bluuebunny/crossref_metadata_2025 huggingface dataset:
The modified frozen elephant trunk may outperform limited and extended-classic repair in acute type I dissection
Authors: Roselli Eric E , Kramer Benjamin , Germano Emidio , Toth Andrew , Vargo Patrick R , Bakaeen Faisal , Menon Venu , Blackstone Eugene H ,   Collaborators from Cleveland Clinic Aorta Center, Gillinov Marc , Pettersson Gosta , Soltesz Edward , Svensson Lars G , Burns Daniel , Hodges Kevin , Koprivanac Marijan , Caputo Francis , Lyden Sean , Kirksey Levester , Quatromoni Jon , Khalifeh Ali , Desai Milind , Kalahasti Vidyasagar , Griffin Brian , Grimm Richard , Cremer Paul , Xu Bo , Hammer Donald , Ramchand Jay , Thamilarasan Maran , Quatromoni Neha , Rampersad Penelope , Jellis Christine , Schoenhagen Paul , Bolen Michael , Rigelsky Christina , Apostalakis John , Bauer Andrew
Published: April 2023

OBJECTIVES

A better surgical approach for acute DeBakey type I dissection has been sought for decades. We compare operative trends, complications, reinterventions and survival after limited versus extended-classic versus modified frozen elephant trunk (mFET) repair for this condition.

METHODS

From 1 January 1978 to 1 January 2018, 879 patients underwent surgery for acute DeBakey type I dissection at Cleveland Clinic. Repairs were limited to the ascending aorta/hemiarch (701.79%) or extended through the arch [extended classic (88.10%) or mFET (90.10%)]. Weighted propensity score matched established comparable groups.

RESULTS

Among weighted propensity-matched patients, mFET repair had similar circulatory arrest times and postoperative complications to limited repair, except for postoperative renal failure, which was twice as high in the limited group [25% (n = 19) vs 12% (n = 9), P = 0.006]. Lower in-hospital mortality was observed following limited compared to extended-classic repair [9.1% (n = 7) vs 19% (n = 16), P = 0.03], but not after mFET repair [12% (n = 9) vs 9.5% (n = 8), P = 0.6]. Extended-classic repair had higher risk of early death than limited repair (P = 0.0005) with no difference between limited and mFET repair groups (P = 0.9); 7-year survival following mFET repair was 89% compared to 65% after limited repair. Most reinterventions following limited or extended-classic repair underwent open reintervention. All reinterventions following mFET repair were completed endovascularly.

CONCLUSIONS

Without increasing in-hospital mortality or complications, less renal failure and a trend towards improved intermediate survival, mFET may be superior to limited or extended-classic repair for acute DeBakey type I dissections. mFET repair facilitates endovascular reintervention, potentially reducing future invasive reoperations and warranting continued study.
An approach for assessing and ranking fisheries management scenarios in spatially delimited marine areas
Authors: Clare D S , Martinez R , Goodsir F , Spence M A , Tyllianakis E , Ware S , Schratzberger M
Published: April 2023

Spatial restrictions to human activities such as bottom trawling are increasingly used to improve the ecological condition of disturbed habitats. Such management interventions typically have socio-economic consequences, which creates a challenge for those making decisions about which activities should be restricted and where restrictions should apply. We present an approach for predicting the effects of fisheries management scenarios in spatially delimited marine areas and ranking them—using a loss function—according to how well they achieve desired outcomes across a set of ecological and socio-economic indicators. This approach is demonstrated by simulating alternative fishing gear restrictions and zoning options within a hypothetical marine protected area (MPA). Relative benthic status (RBS; an indicator of ecological condition) and relative catch value (RCV; an indicator of potential economic cost) were estimated for the baseline environment and 21 potential management scenarios. The rank order depended on which indicator was prioritized (i.e. whether RBS or RCV was given greater weighting in the loss function), with the top-ranked scenarios in each case involving considerably different management measures. The methods presented can be applied anywhere using locally or strategically relevant indicators to help identify spatial fisheries management measures that minimize ecological and socio-economic trade-offs.
Bronchiolitis, Regardless of Its Etiology and Severity, Is Associated With Increased Risk of Asthma: A Population-Based Study
Authors: Muñoz-Quiles Cintia , López-Lacort Mónica , Díez-Domingo Javier , Orrico-Sánchez Alejandro
Published: April 2023

An association exists between severe respiratory syncytial virus (RSV)–bronchiolitis and a subsequent increased risk of recurrent wheezing (RW) and asthma. However, a causal relationship remains unproven. Using a retrospective population-based cohort study (339 814 children), bronchiolitis during the first 2 years of life (regardless of etiology and severity) was associated with at least a 3-fold increased risk of RW/asthma at 2–4 years and an increased prevalence of asthma at ≥5 years of age. The risk was similar in children with mild bronchiolitis as in those with hospitalized RSV-bronchiolitis and was higher in children with hospitalized non-RSV-bronchiolitis. The rate of RW/asthma was higher when bronchiolitis occurred after the first 6 months of life. Our results seem to support the hypothesis of a shared predisposition to bronchiolitis (irrespective of etiology) and RW/asthma. However, 60% of hospitalized bronchiolitis cases in our setting are due to RSV, which should be paramount in decision-making on imminent RSV prevention strategies.
A lizard is never late: Squamate genomics as a recent catalyst for understanding sex chromosome and microchromosome evolution
Authors: Pinto Brendan J , Gamble Tony , Smith Chase H , Wilson Melissa A
Published: April 2023

