bluuebunny/crossref_metadata_2025 huggingface dataset:
The Calar Alto Legacy Integral Field Area survey: extended and remastered data release
Authors: Sánchez S F , Galbany L , Walcher C J , García-Benito R , Barrera-Ballesteros J K
Published: October 2023

This paper describes the extended data release (eDR) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. It comprises science-grade quality data for 895 galaxies obtained with the Potsdam Multi Aperture Spectograph/PPak instrument at the 3.5-m telescope at the Calar Alto Observatory along the last 12 yr, using the V500 setup [3700–7500 Å, 6 Å/full-width at half-maximum (FWHM)] and the CALIFA observing strategy. It includes galaxies of any morphological type, star formation stage, a wide range of stellar masses (∼107–1012 M⊙), at an average redshift of ∼0.015 (90 per cent within 0.005 < z < 0.05). Primarily selected based on the projected size and apparent magnitude, we demonstrate that it can be volume corrected resulting in a statistically limited but representative sample of the population of galaxies in the nearby Universe. All the data were homogeneous re-reduced, introducing a set of modifications to the previous reduction. The most relevant is the development and implementation of a new cube-reconstruction algorithm that provides with an (almost) seeing-limited spatial resolution (FWHMPSF ∼ 1.0 arcsec). To illustrate the usability and quality of the data, we extracted two aperture spectra for each galaxy (central 1.5 arcsec and fully integrated), and analyse them using pyFIT3D. We obtain a set of observational and physical properties of both the stellar populations and the ionized gas, that have been compared for the two apertures, exploring their distributions as a function of the stellar masses and morphologies of the galaxies, comparing with recent results in the literature.
TCP J18224935-2408280: a symbiotic star identified during outburst
Authors: Sonith L S , Kamath U S
Published: October 2023

TCP J18224935-2408280 was reported to be in outburst on 2021 May 19. Follow-up spectroscopic observations confirmed that the system was a symbiotic star. We present optical spectra obtained from the Himalayan Chandra Telescope during 2021–22. The early spectra were dominated by Balmer lines, He i lines and high ionization lines such as He ii. In the later observations, Raman scattered O vi was also identified. Outburst in the system started as a disc instability, and later the signature of enhanced shell burning and expansion of photospheric radius of the white dwarf was identified. Hence we suggest this outburst is of combination nova type. The post-outburst temperature of the hot component remains above 1.5 × 105 K indicating a stable shell burning in the system for a prolonged time after the outburst. Based on our analysis of archival multiband photometric data, we find that the system contains a cool giant of M1-2 III spectral type with a temperature of ∼3600 K and a radius of ∼69 R⊙. The pre- and post-outburst light curve shows a periodicity of 631.25 ± 2.93 d; we consider this as the orbital period.
HIV-PULSE: a long-read sequencing assay for high-throughput near full-length HIV-1 proviral genome characterization
Authors: Lambrechts Laurens , Bonine Noah , Verstraeten Rita , Pardons Marion , Noppe Ytse , Rutsaert Sofie , Van Nieuwerburgh Filip , Van Criekinge Wim , Cole Basiel , Vandekerckhove Linos
Published: October 2023

A deep understanding of the composition of the HIV-1 reservoir is necessary for the development of targeted therapies and the evaluation of curative efforts. However, current near full-length (NFL) HIV-1 proviral genome sequencing assays are based on labor-intensive and costly principles of repeated PCRs at limiting dilution, restricting their scalability. To address this, we developed a high-throughput, long-read sequencing assay called HIV-PULSE (HIV Proviral UMI-mediated Long-read Sequencing). This assay uses unique molecular identifiers (UMIs) to tag individual HIV-1 genomes, allowing for the omission of the limiting dilution step and enabling long-range PCR amplification of many NFL genomes in a single PCR reaction, while simultaneously overcoming poor single-read accuracy. We optimized the assay using HIV-infected cell lines and then applied it to blood samples from 18 individuals living with HIV on antiretroviral therapy, yielding a total of 1308 distinct HIV-1 genomes. Benchmarking against the widely applied Full-Length Individual Proviral Sequencing assay revealed similar sensitivity (11 vs 18%) and overall good concordance, although at a significantly higher throughput. In conclusion, HIV-PULSE is a cost-efficient and scalable assay that allows for the characterization of the HIV-1 proviral landscape, making it an attractive method to study the HIV-1 reservoir composition and dynamics.
Atomistic structure of the SARS-CoV-2 pseudoknot in solution from SAXS-driven molecular dynamics
Authors: He Weiwei , San Emeterio Josue , Woodside Michael T , Kirmizialtin Serdal , Pollack Lois
Published: October 2023

