bluuebunny/crossref_metadata_2025 huggingface dataset:
Emission-line velocity, metallicity, and extinction maps of the Large Magellanic Cloud
Authors: Lah Philip , Colless Matthew , D’Eugenio Francesco , Groves Brent , Gelfand Joseph D
Published: March 2024

We measure the properties of optical emission lines in multiple locations across the Large Magellanic Cloud (LMC) using the Australian National University 2.3-m telescope and the Wide-Field Spectrograph (WiFeS). From these measurements, we interpolate maps of the gas-phase metallicity, extinction, Hα radial velocity, and Hα velocity dispersion across the LMC. The LMC metallicity maps show a complex structure that cannot be explained by a simple radial gradient. The bright H ii region 30 Doradus stands out as a region of high extinction. The Hα and H i gas radial velocities are mostly consistent except for a region to the south and east of the LMC centre. The Hα velocity dispersion is almost always higher than the H i velocity dispersion, except in the region that shows the divergence in radial velocity, where the H i velocity dispersion is greater than the Hα velocity dispersion. This suggests that the H i gas is diverging from the stellar radial velocity, perhaps as a result of inflow or outflow of H i gas. The study of dwarf galaxies like the LMC is important as they are the building blocks of larger galaxies like our own Milky Way. The maps provided in this work show details not accessible in the study of more distant dwarf galaxies.
Metal-poor star formation at z > 6 with JWST: new insight into hard radiation fields and nitrogen enrichment on 20 pc scales
Authors: Topping Michael W , Stark Daniel P , Senchyna Peter , Plat Adele , Zitrin Adi , Endsley Ryan , Charlot Stéphane , Furtak Lukas J , Maseda Michael V , Smit Renske , Mainali Ramesh , Chevallard Jacopo , Molyneux Stephen , Rigby Jane R
Published: March 2024

Nearly a decade ago, we began to see indications that reionization-era galaxies power hard radiation fields rarely seen at lower redshift. Most striking were detections of nebular C iv emission in what appeared to be typical low-mass galaxies, requiring an ample supply of 48 eV photons to triply ionize carbon. We have obtained deep JWST/NIRSpec R = 1000 spectroscopy of the two z > 6 C iv-emitting galaxies known prior to JWST. Here, we present a rest-UV to optical spectrum of one of these two systems, the multiply-imaged z = 6.1 lensed galaxy RXCJ2248-ID. NIRCam imaging reveals two compact (<22 pc) clumps separated by 220 pc, with one comprising a dense concentration of massive stars (>10 400 M⊙ yr−1 kpc−2) formed in a recent burst. We stack spectra of 3 images of the galaxy (J = 24.8–25.9), yielding a very deep spectrum providing a high-S/N template of strong emission line sources at z > 6. The spectrum reveals narrow high-ionization lines (He ii, C iv, N iv]) with line ratios consistent with powering by massive stars. The rest-optical spectrum is dominated by very strong emission lines ([O iii] EW = 2800 Å), albeit with weak emission from low-ionization transitions ([O iii]/[O ii] = 184). The electron density is found to be very high (6.4–31.0 × 104 cm−3) based on three UV transitions. The ionized gas is metal poor ($12+\log (\rm O/H)=7.43^{+0.17}_{-0.09}$), yet highly enriched in nitrogen ($\log (\rm N/O)=-0.39^{+0.11}_{-0.10}$). The spectrum appears broadly similar to that of GNz11 at z = 10.6, without showing the same AGN signatures. We suggest that the hard radiation field and rapid nitrogen enrichment may be a short-lived phase that many z > 6 galaxies go through as they undergo strong bursts of star formation. We comment on the potential link of such spectra to globular cluster formation.
Constraining mass transfer models with galactic neutron star–white dwarf binaries as gravitational wave sources
Authors: He Jian-Guo , Shao Yong , Xu Xiao-Jie , Li Xiang-Dong
Published: March 2024

Neutron star–white dwarf (NSWD) binaries are one of the most abundant sources of gravitational waves (GWs) in the Milky Way. These GW sources are the evolutionary products of primordial binaries that experienced many processes of binary interaction. We employ a binary population synthesis method to investigate the properties of Galactic NSWD binaries detectable by the Laser Interferometer Space Antenna (LISA). In this paper, only the NSWD systems with a COWD or ONeWD component are included. We consider various models related to mass-transfer efficiencies during primordial binary evolution, supernova explosion mechanisms at NS formation, common envelope ejection efficiencies, and critical WD masses that determine the stability of mass transfer between WDs and NSs. Based on our calculations, we estimate that tens to hundreds of LISA NSWD binaries exist in the Milky Way. We find that the detection of LISA NSWD binaries is able to provide profound insights into mass-transfer efficiencies during the evolution of primordial binaries and critical WD masses during mass transfer from a WD to an NS.
Cyclic variations of the structure and energetics of solar magnetic fields
Authors: Obridko V N , Shibalova A S , Sokoloff D D
Published: March 2024

The solar cycle is a complex phenomenon, a comprehensive understanding of which requires the study of various tracers. Here, we consider the solar cycle as manifested in the harmonics of the solar large-scale surface magnetic field, including zonal, sectorial, and tesseral harmonics, divided into odd and even relative to the solar equator. In addition to considering the amplitudes of the harmonics, we analyse their contribution to the magnetic energy. It turns out that the relative contribution of different types of harmonics to the magnetic energy is virtually independent of the cycle height. We identify different phases of the activity cycle using harmonics of different symmetries. A possible way to incorporate the obtained result into the solar dynamo theory is proposed.
Obscured star formation in clusters at z = 1.6–2.0: massive galaxy formation and the reversal of the star formation–density relation
Authors: Smail Ian
Published: March 2024