In 2011, the first high-quality genome assembly of a squamate reptile (lizard or snake) was published for the green anole. Dozens of genome assemblies were subsequently published over the next decade, yet these assemblies were largely inadequate for answering fundamental questions regarding genome evolution in squamates due to their lack of contiguity or annotation. As the “genomics age” was beginning to hit its stride in many organismal study systems, progress in squamates was largely stagnant following the publication of the green anole genome. In fact, zero high-quality (chromosome-level) squamate genomes were published between the years 2012 and 2017. However, since 2018, an exponential increase in high-quality genome assemblies has materialized with 24 additional high-quality genomes published for species across the squamate tree of life. As the field of squamate genomics is rapidly evolving, we provide a systematic review from an evolutionary genomics perspective. We collated a near-complete list of publicly available squamate genome assemblies from more than half-a-dozen international and third-party repositories and systematically evaluated them with regard to their overall quality, phylogenetic breadth, and usefulness for continuing to provide accurate and efficient insights into genome evolution across squamate reptiles. This review both highlights and catalogs the currently available genomic resources in squamates and their ability to address broader questions in vertebrates, specifically sex chromosome and microchromosome evolution, while addressing why squamates may have received less historical focus and has caused their progress in genomics to lag behind peer taxa.
Longitudinal canonical correlation analysis
Authors: Lee Seonjoo , Choi Jongwoo , Fang Zhiqian , Bowman F DuBois
Published: April 2023

This paper considers canonical correlation analysis for two longitudinal variables that are possibly sampled at different time resolutions with irregular grids. We modelled trajectories of the multivariate variables using random effects and found the most correlated sets of linear combinations in the latent space. Our numerical simulations showed that the longitudinal canonical correlation analysis (LCCA) effectively recovers underlying correlation patterns between two high-dimensional longitudinal data sets. We applied the proposed LCCA to data from the Alzheimer’s Disease Neuroimaging Initiative and identified the longitudinal profiles of morphological brain changes and amyloid cumulation.
A leaf-level spectral library to support high-throughput plant phenotyping: predictive accuracy and model transfer
Authors: Wijewardane Nuwan K , Zhang Huichun , Yang Jinliang , Schnable James C , Schachtman Daniel P , Ge Yufeng
Published: April 2023

Leaf-level hyperspectral reflectance has become an effective tool for high-throughput phenotyping of plant leaf traits due to its rapid, low-cost, multi-sensing, and non-destructive nature. However, collecting samples for model calibration can still be expensive, and models show poor transferability among different datasets. This study had three specific objectives: first, to assemble a large library of leaf hyperspectral data (n=2460) from maize and sorghum; second, to evaluate two machine-learning approaches to estimate nine leaf properties (chlorophyll, thickness, water content, nitrogen, phosphorus, potassium, calcium, magnesium, and sulfur); and third, to investigate the usefulness of this spectral library for predicting external datasets (n=445) including soybean and camelina using extra-weighted spiking. Internal cross-validation showed satisfactory performance of the spectral library to estimate all nine traits (mean R2=0.688), with partial least-squares regression outperforming deep neural network models. Models calibrated solely using the spectral library showed degraded performance on external datasets (mean R2=0.159 for camelina, 0.337 for soybean). Models improved significantly when a small portion of external samples (n=20) was added to the library via extra-weighted spiking (mean R2=0.574 for camelina, 0.536 for soybean). The leaf-level spectral library greatly benefits plant physiological and biochemical phenotyping, whilst extra-weight spiking improves model transferability and extends its utility.
The Cm14-3-3μ protein and CCT transcription factor CmNRRa delay flowering in chrysanthemum
Authors: Cheng Hua , Zhang Jiaxin , Zhang Yu , Si Chaona , Wang Juanjuan , Gao Zheng , Cao Peipei , Cheng Peilei , He Yuehui , Chen Sumei , Chen Fadi , Jiang Jiafu
Published: April 2023