SARS-CoV-2 depends on −1 programmed ribosomal frameshifting (−1 PRF) to express proteins essential for its replication. The RNA pseudoknot stimulating −1 PRF is thus an attractive drug target. However, the structural models of this pseudoknot obtained from cryo-EM and crystallography differ in some important features, leaving the pseudoknot structure unclear. We measured the solution structure of the pseudoknot using small-angle X-ray scattering (SAXS). The measured profile did not agree with profiles computed from the previously solved structures. Beginning with each of these solved structures, we used the SAXS data to direct all atom molecular dynamics (MD) simulations to improve the agreement in profiles. In all cases, this refinement resulted in a bent conformation that more closely resembled the cryo-EM structures than the crystal structure. Applying the same approach to a point mutant abolishing −1 PRF revealed a notably more bent structure with reoriented helices. This work clarifies the dynamic structures of the SARS-CoV-2 pseudoknot in solution.
A sensor complements the steric gate when DNA polymerase ϵ discriminates ribonucleotides
Authors: Parkash Vimal , Kulkarni Yashraj , Bylund Göran O , Osterman Pia , Kamerlin Shina Caroline Lynn , Johansson Erik
Published: October 2023

The cellular imbalance between high concentrations of ribonucleotides (NTPs) and low concentrations of deoxyribonucleotides (dNTPs), is challenging for DNA polymerases when building DNA from dNTPs. It is currently believed that DNA polymerases discriminate against NTPs through a steric gate model involving a clash between a tyrosine and the 2′-hydroxyl of the ribonucleotide in the polymerase active site in B-family DNA polymerases. With the help of crystal structures of a B-family polymerase with a UTP or CTP in the active site, molecular dynamics simulations, biochemical assays and yeast genetics, we have identified a mechanism by which the finger domain of the polymerase sense NTPs in the polymerase active site. In contrast to the previously proposed polar filter, our experiments suggest that the amino acid residue in the finger domain senses ribonucleotides by steric hindrance. Furthermore, our results demonstrate that the steric gate in the palm domain and the sensor in the finger domain are both important when discriminating NTPs. Structural comparisons reveal that the sensor residue is conserved among B-family polymerases and we hypothesize that a sensor in the finger domain should be considered in all types of DNA polymerases.
Different elongation factors distinctly modulate RNA polymerase II transcription in Arabidopsis
Authors: Obermeyer Simon , Schrettenbrunner Lukas , Stöckl Richard , Schwartz Uwe , Grasser Klaus D
Published: October 2023

Various transcript elongation factors (TEFs) including modulators of RNA polymerase II (RNAPII) activity and histone chaperones tune the efficiency of transcription in the chromatin context. TEFs are involved in establishing gene expression patterns during growth and development in Arabidopsis, while little is known about the genomic distribution of the TEFs and the way they facilitate transcription. We have mapped the genome-wide occupancy of the elongation factors SPT4–SPT5, PAF1C and FACT, relative to that of elongating RNAPII phosphorylated at residues S2/S5 within the carboxyterminal domain. The distribution of SPT4–SPT5 along transcribed regions closely resembles that of RNAPII-S2P, while the occupancy of FACT and PAF1C is rather related to that of RNAPII-S5P. Under transcriptionally challenging heat stress conditions, mutant plants lacking the corresponding TEFs are differentially impaired in transcript synthesis. Strikingly, in plants deficient in PAF1C, defects in transcription across intron/exon borders are observed that are cumulative along transcribed regions. Upstream of transcriptional start sites, the presence of FACT correlates with nucleosomal occupancy. Under stress conditions FACT is particularly required for transcriptional upregulation and to promote RNAPII transcription through +1 nucleosomes. Thus, Arabidopsis TEFs are differently distributed along transcribed regions, and are distinctly required during transcript elongation especially upon transcriptional reprogramming.
Circulating alternative pathway complement cleavage factor Bb is associated with vascular lesions and outcomes in IgA nephropathy
Authors: Ștefan Gabriel , Jullien Perrine , Masson Ingrid , Alamartine Eric , Mariat Christophe , Maillard Nicolas
Published: October 2023

Background

Complement alternative pathway (AP) activation is linked to immunoglobulin A nephropathy (IgAN) prognosis severity, but Bb fragment's role is unclear. We examined the relationship between serum Bb fragment concentration at IgAN diagnosis and disease activity and outcomes.

Methods

This retrospective study included 125 biopsy-proven IgAN patients [age 39.9 years, 75% male, estimated glomerular filtration rate (eGFR) 82 ml/min, proteinuria 0.5 g/day] enrolled from 1984 to 2010 and followed for a minimum of 18 months. Monitoring continued until the last follow-up, end-stage kidney disease (ESKD) or death. Serum Bb fragment was measured using an enzyme-linked immunosorbent assay at diagnosis. Oxford classification and global optical score (GOS) were utilized for pathology assessment.

Results

Patients were followed for a median of 16 years; 42% developed chronic kidney disease stage ≥3, 19% reached ESKD and 9% died. Serum Bb fragment concentration negatively correlated with eGFR values at the last follow-up and positively with vascular and tubular histopathological indices. In univariate Cox regression analyses, higher Bb fragment concentration was associated with ESKD alongside older age, increased body mass index, arterial hypertension, lower eGFR, higher proteinuria, E1, S1, T1–2, GOS and corticotherapy. Patients with Bb levels ≥14.3 μg/ml had shorter mean kidney survival time (19.5 versus 22.7 years, P = .07); after adjusting for progression risk factors, the association persisted [hazard ratio 4.76 (95% confidence interval 1.56–14.43)].

