bluuebunny/crossref_metadata_2025 huggingface dataset:
Substantial rDNA copy number reductions alter timing of development and produce variable tissue-specific phenotypes in C. elegans
Authors: Morton Elizabeth A , Hall Ashley N , Cuperus Josh T , Queitsch Christine
Published: March 2023

The genes that encode ribosomal RNAs are present in several hundred copies in most eukaryotes. These vast arrays of repetitive ribosomal DNA (rDNA) have been implicated not just in ribosome biogenesis, but also aging, cancer, genome stability, and global gene expression. rDNA copy number is highly variable among and within species; this variability is thought to associate with traits relevant to human health and disease. Here we investigate the phenotypic consequences of multicellular life at the lower bounds of rDNA copy number. We use the model Caenorhabditis elegans, which has previously been found to complete embryogenesis using only maternally provided ribosomes. We find that individuals with rDNA copy number reduced to ∼5% of wild type are capable of further development with variable penetrance. Such individuals are sterile and exhibit severe morphological defects, particularly in post-embryonically dividing tissues such as germline and vulva. Developmental completion and fertility are supported by an rDNA copy number ∼10% of wild type, with substantially delayed development. Worms with rDNA copy number reduced to ∼33% of wild type display a subtle developmental timing defect that was absent in worms with higher copy numbers. Our results support the hypothesis that rDNA requirements vary across tissues and indicate that the minimum rDNA copy number for fertile adulthood is substantially less than the lowest naturally observed total copy number. The phenotype of individuals with severely reduced rDNA copy number is highly variable in penetrance and presentation, highlighting the need for continued investigation into the biological consequences of rDNA copy number variation.
Mid-latitude and equatorial core surface flow variations derived from observatory and satellite magnetic data
Authors: Ropp G , Lesur V
Published: March 2023

A series of models of the Earth magnetic field and core surface flow have been simultaneously and sequentially co-estimated from year 1999 to 2022. The models were derived from magnetic satellite and ground observatory data using a linear Kalman filter approach and prior statistics based on numerical dynamo simulations. The core field and secular variation model components present the same characteristics as the most recent core field models with slightly higher resolution in time. A principal component analysis of the core surface flow series of models shows that the largest flow variations are observed at high latitudes and under the western part of the Pacific Ocean. Filtering out the flow variation periods longer than ∼11.5 yr leads to a filtered azimuthal flow that presents ∼7 yr periodicities with patterns propagating westward by ∼60° longitude per year. These patterns are present mainly at mid- and equatorial latitudes. They are compatible with a perturbation of the main flow made of small columnar flows with rotation axis intersecting the core–mantle boundary between 10° and 15° latitudes, and flow speed of less than 5 km yr–1. Present at all longitudes, these columnar flows are particularly strong under the Pacific Ocean after 2013. They can also be clearly identified under the Atlantic Ocean from 2005 to 2015.
Pepper mild mottle virus coat protein interacts with pepper chloroplast outer envelope membrane protein OMP24 to inhibit antiviral immunity in plants
Authors: Han Kelei , Zheng Hongying , Yan Dankan , Zhou Huijie , Jia Zhaoxing , Zhai Yushan , Wu Jian , Lu Yuwen , Wu Guanwei , Rao Shaofei , Chen Jianping , Peng Jiejun , Qi Rende , Yan Fei
Published: March 2023

Pepper mild mottle virus (PMMoV) is a devastating viral pathogen of pepper (Capsicum annuum) but it is unclear whether and how peppers protect against PMMoV infection. The expression of the chloroplast outer membrane protein 24 (OMP24) of C. annuum was upregulated under PMMoV infection and it interacted with PMMoV coat protein (CP). Silencing of OMP24 in either C. annuum or Nicotiana benthamiana facilitated PMMoV infection, whereas overexpression of N. benthamiana OMP24 in transgenic plants inhibited PMMoV infection. Both C. annuum OMP24 (CaOMP24) and N. benthamiana OMP24 (NbOMP24) localized to the chloroplast and have a moderately hydrophobic transmembrane domain that is necessary for their localization. Overexpression of CaOMP24 induced stromules, perinuclear chloroplast clustering, and accumulation of reactive oxygen species (ROS), the typical defense responses of chloroplasts transferring the retrograde signaling to the nucleus to regulate resistance genes. The expression of PR1 and PR2 was also upregulated significantly in plants overexpressing OMP24. Self-interaction of OMP24 was demonstrated and was required for OMP24-mediated plant defense. Interaction with PMMoV CP interfered with the self-interaction of OMP24 and impaired OMP24-induced stromules, perinuclear chloroplast clustering and ROS accumulation. The results demonstrate the defense function of OMP24 in pepper during viral infection and suggest a possible mechanism by which PMMoV CP modulates the plant defense to facilitate viral infection.
Changes in circulating forms of anti-Muüllerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy
Authors: Peigné M , Simon V , Pigny P , Mimouni N E H , Martin C , Dewailly D , Catteau-Jonard S , Giacobini P
Published: March 2023

STUDY QUESTION

What are the changes in serum concentration of total and cleaved anti-Muüllerian hormone (AMH) molecular forms and of androgens before and throughout pregnancy in women with and without polycystic ovary syndrome (PCOS) in a longitudinal follow-up investigation?