The floral transition from vegetative to reproductive growth is pivotal in the plant life cycle. NUTRITION RESPONSE AND ROOT GROWTH (OsNRRa), as a CONSTANS, CONSTANS-LIKE, TOC1 (CCT) domain protein, delays flowering in rice, and an orthologous protein, CmNRRa, inhibits flowering in chrysanthemum; however, the underlying mechanism remains unknown. In this study, using yeast two-hybrid screening, we identified the 14-3-3 protein family member Cm14-3-3µ as a CmNRRa-interacting protein. A combination of bimolecular fluorescence complementation, pull-down, and co-immunoprecipitation assays was performed to confirm the physical interaction between CmNRRa and Cm14-3-3µ. In addition, expression analysis showed that CmNRRa but not Cm14-3-3µ responded to the diurnal rhythm, whereas both genes were highly expressed in leaves. Moreover, the function of Cm14-3-3µ in flowering time regulation was similar to that of CmNRRa. Furthermore, CmNRRa repressed chrysanthemum FLOWERING LOCUS T-like 3 (CmFTL3) and an APETALA 1 (AP1)/FRUITFULL (FUL)-like gene (CmAFL1) but induced TERMINAL FLOWER1 (CmTFL1) directly by binding to their promoters. Cm14-3-3µ enhanced the ability of CmNRRa to regulate the expression of these genes. These findings suggest that there is a synergistic relationship between CmNRRa and Cm14-3-3µ in flowering repression in chrysanthemum.
Spectroscopy of QUBRICS quasar candidates: 1672 new redshifts and a golden sample for the Sandage test of the redshift drift
Authors: Cristiani Stefano , Porru Matteo , Guarneri Francesco , Calderone Giorgio , Boutsia Konstantina , Grazian Andrea , Cupani Guido , D’Odorico Valentina , Fontanot Fabio , Martins Carlos J A P , Marques Catarina M J , Maitra Soumak , Trost Andrea
Published: April 2023

The QUBRICS (QUasars as BRIght beacons for Cosmology in the Southern hemisphere) survey aims at constructing a sample of the brightest quasars with $z \lower.5ex\hbox{$\,\, \buildrel\gt \over \sim \,\,$}2.5$, observable with facilities in the Southern Hemisphere. QUBRICS makes use of the available optical and IR wide-field surveys in the South and of Machine Learning techniques to produce thousands of bright quasar candidates of which only a few hundred have been confirmed with follow-up spectroscopy. Taking advantage of the recent Gaia Data Release 3, which contains 220 million low-resolution spectra, and of a newly developed spectral energy distribution fitting technique, designed to combine the photometric information with the Gaia spectroscopy, it has been possible to measure 1672 new secure redshifts of QUBRICS candidates, with a typical uncertainty of σz = 0.02. This significant progress of QUBRICS brings it closer to (one of) its primary goals: providing a sample of bright quasars at redshift 2.5 < z < 5 to perform the Sandage test of the cosmological redshift drift. A Golden Sample of seven quasars is presented that makes it possible to carry out this experiment in about 1500 h of observation in 25 yr, using the ANDES spectrograph at the 39m ELT, a significant improvement with respect to previous estimates.
A simple sub-grid model for cosmic ray effects on galactic scales
Authors: Hopkins Philip F , Butsky Iryna S , Ji Suoqing , Kereš Dušan
Published: April 2023

Many recent numerical studies have argued that cosmic rays (CRs) from supernovae (SNe) or active galactic nuclei (AGNs) could play a crucial role in galaxy formation, in particular by establishing a CR-pressure-dominated circumgalactic medium (CGM). But explicit CR-magnetohydrodynamics (CR-MHD) remains computationally expensive, and it is not clear whether those results can be applied to simulations that do not explicitly treat magnetic fields or resolved interstellar medium phase structure. We therefore present an intentionally extremely simplified ‘sub-grid’ model for CRs, which attempts to capture the key qualitative behaviors of greatest interest for those interested in simulations or semi-analytical models including some approximate CR effects on galactic (≳ kpc) scales, while imposing negligible computational overhead. The model is numerically akin to some recently developed sub-grid models for radiative feedback, and allows for a simple constant parametrization of the CR diffusivity and/or streaming speed; it allows for an arbitrary distribution of sources (proportional to black hole accretion rates or star–particle SNe rates or gas/galaxy star formation rates), and interpolates between the limits where CRs escape the galaxies with negligible losses and those where CRs lose most of their energy catastrophically before escape (relevant in e.g. starburst galaxies). The numerical equations are solved trivially alongside gravity in most codes. We compare this to explicit CR-MHD simulations and discuss where the (many) sub-grid approximations break down, and what drives the major sources of uncertainty.
Real-Time and Rapid Detection of Phytopythium vexans Using Loop-Mediated Isothermal Amplification Assay
Authors: Ghimire Bhawana , Avin Farhat A. , Waliullah Sumyya , Ali Emran , Baysal-Gurel Fulya
Published: April 2023