Conclusions

Serum Bb fragment concentration at diagnosis may predict long-term IgAN outcomes, potentially due to AP activation at the endothelial surface. Further research is needed to confirm these results and evaluate Bb fragment's role in IgAN management.
The plethora of immunomodulatory drugs: opportunities for immune-mediated kidney diseases
Authors: Odler Balazs , Tieu Johanna , Artinger Katharina , Chen-Xu Michael , Arnaud Laurent , Kitching Richard A , Terrier Benjamin , Thiel Jens , Cid Maria C , Rosenkranz Alexander R , Kronbichler Andreas , Jayne David R W
Published: October 2023

In recent decades, insights into the molecular pathways involved in disease have revolutionized the treatment of autoimmune diseases. A plethora of targeted therapies have been identified and are at varying stages of clinical development in renal autoimmunity. Some of these agents, such as rituximab or avacopan, have been approved for the treatment of immune-mediated kidney disease, but kidney disease lags behind more common autoimmune disorders in new drug development. Evidence is accumulating as to the importance of adaptive immunity, including abnormalities in T-cell activation and signaling, and aberrant B-cell function. Furthermore, innate immunity, particularly the complement and myeloid systems, as well as pathologic responses in tissue repair and fibrosis, play a key role in disease. Collectively, these mechanistic studies in innate and adaptive immunity have provided new insights into mechanisms of glomerular injury in immune-mediated kidney diseases. In addition, inflammatory pathways common to several autoimmune conditions exist, suggesting that the repurposing of some existing drugs for the treatment of immune-mediated kidney diseases is a logical strategy. This new understanding challenges the clinical investigator to translate new knowledge into novel therapies leading to better disease outcomes. This review highlights promising immunomodulatory therapies tested for immune-mediated kidney diseases as a primary indication, details current clinical trials and discusses pathways that could be targeted in the future.
Road map for, and technical challenges of, carbon-nanotube integrated circuit technology
Authors: Si Jia , Zhang Panpan , Zhang Zhiyong
Published: October 2023

A new targeted observational algorithm was developed to optimize prediction targets across various regions and variables. This approach was utilized to design an optimal ENSO monitoring array in the TPOS 2020 project.
Dissipationless layertronics in axion insulator MnBi2Te4
Authors: Li Shuai , Gong Ming , Cheng Shuguang , Jiang Hua , Xie X C
Published: October 2023

Surface electrons in axion insulators are endowed with a topological layer degree of freedom followed by exotic transport phenomena, e.g., the layer Hall effect. Here, we propose that such a layer degree of freedom can be manipulated in a dissipationless way based on the antiferromagnetic $\rm {MnBi_2Te_4}$ with tailored domain structure. This makes $\rm {MnBi_2Te_4}$ a versatile platform to exploit the ‘layertronics’ to encode, process and store information. Importantly, the layer filter, layer valve and layer reverser devices can be achieved using the layer-locked chiral domain wall modes. The dissipationless nature of the domain wall modes makes the performance of the layertronic devices superior to those in spintronics and valleytronics. Specifically, the layer reverser, a layer version of the Datta–Das transistor, also fills up the blank in designing the valley reverser in valleytronics. Our work sheds light on constructing new generation electronic devices with high performance and low-energy consumption in the framework of layertronics.
Randomized Controlled Trial of Aerobic Exercise for Smoking Cessation Among Individuals With Elevated Depressive Symptoms
Authors: Abrantes Ana M , Browne Julia , Uebelacker Lisa A , Anderson Bradley J , Barter Sarah , Shah Zainab , Kunicki Zachary J , Caviness Celeste , Price Lawrence H , Desaulniers Julie , Brown Richard A
Published: October 2023

Introduction

Adults with depression have higher rates of cigarette smoking and are more likely to relapse than those without depression. Pharmacological, psychological, and combined interventions have largely yielded small improvements in smoking outcomes for adults with depression. Aerobic exercise (AE) may facilitate smoking cessation in this subpopulation.

Methods

This study was a 12-week two-arm randomized controlled trial that evaluated the effect of a moderate-intensity AE program compared to a health education contact (HEC) control on smoking cessation in adults with elevated depressive symptoms (mild to severe). Participants (n = 231) were randomized to AE or HEC and received smoking cessation treatment (telephone counseling and nicotine replacement therapy). Primary (biologically confirmed 7-day point prevalence abstinence) and secondary (depressive symptoms, objective and self-reported physical activity, and cardiorespiratory fitness) outcomes were assessed at baseline, 3, 6, and 12 months. Data were analyzed with mixed-effects generalized linear models controlling for age, gender, nicotine dependence, history of major depression disorder, and month of follow-up assessment.