SUMMARY ANSWER

Serum levels of total and cleaved AMH are higher from preconception to the third trimester of pregnancy in women with PCOS as compared to controls, whereas testosterone and androstenedione levels are higher in women with PCOS than in control women before pregnancy and during the second and third trimester of pregnancy.

WHAT IS KNOWN ALREADY

Cross-sectional or partial longitudinal studies have shown higher AMH and androgen levels in pregnant women with PCOS as compared with non-PCOS women. To date, no complete longitudinal dynamic monitoring of the circulating forms of AMH and androgens from pre-conception to the third trimester of pregnancy have compared women with and without PCOS.

STUDY DESIGN, SIZE, DURATION

This systematic prospective quarterly longitudinal monocentric study was a comparative follow-up of 30 women with PCOS and 29 controls before and during pregnancy from April 2019 to July 2022.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Women aged 18–43 years with a pre-conception measurement of AMH were included during the first trimester of a singleton pregnancy. The PCOS group was defined according to the Rotterdam diagnostic criteria. The control group patients included in the study had normal ovarian reserves. Circulating total and cleaved AMH, and serum estradiol, LH, and androgen levels were measured during the first, second, and third trimester of pregnancy in all study participants.

MAIN RESULTS AND THE ROLE OF CHANCE

Before pregnancy, patients with PCOS had higher levels of AMH than controls. The total and cleaved AMH forms were significantly higher in women with PCOS than controls from pre-conception to the third trimester of pregnancy (all P < 0.001). Androgens (total testosterone and androstenedione) were higher in women with PCOS than controls from mid-pregnancy onwards.

LIMITATIONS, REASONS FOR CAUTION

Our control population was a population of infertile women with no ovarian problems but most of them had undergone ART treatments to achieve pregnancy.

WIDER IMPLICATIONS OF THE FINDINGS

These results strengthen the hypothesis that gestational hyperandrogenism as well as exposure to elevated AMH levels in utero could be driving forces predisposing female progeny to develop PCOS.

STUDY FUNDING/COMPETING INTEREST(S)

Funding was provided by INSERM, France (grant number U1172) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, ERC-2016-CoG to P.G. grant agreement n° 725149/REPRODAMH. The authors have nothing to declare.

TRIAL REGISTRATION NUMBER

NCT03483792
Finite element approximation of Hamilton–Jacobi–Bellman equations with nonlinear mixed boundary conditions
Authors: Jaroszkowski Bartosz , Jensen Max
Published: March 2023

We show strong uniform convergence of monotone P1 finite element methods to the viscosity solution of isotropic parabolic Hamilton–Jacobi–Bellman equations with mixed boundary conditions on unstructured meshes and for possibly degenerate diffusions. Boundary operators can generally be discontinuous across face-boundaries and type changes. Robin-type boundary conditions are discretized via a lower Dini derivative. In time, the Bellman equation is approximated through IMEX schemes. Existence and uniqueness of numerical solutions follows through Howard’s algorithm.
Swirling flow analysis of Eyring–Powell fluid between coaxial disks with variable property
Authors: Nadeem Sohail , Ishtiaq Bushra , Akkurt Nevzat , Eldin Sayed M
Published: March 2023

The main objective of this study is to examine an unsteady swirling flow of a non-Newtonian Eyring–Powell fluid between two coaxial disks. The lower and upper disks are considered to rotate with different angular velocities. The three-dimensional axisymmetric flow phenomenon and heat transfer mechanism are observed with the consequences of the magnetic field and variable thermal conductivity of the fluid. The variable thermal conductivity is taken to be dependent on the fluid temperature. The implementation of the Von Karman similarity transformations on the constituting equations of the flow phenomenon yields the dimensionless system of the non-linear equations. An optimal homotopy analysis technique is adopted to obtain analytical solutions for highly non-linear equations. In view of the same and opposite directions of disks rotation, the various aspects of the flow system corresponding to the pertinent parameters are discussed with physical significance. The obtained results indicate that both radial and axial fields are the escalating functions of the Eyring–Powell fluid parameter. Moreover, the heat transfer rate enhances with the improving variable thermal conductivity parameter.
Dimethylation of histone H3 lysine 36 (H3K36me2) as a potential biomarker for glioma diagnosis, grading, and prognosis
Authors: Cong Huayue , Guo Xiaoqiang , Fan Bo , Liu Yingzi , Dong Changzheng , Sui Aixia
Published: March 2023