Clusters of galaxies at z $\mathrel {\gtrsim }$ 1 are expected to be increasingly active sites of star formation. To test this, an 850 $\mu$m survey was undertaken of eight clusters at z = 1.6–2.0 using SCUBA-2 on the James Clerk Maxwell Telescope. Mid-infrared properties were used to identify 53 probable counterparts to 45 SCUBA-2 sources with colours that suggested they were cluster members. This uncovered a modest overdensity of 850 $\mu$m sources, with far-infrared luminosities of LIR ≥ 1012 L⊙ (SFR $\mathrel {\gtrsim }$ 100 M⊙ yr−1) and colours consistent with being cluster members, of a factor of 4 ± 1 within the central 1 Mpc radius of the clusters. The submillimetre photometry of these galaxies was used to estimate the total cluster star formation rates. These showed that the mass-normalized rates in the clusters are two orders of magnitude higher than in local systems, evolving as (1 + z)5.5 ± 0.6. This rapid evolution means that the mass-normalized star formation rates in these clusters matched that of average haloes in the field at z ∼ 1.8 ± 0.2 marking the epoch where the local star formation–density relation reverses in massive haloes. The estimated stellar masses of the cluster submillimetre galaxies suggests that their descendants will be amongst the most massive galaxies in z ∼ 0 clusters. This reinforces the suggestion that the majority of the massive early-type galaxy population in z ∼ 0 clusters were likely to have formed at z $\mathrel {\gtrsim }$ 1.5–2 through very active, but dust-obscured, starburst events.
The decline in cellular iron is crucial for differentiation in keratinocytes
Authors: Abe Junya , Aono Yuichi , Hirai Yohei
Published: March 2024

Iron is a vital metal for most biological functions in tissues, and its concentration is exquisitely regulated at the cellular level. During the process of differentiation, keratinocytes in the epidermis undergo a noticeable reduction in iron content. Conversely, psoriatic lesions, characterized by disruptions in epidermal differentiation, frequently reveal an excessive accumulation of iron within keratinocytes that have undergone differentiation. In this study, we clarified the significance of attenuated cellular iron content in the intricate course of epidermal differentiation. We illustrated this phenomenon through the utilization of hinokitiol, an iron chelator derived from the heartwood of Taiwanese hinoki, which forcibly delivers iron into cells independent of the intrinsic iron-regulation systems. While primary cultured keratinocytes readily succumbed to necrotic cell death by this iron chelator, mild administration of the hinokitiol-iron complex modestly disrupts the process of differentiation in these cells. Notably, keratinocyte model cells HaCaT and anaplastic skin rudiments exhibit remarkable resilience against the cytotoxic impact of hinokitiol, and the potent artificial influx of iron explains a suppressive effect selectively on epidermal differentiation. Moreover, the augmentation of iron content induced by the overexpression of divalent metal transporter 1 culminates in the inhibition of differentiation in HaCaT cells. Consequently, the diminution in cellular iron content emerges as an important determinant influencing the trajectory of keratinocyte differentiation.
Blastocrithidia nonstop mitochondrial genome and its expression are remarkably insulated from nuclear codon reassignment
Authors: Afonin Dmitry A , Gerasimov Evgeny S , Škodová-Sveráková Ingrid , Záhonová Kristína , Gahura Ondřej , Albanaz Amanda T S , Myšková Eva , Bykova Anastassia , Paris Zdeněk , Lukeš Julius , Opperdoes Fred R , Horváth Anton , Zimmer Sara L , Yurchenko Vyacheslav
Published: March 2024

The canonical stop codons of the nuclear genome of the trypanosomatid Blastocrithidia nonstop are recoded. Here, we investigated the effect of this recoding on the mitochondrial genome and gene expression. Trypanosomatids possess a single mitochondrion and protein-coding transcripts of this genome require RNA editing in order to generate open reading frames of many transcripts encoded as ‘cryptogenes’. Small RNAs that can number in the hundreds direct editing and produce a mitochondrial transcriptome of unusual complexity. We find B. nonstop to have a typical trypanosomatid mitochondrial genetic code, which presumably requires the mitochondrion to disable utilization of the two nucleus-encoded suppressor tRNAs, which appear to be imported into the organelle. Alterations of the protein factors responsible for mRNA editing were also documented, but they have likely originated from sources other than B. nonstop nuclear genome recoding. The population of guide RNAs directing editing is minimal, yet virtually all genes for the plethora of known editing factors are still present. Most intriguingly, despite lacking complex I cryptogene guide RNAs, these cryptogene transcripts are stochastically edited to high levels.
Determinant of m6A regional preference by transcriptional dynamics
Authors: Wang Yalan , Wang Shen , Meng Zhen , Liu Xiao-Min , Mao Yuanhui
Published: March 2024