Results

There were no significant differences in primary or secondary outcomes between the AE and HEC groups.

Conclusions

The AE program was not superior to HEC in facilitating smoking cessation, increases in physical activity, or improved depressive symptoms. Given evidence for the positive acute effects of exercise on mood and smoking urges, future research should consider testing alternative exercise approaches for aiding smoking cessation beyond structured, AE programs.

Implications

This study found that an adjunctive aerobic exercise (AE) program was not superior to a health education contact control for adults with elevated depressive symptoms, all of whom also received standard smoking cessation treatment. This finding adds to the growing body of literature that structured AE programs for smoking cessation may have limited efficacy for cessation outcomes. Future research is needed to test alternative methods of integrating AE into smoking cessation treatment, such as strategically using exercise to manage cravings and low mood in the moment.
An Extended Calibration of the Olivine–Spinel Aluminum Exchange Thermometer: Application to the Melting Conditions and Mantle Lithologies of Large Igneous Provinces
Authors: Zhang Yishen , Namur Olivier , Li Weiran , Shorttle Oliver , Gazel Esteban , Jennings Eleanor , Thy Peter , Grove Timothy L , Charlier Bernard
Published: October 2023

The application of the olivine–spinel aluminum exchange thermometer to natural samples is limited by the restricted experimental data set on which it was calibrated. Here, we present a new data set of 46 high-temperature crystallization experiments and 21 reanalyzed published experiments, which we used to extend the calibration to higher and lower temperatures. The final calibration data set spans a range of conditions relevant to crustal and upper mantle processes: 1174–1606°C, 0.1–1350 MPa, QFM − 2.5 to QFM + 7.2 (oxygen fugacity, fO2, reported in log units relative to the quartz–fayalite–magnetite buffer, QFM), and 0–7.4 wt % H2Omelt. We propose three new models. The first is thermodynamically self-consistent, based on spinel Fe, Mg, Al, and Cr compositions and Al exchange between olivine and spinel. The second and third are empirical models that consider fewer elemental exchanges: the second uses only Al exchange and spinel compositions, whereas the third considers olivine–spinel Al and Cr exchange. All models include the modest effect of pressure on olivine-spinel equilibrium chemistry, whereas fO2 and water content have negligible effects. In general, as fewer elements are considered in the olivine–spinel exchange, the fit to experimental data worsens. Conversely, the associated decrease in model complexity improves their robustness against systematic errors when applied to natural crystal pairs: the thermodynamic model may underestimate crystallization temperatures in natural samples due to spinel subsolidus re-equilibration, whereas the empirical models (independent of Fe and Mg in spinel) are less sensitive to re-equilibration but yield temperatures with larger uncertainties. We applied a statistical test to select the most appropriate model for application to natural samples. When applied to lavas from mid-ocean ridges, Iceland, Skye, Emeishan, Etendeka, and Tortugal, our new temperature estimates are 30–100°C lower than previously proposed. The lower temperature estimates cause a lower mantle melting temperature and significant impacts on the mantle lithology constraints.
Activity-directed selection of natural variants of a receptor kinase facilitates salt-tolerant rice breeding
Authors: Zhang Li-Qing , Xu Da-Jin , Zhang Nan , Gao Peng , Zhang Jun-Wei , Zhao Jian-Hua , Han Yong-Feng , Chen Ying-Long , Sun Ying , Zhao Ji-Long , Zuo Shi-Min , Zhang Sheng-Wei
Published: October 2023

Reduced the kinase activity of SALT INTOLERANCE 1 in a natural variant is better-suited to maintain the balance between growth and salt tolerance in rice.
Strength in numbers: An isoform variety of homogalacturonan modifying enzymes may contribute to pollen tube fitness
Authors: Kamel Hiba , Geitmann Anja
Published: October 2023

Pectin is a major component of the cell wall in land plants. It plays crucial roles in cell wall assembly, cell growth, shaping, and signaling. The relative abundance of pectin in the cell wall is particularly high in rapidly growing organ regions and cell types. Homogalacturonan (HG), a polymer of 1,4-linked α-D-galacturonic acid, is a major pectin constituent in growing and dividing plant cells. In pollen tubes, an extremely rapidly growing cell type, HG is secreted at and inserted into the apical cell wall and is subject to further modification in muro by HG modifying enzymes (HGMEs). These enzymes, including pectin esterases and depolymerases, have multiple isoforms, some of which are specifically expressed in pollen. Given the importance of pectin chemistry for the fitness of pollen tubes, it is of interest to interrogate the potentially crucial roles these isoforms play in pollen germination and elongation. It is hypothesized that different HGME isoforms, through their action on apoplastic HG, may generate differential methylation and acetylation patterns endowing HG polysaccharides with specific, spatially and temporally varying properties that lead to a fine-tuned pattern of cell wall modification. In addition, these isoforms may be differentially activated and/or inhibited depending on the local conditions that may vary at subcellular resolution. In this Update we review the different HGME isoforms identified in recent years in Arabidopsis thaliana and postulate that the multiplicity of these isoforms may allow for specialized substrate recognition and conditional activation, leading to a sophisticated regulation scheme exemplified in the process that governs the dynamic properties of the cell wall in pollen tube growth.
Elevated risk of multimorbidity post-COVID-19 infection: protective effect of vaccination
Authors: Lai F T T , Liu W , Hu Y , Wei C , Chu R Y K , Lum D H , Leung J C N , Cheng F W T , Chui C S L , Li X , Wan E Y F , Wong C K H , Cheung C L , Chan E W Y , Hung I F N , Wong I C K
Published: October 2023

Background

It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association.