Phytopythium vexans (de Bary) Abad, de Cock, Bala, Robideau, A. M. Lodhi & Levesque is an important waterborne and soil-inhabiting oomycete pathogen causing root and crown rot of various plants including certain woody ornamentals, fruit, and forest trees. Early and accurate detection of Phytopythium in the nursery production system is critical, as this pathogen is quickly transported to neighboring healthy plants through the irrigation system. Conventional methods for the detection of this pathogen are tedious, frequently inconclusive, and costly. Hence, a specific, sensitive, and rapid molecular diagnostic method is required to overcome the limitations of traditional identification. In the current study, loop-mediated isothermal amplification (LAMP) for DNA amplification was developed for the identification of P. vexans. It was evaluated using real-time and colorimetric assays. Several sets of LAMP primers were designed and screened, but PVLSU2 was found to be specific to P. vexans as it did not amplify other closely related oomycetes, fungi, and bacteria. Moreover, the developed assays were sensitive enough to amplify DNA up to 102 fg per reaction. The real-time LAMP assay was more sensitive than traditional PCR and culture-based methods to detect infected plant samples. In addition, both LAMP assays detected as few as 100 zoospores suspended in 100 ml water. These LAMP assays are anticipated to save time in P. vexans detection by disease diagnostic laboratories and research institutions and enable early preparedness in the event of disease outbreaks.
A Quality Improvement Pilot Project for Noise Reduction in the NICU
Authors: Hull William , Wright Karen
Published: April 2023

Background:

Increased noxious noise leads to adverse short-term and long-term effects on the growing neonate. The American Academy of Pediatrics recommends maintaining a noise level of less than 45 decibels (dBA). The average baseline noise level in an open-pod neonatal intensive care unit (NICU) was 62.6 dBA.

Purpose:

The purpose of this pilot project was to reduce the average noise levels by 39% at the end of an 11-week period.

Methods:

The location of the project was in a large, high-acuity level IV open-pod layout NICU that consisted of 4 pods, one of which was cardiac-focused. The average baseline noise level in the cardiac pod was 62.6 dBA in a 24-hour period. Noise levels were not monitored before this pilot project. This project was implemented over an 11-week period. Several modes of education were used for parents and staff. Post-education, Quiet Times were implemented at set times twice daily. Noise levels were monitored for 4 weeks during Quiet Times, with weekly noise level updates for staff. General noise levels were collected a final time to evaluate the overall change in the average noise levels.

Results:

At the end of the project, noise levels decreased from 62.6 dBA to 54 dBA, a 13.7% reduction.

Implications for Practice and Research:

At the end of this pilot project it was noted that: Online modules were the best way to educate staff. Parents should be included in the implementation of quality improvement. Healthcare providers need to know and understand that they can make preventative changes to improve the outcomes of the population.
Relationships Between the Auditory Nerve’s Ability to Recover From Neural Adaptation, Cortical Encoding of and Perceptual Sensitivity to Within-channel Temporal Gaps in Postlingually Deafened Adult Cochlear Implant Users
Authors: He Shuman , Yuan Yi , Skidmore Jeffrey
Published: April 2023

Objective:

As a step toward identifying the origin of the across-electrode variation in within-channel gap detection thresholds (GDTs) measured in individual cochlear implant (CI) users, this study assessed the relationships between the auditory nerve’s (AN’s) ability to recover from neural adaptation, cortical encoding of and perceptual sensitivity to within-channel temporal gaps in postlingually deafened adult CI users.

Design:

Study participants included 11 postlingually deafened adults with Cochlear Nucleus devices, including three bilaterally implanted participants. In each of the 14 ears tested, recovery from neural adaptation of the AN was measured using electrophysiological measures of the electrically evoked compound action potential at up to four electrode locations. The two CI electrodes in each ear showing the largest difference in the speed of adaptation recovery were selected for assessing within-channel temporal GDT. GDTs were measured using both psychophysical and electrophysiological procedures. Psychophysical GDTs were evaluated using a three-alternative, forced-choice procedure, targeting 79.4% correct on the psychometric function. Electrophysiological GDTs were measured using the electrically evoked auditory event-related potential (eERP) evoked by temporal gaps embedded in electrical pulse trains (i.e., the gap-eERP). Objective GDT was defined as the shortest temporal gap that could evoke a gap-eERP. Related-samples Wilcoxon Signed Rank test was used to compare psychophysical GDTs and objective GDTs measured at all CI electrode locations. It was also used to compare psychophysical GDTs and objective GDTs measured at the two CI electrode locations with different speeds or amounts of adaptation recovery of the AN. A Kendall Rank correlation test was used to assess the correlation between GDTs measured at the same CI electrode location using psychophysical or electrophysiological procedures.

Results:

Objective GDTs were significantly larger than those measured using psychophysical procedures. There was a significant correlation between objective and psychophysical GDTs. GDTs could not be predicted based on the amount or the speed of adaptation recovery of the AN.

Conclusions:

Electrophysiological measures of the eERP evoked by temporal gaps can potentially be used to assess within-channel GDT in CI users who cannot provide reliable behavioral responses. The difference in adaptation recovery of the AN is not the primary factor accounting for the across-electrode variation in GDT in individual CI users.
What Happens After a Vertebral Body Tether Break? Incidence, Location, and Progression With Five-year Follow-up
Authors: Yang Michael J. , Samdani Amer F. , Pahys Joshua M. , Quinonez Alejandro , McGarry Maureen , Grewal Harsh , Hwang Steven W.
Published: April 2023

Study Design.

Retrospective review.

Objective.

To study risk factors for anterior vertebral body tether (VBT) breakage.