N6-Methyladenosine (m6A) is the most abundant chemical modification occurring on eukaryotic mRNAs, and has been reported to be involved in almost all stages of mRNA metabolism. The distribution of m6A sites is notably asymmetric along mRNAs, with a strong preference toward the 3′ terminus of the transcript. How m6A regional preference is shaped remains incompletely understood. In this study, by performing m6A-seq on chromatin-associated RNAs, we found that m6A regional preference arises during transcription. Nucleosome occupancy is remarkedly increased in the region downstream of m6A sites, suggesting an intricate interplay between m6A methylation and nucleosome-mediated transcriptional dynamics. Notably, we found a remarkable slowdown of Pol-II movement around m6A sites. In addition, inhibiting Pol-II movement increases nearby m6A methylation levels. By analyzing massively parallel assays for m6A, we found that RNA secondary structures inhibit m6A methylation. Remarkably, the m6A sites associated with Pol-II pausing tend to be embedded within RNA secondary structures. These results suggest that Pol-II pausing could affect the accessibility of m6A motifs to the methyltransferase complex and subsequent m6A methylation by mediating RNA secondary structure. Overall, our study reveals a crucial role of transcriptional dynamics in the formation of m6A regional preference.
How tool combinations in different pipeline versions affect the outcome in RNA-seq analysis
Authors: Perelo Louisa Wessels , Gabernet Gisela , Straub Daniel , Nahnsen Sven
Published: March 2024

Data analysis tools are continuously changed and improved over time. In order to test how these changes influence the comparability between analyses, the output of different workflow options of the nf-core/rnaseq pipeline were compared. Five different pipeline settings (STAR+Salmon, STAR+RSEM, STAR+featureCounts, HISAT2+featureCounts, pseudoaligner Salmon) were run on three datasets (human, Arabidopsis, zebrafish) containing spike-ins of the External RNA Control Consortium (ERCC). Fold change ratios and differential expression of genes and spike-ins were used for comparative analyses of the different tools and versions settings of the pipeline. An overlap of 85% for differential gene classification between pipelines could be shown. Genes interpreted with a bias were mostly those present at lower concentration. Also, the number of isoforms and exons per gene were determinants. Previous pipeline versions using featureCounts showed a higher sensitivity to detect one-isoform genes like ERCC. To ensure data comparability in long-term analysis series it would be recommendable to either stay with the pipeline version the series was initialized with or to run both versions during a transition time in order to ensure that the target genes are addressed the same way.
The ATIPAN project: a community-based digital health strategy toward UHC
Authors: Zamora Pia Regina Fatima C , Celeste Jimuel , Rivera Roselle Leah , Petrola John Paul , Aguila Raphael Nelo , Ledesma Jake , Ermoso Miles Kaye , de Castro Romulo
Published: March 2024

The ATIPAN Project is a digital strategy aimed toward providing health services to marginalized and vulnerable communities in Western Visayas, Philippines. This paper presents the implementation of its telemedicine component in 10 partner communities, output and potential utilization in realizing Universal Health Care (UHC), and moving-forward strategies for sustainability. It also describes the hindrances and corresponding solutions identified during the 2-year project implementation. While regional in nature, the adoption of the ATIPAN model for the UHC implementation all over the Philippines could ensure health care delivery in marginalized and underserved areas.
Post-acute sequelae of SARS-CoV-2 infection in health care workers from South Africa
Authors: Mbotwe-Sibanda Sthembile , Kwatra Gaurav , Madhi Shabir A , Nunes Marta C
Published: March 2024

Health care workers (HCWs) are primary health providers therefore ensuring their protection and recovery from Covid-19 is of high interest. We investigated post-acute sequelae of SARS-CoV-2 infection (PASC) in HCWs who had previously been infected with SARS-CoV-2. Overall, 68 HCWs were classified as PASC according to duration of persisting symptoms. The 68 HCWs with PASC were split into two groups according to the mean duration of their symptoms, which were (8 PASC) 122 and (60 PASC) 641 days. The frequencies of common symptoms reported by HWCs with PASC were continuous headaches (45), mild cough (41), fatigue (37), myalgia (25) and shortness of breath (14). When using the Medical Research Council (MRC) dyspnoea scale to examine the degree of breathlessness in relations to activity we found that 4 reported having difficulty breathing after strenuous exercise, 19 were identified with shortness of breath when walking fast or when walking up a slight hill, 2 reported walking slower than most people on level or stopping after 15 minutes walking at own pace, 1 reported stopping to breath after walking 91 meters, or after a few minutes on level ground and 1 reported being too breathless to leave the house, or breathless when dressing/undressing. Our results highlight concern for HCWs with long-term persisting symptoms which may negatively impact their health this represents an emerging public health priority. HCWs with prolonged Covid-19 symptoms especially breathing difficulties need better diagnostic tests and treatments.
Schistosoma mansoni infection induces hepatic metallothionein and S100 protein expression alongside metabolic dysfunction in hamsters
Authors: Ghezellou Parviz , von Bülow Verena , Luh David , Badin Elisa , Albuquerque Wendell , Roderfeld Martin , Roeb Elke , Grevelding Christoph G , Spengler Bernhard
Published: March 2024

