bluuebunny/crossref_metadata_2025 huggingface dataset:
ENRICHing medical imaging training sets enables more efficient machine learning
Authors: Chinn Erin , Arora Rohit , Arnaout Ramy , Arnaout Rima
Published: April 2023

Objective

Deep learning (DL) has been applied in proofs of concept across biomedical imaging, including across modalities and medical specialties. Labeled data are critical to training and testing DL models, but human expert labelers are limited. In addition, DL traditionally requires copious training data, which is computationally expensive to process and iterate over. Consequently, it is useful to prioritize using those images that are most likely to improve a model’s performance, a practice known as instance selection. The challenge is determining how best to prioritize. It is natural to prefer straightforward, robust, quantitative metrics as the basis for prioritization for instance selection. However, in current practice, such metrics are not tailored to, and almost never used for, image datasets.

Materials and Methods

To address this problem, we introduce ENRICH—Eliminate Noise and Redundancy for Imaging Challenges—a customizable method that prioritizes images based on how much diversity each image adds to the training set.

Results

First, we show that medical datasets are special in that in general each image adds less diversity than in nonmedical datasets. Next, we demonstrate that ENRICH achieves nearly maximal performance on classification and segmentation tasks on several medical image datasets using only a fraction of the available images and without up-front data labeling. ENRICH outperforms random image selection, the negative control. Finally, we show that ENRICH can also be used to identify errors and outliers in imaging datasets.

Conclusions

ENRICH is a simple, computationally efficient method for prioritizing images for expert labeling and use in DL.
The Right to the Truth as an Enabler for Missing Persons Efforts
Authors: Klinkner Melanie
Published: April 2023

The right to the truth is often mentioned in conjunction with missing persons cases and is recognized for its propensity to function as an enabling right, helping victims and families to claim their rights. While families, survivors, communities, specialist agencies, NGOs and international organizations readily invoke the right to the truth, the terminology used in the context can be ambiguous, overlapping, mandate-driven or strategic. This contribution reflects on the applicable legal spheres, use of approaches and practices in the context of missing persons investigations and claims made towards the realization of the right to the truth. The article clarifies the legal landscape to underscore what is meant by the right to the truth and how it may function as the starting point for the realization of other rights in the context of missing persons. Further, it examines and dissects conceptualizations of missing persons and resolution efforts; and identifies what actions help realize the right to the truth and to what extent. It argues the merits of a broad definition of missing persons while urging those engaged in solving missing persons cases to be candid in respect of the truth-seeking aspect they may be able to advance. This is by no means a trivial inquiry, for families of the missing rely on the assistance of the law and relevant agencies to further the realization of their right to the truth.
Development of a Kinetic ELISA and Reactive B Cell Frequency Assay to Detect Respiratory Syncytial Virus Pre-Fusion F Protein-Specific Immune Responses in Infants
Authors: Rolsma Stephanie L , Yoder Sandra M , Nargi Rachel S , Brady Eric , Kose Nurgun , Jimenez-Truque Natalia , Thomsen Isaac , Kontos Marissa , Carnahan Robert H , Sutton Rachel E , Armstrong Erica , Dally Len , Crowe James E , Edwards Kathryn M , Creech C Buddy
Published: April 2023

Background

Respiratory syncytial virus (RSV) is a major cause of respiratory disease in infants, making vaccination an attractive preventive strategy. Due to earlier reports of vaccine-enhanced disease in RSV-naive children, assessing prior RSV infection is critical for determining eligibility for future infant vaccine trials. However, this is complicated by the presence of maternally transferred maternal antibodies. We sought to develop assays that measure immune responses to RSV pre-fusion (F) protein that discriminates between maternal and infant responses.

Methods

We measured RSV-specific responses in two groups of children <3 years of age; those with laboratory-confirmed RSV (RSV-infected) and those enrolled prior to their first RSV season (RSV-uninfected). Serial blood samples were obtained and recent infections with RSV and other respiratory viruses were assessed during follow-up. An RSV pre-F-specific kinetic enzyme-linked immunosorbent assay (kELISA) and an F-specific reactive B cell frequency (RBF) assay were developed.

Results

One hundred two young children were enrolled between July 2015 and April 2017; 74 were in the RSV-uninfected group and 28 were in the RSV-infected group. Participants were asked to provide sequential blood samples over time, but only 53 participants in the RSV-uninfected group and 22 participants in the RSV-infected groups provided multiple samples. In the RSV-infected group, most had positive kELISA and RBF during the study. In the RSV-uninfected group, two patterns emerged: declining kELISA values without reactive B cells, due to maternal transplacental antibody transfer, and persistently positive kELISA with reactive B cells, due to asymptomatic undiagnosed RSV infection.

