. , Santoro Nanette , Wolfman Wendy , English Marci , Franklin Catherine , Valluri Udaya , Ottery Faith D.
Published: March 2023

OBJECTIVE:

To evaluate the safety, tolerability, and effect of fezolinetant on endometrial health over 52 weeks.

METHODS:

We conducted a phase 3, randomized, double-blind, 52-week safety study (SKYLIGHT 4 [Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause]) of placebo, fezolinetant 30 mg, and fezolinetant 45 mg once daily (1:1:1). Participants were postmenopausal and seeking treatment for vasomotor symptoms associated with menopause. Primary endpoints were treatment-emergent adverse events, percentage of participants with endometrial hyperplasia, and percentage with endometrial malignancy. Endometrial hyperplasia or malignancy was evaluated according to U.S. Food and Drug Administration guidance (point estimate of 1% or less with an upper bound of one-sided 95% CI of 4% or less). Secondary endpoints included change in bone mineral density (BMD) and trabecular bone score. A sample size of 1,740 was calculated to enable observation of one or more events (≈80% probability for events with background rate of less than 1%).

RESULTS:

A total of 1,830 participants were randomized and took one or more medication dose (July 2019–January 2022). Treatment-emergent adverse events occurred in 64.1% (391/610) of the placebo group, 67.9% (415/611) of the fezolinetant 30-mg group, and 63.9% (389/609) of the fezolinetant 45-mg group. Treatment-emergent adverse events leading to discontinuation were similar across groups (placebo, 26/610 [4.3%]; fezolinetant 30 mg, 34/611 [5.6%]; fezolinetant 45 mg, 28/609 [4.6%]). Endometrial safety was assessed in 599 participants. In the fezolinetant 45-mg group, 1 of 203 participants had endometrial hyperplasia (0.5%; upper limit of one-sided 95% CI 2.3%); there were no cases in the placebo (0/186) or fezolinetant 30 mg (0/210) group. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI 2.2%) with no cases in the other groups. Liver enzyme elevations more than three times the upper limit of normal occurred in 6 of 583 placebo, 8 of 590 fezolinetant 30 mg, and 12 of 589 fezolinetant 45 mg participants; no Hy's law cases were reported (ie, no severe drug-induced liver injury with alanine aminotransferase or aspartate aminotransferase more than three times the upper limit of normal and total bilirubin more than two times the upper limit of normal, with no elevation of alkaline phosphatase and no other reason to explain the combination). Changes in BMD and trabecular bone score were similar across groups.

CONCLUSION:

Results from SKYLIGHT 4 confirm the 52-week safety and tolerability of fezolinetant and support its continued development.

FUNDING SOURCE:

Astellas Pharma Inc.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04003389.
Severe Maternal Morbidity Review and Preventability Assessment in a Large Academic Center
Authors: Grechukhina Olga , Lipkind Heather S. , Lundsberg Lisbet S. , Merriam Audrey A. , Raab Cheryl , Leon-Martinez Daisy , Campbell Katherine H.
Published: March 2023

With the goal of identifying factors contributing to severe maternal morbidity (SMM) at our institution, we established a formal SMM review process. We performed a retrospective cohort study including all SMM cases as defined by American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine consensus criteria that were managed at Yale-New Haven Hospital over a 4-year period. Overall, 156 cases were reviewed. The SMM rate was 0.49% (95% CI 0.40–0.58). The leading causes of SMM were hemorrhage (44.9%) and nonintrauterine infection (14.1%). Two thirds of the cases were deemed to be preventable. Preventability was mostly associated with health care professional–level (79.4%) and system-level (58.8%) factors that could coexist. Detailed case review allowed for identification of preventable causes of SMM, revealed gaps in care, and allowed for implementation of practice changes targeting health care professional–level and system-level factors.
Initiation and Treatment Discontinuation of Medications for Opioid Use Disorder in Pregnant People Compared With Nonpregnant People
Authors: Xu Kevin Y. , Jones Hendrée E. , Schiff Davida M. , Martin Caitlin E. , Kelly Jeannie C. , Carter Ebony B. , Bierut Laura J. , Grucza Richard A.
Published: March 2023

OBJECTIVE:

To examine the association between pregnancy and medications for opioid use disorder (MOUD) initiation and discontinuation among reproductive-aged people receiving treatment for opioid use disorder (OUD) in the United States.