Schistosomiasis, a widespread neglected tropical disease, presents a complex and multifaceted clinical-pathological profile. Using hamsters as final hosts, we dissected molecular events following Schistosoma mansoni infection in the liver—the organ most severely affected in schistosomiasis patients. Employing tandem mass tag–based proteomics, we studied alterations in the liver proteins in response to various infection modes and genders. We examined livers from female and male hamsters that were: noninfected (control), infected with either unisexual S. mansoni cercariae (single-sex) or both sexes (bisex). The infection induced up-regulation of proteins associated with immune response, cytoskeletal reorganization, and apoptotic signaling. Notably, S. mansoni egg deposition led to the down-regulation of liver factors linked to energy supply and metabolic processes. Gender-specific responses were observed, with male hamsters showing higher susceptibility, supported by more differentially expressed proteins than found in females. Of note, metallothionein-2 and S100a6 proteins exhibited substantial up-regulation in livers of both genders, suggesting their pivotal roles in the liver's injury response. Immunohistochemistry and real-time-qPCR confirmed strong up-regulation of metallothionein-2 expression in the cytoplasm and nucleus upon the infection. Similar findings were seen for S100a6, which localized around granulomas and portal tracts. We also observed perturbations in metabolic pathways, including down-regulation of enzymes involved in xenobiotic biotransformation, cellular energy metabolism, and lipid modulation. Furthermore, lipidomic analyses through liquid chromatography–tandem mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry imaging identified extensive alterations, notably in cardiolipin and triacylglycerols, suggesting specific roles of lipids during pathogenesis. These findings provide unprecedented insights into the hepatic response to S. mansoni infection, shedding light on the complexity of liver pathology in this disease.
Thermodynamic Topology of Black Holes in f(R) Gravity
Authors: Hazarika Bidyut , Phukon Prabwal
Published: March 2024

In this work, we study the thermodynamic topology of a static, a charged static, and a charged rotating black hole in f(R) gravity. For charged static black holes, we work in two different ensembles: the fixed charge (q) ensemble and fixed potential (ϕ) ensemble. For charged rotating black holes, four different types of ensembles are considered: fixed (q, J), fixed (ϕ, J), fixed (q, Ω), and fixed (ϕ, Ω) ensemble, where J and Ω denote the angular momentum and the angular frequency, respectively. Using the generalized off-shell free energy method, where the black holes are treated as topological defects in their thermodynamic spaces, we investigate the local and global topologies of these black holes via the computation of winding numbers at these defects. For the static black hole we work in three models. We find that the topological charge for a static black hole is always −1 regardless of the values of the thermodynamic parameters and the choice of f(R) model. For a charged static black hole, in the fixed charge ensemble, the topological charge is found to be zero. Contrastingly, in the fixed ϕ ensemble, the topological charge is found to be −1. For charged static black holes, in both the ensembles, the topological charge is observed to be independent of the thermodynamic parameters. For charged rotating black holes, in the fixed (q, J) ensemble, the topological charge is found to be 1. In the fixed (ϕ, J) ensemble, we find the topological charge to be 1. In the case of the fixed (q, Ω) ensemble, the topological charge is 1 or 0 depending on the value of the scalar curvature (R). In the fixed (Ω, ϕ) ensemble, the topological charge is −1, 0, or 1 depending on the values of R, Ω, and ϕ. Therefore, we conclude that the thermodynamic topologies of the charged static black hole and charged rotating black hole are influenced by the choice of ensemble. In addition, the thermodynamic topology of the charged rotating black hole also depends on the thermodynamic parameters.
Feeling disadvantaged? Type of employment contract and political attitudes
Authors: Gatskova Kseniia , Pilc Michał , Beręsewicz Maciej
Published: March 2024

We tested the theory of relative deprivation in the context of the Polish labour market during the post-crisis period from 2009 to 2015. This period witnessed the highest incidence of temporary contracts in the European Union, providing novel evidence on the causal relationship between the type of employment contract and political attitudes. Our findings suggest that temporary workers are more supportive of income redistribution but less supportive of democracy. Additionally, a shift from permanent to temporary contracts among prime-aged employees leads to a decrease in their support for democracy. Although this effect is modest in magnitude, the article points to an important mechanism influencing shifts in political attitudes. Our findings suggest that the effect of temporary employment on political attitudes is more pronounced among socio-demographic groups less accustomed to unstable employment.
From couplepause to doublepause: the impact of midlife physical, psychological, and social changes on the sexual life of aging couples
Authors: Giraldi Annamaria , Nappi Rossella E , Palacios Santiago , Reisman Yacov , Jannini Emmanuele A
Published: March 2024

Introduction

Midlife men and women are facing frequent sexual problems that affect not only individuals’ sexual health but also the sexual health of aging couples.

Objectives

To review the main sexual life challenges faced by midlife couples, to present the concepts of couplepause and doublepause as 2 new paradigms to address the sexual health needs of aging couples, and to discuss key aspects in couple-focused care.

Methods

An online meeting attended by 5 European experts in sexual health was carried out in June 2023 to discuss the topic. The conversation centered on their clinical experience and expert opinion. Additionally, the indexed literature was reviewed to endorse and complement the expert opinions obtained in the aforementioned meeting.

Results

Midlife men and women face physical, psychological, and sociocultural changes that affect their sexual activity. These changes may be experienced differently between genders. Both members of a couple may experience age-related changes concurrently or in an unsynchronized manner affecting their sexual health. Communication, sharing expectations, defining sexual dynamics, and couple goals are determinant for the sexual health of a midlife couple. Couplepause and doublepause are 2 new complementary paradigms that effectively address the sexual health needs of aging couples as a unit, considering physical, psychological, cultural, social, and dyadic-related factors. Couple-centered strategies should promote open communication about couple intimacy issues, understanding the diverse expectations according to gender and orientation, communication styles, and goals. The following are identified as crucial aspects to promote couple-focused care: education and training of health care professionals, the provision of information to aging couples, physician involvement in addressing sexual problems, the need for collaboration across medical specialties, and the development of effective tools and strategies.