Conclusions

A kELISA targeting RSV pre-F epitopes and an RBF assay targeting RSV F-specific B cells generally allow discrimination between maternally and infant-derived antibodies.
m6A modification: a new avenue for anti-cancer therapy
Authors: Bai Yongtai , Li Kai , Peng Jinying , Yi Chengqi
Published: April 2023

To date, over 170 different kinds of chemical modifications on RNAs have been identified, some of which are involved in multiple aspects of RNA fate, ranging from RNA processing, nuclear export, translation, and RNA decay. m6A, also known as N6-methyladenosine, is a prominent internal RNA modification that is catalyzed primarily by the METTL3-METTL14-WTAP methyltransferase complex in higher eukaryotic mRNA and long noncoding RNA (lncRNA). In recent years, abnormal m6A modification has been linked to the occurrence, development, progression, and prognosis of the majority of cancers. In this review, we provide an update on the most recent m6A modification discoveries as well as the critical roles of m6A modification in cancer development and progression. We summarize the mechanisms of m6A involvement in cancer and list potential cancer therapy inhibitors that target m6A regulators such as “writer” METTL3 and “eraser” FTO.
Touch and Bodily Transparency
Authors: Mizrahi Vivian
Published: April 2023

As most philosophers recognize, the body’s central role in touch differs from the role it plays in the other sense modalities. Any account of touch must then explain the pivotal nature of the body’s involvement in touch. Unlike most accounts of touch, this paper argues that the body’s centrality in touch is not phenomenological or experiential: the body is not felt in any special way in tactile experiences. Building on Aristotle’s account in De Anima, I argue that the body is central in touch because it is the medium of tactile perception. Touch depends on the body as vision and audition depend on air or any medium that can transmit light or sound waves. I show that it is precisely because the body must be transparent in order to transmit tangible properties that it cannot be perceived or experienced in tactile perception. Although this account conflicts with the widespread view that tactile perception is mediated by bodily sensations, I maintain that it explains how the structure and constitution of the human body contribute directly to what we feel in tactile experiences and that it provides a better understanding of the relation between the sense of touch and our bodily feelings.
Enlightening the dynamical evolution of Galactic open clusters: an approach usingGaiaDR3 and analytical descriptions
Authors: Angelo M S , Santos Jr. J F C , Maia F F S , Corradi W J B
Published: April 2023

Most stars in our Galaxy form in stellar aggregates, which can become long-lived structures called open clusters (OCs). Along their dynamical evolution, their gradual depletion leave some imprints on their structure. In this work, we employed astrometric, photometric, and spectroscopic data from the Gaia DR3 catalogue to uniformly characterize a sample of 60 OCs. Structural parameters (tidal, core, and half-light radii, respectively, rt, rc, and rh), age, mass (Mclu), distance, reddening, Jacobi radius (RJ), and half-light relaxation time (trh) are derived from radial density profiles and astrometrically decontaminated colour–magnitude diagrams. Ages and Galactocentric distances (RG) range from 7.2$\, \lesssim \,$log(t.yr$^{-1})\, \lesssim \,$9.8 and 6$\, \lesssim \, R_G$(kpc)$\, \lesssim \,$12. Analytical expressions derived from N-body simulations are also employed to estimate the OC initial mass (Mini) and mass loss due to dynamical effects. Both rc and the tidal filling ratio, rh/RJ, decrease with the dynamical age (= t/trh), indicating the shrinking of the OCs’ internal structure as consequence of internal dynamical relaxation. This dependence seems differentially affected by the external tidal field, since OCs at smaller RG tend to be dynamically older and have smaller Mclu/Mini ratios. For $R_G\lesssim 8\,$ kpc, the rh/RJ ratio presents a slight positive correlation with RG. Beyond this limit, there is a dichotomy in which more massive OCs are more compact and less subject to tidal stripping compared to those less massive and looser OCs at similar RG. Besides, the rt/RJ ratio also correlates positively with RG.
Equilibrium non-self-gravitating tori around black holes in parametrized spherically symmetric space–times
Authors: Cassing Marie , Rezzolla Luciano
Published: April 2023

Non-self-gravitating equilibrium tori orbiting around black holes have a long history and have been employed in numerous simulations of accretion flows on to black holes and other compact objects. We have revisited the problem of constructing such equilibria starting from spherically symmetric black-hole space–times expressed in terms of a fully generic and rapidly converging parametrization: the Rezzolla–Zhidenko metric. Within this framework, we have extended the definitions of all of the quantities characterizing these equilibria, starting from the concept of the von Zeipel cylinders and up to the possible ranges of the specific angular momenta that are employed to construct families of tori. Within the allowed space of parameters we have then encountered both standard ‘single-torus’ solutions and non-standard ‘double-tori’ solutions. While the properties of the first ones in terms of the presence of a single cusp, of a local pressure maximum and of a varying outer radius, are very similar to those encountered in general relativity, the properties of double-tori solutions are far richer and naturally allow for configurations having the same constant specific angular momentum and hence are potentially easier to produce in nature. The existence of these objects is at present very hypothetical, but if these equilibrium tori were to be observed, they would provide very valuable information on the properties of the space–time and on its deviation from general relativity.
Modelling the optical energy profile of the 2021 October Jupiter impact flash
Authors: Arimatsu Ko , Tsumura Kohji , Usui Fumihiko , Watanabe Jun-ichi
Published: April 2023

We have conducted numerical simulations to reproduce the observed optical energy profile of the 2021 October 15 (ut) impact flash on Jupiter, which was the largest and the most well-observed flash event detected by ground-based movie observations. The observed long-duration (∼5.5 s) optical emission can be reproduced by an impact of an object with an exceptionally small angle of entry relative to the horizontal. The apparent lack of the impact debris feature despite the large impact object was possibly due to the shallower angle of entry (≤12°), which resulted in the lower ablation per unit volume at altitudes higher than $50 \, {\rm km}$, and the volume densities of the ablated materials were too low to allow the debris particulates to coagulate. The absence of temporal methane absorption change in the observed flash spectrum is consistent with the best-fitting results. The model better fits the observed optical energy profile for weaker material (cometary and stony) cases than for metallic ones. Based on the simulation results, prospects for future observations of impact flashes are discussed.
Quasi-spiral solution to the mixed intracluster medium and the universal entropy profile of galaxy clusters
Authors: Keshet Uri , Raveh Itay , Ghosh Arka
Published: April 2023