Summary of Background Data.

VBT is used to treat adolescent idiopathic scoliosis in skeletally immature patients. However, tethers break in up to 48% of cases.

Materials and Methods.

We reviewed 63 patients who underwent thoracic and/or lumbar VBT with a minimum five-year follow-up. We radiographically characterized suspected tether breaks as a change in interscrew angle >5°. Demographic, radiographic, and clinical risk factors for presumed VBT breaks were evaluated.

Results.

In confirmed VBT breaks, the average interscrew angle change was 8.1°, and segmental coronal curve change was 13.6°, with a high correlation (r=0.82). Our presumed VBT break cohort constituted 50 thoracic tethers, four lumbar tethers, and nine combined thoracic/lumbar tethers; the average age was 12.1±1.2 years and the mean follow-up was 73.1±11.7 months. Of 59 patients with thoracic VBTs, 12 patients (20.3%) had a total of 18 breaks. Eleven thoracic breaks (61.1%) occurred between two and five years postoperatively, and 15 (83.3%) occurred below the curve apex (P<0.05). The timing of thoracic VBT breakage moderately correlated with more distal breaks (r=0.35). Of 13 patients who underwent lumbar VBT, eight patients (61.5%) had a total of 12 presumed breaks. Six lumbar breaks (50%) occurred between one and two years postoperatively, and seven (58.3%) occurred at or distal to the apex. Age, sex, body mass index, Risser score, and curve flexibility were not associated with VBT breaks, but the association between percent curve correction and thoracic VBT breakage trended toward significance (P=0.054). Lumbar VBTs were more likely to break than thoracic VBTs (P=0.016). Seven of the patients with presumed VBT breaks (35%) underwent revision surgery.

Conclusions.

Lumbar VBTs broke with greater frequency than thoracic VBTs, and VBT breaks typically occurred at levels distal to the curve apex. Only 15% of all patients required revision.

Level of Evidence.

3.
Distal Phalanx Intraosseous Epidermoid Cyst
Authors: AlMarshad Felwa A. , Mahabbat Nehal A. , Alzahrani Abdullah M. , Shash Hayam Ali , Al-Qattan Mohammad M. , Jarman Abdulaziz T.
Published: April 2023

An intraosseous epidermal cyst is a benign cystic lesion that occurs in the bones. It is assumed to be caused by congenital causes or trauma, and because the cyst forms in the soft tissue surrounding the bone, it can lead to bone loss. Intraosseous epidermal cysts have a well-defined radiolucent lesion with cortical extension on radiography. Due to clinical and radiological signs being similar, it is vital to distinguish an intraosseous epidermal cyst from other diseases that develop at the distal phalanx. A rare example of intraosseous epidermal cysts at the distal phalanx is reported. We describe the clinical, radiological, and pathologic aspect of this lesion, as well as our current therapeutic strategy.
An Algorithm in Managing Deep Inferior Epigastric Vessel Interruption in Free Flap Breast Reconstruction
Authors: Kapila Ayush K. , Kempny Tomas , Knoz Martin , Holoubek Jakub , Lipovy Bretislav , Hamdi Moustapha
Published: April 2023

Background:

Previous surgical procedures in the abdomen are no longer contra-indications for free flap breast reconstruction using the deep inferior epigastric artery perforator flap. Nonetheless, a possible consequence of previous surgical procedures may be trauma to the deep inferior epigastric (DIE) pedicle, leading to interruption. In these cases, a modification in operative strategy may be required.

Methods:

A study was performed across two centers, during a 10-year period between January 1, 2010 and December 2019. Patient and outcome data were collected from the patient file and operation notes.

Results:

Four cases with clear evidence of DIE pedicle interruption were found, with an average age of 54 years and an average body mass index of 28.9. Three patients had a preoperative diagnosis of DIE pedicle interruption on CT angiography, whereas in one case this was found peroperatively. For three cases, unilateral reconstruction was performed, and for one, bilateral reconstruction. Four flaps (in three cases) were unipedicled; the contralateral DIE pedicle was used in three, and the superficial system was used in one. For the bipedicled case, two hemiflaps were used, with the interrupted DIE pedicle anastomosed to a branch of the contralateral DIE pedicle.

Conclusions:

Interrupted DIE vessels remain a challenge for free flap breast reconstruction. The four cases demonstrated in this article highlight different surgical strategies, with an emphasis on detailed preoperative planning, including CT angiography. We present an algorithm to aid the reader in approaching cases with an interrupted DIE pedicle.
Management of the Fontan patient during pregnancy
Authors: Gupta Tripti , Thompson Jennifer , Lindley Kathryn J.
Published: April 2023

Purpose of review

Patients with single-ventricle Fontan palliation surgery often wish to pursue pregnancy. Pregnancies should be planned with well tolerated and effective contraception, and preconception risk stratification by adult congenital heart disease and maternal foetal medicine specialists.