METHODS:

We conducted a retrospective cohort study of people with gender recorded as female, aged 18–45 years, in the MerativeTM MarketScan® Commercial and Multi-State Medicaid Databases (2006–2016). Opioid use disorder and pregnancy status were identified based on inpatient or outpatient claims for established International Classification of Diseases, Ninth and Tenth Revision diagnosis and procedure codes. The main outcomes were buprenorphine and methadone initiation and discontinuation, determined by using pharmacy and outpatient procedure claims. Analyses were conducted at the treatment episode level. Adjusting for insurance status, age, and co-occurring psychiatric and substance use disorders, we used logistic regression to estimate MOUD initiation and used Cox regression to estimate MOUD discontinuation.

RESULTS:

Our sample included 101,772 reproductive-aged people with OUD, encompassing 155,771 treatment episodes (mean age 30.8 years, 64.4% Medicaid insurance, 84.1% White), of whom 2,687 (3.2%, encompassing 3,325 episodes) were pregnant. In the pregnant group, 51.2% of treatment episodes (1,703/3,325) involved psychosocial treatment without MOUD, in comparison with 61.1% (93,156/152,446) in the nonpregnant comparator group. In adjusted analyses assessing likelihood of initiation for individual MOUD, pregnancy status was associated with an increase in buprenorphine (adjusted odds ratio [aOR] 1.57, 95% CI 1.44–1.70) and methadone initiation (aOR 2.04, 95% CI 1.82–2.27). Discontinuation rates of MOUD at 270 days were high for both buprenorphine (72.4% for nonpregnant episodes vs 59.9% for pregnant episodes) and methadone (65.7% for nonpregnant episodes vs 54.1% for pregnant episodes). Pregnancy was associated with a decreased likelihood of discontinuation at 270 days for both buprenorphine (adjusted hazard ratio [aHR] 0.71, 95% CI 0.67–0.76) and methadone (aHR 0.68, 95% CI 0.61–0.75), in comparison with nonpregnant status.

CONCLUSION:

Although a minority of reproductive-aged people with OUD in the United States are initiated on MOUD, pregnancy is associated with a significant increase in treatment initiation and a reduced risk of medication discontinuation.
Increased Scheduled Intravenous Ketorolac After Cesarean Delivery and Its Effect on Opioid Use
Authors: Hostage Jean , Kolettis Diana , Sverdlov Deanna , Ludgin Jennifer , Drzymalski Dan , Sweigart Benjamin , Mhatre Mohak , House Michael
Published: March 2023

OBJECTIVE:

To evaluate the efficacy of scheduled ketorolac in reducing opioid use after cesarean delivery.

METHODS:

This was a single-center, randomized, double-blind, parallel-group trial to assess pain management after cesarean delivery with scheduled ketorolac compared with placebo. All patients undergoing cesarean delivery with neuraxial anesthesia received two doses of 30 mg intravenous ketorolac postoperatively and then were randomized to receive four doses of 30 mg of intravenous ketorolac or placebo every 6 hours. Additional nonsteroidal anti-inflammatory drugs were held until 6 hours after the last study dose. The primary outcome was total morphine milligram equivalents (MME) used in the first 72 postoperative hours. Secondary outcomes included the number of patients who used no opioid postoperatively, postoperative pain scores, postoperative change in hematocrit and serum creatinine, and postoperative satisfaction with inpatient care and pain management. A sample size of 74 per group (n=148) provided 80% power to detect a population mean difference in MME of 32.4, with an SD for both groups of 68.7 after accounting for protocol noncompliance.