Well-resolved galaxy clusters often show a large-scale quasi-spiral structure in deprojected density ρ and temperature T fields, delineated by a tangential discontinuity known as a cold front, superimposed on a universal radial entropy profile with a linear K(r) ∝ Tρ−2/3 ∝ r adiabat. We show that a spiral structure provides a natural quasi-stationary solution for the mixed intracluster medium (ICM), introducing a modest pressure spiral that confines the locally buoyant or heavy plasma phases. The solution persists in the presence of uniform or differential rotation, and can accommodate both an inflow and an outflow. Hydrodynamic adiabatic simulations with perturbations that deposit angular momentum and mix the plasma thus asymptote to a self-similar spiral structure. We find similar spirals in Eulerian and Lagrangian simulations of 2D and 3D, merger and offset, clusters. The discontinuity surface is given in spherical coordinates {r, θ, ϕ} by ϕ(r, θ) ∝ Φ(r) , where Φ is the gravitational potential, combining a trailing spiral in the equatorial (θ = π/2) plane and semicircles perpendicular to the plane, in resemblance of a snail shell. A local convective instability can develop between spiral windings, driving a modified global instability in sublinear K(r) regions; evolved spirals thus imprint the observed K ∝ r onto the ICM even after they dissipate. The spiral structure brings hot and cold phases to close proximity, suggesting that the observed fast outflows could sustain the structure even in the presence of radiative cooling.
On the use of temporal filtering for mitigating galactic synchrotron calibration bias in 21 cm reionization observations
Authors: Charles Ntsikelelo , Kern Nicholas , Bernardi Gianni , Bester Landman , Smirnov Oleg , Fagnoni Nicolas , Acedo Eloy de Lera
Published: April 2023

Precision antenna calibration is required for mitigating the impact of foreground contamination in 21 cm cosmological radio surveys. One widely studied source of error is the effect of missing point sources in the calibration sky model; however, poorly understood diffuse galactic emission also creates a calibration bias that can complicate the clean separation of foregrounds from the 21 cm signal. In this work, we present a technique for suppressing this bias with temporal filtering of radio interferometric visibilities observed in a drift-scan mode. We demonstrate this technique on mock simulations of the Hydrogen Epoch of Reionization Array (HERA) experiment. Inspecting the recovered calibration solutions, we find that our technique reduces spurious errors by over an order of magnitude. This improved accuracy approaches the required accuracy needed to make a fiducial detection of the 21 cm signal with HERA, but is dependent on a number of external factors that we discuss. We also explore different types of temporal filtering techniques and discuss their relative performance and trade-offs.
Sky-averaged 21-cm signal extraction using multiple antennas with an SVD framework: the REACH case
Authors: Saxena Anchal , Meerburg P Daniel , de Lera Acedo Eloy , Handley Will , Koopmans Léon V E
Published: April 2023

In a sky-averaged 21-cm signal experiment, the uncertainty of the extracted signal depends mainly on the covariance between the foreground and 21-cm signal models. In this paper, we construct these models using the modes of variation obtained from the singular value decomposition of a set of simulated foreground and 21-cm signals. We present a strategy to reduce this overlap between the 21-cm and foreground modes by simultaneously fitting the spectra from multiple different antennas, which can be used in combination with the method of utilizing the time dependence of foregrounds while fitting multiple drift scan spectra. To demonstrate this idea, we consider two different foreground models (i) a simple foreground model, where we assume a constant spectral index over the sky, and (ii) a more realistic foreground model, with a spatial variation of the spectral index. For the simple foreground model, with just a single antenna design, we are able to extract the signal with good accuracy if we simultaneously fit the data from multiple time slices. The 21-cm signal extraction is further improved when we simultaneously fit the data from different antennas as well. This improvement becomes more pronounced while using the more realistic mock observations generated from the detailed foreground model. We find that even if we fit multiple time slices, the recovered signal is biased and inaccurate for a single antenna. However, simultaneously fitting the data from different antennas reduces the bias and the uncertainty by a factor of 2–3 on the extracted 21-cm signal.
Fine-structure transitions of Si and S induced by collisions with atomic hydrogen
Authors: Yan Pei-Gen , Babb James F
Published: April 2023

Using a quantum-mechanical close-coupling method, we calculate cross-sections for fine-structure excitation and relaxation of Si and S atoms in collisions with atomic hydrogen. Rate coefficients are calculated over a range of temperatures for astrophysical applications. We determine the temperature-dependent critical densities for the relaxation of Si and S in collisions with H and compare these to the critical densities for collisions with electrons. The present calculations should be useful in modelling environments exhibiting the [S i] 25 μm and [S i] 57 μm far-infrared emission lines or where cooling of S and Si by collisions with H is of interest.
Analysis of integral field spectroscopy observations of the planetary nebula Hen 2-108 and its central star
Authors: Miranda Marques Bárbara L , Monteiro Hektor , Aleman Isabel , Akras Stavros , Todt Helge , Corradi Romano L M
Published: April 2023