Aim

To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination.

Design

Nested case–control study.

Methods

We conducted a territory-wide nested case–control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020–15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity.

Results

In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI −2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger.

Conclusions

We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.
Endorsing a Biopsychosocial Perspective of Pain in Individuals With Chronic Pain
Authors: Kleinstäuber Maria , Garland Eric L. , Sisco-Taylor Brittany L. , Sanyer Mathias , Corfe-Tan Julia , Barke Antonia
Published: October 2023

Objectives:

Patients’ beliefs about pain play an important role in their readiness to engage with chronic pain self-management. The central aim of this study was to validate a self-report instrument to assess a specific set of pain beliefs, patients’ endorsement of a biopsychosocial model of chronic pain (PEB).

Methods:

Interdisciplinary experts in the field of pain were involved in creating an instrument, the PEB Scale, to operationalize patients’ endorsement of a biopsychosocial model. A sample of 199 patients with chronic pain was recruited to evaluate the factorial structure (principal axis factoring), the internal consistency (Cronbach’s alpha), the convergent and discriminant validity (correlational analyses), incremental validity (multiple, hierarchical regression analyses), and construct validity (differential population analysis) of the instrument.

Results:

The factor analysis resulted in a unidimensional, 11-item instrument that explained 51.2% of the total variance. Cronbach’s alpha (= 0.92) indicated high internal consistency of the created set of pain-related beliefs. Regression analyses demonstrated that PEB is a strong predictor of patients’ engagement with pain self-management (P < 0.001), after controlling for demographic variables, anxiety, depression, and other pain-related beliefs.

Discussion:

Our results show that the PEB Scale is a highly reliable self-report instrument, which has the potential to predict patients’ readiness to adopt pain self-management. Future research should focus on re-validating the scale we developed to operationalize PEB. Moreover, the PEB Scale should be implemented in longitudinal study designs to investigate its ability to predict the transition from acute to chronic pain and patients’ long-term pain management.
Medications for Opioid Use Disorder and Mortality and Hospitalization Among People With Opioid Use-related Infections
Authors: Figgatt Mary C. , Hincapie-Castillo Juan M. , Schranz Asher J. , Dasgupta Nabarun , Edwards Jessie K. , Jackson Bradford E. , Marshall Stephen W. , Golightly Yvonne M.
Published: October 2023

Background:

Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections.

Methods:

An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007–2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan–Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay.

Results:

In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan–Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6).

Conclusion:

In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.
Eyebrow Restoration in Deep Facial Burn: Follicular Unit Extraction Hair Transplantation after Nanofat Graft
Authors: Ali Rama A. , Fayek Mina , Noureldin Marwan , El-Essawy Nadeen M.
Published: October 2023

Background:

Eyebrows play an important role in protecting the eyes, and also transmit facial expression. Restoration of eyebrow loss after deep thermal burns is a challenging task because a scarred recipient area may affect the success rate of the hair transplantation outcome. Trials to improve this outcome via preparation of pretransplantation recipient area are mandatory.

Methodology:

Seventeen patients (20 eyebrows) with partial or total postburn eyebrow loss were recruited. Nanofat injection was done as a preparatory step before hair transplantation. Patients were followed up monthly for 6 months after follicular unit extraction. The outcome was assessed both objectively by phototrichoscopy and patient satisfaction, and by incidence of complications.

Results:

The mean eyebrow density of the recipient side was found to be 88.60 ± 29.96 hair follicle per cm2, compared with 133.95 ± 38.38 on the control side. The mean eyebrow thickness of the recipient side was found to be 0.07 ± 0.01 mm, compared with 0.06 ± 0.01 on the control side, The overall satisfaction was 60% regarding the density, 80% regarding direction, and 65% regarding symmetry. However, when it comes to texture, 45% were satisfied.

Conclusions:

Restoration of eyebrow loss after deep facial burn is a challenging procedure. Improving the recipient area before hair transplantation is recommended to achieve a satisfactory outcome. Waiting until maturation of the scarred tissue of the recipient area and preparation of it with nanofat can achieve a satisfactory outcome.
A Retrospective Review of Arthroscopic Shaver Utilization in Adolescent Gynecomastia
Authors: Belza Caitlyn C. , Blum Jessica D. , Neubauer Daniel , Reid Christopher M. , Ortiz-Pomales Yan T. , Lance Samuel H.
Published: October 2023

Background:

This study compares the arthroscopic shaver and liposuction with other established methods for treatment of adolescent gynecomastia.