Conclusions

The sexual problems of aging couples should be managed following couple-centered strategies that effectively address their sexual health needs as a couple.
Lower limb coronal malalignment correction by percutaneous osteotomy and schanz screws fixation
Authors: Emara Khaled Mohamed , Diab Ramy Ahmed , Essa Mohamed N. , Eissa Mohamed , Elshobaky Mahmoud Ahmed , Emara , Ahmed K. , Rashid Kyrillos , Abuelwafa Mahmoud , Gemeah Mostafa
Published: March 2024

Pediatric knee deformities are common, and the classic treatment is corrective osteotomy. The aim of this study to assess the safety and efficacy of percutaneous low-energy osteotomy and casting with shanz screws fixation in treatment of Genu varum in children equal or younger than 7 years. This is a prospective nonrandomized case series study was conducted. A total of 38 patients (total of 60 limbs: 36 varus and 24 valgus) were treated by percutaneous low-energy osteotomy and casting with shanz screws fixation and observed over 2–5 years. Clinical and radiological outcomes were evaluated at the end of follow-up period by standing scanogram which enabled tibiofemoral angles and the mechanical axis to be measured and the rate of complications. There was a statistically significant improvement of the radiographic parameters in the form of tibiofemoral angle and MAD. Clinically, all the cases were completely corrected just one patient (two limbs) complicated by over-correction but statically non-significant and. pin tract infection in shanz screws fixation was noticed in one Patient. Percutaneous low-energy osteotomy and casting with shanz screws fixation is a simple, safe, and effective method in dealing with 7 years and younger children with pathological knee deformities. Level of evidence: Therapeutic level IV.
Intrawound Vancomycin Powder Reduces Delayed Deep Surgical Site Infections Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Authors: Shinohara Kensuke , Newton Peter O. , Kelly Michael P. , Upasani Vidyadhar V. , Bartley Carrie E. , Bryan Tracey P. ,   Harms Study Group
Published: March 2024

Study Design.

Retrospective.

Objective.

Evaluate whether the use of vancomycin powder (VP) placed in the surgical site before wound closure prevents delayed deep surgical site infections (DDI).

Summary of Background Data.

DDI after posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS) patients remains a significant and major complication. The use of VP to prevent acute surgical site infection has been reported, but the impact on DDI is unknown.

Materials and Methods.

AIS patients treated over the past 20 years with PSF or instrumentation from a large multicenter registry were reviewed. Patients were divided into two groups: intraoperative vancomycin powder placed in the wound (VP) or no antibiotics placed in the wound (NVP). DDI was defined as an infection that occurred >90 days after surgery and required surgical intervention in the operating room. Patients who developed a DDI had secondary verification of VP use or not. χ2 and Kaplan-Meier (K-M) survivorship analyses were used to compare demographics and the incident rate of DDI between groups.

Results.

Totally, 4145 cases met the inclusion criteria for this study. A total of 43 DDI cases were identified (1.0%). The incidence of DDI for the VP group was 0.2% (4/2111), and 1.9% (39/2034) in the NVP group (P<0.001). Given the difference in follow-up for the two groups, a cumulative survival and Kaplan-Meier analysis revealed the VP group had significantly better “survival” (no DDI) than the NVP group (P<0.001).

Conclusion.

DDIs are significant adverse events that can greatly complicate patient recovery after PSF for AIS, including rehospitalization. This study found that patients who received VP intraoperatively were 10 times less likely to develop a DDI than those who did not receive VP. Although other advances and changes in surgical techniques may contribute to the significant decrease in infections found in the more recent VP cohort, VP should be considered as a prophylactic measure.

Level of Evidence.

4
The predictive role of N-terminal pro-B-type natriuretic peptide in assessing outcomes for atrial fibrillation patients, with or without heart failure: a comprehensive systematic review and meta-analysis
Authors: Lidvihurin Afina Syarah , Fikri Yusuf Ananda
Published: March 2024

Background and purpose:

Brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are commonly used to predict clinical outcomes in patients with heart failure (HF). The prognostic role of BNP/NT-proBNP in patients with atrial fibrillation (AF) and comorbid HF is controversial. The current study aimed to understand the clinical importance of BNP/NT-proBNP measurement in predicting the outcomes of AF patients regardless of HF status.

Methods:

This is a systematic review and meta-analysis. A comprehensive literature search was conducted using PubMed, EBSCOHost, Cochrane, ScienceDirect, and ClinicalKey. Studies that reported all-cause mortality, stroke/systemic embolic events (SEE)/thromboembolic events (TE), major adverse cardiovascular events (MACE), and major bleeding were included in this study. All-cause mortality was the primary outcome. Studies that reported BNP data but not NT-proBNP were also included. BNP/NT-proBNP is categorized as high and low level based on the highest and lowest groups compared in the included studies.

Results:

Sixteen studies (n = 45,400) were included in data synthesis: six were post hoc analysis of randomized controlled trials and the remaining were prospective cohort studies. The included studies were published between 2011 and 2022. The follow-up duration ranged from 1.0 to 5.2 years. High level of BNP/NT-proBNP was associated with a significantly increased risk of all-cause mortality (pooled hazard ratio [HR]: 2.26, 95% confidence interval [95% CI]: 1.98–2.56), stroke/SEE/TE (pooled HR: 2.45, 95% CI: 2.07–2.90), and MACE (pooled HR: 2.38, 95% CI: 1.90–2.99) in patients with AF; the pooled HR of major bleeding was 1.17 (95% CI: 1.01–1.36). Sensitivity analysis in patients with AF and HF produced similar results.