The study of planetary nebulae provides important constraints for many aspects of stellar and Galactic evolution. Hen 2-108 is a poorly known planetary nebula with a slight elliptical morphology and a peculiar central star (CS), which has defied classification. In this work, we present the first detailed integral field spectroscopic study of the planetary nebula Hen 2-108 and its CS. We provide spatially resolved flux maps for important emission lines, as well as diagnostic maps of extinction and electronic density and temperature. Physical conditions and chemical abundances were also calculated from the integrated spectrum. The analysis was also performed with the code satellite that uses a distinct strategy to evaluate physical and chemical properties. Both satellite and traditional procedure give consistent results, showing some variation in physical and chemical properties. We detect and measure a number of faint heavy element recombination lines from which we find a significant abundance discrepancy factor for O/H, and possibly for N/H. Pseudo-3D photoionization models were used to assist in the interpretation with results supporting the low-ionization nature of this nebula, indicating a CS with Teff = 40 kK and a shell structure. The spectrum of the CS has been analysed with a detailed model for expanding atmospheres to infer stellar parameters, finding that it is a [Of/WN8] type with T* = 41.5 kK, making it a new addition to a small set (∼20) of rare objects.
Population Genomic Evidence of Adaptive Response during the Invasion History ofPlasmodium falciparumin the Americas
Authors: Lefebvre Margaux J M , Daron Josquin , Legrand Eric , Fontaine Michael C , Rougeron Virginie , Prugnolle Franck
Published: April 2023

Plasmodium falciparum, the most virulent agent of human malaria, spread from Africa to all continents following the out-of-Africa human migrations. During the transatlantic slave trade between the 16th and 19th centuries, it was introduced twice independently to the Americas where it adapted to new environmental conditions (new human populations and mosquito species). Here, we analyzed the genome-wide polymorphisms of 2,635 isolates across the current P. falciparum distribution range in Africa, Asia, Oceania, and the Americas to investigate its genetic structure, invasion history, and selective pressures associated with its adaptation to the American environment. We confirmed that American populations originated from Africa with at least two independent introductions that led to two genetically distinct clusters, one in the North (Haiti and Colombia) and one in the South (French Guiana and Brazil), and an admixed Peruvian group. Genome scans revealed recent and more ancient signals of positive selection in the American populations. Particularly, we detected positive selection signals in genes involved in interactions with hosts (human and mosquito) cells and in genes involved in resistance to malaria drugs in both clusters. Analyses suggested that for five genes, adaptive introgression between clusters or selection on standing variation was at the origin of this repeated evolution. This study provides new genetic evidence on P. falciparum colonization history and on its local adaptation in the Americas.
Genetics of caffeine and brain-related outcomes – a systematic review of observational studies and randomized trials
Authors: Kapellou Angeliki , King Alexandra , Graham Catherine A M , Pilic Leta , Mavrommatis Yiannis
Published: April 2023

Context

Although the stimulant and anxiogenic properties of caffeine are widely accepted, research on its specific effects on the brain remains controversial. Growing evidence shows that interindividual differences in caffeine response may be partly due to variations in genes such as CYP1A2 and ADORA2A, which have been used to identify individuals as “fast” or “slow” caffeine metabolizers and as having a “high” or “low” caffeine sensitivity, respectively.

Objective

The objective of this review was to identify, evaluate, and discuss current evidence on the associations between common genetic variants, caffeine consumption, and brain-related outcomes in humans.

Data Sources

PubMed and Embase databases were searched for relevant reports based on a predetermined search strategy.

Data Extraction

Reports of observational and experimental studies on healthy adults who underwent (a) genetic analysis for polymorphisms in genes associated with caffeine metabolism and effects and (b) measurements of brain-related effects such as anxiety, insomnia, and cognitive performance associated with the consumption of caffeine (habitual intake or supplementation) were included.

Data Analysis

Of the 22 records included, 15 were randomized controlled trials, 6 were cross-sectional studies, and 1 was a genome-wide association study. The main outcomes identified were cognitive performance (n = 9), anxiety (n = 7), and sleep disturbance/insomnia (n = 6). Polymorphisms in the CYP1A2 gene were associated with cognitive function, while variations in the ADORA2A gene were associated with anxiety and sleep disturbance.

Conclusion

The present review has provided evidence that variability in the CYP1A2 and the ADORA2A genes may modulate the association between caffeine and brain-related outcomes. Future studies are warranted to investigate the specific polymorphisms implicated in each brain outcome, which cognitive functions are particularly related to caffeine (simple vs complex), whether there are gender differences in anxiety effects, and how habitual caffeine intake may influence the acute effects of caffeine.

Systematic review registration

PROSPERO registration no. CRD42021257556.
Surgical Margin Affects the Long-Term Prognosis of Patients With Hepatocellular Carcinoma Undergoing Radical Hepatectomy Followed by Adjuvant TACE
Authors: Bai Shilei , Yang Pinghua , Liu Jianwei , Xue Hui , Xia Yong , Liu Fuchen , Yang Zhao , Zhang Lei , Wu Yeye , Shen Feng , Wang Kui
Published: April 2023

Background

The aim of this study was to investigate whether postoperative adjuvant transcatheter arterial chemoembolization (TACE) treatment in wide- and narrow-margin groups could improve the long-term prognosis of patients with hepatocellular carcinoma (HCC).