Methods:

Surgical management was via four operative techniques: open excision, open excision/liposuction, arthroscopic shaver/liposuction, or open excision and free nipple graft. Data were collected and compared using independent t tests, linear regression models, and one-way analysis of variance.

Results:

Patients were stratified by Rohrich grades I -II (low) (N = 47) or III -IV (high) (N = 13). The groups were similar in age (P = 0.662) with lower BMI in the low-grade group (x̄ = 25.36 ± 2.1) vs. high-grade group (x̄ = 27.62 ± 4.0; P < 0.001). The low-grade group showed no significant difference in operative time across surgical techniques with decreased mean operative time in the high-grade group using the arthroscopic shaver technique (x̄ = 55.8 ± 7.56) compared with open excision (x̄ = 70.83 ± 11.02, P = 0.04), open excision plus liposuction (x̄ = 89.5 ± 24.93, P = 24.93), and open excision plus free nipple graft (x̄ = 81.67 ± 19.11, P = 0.05). There was no significant difference in complication (P = 0.84) or reoperation (P = 0.68) rates across surgical techniques regardless of grade.

Conclusions:

These findings suggest that the arthroscopic shaver is safe and effective for treatment of both low- and high-grade gynecomastia in adolescents. The results yielded a similar incidence of complications and reoperation across surgical techniques, and the arthroscopic shaver approach demonstrated a shorter operative time compared with other techniques for high-grade gynecomastia.
Risk of injuries before and after a diagnosis of cirrhosis: A population-based cohort study
Authors: Shang Ying , Shen Qing , Tapper Elliot B. , Wester Axel , Hagström Hannes
Published: October 2023

Background:

Cirrhosis is often asymptomatic prior to decompensation. Still, cognitive impairment and sarcopenia may be present before decompensation, possibly increasing the risk of injuries. We estimated the risk of injuries during the period shortly before and after cirrhosis diagnosis.

Methods:

All patients (N=59,329) with a diagnosis of cirrhosis from 1997 to 2019 were identified from the Swedish National Patient Register. We used a self-controlled case series design to compare the incidence rates (IR) of injuries during a “diagnostic period” (within 3 months before or after the cirrhosis diagnosis date) to a self-controlled “prediagnostic period” (the same 6 calendar months 3 years before diagnosis), using conditional Poisson regression. Injuries were ascertained from the National Patient Register.

Results:

We identified 23,733 (40.0%) patients with compensated and 35,595 (60.0%) with decompensated cirrhosis. There were 975 injuries (IR 2.8/1000 person-months) during the prediagnostic period, and 3610 injuries (IR 11.6/1000 person-months) identified during the diagnostic period. The IR ratio was 8.1 (95% CI 7.5–8.7) comparing the diagnostic period with the prediagnostic period. For patients with compensated cirrhosis, the risk increment of injuries was highest just before the diagnosis of cirrhosis, whereas the risk increase was highest shortly after the diagnosis for those with decompensation.

Conclusions:

The incidence of injuries increases shortly before and after the diagnosis of cirrhosis. These findings indicate that cirrhosis is frequently diagnosed in conjunction with an injury, and highlight the need for injury prevention after cirrhosis diagnosis, especially in patients with decompensation.
Interference with the HNF4-dependent gene regulatory network diminishes endoplasmic reticulum stress in hepatocytes
Authors: Shah Anit , Huck Ian , Duncan Kaylia , Gansemer Erica R. , Liu Kaihua , Adajar Reed C. , Apte Udayan , Stamnes Mark A. , Rutkowski D. Thomas
Published: October 2023

Background:

In all eukaryotic cell types, the unfolded protein response (UPR) upregulates factors that promote protein folding and misfolded protein clearance to help alleviate endoplasmic reticulum (ER) stress. Yet, ER stress in the liver is uniquely accompanied by the suppression of metabolic genes, the coordination and purpose of which are largely unknown.

Methods:

Here, we combined in silico machine learning, in vivo liver-specific deletion of the master regulator of hepatocyte differentiation HNF4α, and in vitro manipulation of hepatocyte differentiation state to determine how the UPR regulates hepatocyte identity and toward what end.

Results:

Machine learning identified a cluster of correlated genes that were profoundly suppressed by persistent ER stress in the liver. These genes, which encode diverse functions including metabolism, coagulation, drug detoxification, and bile synthesis, are likely targets of the master regulator of hepatocyte differentiation HNF4α. The response of these genes to ER stress was phenocopied by liver-specific deletion of HNF4α. Strikingly, while deletion of HNF4α exacerbated liver injury in response to an ER stress challenge, it also diminished UPR activation and partially preserved ER ultrastructure, suggesting attenuated ER stress. Conversely, pharmacological maintenance of hepatocyte identity in vitro enhanced sensitivity to stress.