Abnormal histone methylation plays a key role in glioma development but the clinical value of specific alterations is still unclear. Here, the potential significance of histone H3 lysine 36 dimethylation (H3K36me2) was investigated as a biomarker for glioma. Seventy-three glioma patients were included in the study and the level of H3K36me2 in the tumor tissues was determined by immunohistochemistry. The χ2 test was used to explore the influence of clinical and pathological characteristics on H3K36me2 levels. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). COX regression was used to explore the relationship between H3K36me2 levels and glioma prognosis. The results indicated that the H3K36me2 level increases with glioma grade. The proportion of high H3K36me2 levels was lower in glioma patients under the age of 52 years. H3K36me2 levels were negatively correlated with IDH1 mutation and MGMT promoter methylation, and positively correlated with p53 expression. Thus, high H3K36me2 levels positively correlated with poor prognosis of gliomas. In conclusion, H3K36me2 may be considered as a potential biomarker for glioma diagnosis, grading, and prognosis, but the overall clinical value of H3K36me2 determination deserves further investigation. These results may have important implications for accurate diagnosis and future precision treatment of gliomas.
Why we stopped listening to the other side: how partisan cues in news coverage undermine the deliberative foundations of democracy
Authors: Arendt Florian , Northup Temple , Forrai Michaela , Scheufele Dietram
Published: March 2023

Recent theorizing on deliberative democracy has put political listening at the core of meaningful democratic deliberation. In the present experiment (N = 827), we investigated whether news media can improve diverse political listening in the United States via a reduction in party cue salience. Although Republican (Democratic) participants showed a strong preference for listening to speeches given by Republican (Democratic) politicians when party cues were highly salient, this bias in selective political listening was reduced or even absent when news items provided no or only low-salience cues. Conditional process analysis indicated that (automatically activated) implicit and (overtly expressed) explicit party attitudes mediated this effect. There are important implications: Current journalism practices tend to exacerbate tribal us-vs-them thinking by emphasizing partisan cues, nudging citizens toward not listening to political ideas from the other political camp. A more helpful news-choice architecture tones down partisan language, nudging citizens toward more diverse political listening.
A multimodal turn in Digital Humanities. Using contrastive machine learning models to explore, enrich, and analyze digital visual historical collections
Authors: Smits Thomas , Wevers Melvin
Published: March 2023

Until recently, most research in the Digital Humanities (DH) was monomodal, meaning that the object of analysis was either textual or visual. Seeking to integrate multimodality theory into the DH, this article demonstrates that recently developed multimodal deep learning models, such as Contrastive Language Image Pre-training (CLIP), offer new possibilities to explore and analyze image–text combinations at scale. These models, which are trained on image and text pairs, can be applied to a wide range of text-to-image, image-to-image, and image-to-text prediction tasks. Moreover, multimodal models show high accuracy in zero-shot classification, i.e. predicting unseen categories across heterogeneous datasets. Based on three exploratory case studies, we argue that this zero-shot capability opens up the way for a multimodal turn in DH research. Moreover, multimodal models allow scholars to move past the artificial separation of text and images that was dominant in the field and analyze multimodal meaning at scale. However, we also need to be aware of the specific (historical) bias of multimodal deep learning that stems from biases in the training data used to train these models.
The need for obscured supermassive black hole growth to explain quasar proximity zones in the epoch of reionization
Authors: Satyavolu Sindhu , Kulkarni Girish , Keating Laura C , Haehnelt Martin G
Published: March 2023

Proximity zones of high-redshift quasars are unique probes of supermassive black hole formation, but simultaneously explaining proximity zone sizes and black hole masses has proved to be challenging. We study the robustness of some of the assumptions that are usually made to infer quasar lifetimes from proximity zone sizes. We show that small proximity zones can be readily explained by quasars that vary in brightness with a short duty cycle of fduty ∼ 0.1 and short bright periods of ton ∼ 104 yr, even for long lifetimes. We further show that reconciling this with black hole mass estimates requires the black hole to continue to grow and accrete during its obscured phase. The consequent obscured fractions of ≳ 0.7 or higher are consistent with low-redshift measurements and models of black hole accretion. Such short duty cycles and long obscured phases are also consistent with observations of large proximity zones, thus providing a simple, unified model for proximity zones of all sizes. The large dynamic range of our simulation, and its calibration to the Lyman-α forest, allows us to investigate the influence of the large-scale topology of reionization and the quasar’s host halo mass on proximity zones. We find that incomplete reionization can impede the growth of proximity zones and make them smaller up to 30 per cent, but the quasar host halo mass only affects proximity zones weakly and indirectly. Our work suggests that high-redshift proximity zones can be an effective tool to study quasar variability and black hole growth.
Epigenetic CpG duplex marks probed by an evolved DNA reader via a well-tempered conformational plasticity
Authors: Singh Himanshu , Das Chandan K , Buchmuller Benjamin C , Schäfer Lars V , Summerer Daniel , Linser Rasmus
Published: March 2023

