bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the in situ biomethanation potential of a deep aquifer used for natural gas storage
Authors: Ranchou-Peyruse Magali , Guignard Marion , Chiquet Pierre , Caumette Guilhem , Cézac Pierre , Ranchou-Peyruse Anthony
Published: April 2024

The dihydrogen (H2) sector is undergoing development and will require massive storage solutions. To minimize costs, the conversion of underground geological storage sites, such as deep aquifers, used for natural gas storage into future underground hydrogen storage sites is the favored scenario. However, these sites contain microorganisms capable of consuming H2, mainly sulfate reducers and methanogens. Methanogenesis is, therefore expected but its intensity must be evaluated. Here, in a deep aquifer used for underground geological storage, 17 sites were sampled, with low sulfate concentrations ranging from 21.9 to 197.8 µM and a slow renewal of formation water. H2-selected communities mainly were composed of the families Methanobacteriaceae and Methanothermobacteriaceae and the genera Desulfovibrio, Thermodesulfovibrio, and Desulforamulus. Experiments were done under different conditions, and sulfate reduction, as well as methanogenesis, were demonstrated in the presence of a H2 or H2/CO2 (80/20) gas phase, with or without calcite/site rock. These metabolisms led to an increase in pH up to 10.2 under certain conditions (without CO2). The results suggest competition for CO2 between lithoautotrophs and carbonate mineral precipitation, which could limit microbial H2 consumption.
Terraced slope metasurface in granular media
Authors: Aravantinos-Zafiris N , Chondrogiannis K A , Thomsen H R , Dertimanis V K , Colombi A , Sigalas M M , Chatzi E
Published: April 2024

In this work, the propagation and attenuation of vertically polarized surface waves when interacting with terraced slopes is studied experimentally and numerically. To validate the devised simulation, a laboratory-scale physical model is tested in order to examine the attenuation properties of this well-known artificial landform. The experiment involves formation of a terraced slope, in a laboratory setup, via use of an unconsolidated granular medium made of silica microbeads. This granular medium exhibits a gravity-induced power-law stiffness profile, resulting in a depth-dependent velocity profile. A piezoelectric actuator was used to excite vertically polarized surface acoustic modes localized near the surface of the medium. The three components of the particle velocity field of these modes were measured by means of a 3-D laser Doppler vibrometer. In accordance with the terraced slope, a simple inclined plane was further tested to investigate and highlight the differences in terms of wave propagation along these two different ground formations. The results of this research provide significant experimental evidence that the terraced slopes form mechanisms which attenuate low-frequency surface waves, thus acting as metasurfaces. This work suggests the use of laboratory-scale physical models to investigate the wave propagation in different landforms, which extend beyond typical horizontal ground morphologies, and which could be linked to atypical wave propagation properties, possibly even influencing propagation of seismic waves.
Extremal Numbers and Sidorenko’s Conjecture
Authors: Conlon David , Lee Joonkyung , Sidorenko Alexander
Published: April 2024

Sidorenko’s conjecture states that, for all bipartite graphs $H$, quasirandom graphs contain asymptotically the minimum number of copies of $H$ taken over all graphs with the same order and edge density. While still open for graphs, the analogous statement is known to be false for hypergraphs. We show that there is some advantage in this, in that if Sidorenko’s conjecture does not hold for a particular $r$-partite $r$-uniform hypergraph $H$, then it is possible to improve the standard lower bound, coming from the probabilistic deletion method, for its extremal number $\textrm{ex}(n,H)$, the maximum number of edges in an $n$-vertex $H$-free $r$-uniform hypergraph. With this application in mind, we find a range of new counterexamples to the conjecture for hypergraphs, including all linear hypergraphs containing a loose triangle and all $3$-partite $3$-uniform tight cycles.
Burst-induced spin variations in the accreting magnetic white dwarf PBC J0801.2–4625
Authors: Irving Z A , Altamirano D , Scaringi S , Veresvarska M , Knigge C , Castro Segura N , De Martino D , Iłkiewicz K
Published: April 2024

PBC J0801.2–4625 is an intermediate polar with a primary spin frequency of 66.08 d−1 and an unknown orbital period. The long-term All Sky Automated Survey for Supernovae (ASAS-SN) light curve of this system reveals four bursts, all of which have similar peak amplitudes (∼2 mag) and durations (∼2 d). In this work, we primarily study the timing properties of this system’s 2019 February burst, which was simultaneously observed by both ASAS-SN and the Transiting Exoplanet Survey Satellite (TESS). Pre-burst, a frequency of 4.064 ± 0.002 d−1(5.906 ± 0.003 h period), likely attributed to the binary orbit, is identified in addition to previous measurements for the white dwarf’s spin. During the burst, however, we find a spin frequency of 68.35 ± 0.28 d−1. Post-burst, the spin returns to its pre-brust value but with a factor 1.82 ± 0.05 larger amplitude. The burst profile is double-peaked, and we estimate its energy to be 3.3 × 1039 erg. We conclude that the burst appears most consistent with thermonuclear runaway (i.e. a 'micronova'), and suggest that the spin variations may be an analogue to burst oscillations (i.e. 'micronova oscillations'). However, we also note that the above findings could be explained by a dwarf nova outburst. With the available data, we are unable to distinguish between these two scenarios.
ExoMol line lists – LVIII. High-temperature molecular line list of carbonyl sulphide (OCS)
Authors: Owens Alec , Yurchenko Sergei N , Tennyson Jonathan
Published: April 2024