Recent findings

Although infertility and foetal complications, including pregnancy loss, preterm birth and foetal growth restriction, are common, most patients with Fontan palliations can successfully complete pregnancy with a team-based approach. Important risk predictors are resting oxygen saturations, baseline functional status and the presence of systemic complications of the Fontan repair, including advanced Fontan associated liver disease, plastic bronchitis and ventricular dysfunction. Common maternal cardiovascular complications include arrhythmia, heart failure and thromboembolism. Delivery planning with input from an obstetric anaesthesiologist who has knowledge of complex congenital heart defects can facilitate appropriate, individualized monitoring and pain control. A vaginal delivery with consideration of an assisted second stage is appropriate for most single ventricle patients, in the absence of obstetric or foetal indications for caesarean delivery. Close postpartum monitoring and follow up is recommended, as the early postpartum period is the highest risk time for cardiovascular complications in patients with congenital heart disease.

A multidisciplinary approach to managing pregnancy and delivery in patients with Fontan circulation facilitates optimal maternal and infant outcomes.
Assessment and management of neonates with unrepaired congenital heart disease
Authors: Kohbodi GoleNaz Adeli , Ashrafi Amir H. , Levy Victor Y.
Published: April 2023

Purpose of review

To review preoperative assessment and management of neonates with congenital heart disease (CHD).

Recent findings

The spectrum for neonates with CHD can be wide and complex. An in-depth understanding of their physiology is the first step in assessing their hemodynamics and developing an effective therapeutic strategy.

There is significant heterogeneity in the anatomy and physiology in newborns with CHD. Their complex pathophysiology can be simplified into seven basic subtypes, which include systolic dysfunction, diastolic dysfunction, excessive pulmonary blood flow, obstructed pulmonary blood flow, obstructed systemic blood flow, transposition physiology, and single ventricle physiology. It is important to note these physiologies are not mutually exclusive, and this review summarizes the hemodynamic and therapeutic strategies available for the preoperative neonate with CHD.
Heterogeneity, crosstalk, and targeting of cancer-associated fibroblasts in cholangiocarcinoma
Authors: Cantallops Vilà Paula , Ravichandra Aashreya , Agirre Lizaso Aloña , Perugorria Maria J. , Affò Silvia
Published: April 2023

Cholangiocarcinoma (CCA) comprises diverse tumors of the biliary tree and is characterized by late diagnosis, short-term survival, and chemoresistance. CCAs are mainly classified according to their anatomical location and include diverse molecular subclasses harboring inter-tumoral and intratumoral heterogeneity. Besides the tumor cell component, CCA is also characterized by a complex and dynamic tumor microenvironment where tumor cells and stromal cells crosstalk in an intricate network of interactions. Cancer-associated fibroblasts, one of the most abundant cell types in the tumor stroma of CCA, are actively involved in cholangiocarcinogenesis by participating in multiple aspects of the disease including extracellular matrix remodeling, immunomodulation, neo-angiogenesis, and metastasis. Despite their overall tumor-promoting role, recent evidence indicates the presence of transcriptional and functional heterogeneous CAF subtypes with tumor-promoting and tumor-restricting properties. To elucidate the complexity and potentials of cancer-associated fibroblasts as therapeutic targets in CCA, this review will discuss the origin of cancer-associated fibroblasts, their heterogeneity, crosstalk, and role during tumorigenesis, providing an overall picture of the present and future perspectives toward cancer-associated fibroblasts targeting CCA.
Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study
Authors: Hirschfield Gideon M. , Shiffman Mitchell L. , Gulamhusein Aliya , Kowdley Kris V. , Vierling John M. , Levy Cynthia , Kremer Andreas E. , Zigmond Ehud , Andreone Pietro , Gordon Stuart C. , Bowlus Christopher L. , Lawitz Eric J. , Aspinall Richard J. , Pratt Daniel S. , Raikhelson Karina , Gonzalez-Huezo Maria S. , Heneghan Michael A. , Jeong Sook-Hyang , Ladrón de Guevara Alma L. , Mayo Marlyn J. , Dalekos George N. , Drenth Joost P.H. , Janczewska Ewa , Leggett Barbara A. , Nevens Frederik , Vargas Victor , Zuckerman Eli , Corpechot Christophe , Fassio Eduardo , Hinrichsen Holger , Invernizzi Pietro , Trivedi Palak J. , Forman Lisa , Jones David E.J. , Ryder Stephen D. , Swain Mark G. , Steinberg Alexandra , Boudes Pol F. , Choi Yun-Jung , McWherter Charles A. ,   ENHANCE Study Group*
Published: April 2023

Background and Aims:

ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).

Approach and Results:

Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) (p < 0.0001). ALP normalization occurred in 5.4% (p=0.08) and 27.3% (p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: −3.14 (p=0.02); placebo: −1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% (p=0.0008); 10 mg: 16.7% (p=0.03); placebo: 4%]. There were no serious treatment-related adverse events.