5-methylcytosine (mC) and its TET-oxidized derivatives exist in CpG dyads of mammalian DNA and regulate cell fate, but how their individual combinations in the two strands of a CpG act as distinct regulatory signals is poorly understood. Readers that selectively recognize such novel ‘CpG duplex marks’ could be versatile tools for studying their biological functions, but their design represents an unprecedented selectivity challenge. By mutational studies, NMR relaxation, and MD simulations, we here show that the selectivity of the first designer reader for an oxidized CpG duplex mark hinges on precisely tempered conformational plasticity of the scaffold adopted during directed evolution. Our observations reveal the critical aspect of defined motional features in this novel reader for affinity and specificity in the DNA/protein interaction, providing unexpected prospects for further design progress in this novel area of DNA recognition.
Generating minimum set of gRNA to cover multiple targets in multiple genomes with MINORg
Authors: Lee Rachelle R Q , Cher Wei Yuan , Wang Jinge , Chen Yujie , Chae Eunyoung
Published: March 2023

MINORg is an offline gRNA design tool that generates the smallest possible combination of gRNA capable of covering all desired targets in multiple non-reference genomes. As interest in pangenomic research grows, so does the workload required for large screens in multiple individuals. MINORg aims to lessen this workload by capitalising on sequence homology to favour multi-target gRNA while simultaneously screening multiple genetic backgrounds in order to generate reusable gRNA panels. We demonstrated the practical application of MINORg by knocking out 11 homologous genes tandemly arrayed in a multi-gene cluster in two Arabidopsis thaliana lineages using three gRNA output by MINORg. We also described a new PCR-free modular cloning system for multiplexing gRNA, and used it to knockout three tandemly arrayed genes in another multi-gene cluster with gRNA designed by MINORg. Source code is freely available at https://github.com/rlrq/MINORg.
Widely spaced and divergent inverted repeats become a potent source of chromosomal rearrangements in long single-stranded DNA regions
Authors: Ait Saada Anissia , Guo Wenying , Costa Alex B , Yang Jiaxin , Wang Jianrong , Lobachev Kirill S
Published: March 2023

DNA inverted repeats (IRs) are widespread across many eukaryotic genomes. Their ability to form stable hairpin/cruciform secondary structures is causative in triggering chromosome instability leading to several human diseases. Distance and sequence divergence between IRs are inversely correlated with their ability to induce gross chromosomal rearrangements (GCRs) because of a lesser probability of secondary structure formation and chromosomal breakage. In this study, we demonstrate that structural parameters that normally constrain the instability of IRs are overcome when the repeats interact in single-stranded DNA (ssDNA). We established a system in budding yeast whereby >73 kb of ssDNA can be formed in cdc13-707fs mutants. We found that in ssDNA, 12 bp or 30 kb spaced Alu-IRs show similarly high levels of GCRs, while heterology only beyond 25% suppresses IR-induced instability. Mechanistically, rearrangements arise after cis-interaction of IRs leading to a DNA fold-back and the formation of a dicentric chromosome, which requires Rad52/Rad59 for IR annealing as well as Rad1-Rad10, Slx4, Msh2/Msh3 and Saw1 proteins for nonhomologous tail removal. Importantly, using structural characteristics rendering IRs permissive to DNA fold-back in yeast, we found that ssDNA regions mapped in cancer genomes contain a substantial number of potentially interacting and unstable IRs.
Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects
Authors: Satange Roshan , Chang Chih-Chun , Li Long-Yuan , Lin Sheng-Hao , Neidle Stephen , Hou Ming-Hon
Published: March 2023

Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex–drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.
Nerve pathology is prevented by linker proteins in mouse models forLAMA2-related muscular dystrophy
Authors: Reinhard Judith R , Porrello Emanuela , Lin Shuo , Pelczar Pawel , Previtali Stefano C , Rüegg Markus A
Published: March 2023

LAMA2-related muscular dystrophy (LAMA2 MD or MDC1A) is a devastating congenital muscular dystrophy that is caused by mutations in the LAMA2 gene encoding laminin-α2, the long chain of several heterotrimeric laminins. Laminins are essential components of the extracellular matrix that interface with underlying cells. The pathology of LAMA2 MD patients is dominated by an early-onset, severe muscular dystrophy that ultimately leads to death by respiratory insufficiency. However, pathology in nonmuscle tissues has been described. Prior work in the dyW/dyW mouse model for LAMA2 MD has shown that two linker proteins, mini-agrin and αLNNd, when expressed in skeletal muscle fibers, greatly increase survival from a few months up to more than 2 years. However, the restoration of skeletal muscle function accentuates the pathology in nonmuscle tissue in dyW/dyW mice, first and foremost in the peripheral nerve resulting in paralysis of the hind limbs. We now show that the expression of the two linker proteins in all tissues ameliorates the muscular dystrophy and prevents the appearance of the hind limb paralysis. Importantly, the same ameliorating effect of the linker proteins was seen in dy3K/dy3K mice, which represent the most severe mouse model of LAMA2 MD. In summary, these data show that the two linker proteins can compensate the loss of laminin-α2 in muscle and peripheral nerve, which are the two organs most affected in LAMA2 MD. These results are of key importance for designing appropriate expression constructs for mini-agrin and αLNNd to develop a gene therapy for LAMA2 MD patients.
Feasibility and preliminary efficacy of app-based audio tools to improve sleep health in working adults experiencing poor sleep: a multi-arm randomized pilot trial
Authors: Economides Marcos , Male Rhian , Bolton Heather , Cavanagh Kate
Published: March 2023

Study Objectives

Many adults without a diagnosed sleep disorder report poor sleep. Recently, there has been a dramatic increase in the use of app-based audio tools to aid sleep by the general public, yet there is a paucity of evidence on whether such tools are efficacious. This study evaluated the feasibility and preliminary efficacy of two categories of audio tools, comprising music and narrated stories, featured on the Unmind app.