Materials and Methods

A total of 670 patients with HCC who underwent radical hepatectomy from January 2016 to December 2017 were enrolled, including 397 patients and 273 patients in the wide- and narrow-margin groups. Recurrence-free survival (RFS) and overall survival (OS) outcomes were compared in the wide-margin and narrow-margin groups with and without adjuvant TACE postoperatively, respectively. Propensity score matching (PSM) analysis was used to match patients between TACE and no TACE groups in a 1:1 ratio.

Results

The wide-margin resection was associated with better RFS and OS rates than narrow-margin resection for patients with HCC. Patients with postoperative adjuvant TACE had a better RFS and OS than patients without postoperative adjuvant TACE in the narrow-margin group and reduced the intrahepatic recurrence rate (39.1% vs. 52.6%, P = .036) and the local recurrence rate in the liver (11.2% vs. 21.4%, P = .032). But postoperative adjuvant TACE did not alter recurrence and survival outcomes in the wide-margin group. Similar results were noted after propensity score matching (PSM).

Conclusion

The wide-margin resection had better RFS and OS than the narrow-margin resection for patients with HCC. Postoperative adjuvant TACE was associated with reduced recurrence and improved OS after narrow-margin resection, but was not effective in the wide-margin resection.
Experiences of Mothers of Preterm Infants in the Neonatal Intensive Care Unit During the COVID-19 Pandemic
Authors: Richter Lindsay L. , Ku Connie , Mak Meagan Yan Yu , Holsti Liisa , Kieran Emily , Alonso-Prieto Esther , Ranger Manon
Published: April 2023

Background:

The neonatal intensive care unit (NICU) stay following the birth of a preterm infant can be stressful and traumatic for families. During the COVID-19 pandemic, the NICU environment changed precipitously as infection control and visitor restriction measures were implemented.

Purpose:

Our study aimed to examine the impact of the pandemic policies on the experiences of mothers of preterm infants during their stay in the NICU.

Methods:

Semistructured interviews were conducted with mothers of preterm infants hospitalized in a Canadian tertiary-level NICU. Informed by interpretive description methodology, interview content was transcribed and analyzed using a thematic analysis approach. The identified themes were validated, clarified, or refined using investigator triangulation.

Results:

Nine English-speaking mothers, aged 28 to 40 years, were interviewed. Four themes emerged from the analysis of their experiences: (1) disrupted family dynamic, support, and bonding; (2) physical and emotional isolation; (3) negative psychological impact compounded by added concerns, maternal role change, and survival mode mentality; and (4) positive aspects of the pandemic management measures.

Implications for Practice:

During the pandemic, the way that care was provided in the NICU changed. This study helps to explore how neonatal clinicians can foster individual and organizational resilience to keep patients and families at the center of care, even when the healthcare system is under intense stress.

Implications for Research

: Our results show that these changes heightened mothers' distress, but also had a modest positive impact. Further research about long-term consequences of pandemic policies on the mother and preterm infant after NICU discharge is warranted.
Parental Perceptions of the Impact of NICU Visitation Policies and Restrictions Due to the COVID-19 Pandemic
Authors: Yance Brittany , Do Kayla , Heath Jenna , Fucile Sandra
Published: April 2023

Background:

The COVID-19 pandemic has impacted parents' ability to participate in their infants' care during the neonatal intensive care unit (NICU) stay in unprecedented ways.

Purpose:

The purpose of this study was to explore the lived experience of parents whose infants was in the NICU during the COVID-19 pandemic.

Methods:

A qualitative telephone interview survey was conducted. Participants included parents of preterm infants who were born less than 34 weeks' gestation during the first wave of the COVID-19 pandemic (March 2020-August 2020). Telephone surveys were conducted through open-ended questions. A thematic content analysis identifying themes was performed after interviews were completed and transcribed.

Results:

A total of 8 mothers completed the telephone survey. Key themes from this study include parents experiencing increased stress due to the restricted visitation policies, limited opportunities to care for their infant, lack of support, and inconsistent communication regarding their infant status and COVID-19 protocols.

Implications for Practice:

Suggestions provided to enhance NICU services during the pandemic include increasing parental engagement opportunities to care for their infant in the NICU, enhanced empathy and compassion from the neonatal team, and open and transparent communication.

Implications for Research:

Further research investigating cultural impact on parents' perspectives, perspectives of fathers, long-term impact of how parents coped after discharge from the NICU, and emotional impact on NICU staff members may be beneficial to aid improvements in NICU service delivery during the ongoing and future pandemic.
MicroRNA-322 inhibition of calcification of arterial smooth muscle cells by regulation of galactosyltransferase 1-associating protein UBE2Q1 and Runx2
Authors: Gao Shanshan , Gao Song , Sun Zhen , Akesson Mikael , Shelat Harnath S. , Geng Yongjian
Published: April 2023

Background and purpose:

Vascular smooth muscle cell (SMC) calcification represents a prominent phenotypic alteration in atherosclerosis. MicroRNA-322 (miR-322) is crucially involved in myogenic stem cell growth and differentiation. The galactosyltransferase 1-associated protein (GTAP) is a ubiquitin-conjugating enzyme E2Q1 (UBE2Q1) that serves as a critical mediator of post-translational regulation of certain cellular enzymes and transcription factors. Runt-related transcription factor 2 (Runx2) plays a critical role in arterial calcification. However, the interplay between miR-322, UBE2Q1, and Runx2 during cardiovascular calcification remain largely unknown. Therefore, the purpose of this study is to delineate the molecular mechanisms by which miR-322 regulates vascular calcification.