Conclusions:

BNP and NT-proBNP are strong predictors of clinical outcomes in patients with AF regardless of HF.
Guideline-directed medical therapy in chemotherapy-induced cardiotoxicity and heart failure: current perspectives and practices
Authors: Cheang Iokfai , Chen Ziqi , Yao Wenming , Zhang Haifeng , Li Xinli
Published: March 2024

Chemotherapy-induced cardiotoxicity and heart failure have become significant concerns in cancer treatment. Advancements in cancer therapies have increased survival rates, with consequent increase in the prevalence of chemotherapy-induced cardiotoxicity and subsequent heart failure. Guideline-directed medical therapy (GDMT) has emerged as a crucial approach for managing these conditions. GDMT encompasses evidence-based medications and interventions backed by clinical guidelines that aim to optimize the treatment and outcomes of heart failure. This review critically summarizes the existing evidence on the roles of GDMT in the management and prevention of chemotherapy-induced cardiotoxicity and heart failure.
Neurodevelopmental Disorders Including Autism Spectrum Disorder and Intellectual Disability as a Risk Factor for Delayed Diagnosis of Catatonia
Authors: Zappia Katherine J. , Shillington Amelle , Fosdick Cara , Erickson Craig A. , Lamy Martine , Dominick Kelli C.
Published: March 2024

Objective:

Catatonia is a distinct and severe medical syndrome comprising motor, somatic, and psychiatric symptoms that is reported in upwards of 17% of young patients with autism spectrum disorders. Clinical experience indicates catatonia is often under-recognized in this clinical population. Here we characterize the clinical presentation of catatonia in patients with and without neurodevelopmental disorders (NDDs) including autism, including the time from symptom onset to diagnosis of catatonia.

Method:

Retrospective chart review of electronic medical records at a large, academic pediatric medical center identified 113 pediatric and young adult patients with a charted history of catatonia, as identified by an encounter diagnosis or problem list entry between September 2017 and September 2021. Workup, treatments, and diagnoses (psychiatric, neurodevelopmental, and genetic) were identified.

Results:

We observed a clear and substantial delay in identification of catatonia in those with NDDs (diagnosis after 330 days for those without psychosis) compared with neurotypical patients (∼16 days). Psychiatry involvement was associated with shorter delays.

Conclusion:

Intellectual disability and autism are risk factors for significantly delayed diagnosis of catatonia. It is unknown whether delayed diagnosis contributes to the difficulty in treating catatonia in this patient population or whether the treatment difficulties relate instead to differential and ongoing biological mechanisms and underlying encephalopathy. Overall, these findings highlight the importance of increased recognition of catatonia symptoms in patients with NDDs and suggest early referral to psychiatric specialists may shorten the delay to diagnosis.
Neuronal nicotinic acetylcholine receptor of the central amygdala modulates the ethanol-induced tolerance to anxiolysis and withdrawal-induced anxiety in male rats
Authors: Duratkar Antariksha , Patel Richa , Jain Nishant Sudhir
Published: March 2024

The nicotine acetylcholinergic receptor (nAchR) in the central nucleus of the amygdala (CeA) is known to modulate anxiety traits as well as ethanol-induced behavioral effects. Therefore, the present study investigated the role of CeA nAChR in the tolerance to ethanol anxiolysis and withdrawal-induced anxiety-related effects in rats on elevated plus maze (EPM). To develop ethanol dependence, rats were given free access to an ethanol-containing liquid diet for 10 days. To assess the development of tolerance, separate groups of rats were challenged with ethanol (2 g/kg, i.p.) on days 1, 3, 5, 7 and 10 during the period of ethanol exposure, followed by an EPM assessment. Moreover, expression of ethanol withdrawal was induced after switching ethanol-dependent rats to a liquid diet on day 11, and withdrawal-induced anxiety-like behavior was noted at different post-withdrawal time points using the EPM test. The ethanol-dependent rats were pretreated with intra-CeA (i.CeA) (bilateral) injections of nicotine (0.25 µg/rat) or mecamylamine (MEC) (5 ng/rat) before the challenge dose of ethanol on subthreshold tolerance on the 5th day or on peak tolerance day, that is, 7th or 10th, and before assessment of postwithdrawal anxiety on the 11th day on EPM. Bilateral i.CeA preadministration of nicotine before the challenge dose of ethanol on days 5, 7 and 10 exhibited enhanced tolerance, while injection of MEC, completely mitigated the tolerance to the ethanol-induced antianxiety effect. On the other hand, ethanol-withdrawn rats pretreated i.CeA with nicotine exacerbated while pretreatment with MEC, alleviated the ethanol withdrawal-induced anxiety on all time points. Thus, the present investigation indicates that stimulation of nAChR in CeA negatively modulates the ethanol-induced chronic behavioral effects on anxiety in rats. It is proposed that nAChR antagonists might be useful in the treatment of alcohol use disorder and ethanol withdrawal-related anxiety-like behavior.
Development of a liver disease–specific large language model chat interface using retrieval-augmented generation
Authors: Ge Jin , Sun Steve , Owens Joseph , Galvez Victor , Gologorskaya Oksana , Lai Jennifer C. , Pletcher Mark J. , Lai Ki
Published: March 2024

Background and Aims:

Large language models (LLMs) have significant capabilities in clinical information processing tasks. Commercially available LLMs, however, are not optimized for clinical uses and are prone to generating hallucinatory information. Retrieval-augmented generation (RAG) is an enterprise architecture that allows the embedding of customized data into LLMs. This approach “specializes” the LLMs and is thought to reduce hallucinations.