A new molecular line list covering wavelengths λ > 1 μm (the 0–10 000 cm−1 range) for the main isotopologue of carbonyl sulphide 16O12C32S is presented. The OCS line list, named OYT8, contains almost 2.5 billion transitions between 2.4 million rotation-vibration energy levels with the total angular momentum up to J = 223. It is suitable for high-temperature environments up to T = 2000 K. Line list calculations were performed with the variational nuclear motion code trove in conjunction with a highly accurate, empirically refined potential energy surface and a newly computed ab initio dipole moment surface of OCS. The OYT8 line list is adapted for high-resolution applications by replacing computed energy levels with empirically derived values of OCS where available. Comparisons of the OYT8 line list with other OCS line lists and spectra yields excellent agreement for both strong and weak spectroscopic bands. The increased coverage of the OYT8 line list and the many new spectral features that are available will greatly facilitate the future observation of OCS on exoplanets. Carbonyl sulphide joins a growing number of sulphur-bearing molecules available from the ExoMol database. The OYT8 line list along with the associated temperature- and pressure-dependent molecular opacities can be downloaded from www.exomol.com and the CDS astronomical database.
Climate change, strict Pareto improvements in welfare and multilateral financial transfers
Authors: Kotsogiannis Christos , Woodland Alan
Published: April 2024

Climate change discussions and negotiations have emphasized the need for developing countries to take the lead by undertaking economy-wide absolute emission reduction targets but also the obligation of developed countries to provide financial resources to assist them in their mitigation efforts. This article explores the role of such financial resources in achieving strict welfare gains for all countries (strict Pareto improvements) when emission targets, due to inefficient carbon pricing, deviate from the global welfare optimum and there are impediments to international trade. It is shown that such transfers exist if and only if a Generalized Hatta Normality Emissions Condition is violated. Numerical examples illustrate the financial transfer mechanism.
Celine, a long interspersed nuclear element retrotransposon, colonizes in the centromeres of poplar chromosomes
Authors: Xin Haoyang , Wang Yiduo , Zhang Wenli , Bao Yu , Neumann Pavel , Ning Yihang , Zhang Tao , Wu Yufeng , Jiang Ning , Jiang Jiming , Xi Mengli
Published: April 2024

Centromeres in most multicellular eukaryotes are composed of long arrays of repetitive DNA sequences. Interestingly, several transposable elements, including the well-known long terminal repeat centromeric retrotransposon of maize (CRM), were found to be enriched in functional centromeres marked by the centromeric histone H3 (CENH3). Here, we report a centromeric long interspersed nuclear element (LINE), Celine, in Populus species. Celine has colonized preferentially in the CENH3-associated chromatin of every poplar chromosome, with 84% of the Celine elements localized in the CENH3-binding domains. In contrast, only 51% of the CRM elements were bound to CENH3 domains in Populus trichocarpa. These results suggest different centromere targeting mechanisms employed by Celine and CRM elements. Nevertheless, the high target specificity seems to be detrimental to further amplification of the Celine elements, leading to a shorter life span and patchy distribution among plant species compared with the CRM elements. Using a phylogenetically guided approach, we were able to identify Celine-like LINE elements in tea plant (Camellia sinensis) and green ash tree (Fraxinus pennsylvanica). The centromeric localization of these Celine-like LINEs was confirmed in both species. We demonstrate that the centromere targeting property of Celine-like LINEs is of primitive origin and has been conserved among distantly related plant species.
Comparison of tibial nerve pulsed radiofrequency and intralesional radiofrequency thermocoagulation in the treatment of painful calcaneal spur and plantar fasciitis: a randomized clinical trial
Authors: Yildiz Gokhan , Perdecioglu Gevher Rabia Genc , Yuruk Damla , Can Ezgi , Akkaya Omer Taylan
Published: April 2024

Objective

Ultrasound-guided tibial nerve pulsed radiofrequency (US-guided TN PRF) and fluoroscopy-guided intralesional radiofrequency thermocoagulation (FL-guided intralesional RFT) adjacent to the painful calcaneal spur are two interventions for pain management in painful calcaneal spur and plantar fasciitis. This study aimed to compare the effectiveness of the two procedures.

Design

A prospective, randomized, single-blind study.

Setting

Single-center pain clinic.

Subjects

Forty-nine patients who met the inclusion criteria were randomized into two groups.