Methods:

Here we examined miR-322 expression in murine SMC, and determined whether miR-322 regulates SMC calcification via modulating expression of UBE2Q1 and calcifying proteins. Murine SMC cultures or aortic segments were exposed to inorganic phosphate (Pi) for induction of calcification. Expressions of calcification-related genes in SMC with lentivirus-mediated knockdown of UBE2Q1 were determined with Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Luciferase reporter assay was performed to validate miR-322 target binding and SMC were transfected with anti-miR-322 oligonucleotides to inhibit miR-322 function.

Results:

Aortic rings derived from UBE2Q1−/− mice exhibited much higher calcium content compared to aortic rings from wildtype (WT) animals, following calcification induction. Knockdown of UBE2Q1 by lentiviral short hairpin RNA (shRNA) significantly enhanced the calcium deposition and expression of osteogenic gene Runx2 in SMC. Enhanced UBE2Q1 expression dramatically reduced calcification while promoting expression of contractile proteins SM22α and α-SMA. Treatment with anti-miR-322 diminished the luciferase activity in SMC transfected with the reporter gene driven by the 3′-untranslated region of UBE2Q1 mRNA. Anti-miR-322 treatment also inhibited calcification significantly.

Conclusions:

Our study identified miR-322 regulates vascular calcification by targeting UBE2Q1. The miR-322–dependent regulation of UBE2Q1 and calcification represents a novel regulatory mechanism that controls vascular SMC function during the pathogenesis of vascular calcification.
The role of microbiome analysis in precision medicine and personalized nutrition for improving health outcomes in Africa: a correspondence
Authors: Aderinto Nicholas , Olatunji Gbolahan D.
Published: April 2023

Microbiome analysis has the potential to revolutionize precision medicine and personalized nutrition in Africa by identifying disease-causing organisms, predicting disease risk, and personalizing nutrition. Despite the potential benefits, there are several challenges to implementing microbiome analysis in the region, including a lack of infrastructure and resources, limited access to technology and data, and a lack of awareness and education. This paper reviews the potential of microbiome analysis for improving health outcomes in Africa, discusses the challenges and opportunities for implementation, and explores the future of microbiome analysis in precision medicine and personalized nutrition in the region. The development of partnerships between healthcare providers and technology companies, investment in research and development, and the development of targeted education and outreach programs are crucial for overcoming the challenges of implementing microbiome analysis in Africa and facilitating the development of locally relevant microbiome research.
Coloboma Accompanying Microphthalmos With Orbital Cyst in a Mother and Child
Authors: Ciftci Mukaddes Damla , Demirkilinc Biler Elif , Palamar Melis
Published: April 2023

Microphtalmos with orbital cyst is a rare congenital abnormality of the eye and orbit that is caused by incomplete closure of the embryonic fissure. The cysts project through in a coloboma of the affected eye. It may be sporadic or genetic. Herein, the authors present a 32-year-old mother with unilateral and her 4-month-old daughter with bilateral microphtalmos and accompanying orbital cyst.
A Case of Penile Herpes Zoster
Authors: Aflatooni S. , Ahadiat O.
Published: April 2023

Introduction:

Herpes zoster (HZ) manifests as vesicular lesions typically involving thoracic dermatomes and rarely sacral dermatomes.

Here, we present the case of a 32-year-old immunocompetent man with an atypical presentation of HZ misdiagnosed as herpes simplex virus (HSV).

Case presentation:

A 32-year-old man first presented with an erythematous rash with increasing pain severity on the right side of the glans penis involving the S2–S3 dermatomes. Repeated polymerase chain reaction (PCR) tests yielded negative results for both HZ and HSV. The appearance of vesicular lesions on the penis led to an initial misdiagnosis of HSV, causing a great emotional burden on the patient.

Discussion:

HZ occurs uncommonly in the sacral dermatomes. The clinical manifestations of HSV and HZ are similar and must be distinguished via careful diagnostic approaches using PCR testing. The unique symptoms of HZ are unilateral vesicular lesions and post-herpetic neuralgia.

Conclusion:

Penile HZ should be considered in patients presenting with unilateral, localized vesicular lesions.
Most Frequent Comorbidities in Patients with Lichen Planopilaris: A Cross-Sectional Study
Authors: Gharaei Nejad Kaveh , Ghadarjani Reyhaneh , Eftekhari Hojat , Sheykholeslami Saba
Published: April 2023

Background:

Lichen planopilaris (LPP) is a rare skin disorder, but it is also the most common cause of scarring alopecia in adults. The main cause of this disease is unknown, but it is considered to be related to the immune status of the body. Several comorbidities are reportedly associated with LPP, such as hypertension, depression, thyroiditis, diabetes, and vitiligo.

Objective:

In the present study, we aimed to investigate the frequency of comorbidities in patients with LPP who were referred to Razi Hospital in Rasht, Iran from 2016 to 2019.

Methods:

This cross-sectional study involved 60 patients with cicatricial alopecia patches (scarring and irreversible) and clinical signs and symptoms consistent with active LPP. The patients’ demographic data and clinical characteristics were recorded and analyzed using SPSS Version 21, and the level of statistical significance was set at 0.05.