Approach and Results

We developed “LiVersa,” a liver disease–specific LLM, by using our institution’s protected health information-complaint text embedding and LLM platform, “Versa.” We conducted RAG on 30 publicly available American Association for the Study of Liver Diseases guidance documents to be incorporated into LiVersa. We evaluated LiVersa’s performance by conducting 2 rounds of testing. First, we compared LiVersa’s outputs versus those of trainees from a previously published knowledge assessment. LiVersa answered all 10 questions correctly. Second, we asked 15 hepatologists to evaluate the outputs of 10 hepatology topic questions generated by LiVersa, OpenAI’s ChatGPT 4, and Meta’s Large Language Model Meta AI 2. LiVersa’s outputs were more accurate but were rated less comprehensive and safe compared to those of ChatGPT 4.

Results:

We evaluated LiVersa’s performance by conducting 2 rounds of testing. First, we compared LiVersa’s outputs versus those of trainees from a previously published knowledge assessment. LiVersa answered all 10 questions correctly. Second, we asked 15 hepatologists to evaluate the outputs of 10 hepatology topic questions generated by LiVersa, OpenAI’s ChatGPT 4, and Meta’s Large Language Model Meta AI 2. LiVersa’s outputs were more accurate but were rated less comprehensive and safe compared to those of ChatGPT 4.

Conclusions:

In this demonstration, we built disease-specific and protected health information-compliant LLMs using RAG. While LiVersa demonstrated higher accuracy in answering questions related to hepatology, there were some deficiencies due to limitations set by the number of documents used for RAG. LiVersa will likely require further refinement before potential live deployment. The LiVersa prototype, however, is a proof of concept for utilizing RAG to customize LLMs for clinical use cases.
Vitrectomy with Subretinal Injection of Recombinant Tissue Plasminogen Activator for Submacular Hemorrhage with or without Vitreous Hemorrhage
Authors: Shi Tingkun , Wen Jing , Xia Honghe , Chen Haoyu
Published: March 2024

Purpose:

To evaluate the outcomes and prognostic factors of pars plana vitrectomy (PPV) combined with subretinal injection of recombinant tissue plasminogen activator (rt-PA) for submacular hemorrhage (SMH) patients with or without vitreous hemorrhage.

Methods:

Sixty-four eyes of 64 patients with SMH patients underwent PPV with subretinal injection of rt-PA. Best-corrected visual acuity (BCVA), SMH displacement, and postoperative complications were analyzed. Predictive factors of the final BCVA were determined using multivariant linear regression.

Results:

There were 26 eyes with VH and 38 without VH BCVA significantly improved in both VH group (from 2.27±0.40 to 1.25±0.70 LogMAR) and non-VH group (from 1.76±0.55 to 0.85±0.65 LogMAR). Completely displacement of SMHs was observed in 47 (73.43%) eyes. Postoperative complications included recurrent SMH (4.69%), recurrent vitreous hemorrhage (10.94%), rhegmatogenous retinal detachment (3.13%), and epiretinal membrane (4.68%). Treatment-naive condition, early surgery, and younger age were significantly associated with better final BCVA (B =0.502, 0.303, and 0.021, respectively, with all p <0.05).

Conclusion:

PPV combined with subretinal rt-PA injection is an effective treatment for SMH patients with and without VH.
Mound-like Epiretinal Material: Its Short-term Changes and Association with Posterior Vitreous Detachment
Authors: Tetsumura Issei , Aoki Shuichiro , Inoue Tatsuya , Kitamoto Kohdai , Arai Takahiro , Azuma Keiko , Obata Ryo
Published: March 2024

Purpose:

To describe clinical characteristics of a retinal finding termed mound-like epiretinal material (MOLEM), and distinguish it from epiretinal proliferation, a similar epiretinal finding previously described in various pathologies.

Methods:

Five eyes from five patients were retrospectively identified from medical records. Clinical findings and images, including fundus photographs and optical coherence tomography (OCT), were reviewed.

Results:

All eyes displayed mound-like material with uniform and low-to-moderate reflectivity on an otherwise intact retinal surface detected on OCT. No eyes presented with concurrent pathology typically observed in cases of epiretinal proliferation, such as lamellar/full-thickness macular hole, epiretinal membrane, vitreomacular traction, or uveitis. Two eyes exhibited central serous chorioretinopathy, but there was no association of MOLEM with serous retinal detachment. In three out of five eyes, MOLEM appeared simultaneously with posterior vitreous detachment (PVD). Some lesions underwent irregular transformations over months and occasionally disappeared. While all cases were monitored without intervention, no visual decline or complications attributed to MOLEM were detected.