Conclusions:

Together, our findings suggest that the UPR regulates hepatocyte identity through HNF4α to protect ER homeostasis even at the expense of liver function.
HBV suppresses macrophage immune responses by impairing the TCA cycle through the induction of CS/PDHC hyperacetylation
Authors: Bei Jiaxin , Chen Ye , Zhang Qianbing , Wang Xiaobin , Lin Liteng , Huang Jingjun , Huang Wensou , Cai Mingyue , Cai Weiguo , Guo Yongjian , Zhu Kangshun
Published: October 2023

Background:

It is now understood that HBV can induce innate and adaptive immune response disorders by affecting immunosuppressive macrophages, resulting in chronic HBV infection. However, the underlying mechanism is not fully understood. Dysregulated protein acetylation can reportedly influence the differentiation and functions of innate immune cells by coordinating metabolic signaling. This study aims to assess whether HBV suppresses macrophage-mediated innate immune responses by affecting protein acetylation and to elucidate the underlying mechanisms of HBV immune escape.

Methods:

We investigated the effect of HBV on the acetylation levels of human THP-1 macrophages and identified potential targets of acetylation that play a role in glucose metabolism. Metabolic and immune phenotypes of macrophages were analyzed using metabolomic and flow cytometry techniques. Western blot, immunoprecipitation, and immunofluorescence were performed to measure the interactions between deacetylase and acetylated targets. Chronic HBV persistent infected mice were established to evaluate the role of activating the tricarboxylic acid (TCA) cycle in macrophages for HBV clearance.

Results:

Citrate synthase/pyruvate dehydrogenase complex hyperacetylation in macrophages after HBV stimulation inhibited their enzymatic activities and was associated with impaired TCA cycle and M2-like polarization. HBV downregulated Sirtuin 3 (SIRT3) expression in macrophages by means of the toll-like receptor 2 (TLR2)-NF-κB- peroxisome proliferatoractivated receptor γ coactivator 1α (PGC-1α) axis, resulting in citrate synthase/pyruvate dehydrogenase complex hyperacetylation. In vivo administration of the TCA cycle agonist dichloroacetate inhibited macrophage M2-like polarization and effectively reduced the number of serum HBV DNA copies.

Conclusions:

HBV-induced citrate synthase/pyruvate dehydrogenase complex hyperacetylation negatively modulates the innate immune response by impairing the TCA cycle of macrophages. This mechanism represents a potential therapeutic target for controlling HBV infection.
A specialized HE testing clinic improves rational decision-making for therapy in cirrhosis
Authors: Nadeem Mahum , Tafader Asiya , Park Dan , Fagan Andrew , Wade James B. , Bajaj Jasmohan S.
Published: October 2023

Background:

Cognitive complaints in cirrhosis are often attributed to HE with reflexive therapy if specialized tests are not performed. The aim was to determine the utility of a specialized HE clinic for management decisions.

Methods:

Cirrhosis patients with cognitive complaints were referred through a dedicated consult pathway to a specialized clinic and followed for 6 months. This clinic included detailed history, medication review, standardized tests [Mini-Mental Status Exam (MMSE), Psychometric HE Score, and others], and obstructive sleep apnea screening. Results were communicated with patients and referring providers. A subset was offered repeat testing.

Results:

A total of 286 patients were tested between 2012 and 2022. Of the 286 patients, 4 patients who showed a Mini-Mental State Exam <25 were referred to neurology. Thirty-nine percent had normal Psychometric HE Score (higher in younger patients, without prior HE, depression, and lower Model for End-Stage Liver Disease-Sodium), while 172 (61%) patients had cognitive impairment. Of the 172 patients, 51 did not want management change, 84 were started on HE therapy, and 37 were considered impaired due to other causes. In 51 without management change, 32 refused lactulose, while the remaining were counseled regarding lactulose titration. Of the 84 patients with HE-therapy initiation, lactulose was initiated in 56 and rifaximin in 28; most therapies continued over 6 months. The ones who were retested improved their Psychometric HE Score. The 37 with other causes (obstructive sleep apnea, mood disorders, substance use, and mild cognitive impairment) led to specialized referrals. No overt HE was found over 6 months in those without HE-related impairment. The clinic was billed for.

Conclusions:

A specialized HE clinic for patients with cirrhosis and cognitive complaints established through a dedicated consult pathway showed that 39% of referred patients had normal cognitive performance, while the results guided management changes, including for HE and other causes in the remaining patients.
Radiofrequency lesion formation prediction with contact force versus local impedance
Authors: Issa Ziad F.
Published: October 2023

Purpose of review

Safe and effective radiofrequency (RF) myocardial ablation requires real-time monitoring of lesion formation. Here, we review conventional and novel approaches proposed to guide titration of RF energy application.

Recent findings

Conventional monitoring modalities, such as ablation electrode temperature, generator impedance, and tissue electrophysiological properties have been of limited value in predicting efficacy and safety of ablation. Therefore, several input-driven indices have been proposed to improve the quality and durability of RF ablation lesion while maintaining safety. These metrics predominantly incorporate RF power output, duration of RF application, and firmness and stability of electrode-tissue contact. More recently, novel catheters have enabled measuring local impedance at the catheter-tissue interface, which has been found valuable for real-time monitoring of RF lesion formation.