RESULTS:

From May 2019 to January 2022, 245 patients were screened and 148 patients were randomized (74 per group). Patient characteristics were similar between groups. The median (quartile 1–3) MME from arrival in the recovery room until postoperative hour 72 was 30.0 (0.0–67.5) for the ketorolac group and 60.0 (30.0–112.5) for the placebo group (Hodges–Lehmann median difference −30.0, 95% CI −45.0 to −15.0, P<.001). In addition, participants who received placebo were more likely to have numeric rating scale pain scores higher than 3 out of 10 (P=.005). The mean±SD decrease from baseline hematocrit to postoperative day 1 was 5.5±2.6% for the ketorolac group and 5.4±3.5% for the placebo group (P=.94). The mean±SD postoperative day 2 creatinine was 0.61±0.06 mg/dL in the ketorolac group and 0.62±0.08 mg/dL in the placebo group (P=.26). Participant satisfaction with inpatient pain control and postoperative care was similar between groups.

CONCLUSION:

Compared with placebo, scheduled intravenous ketorolac significantly decreased opioid use after cesarean delivery.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03678675.
Occurrence and prognosis of lung cancer metastasis to major organs: a population-based study
Authors: Wang Huyu , Shui Lili , Chen Rouqian , Chen Yuhao , Guo Jing , Chen Yajuan
Published: March 2023

Background

Lung cancer metastasis to major organs is an important factor affecting survival. We analyzed the influence of patient characteristics on the incidence and survival of metastasis to major organs.

Methods

We collected data from the Surveillance, Epidemiology, and End Results database on 58 659 patients diagnosed with stage IV primary lung cancer, including age, sex, race, histological type of tumor, laterality, primary site, number of extrametastatic sites, and treatment.

Results

Multiple variables affected the incidence of metastasis to major organs and survival. According to histological type of tumor, the following were more common: bone metastasis from adenocarcinoma; brain metastasis from large-cell carcinoma and adenocarcinoma; liver metastasis from small-cell carcinoma; and intrapulmonary metastasis from squamous-cell carcinoma. A larger number of metastatic sites increased the risk of other metastases and shorter survival. Liver metastasis conferred the worst prognosis, followed by bone metastasis, and brain or intrapulmonary metastasis conferred better prognosis. The effect of radiotherapy alone was poorer than chemotherapy alone or combined chemotherapy and radiotherapy. In most cases, the effects of chemotherapy and combined chemotherapy and radiotherapy were equivalent.

Conclusion

Multiple variables affected the incidence of metastasis to major organs and survival. Compared with radiotherapy alone or combined chemotherapy and radiotherapy, chemotherapy alone may be the most cost-effective option for patients with stage IV lung cancer.
Correction of Rippling in Implant-based Breast Reconstruction with Serratus Fascia Flap
Authors: Faenza Mario , Lanzano Giuseppe , Grella Elisa , Izzo Sara , Ferraro Giuseppe Andrea
Published: March 2023

Implant-based breast reconstruction represents the most popular procedure for the treatment of women undergoing skin-sparing mastectomy. In selected patients, it allows for obtaining an excellent appearance of the reconstructed breast with great satisfaction to the patient. However, aesthetic and functional results can be affected by complications requiring reoperation. Among them, rippling is an undesired occurrence associated with implant-based reconstruction. It consists of a cutaneous manifestation, visible and/or palpable, of the implant wrinkles and edge which appear mostly when the patient leans forward. To treat this contour deformity, several techniques have been described such as acellular dermal matrices and autologous tissues. In this study, we intend to add the serratus anterior fascial flap within the autologous options in the treatment of implant rippling, reporting our experience.
TWEAK/FN14 promotes profibrogenic pathway activation in Prominin-1-expressing hepatic progenitor cells in biliary atresia
Authors: Short Celia , Zhong Allen , Xu Jiabo , Mahdi Elaa , Glazier Alison , Malkoff Nicolas , Noriega Nicolas , Yeo Theresa , Asahina Kinji , Wang Kasper S.
Published: March 2023

Background and Aims:

Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 (Prom1)-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1-expressing HPC proliferation leading to profibrogenic ductular reactions in BA.

Approach and Results:

The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1-expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1, FN14, and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression.