Conclusion:

MOLEM represents a novel clinical finding, characterized by transient morphological changes without symptoms and potential association with PVD. It may occur in eyes lacking macular diseases linked with epiretinal proliferation, a similar yet distinct lesion. The incidence, etiology, and clinical significance of MOLEM warrant further investigation by accumulating comparable cases, although the lesion appears benign and self-limiting.
Hantavirus Pulmonary Syndrome in an Adolescent from North Dakota
Authors: Hall Ashton D. , Fayad Danielle , Staat Mary A.
Published: March 2024

Hantavirus pulmonary syndrome remains an uncommon yet emerging viral zoonosis that causes respiratory failure and hemodynamic instability in children and adolescents. Due to its acutely progressive course and high mortality rate, clinicians treating hantavirus pulmonary syndrome should understand its epidemiologic risk factors, clinical syndrome and radiographic findings. We present a case of hantavirus pulmonary syndrome in a 14-year-old female from North Dakota who survived the infection without sequelae.
“I wish I knew then what I know now” — pain science education concepts important for female persistent pelvic pain: a reflexive thematic analysis
Authors: Mardon Amelia K. , Chalmers K. Jane , Heathcote Lauren C. , Curtis Lee-Anne , Freedman Lesley , Malani Rinkle , Parker Romy , Neumann Patricia B. , Moseley G. Lorimer , Leake Hayley B.
Published: March 2024

Pain science education (PSE) provides people with an understanding of “how pain works” grounded in the biopsychosocial model of pain; it has been demonstrated to improve outcomes in musculoskeletal pain conditions. Preliminary evidence suggests PSE may be effective for female individuals with persistent pelvic pain, but how the content of PSE needs to be modified for this group remains to be determined. A reflexive thematic analysis of qualitative data was performed to identify PSE concepts that female individuals with persistent pelvic pain consider important and why. Twenty individual, semistructured interviews were conducted with adult females who had engaged with PSE and had self-identified as having “improved” pelvic pain. Most participants had been diagnosed with endometriosis (n = 16). Four themes were generated capturing PSE concepts considered important by female individuals with “improved” pelvic pain: (1) “A sensitised nervous system leads to overprotective pain” validated their pelvic pain as being real; (2) “Pain does not have to mean the body is damaged (although sometimes it does)” provided reassurance that pelvic pain does not mean their condition is worsening; (3) “How I think, feel, and ‘see’ my pain can make it worse” enabled participants to find optimal ways to manage their pain; and (4) “I can change my pain… slowly” provided hope that pelvic pain can improve and empowered them to pursue pain improvement as a viable goal. This study generated 4 PSE learning concepts that were important to female individuals with improved pelvic pain and may be incorporated into PSE curricula for female individuals with pelvic pain.
The ketogenic diet mitigates opioid–induced hyperalgesia by restoring short–chain fatty acids–producing bacteria in the gut
Authors: Crawford Joshua , Liu Sufang , Tao Ran , Kramer Phillip , Bender Steven , Tao Feng
Published: March 2024

Opioids are commonly prescribed to patients with chronic pain. Chronic opioid usage comes with a slew of serious side effects, including opioid-induced hyperalgesia (OIH). The patients with long-term opioid treatment experience paradoxical increases in nociceptive hypersensitivity, namely, OIH. Currently, treatment options for OIH are extremely lacking. In this study, we show that the ketogenic diet recovers the abnormal pain behavior caused by chronic morphine treatment in male mice, and we further show that the therapeutic effect of the ketogenic diet is mediated through gut microbiome. Our 16S rRNA sequencing demonstrates that chronic morphine treatment causes changes in mouse gut microbiota, specifically a decrease in short-chain fatty acids–producing bacteria, and the sequencing data also show that the ketogenic diet rescues those bacteria in the mouse gut. More importantly, we show that supplementation with short-chain fatty acids (butyrate, propionate, and acetate) can delay the onset of OIH, indicating that short-chain fatty acids play a direct role in the development of OIH. Our findings suggest that gut microbiome could be targeted to treat OIH, and the ketogenic diet can be used as a complementary approach for pain relief in patients with chronic opioid treatment. We only used male mice in this study, and thus, our findings cannot be generalized to both sexes.
Validation of a Novel Neurologic Assessment Test for Healthcare Staff
Authors: Doyle Brittany R. , von Gaudecker Jane R. , Techan Asmiet K. , Nairon Emerson B. , Olson DaiWai M.
Published: March 2024

BACKGROUND:To measure the effectiveness of an educational intervention, it is essential to develop high-quality, validated tools to assess a change in knowledge or skills after an intervention. An identified gap within the field of neurology is the lack of a universal test to examine knowledge of neurological assessment.METHODS:This instrument development study was designed to determine whether neuroscience knowledge as demonstrated in a Neurologic Assessment Test (NAT) was normally distributed across healthcare professionals who treat patients with neurologic illness. The variables of time, knowledge, accuracy, and confidence were individually explored and analyzed in SAS.RESULTS:The mean (standard deviation) time spent by 135 participants to complete the NAT was 12.9 (3.2) minutes. The mean knowledge score was 39.5 (18.2), mean accuracy was 46.0 (15.7), and mean confidence was 84.4 (24.4). Despite comparatively small standard deviations, Shapiro-Wilk scores indicate that the time spent, knowledge, accuracy, and confidence are nonnormally distributed (P< .0001). The Cronbachαwas 0.7816 considering all 3 measures (knowledge, accuracy, and confidence); this improved to anαof 0.8943 when only knowledge and accuracy were included in the model. The amount of time spent was positively associated with higher accuracy (r2= 0.04,P< .05), higher knowledge was positively associated with higher accuracy (r2= 0.6543,P< .0001), and higher knowledge was positively associated with higher confidence (r2= 0.4348,P< .0001).CONCLUSION:The scores for knowledge, confidence, and accuracy each had a slightly skewed distribution around a point estimate with a standard deviation smaller than the mean. This suggests initial content validity in the NAT. There is adequate initial construct validity to support using the NAT as an outcome measure for projects that measure change in knowledge. Although improvements can be made, the NAT does have adequate construct and content validity for initial use.