Methods

We conducted an online, parallel, multi-arm, external pilot randomized controlled trial, with two intervention arms and a waitlist (WL) control group. Participants were working adults who were screened for poor sleep. Feasibility was assessed via objective and self-report measures. Preliminary efficacy was evaluated via self-report measures of sleep disturbance, work productivity, and other mental health outcomes, captured at baseline (t0) and following a 4-week intervention period (t1), and analyzed using mixed effects models with intention-to-treat principles.

Results

Three hundred participants were randomized, and 92% were retained at t1. 90.5% of participants completed at least one intervention session. 82.1% reported being “satisfied” or “very satisfied” with their intervention, and 84.3% rated their intervention as “good” or “excellent.” The between-group Hedges’ g effect size for sleep disturbance was 0.92 [0.63–1.22] and 1.09 [0.80–1.39] for the two interventions compared to the WL group.

Conclusions

Both interventions are feasible and acceptable. Preliminary efficacy findings suggest that audio tools designed to aid sleep could have widespread financial and public health implications, and should be investigated in a definitive trial.

Clinical Trial

International Standard Randomized Controlled Trial Number (ISRCTN), 12614821, http://www.isrctn.com/ISRCTN12614821.
Parties, Voters and Political Change in Early Twentieth-Century Manchester: Reconnecting Politics and Society
Authors: Adams Tony
Published: March 2023

In the wake of the linguistic turn the ‘new political history’ has recognized the importance of both political language and social context. In practice, however, over recent years much political history of the pre-1918 period has become increasingly focused on language and party, relegating society and economy to the margins. This study emphasizes the interconnectedness of party politics and society, arguing that smaller municipal electoral districts offer potential new insights into the impact of religion, class, gender and ethnicity upon both, party policy and practice, and voter behaviour. Parties adapted their campaign strategies and policy stances to reflect their understanding of the social make-up of local electorates. Voter responses to party campaigns could be strongly influenced, but not determined, by individual or group perceptions of social standing. By exploring the connected fortunes of all three major parties new light is shed on the development of local political culture before 1914. The article also assesses the shifting strengths and weaknesses of Conservative, Liberal, and Labour parties, and contributes to historiographical debates on the politics of slum and suburban communities, and the pre-war trajectories of the major parties.
Individual Differences in Pain Catastrophizing and Regional Gray Matter Volume Among Community-dwelling Adults With Chronic Pain
Authors: Liu Shuyang , You BeiBei , Zhang Xin , Shaw Amy , Chen Hong , Jackson Todd
Published: March 2023

Objectives:

Elevations in pain catastrophizing (PC) are associated with more severe pain, emotional distress, and impairment within samples with chronic pain. However, brain structure correlates underlying individual differences in PC are not well understood and predict more severe pain and impairment within samples with chronic pain. This study assessed links between regional gray matter volume (GMV) and individual differences in PC within a large mixed chronic pain sample.

Materials and Methods:

Chinese adult community dwellers with chronic pain of at least 3 months duration (101 women and 59 men) completed self-report measures of background characteristics, pain severity, depression, and a widely validated PC questionnaire as well as a structural magnetic resonance imagining scan featuring voxel-based morphology to assess regional GMV correlates of PC.

Results:

After controlling for demographic correlates of PC, pain severity, and depression, higher PC scores had a significant, unique association with lower GMV levels in the inferior temporal area of the right fusiform gyrus, a region previously implicated in emotion regulation.

Discussion:

GMV deficits, particularly in right temporal-occipital emotion regulation regions, correspond to high levels of PC among individuals with chronic pain.
Is Severe Neck Pain a Contraindication to Performing Laminoplasty in Patients With Cervical Spondylotic Myelopathy?
Authors: Pinter Zachariah W. , Mikula Anthony L. , Reed Ryder , Lakomkin Nikita , Townsley Sarah E. , Wright Breydan , Kazarian Erick , Michalopoulos Giorgos D. , Currier Bradford , Freedman Brett A. , Bydon Mohamad , Elder Benjamin D. , Fogelson Jeremy , Sebastian Arjun S. , Nassr Ahmad
Published: March 2023

Study Design:

Retrospective review.

Objective:

The purpose of this study was to investigate the surgical outcomes in a cohort of patients with severe preoperative axial neck pain undergoing laminoplasty for cervical spondylotic myelopathy (CSM).