Results:

The results showed that the most common comorbidities were vitamin D deficiency (24.3%), hypothyroidism (17.6%), anemia (16.2%), asthma and allergy (14.8%), hypertension (13.5%), diabetes (9.5%), and vitiligo (4.5%). There was no statistically significant association of sex, age, or body mass index with LPP according to the presence or absence of underlying disease (P = 0.44, P = 0.108, and P = 0.34, respectively); however, there was a statistically significant difference in the presence of comorbidities according to age (P = 0.018).

Conclusion:

The results illustrated that women with vitamin D deficiency are more prone to LPP than are patients with other pre-existing underlying diseases.
Improved recurrence-free survival in patients with HCC with post-transplant plasma exchange
Authors: Oh Namkee , Rhu Jinsoo , Kim Jong Man , Han Seungwook , Jo Sung Jun , An Sunghyo , Park Sunghae , Yoon Sang Oh , Lim Manuel , Yang Jaehun , Kwon Jieun , Choi Gyu-Seong , Joh Jae-Won
Published: April 2023

Total plasma exchange (TPE) can play a role in cancer treatment by eliminating immune checkpoint inhibitors. This study investigated whether TPE improved oncological outcomes in patients with HCC who underwent ABO-incompatible living donor liver transplantation (LT). The study included 152 patients who underwent ABO-incompatible living donor LT for HCC between 2010 and 2021 at Samsung Medical Center. Overall survival was analyzed using the Kaplan-Meier curve, whereas HCC-specific recurrence-free survival (RFS) was analyzed using the cumulative incidence curve after propensity score matching. Cox regression and competing risks subdistribution hazard models were used to identify the risk factors associated with overall survival and HCC-specific RFS, respectively. The propensity score matching resulted in 54 matched pairs, grouped according to whether they underwent postoperative TPE [post-transplant TPE(+)] or not [post-transplant TPE(−)]. The 5-year HCC-specific RFS cumulative incidence was superior in the post-transplant TPE (+) group [12.5% (95% CI: 3.1%–21.9%)] compared with the post-transplant TPE(−) group [38.1% (95% CI: 24.4%–51.8%), p = 0.005]. In subgroup analysis for patients with microvascular invasion and those beyond the Milan criteria, the post-transplant TPE(+) group showed significantly superior HCC-specific survival. The multivariable analysis also showed that postoperative TPE had a protective effect on HCC-specific RFS (HR = 0.26, 95% CI: 0.10–0.64, p = 0.004) and that the more post-transplant TPE was performed, the better RFS was observed (HR = 0.71, 95% CI: 0.55–0.93, p = 0.012). Post-transplant TPE was found to improve RFS after ABO-incompatible living donor LT for HCC, particularly in advanced cases with microvascular invasion and beyond Milan criteria. These findings suggest that TPE may have a potential role in improving oncological outcomes in patients with HCC undergoing LT.
Long-term Survival, Quality of Life, and Molecular Features of the Patients With Solid Pseudopapillary Neoplasm of the Pancreas
Authors: Liu Qiaofei , Dai Menghua , Guo Junchao , Wu Huanwen , Wang Weibin , Chen Ge , Hu Ya , Han Xianlin , Xu Qiang , Zhang Xiang , Yang Sen , Zhang Yalu , Kleeff Jorg , Liao Quan , Wu Wenming , Liang Zhiyong , Zhang Taiping , Zhao Yupei
Published: April 2023

Objective:

To present comprehensive information on the clinicopathological, molecular, survival characteristics, and quality of life (QOL) after surgery for solid pseudopapillary neoplasm (SPN) of the pancreas in a large cohort after long-term follow-up.

Background:

SPN is a rare tumor with an uncertain malignant potential, and solid information on long-term prognosis and QOL remains limited.

Methods:

All hospitalized patients with SPNs who underwent surgery between 2001 and 2021 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinicopathological characteristics of the patients were retrieved. A cross-sectional telephone questionnaire was administered to inquire about the QOL. Molecular analyses were performed using whole-exome sequencing.

Results:

Exactly 454 patients with SPN were enrolled, of whom 18.5% were males and 81.5% were females. The mean patient age was 31 ± 12 years. In total, 61.3% of the patients had no symptoms. The size of the tumors was 5.38 ± 3.70 cm; 83.4% were solid cystic tumors, and 40.1% had calcifications. The proportions of local resection, distal pancreatectomy with or without splenectomy, and pancreaticoduodenectomy with or without pylorus preservation were 29.7%, 28.9% or 22.9%, and 11% or 6.8%, respectively. Over the years, there has been a significant shift from open to minimally invasive surgery. Among all surgical procedures, pylorus-preserving pancreaticoduodenectomy (PPPD) had the highest incidence of grade 2 to 4 complications (up to 32.3%), compared with 6.7% in distal pancreatectomy (P < 0.001). Regarding histopathology, tissue invasion, perineural invasion, cancerous microvascular emboli, lymph node metastasis, and distant metastasis were present in 16.5%, 2.2%, 0.7%, 2.0%, and 3.1% of patients, respectively. Sixty patients were lost to follow-up. Sixteen of the 390 patients who underwent resection (4.1%) experienced local recurrence or distant metastasis after surgery. In total, 361 patients responded to the telephone survey. Nearly 80% of patients claimed their QOL was not significantly affected after surgery; however, the remaining 20% complained of lower QOL during 3 to 6 years of follow-up after surgery. No clinicopathological factor could reliably predict clinical recurrence or metastasis after resection. A total of 28 driver genes were detected with mutations in at least 2 tumor samples and the top 3 frequently mutated genes were CTNNB1, ATRNL1, and MUC16.