Conclusions:

Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.
Effects of body positions on arterial stiffness as assessed by pulse wave velocity
Authors: Alhalimi Taha A. , Wang Tianyu , Meyer Michelle L. , Tanaka Hirofumi
Published: April 2023

Background:

Assessing arterial stiffness through pulse wave velocity (PWV) usually requires participants to be in a supine position. If this position is not feasible, adjustments such as tilting the bed or bending the knees may be made. The Vicorder device also recommends tilting the upper body to prevent jugular vein interference in the recorded carotid pulse.

Objective:

To examine the impact of varying body positions on PWV.

Methods:

Seventy adults were studied in the fully supine (0°) to 40° upper body tilted-up positions with and without knee bend. Carotid-femoral PWV (cfPWV) was measured using two different testing devices (Omron VP-1000plus and Vicorder) and brachial-ankle PWV (baPWV) was measured using Omron.

Results:

cfPWV measured at 10° tilt-up was not different from 0° position while baPWV increased significantly from 10°. Elevations in cfPWV were 7% at 20° and 15% at 40° compared with 0° position. Knee bend did not affect cfPWV but decreased baPWV at each angle (P < 0.05). Jugular vein interference on the Vicorder was observed in 78% of participants in supine position, decreasing as body angle increased (7% at 30°). However, cfPWV values measured by Vicorder were consistent with those obtained by Omron even with jugular vein interference.

Conclusion:

Arterial stiffness assessed by PWV increased gradually and significantly in semi-Fowler's position ≥20°. Knee bend decreased baPWV but did not seem to affect cfPWV. PWV should be measured in supine position if possible. If the supine posture is not tolerated, knee bend followed by a slight incline position may be recommended.
The impact of blood pressure variability on cognition: current limitations and new advances
Authors: Sun Fen
Published: April 2023

Dementia is the most common neurodegenerative disease in the aging population. Emerging evidence indicates that blood pressure (BP) variability is correlated with cognitive impairment and dementia independent of mean BP levels. The state-of-the-art review summarizes the latest evidence regarding the impact of BP variability on cognition in cognitively intact populations, patients with mild cognitive impairment, and different dementia types, focusing on the important confounding factors and new advances. This review also summarizes the potential mechanisms underlying the relationship between BP variability and cognitive impairment, and dementia, briefly discussing sex differences in the relationship. At last, current limitations and future perspectives are discussed to optimize BP management in preventing cognitive impairment and dementia.
Association of genetically-predicted placental gene expression with adult blood pressure traits
Authors: Hellwege Jacklyn N. , Stallings Sarah C. , Piekos Jacqueline A. , Jasper Elizabeth A. , Aronoff David M. , Edwards Todd L. , Velez Edwards Digna R.
Published: April 2023

Objective:

Blood pressure is a complex, polygenic trait, and the need to identify prehypertensive risks and new gene targets for blood pressure control therapies or prevention continues. We hypothesize a developmental origins model of blood pressure traits through the life course where the placenta is a conduit mediating genomic and nongenomic transmission of disease risk. Genetic control of placental gene expression has recently been described through expression quantitative trait loci (eQTL) studies which have identified associations with childhood phenotypes.

Methods:

We conducted a transcriptome-wide gene expression analysis estimating the predicted gene expression of placental tissue in adult individuals with genome-wide association study (GWAS) blood pressure summary statistics. We constructed predicted expression models of 15 154 genes from reference placenta eQTL data and investigated whether genetically-predicted gene expression in placental tissue is associated with blood pressure traits using published GWAS summary statistics. Functional annotation of significant genes was generated using FUMA.

Results:

We identified 18, 9, and 21 genes where predicted expression in placenta was significantly associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), respectively. There were 14 gene-tissue associations (13 unique genes) significant only in placenta.

Conclusions:

In this meta-analysis using S-PrediXcan and GWAS summary statistics, the predicted expression in placenta of 48 genes was statistically significantly associated with blood pressure traits. Notable findings included the association of FGFR1 expression with increased SBP and PP. This evidence of gene expression variation in placenta preceding the onset of adult blood pressure phenotypes is an example of extreme preclinical biological changes which may benefit from intervention.
Masked hypertension in a middle-aged population and its relation to manifestations of vascular disease
Authors: af Geijerstam Peder , Engvall Jan , Östgren Carl Johan , Rådholm Karin , Nyström Fredrik H.
Published: April 2023

Background:

Masked hypertension is associated with cardiovascular disease (CVD). However, previous large studies have not used the same device to measure office and home blood pressure (BP) and adhered to current home BP measurement recommendations of the European Society of Hypertension. We aimed to characterize masked hypertension and explore its relation to manifestations of CVD.

Methods:

A randomly selected cohort of 5057 participants aged 50–64 years from the Swedish CardioPulmonary BioImage Study (SCAPIS) was evaluated with office and home BP using the semi-automatic Omron M10-IT oscillometric device. Additional analyses included pulse wave velocity (PWV) and coronary artery calcium score (CACS).