Summary of Background Data:

No study has investigated whether patients with severe axial symptoms may achieve satisfactory neck pain and disability outcomes after laminoplasty.

Methods:

We performed a retrospective review of 91 patients undergoing C4-6 laminoplasty for CSM at a single academic institution between 2010 and 2021. Patient-reported outcome measures (PROMs), including Neck Disability Index (NDI), visual analog scale (VAS) Neck, and VAS Arm, were recorded preoperatively and at 6 months and 1 year postoperatively. Patients were stratified as having mild pain if VAS neck was 0–3, moderate pain if 4–6, and severe pain if 7–10. PROMs were then compared between subgroups at all the perioperative time points.

Results:

Both the moderate and severe neck pain subgroups demonstrated a substantial improvement in VAS neck from preoperative to 6 months postoperatively (−3.1±2.2 vs. −5.6±2.8, respectively; P<0.001), and these improvements were maintained at 1 year postoperatively. There was no difference in VAS neck between subgroups at either the 6-month or 1-year postoperative time points. Despite the substantially higher mean NDI in the moderate and severe neck pain subgroups preoperatively, there was no difference in NDI at 6 months or 1 year postoperatively (P=0.99). There were no differences between subgroups in the degree of cord compression, severity of multifidus sarcopenia, sagittal alignment, or complications.

Conclusions:

Patients with moderate and severe preoperative neck pain undergoing laminoplasty achieved equivalent PROMs at 6 months and 1 year as patients with mild preoperative neck pain. The results of this study highlight the multifactorial nature of neck pain in these patients and indicate that severe axial symptoms are not an absolute contraindication to performing laminoplasty in well-aligned patients with CSM.
Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: a prospective Chinese cohort study
Authors: Geng Yan , Fan Yong , Wang Yu , Deng Xuerong , Ji Lanlan , Zhang Xiaohui , Song Zhibo , Huang Hong , Gui Yanni , Zhang Haoze , Sun Xiaoying , Li Guangtao , Zhao Juan , Zhang Zhuoli
Published: March 2023

Background:

Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA).

Methods:

A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups.

Results:

A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment (P = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred.

Conclusions:

COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Felix von Bärensprung—A Review of His Life and Work on the Occasion of His 200th Birthday
Authors: Weyers Wolfgang
Published: March 2023

Felix von Bärensprung was a pioneer of dermatopathology. His monograph of 1848, “Contributions to the Anatomy and Pathology of the Human Skin,” was one of the first publications on that subject. Von Bärensprung also described and named erythrasma, elucidated the pathogenesis of herpes zoster, contributed a comprehensive review of the history of dermatology in an unfinished textbook of skin diseases, and was coauthor, together with Ferdinand Hebra of Vienna, of one of the most influential clinical atlases in the history of dermatology. The 200th anniversary of his birthday in 2022 provides an occasion for reminding of one of the leading dermatologists of the mid 19th century.
Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis
Authors: Khurana Maya , Mandal Ria , Cassarino David S.
Published: March 2023

Basal cell carcinomas are one of the most common cutaneous carcinomas and show classical histologic features of basaloid nests with peripheral palisading. Pagetoid and intraepidermal spread has not been described in basal cell carcinoma to the best of our knowledge. We report 5 cases of basal cell carcinoma with classic histologic patterns and overlying basaloid nests and single intraepidermal tumor cells. A panel of immunostains were performed that included CK7, MOC31, CEA-m, EMA, androgen receptor, and Bcl2. Most of our cases were positive for both MOC31 and CK7, and all cases were negative for CEA-m and EMA excluding extramammary Paget disease, one of the most common differential diagnoses. These cases expand the spectrum of findings that can be seen in basal cell carcinoma and can help prevent misdiagnoses of basal cell carcinomas as more aggressive tumors.
Clinical Features of Pediatric Age Herpes Simplex Virus Keratitis
Authors: Ulman Elif Akbas , Selver Ozlem Barut , Biler Elif Demirkilinc , Palamar Melis
Published: March 2023

Purpose:

The objective of this study is to evaluate the clinical features of pediatric herpes simplex virus keratitis, its recurrence rates, and its effects on visual acuity.

Methods:

In this retrospective case series, records of pediatric patients (0–16 years) who presented with herpes simplex virus keratitis between January 2012 and September 2021 were evaluated. Data including age, gender, additional systemic diseases, the number of recurrences, recurrence time, treatment protocol, follow-up period, and presence of amblyopia were reviewed.

Results:

Twenty-four patients (16 females and 8 males) with a mean age of 6.6 ± 4 (1.1–15) years were included in the study. The mean follow-up time was 21 ± 19.9 (7–94) months. Four patients (16.6%) had bilateral keratitis. Including all 4 patients with bilateral involvement, a total of 10 (41.6%) patients had additional systemic diseases that cause immunodeficiency. After prophylactic antiviral treatment for at least 6 months (except for isolated epithelial keratitis), recurrence was detected in 5 (22.7%) patients, who were all immunodeficient. Among immunodeficient individuals, the recurrence rate was found to be 50%. Keratitis recurrence was significantly associated with immunodeficiency (P = 0.03). However, type of keratitis (P = 0.42), gender (P = 0.47), and bilaterality (P = 0.54) were not related with recurrence. 66.7% of the patients younger than 10 years developed amblyopia during follow-up.