Conclusion:

TWEAK/FN14 signaling activation in Prom1-expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.
HBV with precore and basal core promoter mutations exhibits a high replication phenotype and causes ER stress-mediated cell death in humanized liver chimeric mice
Authors: Uchida Takuro , Imamura Michio , Hayes C. Nelson , Suehiro Yosuke , Teraoka Yuji , Ohya Kazuki , Aikata Hiroshi , Abe-Chayama Hiromi , Ishida Yuji , Tateno Chise , Hara Yuichi , Hino Keisuke , Okamoto Toru , Matsuura Yoshiharu , Aizaki Hideki , Wake Kenjiro , Kohara Michinori , Liang T. Jake , Oka Shiro , Chayama Kazuaki
Published: March 2023

Background and Aims:

Mutations within the precore (PC) and basal core promoter (BCP) regions of the HBV genome are associated with fulminant hepatitis and HBV reactivation. These mutations may enhance viral replication, but little is known about whether they directly induce damage to the liver. We investigated mechanisms of direct cytopathic effects induced by the infection with PC/BCP mutants in the absence of immune response in vitro and in vivo.

Approach and Results:

Mice with humanized livers and hepatocytes derived from humanized mice were infected with either wild-type or mutant-type PC/BCP HBV, and the HBV replication and human hepatocyte damage were evaluated. HBV proliferated vigorously in mice with PC/BCP-mutant infection, and the severe loss of human hepatocytes with a slight human ALT elevation subsequently occurred only in PC/BCP mutant mice. In PC/BCP mutant infection, the accumulation of HBsAg in humanized livers colocalized with the endoplasmic reticulum, leading to apoptosis through unfolded protein response in HBV-infected hepatocytes. RNA-sequencing revealed the molecular characteristics of the phenotype of PC/BCP mutant infection in a humanized mouse model. Reduced ALT elevation and higher HBV DNA levels in this model are consistent with characteristics of HBV reactivation, indicating that the hepatocyte damage in this model might mimic HBV reactivation followed by hepatocyte damage under immunosuppressive conditions.

Conclusion:

PC and BCP mutations were associated with enhanced viral replication and cell death induced by ER stress using HBV infection models. These mutations might be associated with liver damage in patients with fulminant hepatitis or HBV reactivation.
Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial
Authors: Rowe Ian A. , Villanueva Càndid , Shearer Jessica E. , Torres Ferran , Albillos Agustín , Genescà Joan , Garcia-Pagan Joan C. , Tripathi Dhiraj , Hayes Peter C. , Bosch Jaume , Abraldes Juan G. ,   for the PREDESCI trial investigators
Published: March 2023

Background and Aims:

Beta-blockers have been studied for the prevention of variceal bleeding and, more recently, for the prevention of all-cause decompensation. Some uncertainties regarding the benefit of beta-blockers for the prevention of decompensation remain. Bayesian analyses enhance the interpretation of trials. The purpose of this study was to provide clinically meaningful estimates of both the probability and magnitude of the benefit of beta-blocker treatment across a range of patient types.

Approach and Results:

We undertook a Bayesian reanalysis of PREDESCI incorporating 3 priors (moderate neutral, moderate optimistic, and weak pessimistic). The probability of clinical benefit was assessed considering the prevention of all-cause decompensation. Microsimulation analyses were done to determine the magnitude of the benefit. In the Bayesian analysis, the probability that beta-blockers reduce all-cause decompensation was >0.93 for all priors. The Bayesian posterior hazard ratios (HR) for decompensation ranged from 0.50 (optimistic prior, 95% credible interval 0.27–0.93) to 0.70 (neutral prior, 95% credible interval 0.44–1.12). Exploring the benefit of treatment using microsimulation highlights substantial treatment benefits. For the neutral prior derived posterior HR and a 5% annual incidence of decompensation, at 10 years, an average of 497 decompensation-free years per 1000 patients were gained with treatment. In contrast, at 10 years 1639 years per 1000 patients were gained from the optimistic prior derived posterior HR and a 10% incidence of decompensation.