Conclusions:

This study presented the largest cohort of patients with SPN after surgery from a single center and reported the QOL of these patients. SPN is associated with extremely favorable long-term survival, even in patients with metastasis, and most patients have a good QOL after surgery.
Mechanistic basis for oxidative stress protection of the human tRNA ligase complex by the oxidoreductase PYROXD1
Authors: Loeff Luuk , Kroupova Alena , Asanović Igor , Boneberg Franziska , Pfleiderer Moritz , Ferdigg Andrè , Ackle Fabian , Martinez Javier , Jinek Martin
Published: April 2023

RTCB is the catalytic subunit of the metazoan tRNA ligase complex (tRNA-LC) that plays essential roles in tRNA biogenesis and unfolded protein response. The catalytic center of RTCB contains a conserved cysteine that is susceptible to metal ion-induced oxidative inactivation. The flavin-containing oxidoreductase PYROXD1 preserves the activity of mammalian tRNA-LC in a NAD(P)H-dependent manner, but its protective mechanism remains elusive. Here we report a cryo-EM structure of human RTCB in complex with PYROXD1, revealing that PYROXD1 directly interacts with the catalytic center of RTCB through its C-terminal tail. NAD(P)H binding and FAD reduction allosterically control PYROXD1 activity and RTCB recruitment and PYROXD1, while PYROXD1 reoxidation enables timed release of RTCB. PYROXD1 interaction is mutually exclusive with Archease-mediated RTCB guanylylation, and guanylylated RTCB is intrinsically protected from oxidative inactivation. Together, these findings provide a mechanistic framework for the protective function of PYROXD1 that maintains the activity of tRNA-LC under aerobic conditions.
Systematic visualisation of molecular QTLs reveals variant mechanisms at GWAS loci
Authors: Kerimov Nurlan , Tambets Ralf , Hayhurst James D. , Rahu Ida , Kolberg Peep , Raudvere Uku , Kuzmin Ivan , Chowdhary Anshika , Vija Andreas , Teras Hans J. , Kanai Masahiro , Ulirsch Jacob , Ryten Mina , Hardy John , Guelfi Sebastian , Trabzuni Daniah , Kim-Hellmuth Sarah , Rayner Will , Finucane Hilary , Peterson Hedi , Mosaku Abayomi , Parkinson Helen , Alasoo Kaur
Published: April 2023

Splicing quantitative trait loci (QTLs) have been implicated as a common mechanism underlying complex trait associations. However, utilising splicing QTLs in target discovery and prioritisation has been challenging due to extensive data normalisation which often renders the direction of the genetic effect as well as its magnitude difficult to interpret. This is further complicated by the fact that strong expression QTLs often manifest as weak splicing QTLs and vice versa, making it difficult to uniquely identify the underlying molecular mechanism at each locus. We find that these ambiguities can be mitigated by visualising the association between the genotype and average RNA sequencing read coverage in the region. Here, we generate these QTL coverage plots for 1.7 million molecular QTL associations in the eQTL Catalogue identified with five quantification methods. We illustrate the utility of these QTL coverage plots by performing colocalisation between vitamin D levels in the UK Biobank and all molecular QTLs in the eQTL Catalogue. We find that while visually confirmed splicing QTLs explain just 6/53 of the colocalising signals, they are significantly less pleiotropic than eQTLs and identify a prioritised causal gene in 4/6 cases. All our association summary statistics and QTL coverage plots are freely available athttps://www.ebi.ac.uk/eqtl/.
Frugivory and seed predation of fishtail palm (Caryota mitisLour.) on the remote oceanic island of Narcondam, India
Authors: Gopal Abhishek , Ghuman Sartaj , Ramachandran Vivek , Page Navendu , Naniwadekar Rohit
Published: April 2023

Oceanic islands, due to their evolutionary history and isolation, hold a disproportionately high proportion of endemic species. However, their evolutionary history also makes them vulnerable to extinctions, with most known extinctions occurring on islands. Plant-animal interactions are particularly important on islands, as island systems generally have low redundancy and are more vulnerable to disruption either via extinction or by invasive species. Here, we examined the fruit removal and seed predation of a keystone palm,Caryota mitis, on the remote oceanic island of Narcondam. The island endemic Narcondam hornbill (Rhyticeros narcondami), was the sole seed disperser of theCaryota mitis(90 hours; N = 15 trees), indicating a lack of redundancy in seed dispersal of the palm on this island. While the invasive rodent,Rattuscf.tiomanicuswas the sole predator of theCaryota mitisseeds in the forest (N = 15 individual fruiting palms, 416 trap nights). Overall, 17.1% of the seeds placed (N = 375 seeds) were removed. Seeds placed under and away from the canopy, and at different densities (2 plots with 10 seeds each; 1 plot with 5 seeds, respectively), showed similar removal rates. This is indicative of ambient seed predation and the lack of safe sites for the regeneration ofCaryota mitis, with potential deleterious effects on the subsequent stages of the “seed dispersal cycle”. Here, from a data deficient site, we provide baseline information on the plant-frugivore interaction of a keystone palm and the potential impacts by an invasive rodent.