Conclusions:

In childhood, the most frequent corneal manifestation of herpes simplex virus is stromal keratitis that mostly progresses with corneal scarring, residual astigmatism, and amblyopia. The recurrence rate increases in the presence of immunosuppression. Close follow-up, rapid diagnosis, and treatment are critical for battling against amblyopia and achieving good visual prognosis.
Nonlinear Relationship Between C-Reactive Protein and Depression Among Obese Middle-Aged Adults
Authors: Lee Chiyoung , Min Se Hee , Niitsu Kosuke
Published: March 2023

Background

Despite the agreement on the significance of the relationship between the C-reactive protein (CRP) and depression, research results have been discrepant by gender.

Objective

We attempted to address this uncertainty via a generalized additive model (GAM) and more carefully analyzed the shape of the CRP-depression relationship in terms of sex.

Methods

This is a secondary data analysis using the National Health and Nutrition Examination Survey (2017–2020) data targeting 1,581 obese middle-aged adults (40–70 years; 51.4% women) with CRP ≤ 10 mg/L. The study outcome was depression severity, assessed by the Patient Health Questionnaire-9. Several models were built, adjusting for relevant sociodemographic, lifestyle, and clinical covariates. The value of the effective degree of freedom (EDF) quantifies curvature of the relationship. The threshold effect was investigated using a two-piecewise linear regression model, when needed.

Results

Among men, an increasing linear pattern was found (EDF ≈ 1). Contrastingly among women, the EDF value was >2 in all unadjusted and adjusted models, indicating the smooth (curved) association. The threshold level affected the association pattern particularly for women, among whom the depression severity related to CRP significantly increased as the CRP level increased to an inflection point of 3.6 mg/L but decreased thereafter.

Discussion

Assuming linearity for the CRP association with depression may not be appropriate for middle-aged obese women. While we do not claim to provide a definite method of assessing the CRP-depression relationship, we hope to offer a different perspective when exploring this relationship. Thus, the results should be interpreted cautiously, and future studies on this topic should replicate this approach with GAMs.
Differential Gene Expression Among Patients With Heart Failure Experiencing Pain
Authors: Smith Asa B. , Jung Miyeon , Pressler Susan J. , Mocci Evelina , Dorsey Susan G.
Published: March 2023

Background

Chronic pain is frequently experienced by patients with heart failure (HF) and is associated with higher mortality, higher symptom burden, and worsened health-related quality of life. However, the genomic mechanisms underlying chronic pain in HF are understudied. Building an understanding of the mechanistic underpinnings of pain may inform novel interventions.

Objective

The objective was to identify genes associated with pain from mRNA sequence data collected from patients with HF with and without pain.

Methods

The current study analyzed data from 40 patients with HF previously enrolled in a clinical trial. Pain presence was measured using the Health Utilities Index Mark-3. Genes were tested for differential expression using DESeq2, and differentially expressed genes were analyzed for protein–protein interaction (PPI) and relevant ontological pathways using Metascape. Genes located within the core of the PPI network were considered key in disease-relevant biological pathways. Differentially expressed genes within this PPI network were reviewed in existing literature to narrow down candidate genes of interest. These target genes of interest were reanalyzed in a second sample of 24 patients with HF using validation quantitative polymerase chain reaction.

Results

A total of 334 genes (279 upregulated, 55 downregulated) were differentially expressed between patients with and without pain in the primary sample of 40. These genes were largely aligned with neutrophil degranulation pathways. Seven genes of interest were identified from a core network of 15 co-expressed genes in the PPI network and existing literature. Three of these seven genes: matrix metallopeptidase 8 (MMP8), proprotein convertase subtilisin/kexin type 9 (PCSK9), and neutrophil defensin 3 (DEFA3) were upregulated in patients with pain versus without pain in both the primary and validation samples. All seven genes of interest are involved in immune, inflammatory, and atherosclerotic processes.

Discussion

These results identify potential genes that may play a mechanistic role in chronic pain in HF. Further research is needed to evaluate these potential genes among clearly delineated pain phenotypes.
Nutritional prehabilitation strategies for patients undergoing head and neck cancer: a scoping review
Authors: Xue Fang , Zhang Mengli , Duan Huan , Zhang Jing
Published: March 2023

Background:

Given the high incidence of malnutrition before anti-cancer treatment in patients with head and neck cancer (HNC), it is necessary to pay attention to nutritional interventions for them before surgery, radiotherapy, and chemotherapy. Nutritional prehabilitation strategies vary considerably in their implementations.

Objective:

This scoping review aimed to summarize the nutritional prehabilitation strategies for HNC patients.