It is likely that using the combination of multiple metrics would be required to improve the quality and safety of RF lesions, but further investigation is still required.
An entropy weight method to integrate big omics and mechanistically evaluate DILI
Authors: Jin Yuan , Shou Yingqing , Lei Qinkai , Du Chenlong , Xu Lin , Chen Ningning , Ma Wanli , Zhu Xiaoxiao , Zhou Shuya , Zheng Yuxin , Yu Dianke
Published: October 2023

Background and Aims:

DILI accounts for more than half of acute liver failure cases in the United States and is a major health care issue for the public worldwide. As investigative toxicology is playing an evolving role in the pharmaceutical industry, mechanistic insights into drug hepatotoxicity can facilitate drug development and clinical medication.

Methods:

By integrating multisource datasets including gene expression profiles of rat livers from open TG-GATE database and DrugMatrix, drug labels from FDA Liver Toxicity Knowledge Base, and clinical reports from LiverTox, and with the employment of bioinformatic and computational tools, this study developed an approach to characterize and predict DILI based on the molecular understanding of the processes (toxicity pathways).

Results:

A panel of 11 pathways widely covering biological processes and stress responses was established using a training set of six positive and one negative DILI drugs from open TG-GATEs. An entropy weight method-based model was developed to weight responsive genes within a pathway, and an interpretable machine-learning (ML) model XGBoot-SHAP was trained to rank the importance of pathways to the panel activity. The panel activity was proven to differentiate between injured and noninjured sample points and characterize DILI manifestation using six training drugs. Next, the model was tested using an additional 89 drugs (61 positives + 28 negatives), and a precision of 86% and higher can be achieved.

Conclusions:

This study provides a novel approach to mechanisms-driven prediction modeling, as well as big data integration for insights into pharmacology and other human biology areas.
Keratitis Fugax Hereditaria Associated With a Novel NLRP3 Mutation in a Non-Finnish Patient
Authors: Jatavallabhula Kavya , Onyia Onyinye , Chung Doug D. , Williams Dominic , Wang Kaidi , Aldave Anthony J.
Published: October 2023

Purpose:

The aim of this study was to report a novel heterozygous variant c.1712G>T (p.Gly571Val) in the nucleotide-binding domain, leucine-rich repeat family, pyrin domain–containing 3 gene (NLRP3) in a previously unreported non-Finnish individual with keratitis fugax hereditaria (KFH).

Methods:

Ophthalmologic examination of the proband was performed with slit-lamp biomicroscopy and anterior segment optical coherence tomography. Saliva was collected as a source of DNA, after which targeted exome sequencing of candidate genes was performed using a commercially available panel. Identified presumed pathogenic variants were confirmed by Sanger sequencing.

Results:

Slit-lamp examination of the 52-year-old female proband revealed peripheral arcus-like degeneration and bilateral central corneal opacification, observed on anterior segment optical coherence tomography to involve the anterior half of the corneal stroma. Examination of the proband's parents revealed clear corneas in each eye. Genetic testing of the proband identified the presence of a novel heterozygous NLRP3 missense mutation (c.1712G>T, p.Gly571Val), which was confirmed by Sanger sequencing. This mutation was absent in the proband's parents.

Conclusions:

Although KFH has been reported only in individuals of Finnish descent and only in association with a missense mutation in exon 1 of NLRP3, we report an individual of non-Finnish descent with KFH associated with a novel heterozygous variant in exon 2 of NLRP3. Thus, ophthalmologists should be aware of the ethnic and genetic heterogeneity associated with KFH.
An update on intraocular lens power calculations in eyes with previous laser refractive surgery
Authors: Savage Daniel E. , Pantanelli Seth M.
Published: October 2023

Purpose of review

There is an ever-growing body of research regarding intraocular lens (IOL) power calculations following photorefractive keratectomy (PRK), laser-assisted in-situ keratomileusis (LASIK), and small-incision lenticule extraction (SMILE). This review intends to summarize recent data and offer updated recommendations.

Recent findings

Postmyopic LASIK/PRK eyes have the best refractive outcomes when multiple methods are averaged, or when Barrett True-K is used. Posthyperopic LASIK/PRK eyes also seem to do best when Barrett True-K is used, but with more variable results. With both aforementioned methods, using measured total corneal power incrementally improves results. For post-SMILE eyes, the first nontheoretical data favors raytracing.

Refractive outcomes after cataract surgery in eyes with prior laser refractive surgery are less accurate and more variable compared to virgin eyes. Surgeons may simplify their approach to IOL power calculations in postmyopic and posthyperopic LASIK/PRK by using Barrett True-K, and employing measured total corneal power when available. For post-SMILE eyes, ray tracing seems to work well, but lack of accessibility may hamper its adoption.