Results:

Of participants, 4122 did not have current antihypertensive treatment, and were thus included in our analyses. Of these, 2634 (63.9%) had sustained normotension, and 172 (4.2%) had masked hypertension. Participants with masked hypertension vs. sustained normotension were more often men (66.9 vs. 46.2%, P < 0.001). Those with masked hypertension had higher mean PWV [9.3 (95% confidence interval, 95% CI 9.1–9.5) vs. 8.3 (95% CI 8.2–8.4) m/s, P < 0.001] and odds ratio for CACS at least 100 [1.65 (95% CI 1.02–2.68), P = 0.040]. These associations were similar in a posthoc analysis of masked hypertension and sustained normotension, matched for age, sex and systolic office BP.

Conclusion:

Masked hypertension was associated with markers of CVD. This suggests that home BP is a better predictor of risk, even when the recordings are performed with the same measurement device, in a population-based setting with randomized recruitment.
Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials
Authors: Martins Vítor M. , Ziegelmann Patrícia K. , Ferrari Filipe , Bottino Leonardo G. , Lucca Marcelo B. , Corrêa Henrique L. Ruchaud , Blum Gabriela B. , Helal Lucas , Fuchs Sandra C. , Fuchs Flávio D.
Published: April 2023

Background:

The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension.

Methods:

A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer.

Results:

Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from –7.66 mmHg [95% credible interval (95% CrI), –8.53 to –6.79] for T- to –12.77 mmHg (95% CrI, –15.22 to –10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents.

Conclusion:

Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.
Keratoconus and Personality Traits: A Case–Control Study
Authors: Aiello Francesco , Gallo Afflitto Gabriele , Ceccarelli Francesca , Garzione Flavia , Pocobelli Giulio , Pinci Carolina , Di Lorenzo Giorgio , Siracusano Alberto , Nucci Carlo
Published: April 2023

Purpose:

The aim of this study was to delineate the personality traits of patients affected by keratoconus (KC) compared with a group of nonkeratoconic controls matched in age and sex.

Methods:

In this prospective interventional case–control study, 60 consecutive subjects (30 KC cases and 30 healthy controls), aged 18 to 30, were enrolled at the time of their first encounter at the ophthalmology unit of the Fondazione Policlinico “Tor Vergata”, Roma. After completing the ophthalmic evaluation, participants were asked to respond to the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). A complete psychiatric assessment was performed, including the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (SCID-5); the Symptom Check List-90-Revised (SCL-90); the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Modified (TEMPS-M); and the NEO Five-Factor Inventory (NEO-FFI).

Results:

Cases had lower quality of life than controls, as demonstrated by lower scores in all NEI VFQ-25 subdomains. Nine patients with KC (30.0%) were diagnosed by the SCID-5 with at least 1 cluster C personality disorder, resulting in a 9-fold increased risk compared with controls. Moreover, keratoconic patients showed a more pronounced psychosomatic symptomatology (SCL-90) and a characteristic neurotic temperament (TEMPS-M and NEO-FFI).

Conclusions:

Our results support the hypothesis that subjects with KC feature dysfunctional coping mechanisms and personality traits, which might already be present at the first clinical encounter. Ophthalmologists should question the mental and emotional status of patients with KC and be especially careful in managing these patients.
Maternal diabetes mellitus and birth defects in Taiwan: A 5-year nationwide population-based cohort study
Authors: Chen Lih-Ju , Chiu Chih-Huang , Huang Jing-Yang , Chen Ping-Ju , Su Pen-Hua , Yang Shun-Fa , Chen Jia-Yuh
Published: April 2023

Background:

Birth defects (BDs) are the main causes of mortality and disability in infants and children. Associations between maternal diabetes mellitus (DM), including gestational DM (GDM) and pregestational DM (type 1 or type 2), and the risk of BDs have been reported. This study aims to determine the relationship between maternal DM and BDs and to investigate whether reducing the incidence of DM can decrease the incidence of BDs.

Methods:

We identified all births in Taiwan from the National Birth Defects Surveillance Program between January 1, 2010, and December 31, 2014. Information on the infants’ characteristics (sex, gestational age, and birth weight) and mothers’ characteristics (age, parity, and associated diseases, including DM) were obtained from the National Birth Registry and National Health Insurance Research Database (NHIRD) in Taiwan. BDs were coded according to the International Classification of Diseases, 9th Revision—Clinical Modification (ICD-9-CM) codes 740-759.

Results:

Multiple logistic regression analysis with adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for all BDs showed that the aOR (95% CI) was 1.002 (0.965-1.041), and the p-value was 0.9139 in the GDM group. In the type 1 DM group, the aOR (95% CI) was 1.748 (1.110-2.754), and the p-value was 0.016. In the type 2 DM group, the aOR (95%CI) was 1.175 (1.005-1.375), 1.331 (1.196-1.482), and 1.391 (1.216-1.592), and the p-value was 0.0437, <0.0001, and <0.0001 for the duration of mothers with type 2 DM <2, 2 to 5, >5 years, respectively.

Conclusion:

Mothers with pregestational DM (type 1 or type 2) increase the incidence of BD. Appropriate maternal glycemic control may achieve good pregnancy and perinatal outcomes.