Methods:

We conducted a scoping review based on the framework outlined by the Joanna Briggs Institute (JBI) methodology (Joanna Briggs Institute, 2020). Twelve articles focused on the effects of preoperative nutritional intervention on the nutritional status of patients with HNC who underwent surgery, radiotherapy, or chemotherapy. We synthesized the screening or evaluation tool for the nutrition prerehabilitation intervention strategy, type of nutrition supplement, intervention goal, frequency, duration, re-evaluation, and supervision.

Results:

Findings suggest that preoperative nutritional intervention can improve recovery from anti-cancer treatment and patient physical reserves for coping with surgical stress. Therefore, patients with HNC who are at risk of malnutrition are recommended for early nutritional interventions.
Application of Paranasal Augmentation Rhinoplasty in Asians With Midfacial Concavity
Authors: Zhao Runlei , Pan Bailin , Li Dong , An Yang
Published: March 2023

Background

For Asian rhinoplasty patients with midfacial concavity, the conventional method is to solve the problem by using structural rhinoplasty to increase the nasal height and length. However, the results are not satisfying, and many complications are caused.

Paranasal augmentation as an adjunct to rhinoplasty can improve surgical results and increase satisfaction. However, there are limited studies focusing on the details and evaluation of this technique.

Objectives

To investigate a minimally invasive method to correct midfacial concavity simultaneously with rhinoplasty, as well as improve satisfaction and reduce complications.

Materials and Methods

Between January 2010 and December 2019, we reviewed all rhinoplasty patient records from patients who had midfacial concavity and underwent simultaneous paranasal augmentation with our technique. The patient demographics, surgical characteristics, and outcomes were reviewed retrospectively. Satisfaction was evaluated by an independent medical staff who reviewed the preoperative and postoperative photos.

Results

Sixty-seven patients were included in the study. The mean age of the patients was 28.7 ± 8.0 years, and the median follow-up time was 26 months (range, 2–60 months). Overall satisfaction was high (90%). Eight (12%) patients had complications, including 5 (7.4%) cases of implant displacement and 3 (4.4%) cases of infection. All patients healed uneventfully after revision surgery.

Conclusions

Paranasal augmentation can improve the outcome and increase satisfaction in Asian rhinoplasty patients who have midfacial concavity. Preoperative patient evaluation, surgery planning, and surgery details are crucial to ensure a favorable result. The expanded polytetrafluoroethylene implant has advantages over other materials and therefore is recommended in paranasal augmentation surgery.
Gracilis Muscle Interposition to Fill the Perianal Dead Space May Decrease Hospital Length of Stay in Fournier's Gangrene
Authors: Ismayilzade Majid , Dadaci Mehmet , Kendir Münür Selçuk , Ince Bilsev
Published: March 2023

Purpose

The treatment of Fournier's gangrene (FG) includes aggressive debridement of the affected necrotic area, broad-spectrum antibiotic therapy, and reconstructive procedures, respectively. One of the main reasons of unfavorable outcomes in FG surgery is that the dead space occurs in the perianal region because of destruction of fascias and soft tissues. In this study, we aimed to evaluate the results of gracilis muscle flap transposition to fill the FG-associated perianal dead spaces.

Methods

Patients treated for FG-associated dead spaces in their perianal region between the years 2017 and 2021 were included in the study. The patients who underwent the pedicled gracilis muscle flap surgery were included in group 1, whereas group 2 consisted of the patients with no additional surgical procedure for dead spaces but only the reconstruction of the soft tissue defects. Demographic data (age, sex), comorbid diseases, localization and length of perianal dead space, and management method for the soft tissue defects and complications were noted. The length of hospital stay and discharge day after surgery were also recorded.

Results

In group 1, the mean duration of hospital stay was 23.5 ± 5.0 (range, 14–48) days, whereas the mean period between the surgery and discharge was 5.1 ± 2.2 (range, 3–12) days. These numbers were 31 ± 8.3 (range, 19–58) days and 12.7 ± 6.1 (range, 7–22) days in group 2, respectively. Statistical comparison of the periods between the surgery and discharge was found to be significantly different (P = 0.022). The duration of hospital stay was also shorter in the patients with gracilis muscle flap (P = 0.039).

Conclusions

Perianal dead spaces accompanying many of the patients with FG provide appropriate conditions for bacterial colonization. Filling these pouches by the gracilis muscle flap prevented the progression of infection and enabled the patients to return to their normal life earlier.
Masson Tumor of the Heel Fat Pad
Authors: Sung Kunyong , Jeong Chanho , Lee Seungkoo , Oh Ha Yeun , Lee Sang-Yeul
Published: March 2023

Intravascular papillary endothelial hyperplasia (Masson tumor) is an uncommon benign vascular lesion characterized by a reactive proliferation of endothelial cells. This lesion commonly occurs in the head, neck, and upper extremities. Although it can be found anywhere in the body, the lesion has never affected the heel fat pad. This report presents a rare case of Masson tumor of the heel fat pad to facilitate the recognition of this uncommon lesion and also suggests other conditions to be considered when diagnosing heel lesions.