Conclusions:

Beta-blocker treatment is associated with a high probability of clinical benefit. This likely translates to a substantial gain in decompensation-free life years at the population level.
Short-chain acyl-CoA dehydrogenase is a potential target for the treatment of vascular remodelling
Authors: Zhong Xiaoyi , Li Zhonghong , Xu Qingping , Peng Huan , Su Yongshao , Le Kang , Shu Zhaohui , Liao Yingqin , Ma Zhichao , Pan Xuediao , Xu Suowen , Zhou Sigui
Published: March 2023

Objectives:

Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme in the fatty acid oxidation process, is not only involved in ATP synthesis but also regulates the production of mitochondrial reactive oxygen species (ROS) and nitric oxide synthesis. The purpose of this study was to investigate the possible role of SCAD in hypertension-associated vascular remodelling.

Methods:

In-vivo experiments were performed on spontaneously hypertensive rats (SHRs, ages of 4 weeks to 20 months) and SCAD knockout mice. The aorta sections of hypertensive patients were used for measurement of SCAD expression. In-vitro experiments with t-butylhydroperoxide (tBHP), SCAD siRNA, adenovirus-SCAD (MOI 90) or shear stress (4, 15 dynes/cm2) were performed using human umbilical vein endothelial cells (HUVECs).

Results:

Compared with age-matched Wistar rats, aortic SCAD expression decreased gradually in SHRs with age. In addition, aerobic exercise training for 8 weeks could significantly increase SCAD expression and enzyme activity in the aortas of SHRs while decreasing vascular remodelling in SHRs. SCAD knockout mice also exhibited aggravated vascular remodelling and cardiovascular dysfunction. Likewise, SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and the aortas of hypertensive patients. SCAD siRNA caused HUVEC apoptosis in vitro, whereas adenovirus-mediated SCAD overexpression (Ad-SCAD) protected against HUVEC apoptosis. Furthermore, SCAD expression was decreased in HUVECs exposed to low shear stress (4 dynes/cm2) and increased in HUVECs exposed to 15 dynes/cm2 compared with those under static conditions.

Conclusion:

SCAD is a negative regulator of vascular remodelling and may represent a novel therapeutic target for vascular remodelling.

Supplemental Graphical abstract:

http://links.lww.com/HJH/C151
Impact of atrial fibrillation on the accuracy of oscillometric blood pressure monitoring in ICU patients from a large real-world database
Authors: Li Yuxi , Wang Beining , Fan Fangfang , Weng Haoyu , Zhang Long , Jiang Jie , Zheng Bo , Zhang Yan , Li Jianping
Published: March 2023

Objectives:

Oscillometric blood pressure (BP) measurement in atrial fibrillation patients is controversial due to stroke volume variation. Here, we performed a cross-sectional study to investigate the impact of atrial fibrillation on the accuracy of oscillometric BP in the ICU setting.

Methods:

Adult patients with atrial fibrillation or sinus rhythm records were enrolled from Medical Information Mart for Intensive Care-III database. Concurrently recorded noninvasive oscillometric BPs (NIBPs) and intra-arterial BPs (IBPs) were classified as atrial fibrillation or sinus rhythm group according to heart rhythm. Bland–Altmann plots assessed bias and limits of agreement of NIBP to IBP. Pairwise comparison was performed on NIBP/IBP bias between atrial fibrillation and sinus rhythm. Linear mixed-effect model was used to assess the impact of heart rhythm on NIBP/IBP bias after adjusting confounders.

Results:

Two thousand, three hundred and thirty-five patients (71.95 ± 11.23 years old, 60.90% were men) were included. Systolic, diastolic, and mean NIBP/IBP biases were not clinically different between atrial fibrillation and sinus rhythm circumstances (SBP bias: 0.66 vs. 1.21 mmHg, P = 0.002; DBP: −5.29 vs. −5.17, P = 0.1; mean BP: −4.45 vs. −4.19, P = 0.01). After adjusting for age, sex, heart rate, arterial BP, and vasopressor usage, the effect of heart rhythm on NIBP/IBP bias was within ±5 mmHg for SBP and DBP [effect on SBP bias: 3.32 mmHg (95% confidence interval (CI) 2.89–3.74), P < 0.001; DBP: −0.89 (−1.17 to −0.60), P < 0.001], while the effect on mean BP bias was not significant [0.18 mmHg (−0.10 to 0.46), P = 0.2].

Conclusion:

Atrial fibrillation would not influence the agreement of oscillometric BP to IBP in ICU patients compared with sinus rhythm.