Methods

Group U (25 patients) received US-guided TN PRF at 42°C for 240 s, whereas Group F (24 patients) received FL-guided intralesional RFT at 80°C for 90 s. The most severe numeric rating scale (NRS) score during the first morning steps and the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores were used to evaluate the effectiveness of the procedures. The study’s primary outcome assessed treatment effectiveness via the NRS, whereas the secondary outcomes included changes in the AOFAS score and the incidence of procedure-related mild adverse events.

Results

NRS and AOFAS scores significantly improved in Groups U and F at 1 and 3 months compared with baseline (P < .05), and there was no significant difference between the groups. At month 1, 50% or greater pain relief was achieved in 72% of patients in Group U and 75% of patients in Group F. No significant difference was observed in the incidence of mild adverse events between the groups.

Conclusions

US-guided TN PRF and FL-guided intralesional RFT have shown significant effectiveness in the treatment of painful calcaneal spur and plantar fasciitis. Larger randomized controlled trials are needed.

Clinical Trial Number

NCT06240507.
Diverse physiological roles of the MqsR/MqsA toxin/antitoxin system
Authors: Sanchez-Torres Viviana , Kirigo Joy , Wood Thomas K
Published: April 2024

There is tremendous interest in the use of bacteriophages (phages) to combat multi-drug resistant bacteria. However, to implement successfully phage therapy, host defense systems must be understood. Toxin/antitoxins (TAs) are the most prevalent phage defense system, and the MqsR/MqsA TA system is one of the best-studied systems. This phage-defense system was discovered in a whole-cell, population-averaged, transcriptome study designed to elucidate the biofilm-related genes of Escherichia coli in 2004. Biofilms are cells cemented to themselves or to surfaces. Since its characterization (as of April 2024), MqsR/MqsA has been utilized in over 1200 manuscripts, although its role in cell physiology has been contested. Here, we summarize the important physiological roles of this TA system, including its role in (i) the general stress response via repression of rpoS, (ii) biofilm formation via repression of csgA, (iii) combating bile acid stress in the gastrointestinal tract by inhibiting uptake of the bile salt deoxycholate, (iv) oxidative stress based on single-cell transcriptome studies, and (v) phage defense leading to the persister state.
The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: an analysis of the data from Toxicity Reference Database (ToxRefDB)
Authors: Mezencev Roman , Feshuk Madison , Kolaczkowski Lori , Peterson Geoffrey Colin , Zhao Q Jay , Watford Sean , Weaver J Andre
Published: April 2024

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.
Science of Learning Strategy Series: Article 4, Application to Educational Meetings
Authors: Van Hoof Thomas J. , Madan Christopher R. , Sumeracki Megan A.
Published: April 2024

The science of learning (learning science) is an interprofessional field that concerns itself with how the brain learns and remembers important information. Learning science has compiled a set of evidence-based strategies, such as distributed practice, retrieval practice, and interleaving, which are quite relevant to continuing professional development. Spreading out study and practice separated by cognitive breaks (distributed practice), testing oneself to check mastery and memory of previously learned information (retrieval practice), and mixing the learning of distinct but related material (interleaving) represent strategies that are underutilized in continuing professional development. Participants and planners alike can benefit from learning science recommendations to inform their decisions. The common intervention of the educational meeting provides an opportunity to illustrate the benefits of these three learning-science strategies in continuing professional development.
Intestinal ultrasound scan predicts corticosteroid failure and colectomy risk in patients with ulcerative colitis
Authors: Yuan Baisi , Huang Pengfei , Yang Miaofang , Tang Guoxing , Wang Fangyu
Published: April 2024

Objective

Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis.

Methods

We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis.

Results

This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group (P < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%).

Conclusion

IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.
Recent contributions of single-cell and spatial profiling to the understanding of bladder cancer
Authors: Grausenburger Reinhard , Herek Paula , Shariat Shahrokh F. , Englinger Bernhard
Published: April 2024

Purpose of review

Current risk stratification and treatment decision-making for bladder cancer informed by histopathology as well as molecular diagnostics face limitations. This review summarizes recent advancements in single-cell and spatial omics methodologies for understanding bladder cancer biology and their potential impact on development of novel therapeutic strategies.

Recent findings

Single-cell RNA sequencing and spatial omics techniques offer unprecedented insights into various aspects of tumor microenvironment (TME), bladder cancer heterogeneity, cancer stemness, and cellular plasticity. Studies have identified multiple malignant cell subpopulations within tumors, revealing diverse transcriptional states and clonal evolution. Additionally, intratumor heterogeneity has been linked to tumor progression and therapeutic response. Immune cell composition analysis has revealed immunosuppressive features in the TME, impacting treatment response. Furthermore, studies have elucidated the role of cancer-associated fibroblasts and endothelial cells in shaping the tumor immune landscape and response to therapy.

Single-cell and spatial omics technologies have revolutionized our understanding of bladder cancer biology, uncovering previously unseen complexities. These methodologies provide valuable insights into tumor heterogeneity and microenvironmental interactions, with implications for therapeutic development. However, challenges remain in translating research findings into clinical practice and implementing personalized treatment strategies. Continued interdisciplinary collaboration and innovation are essential for overcoming these challenges and leveraging the full potential of single-cell and spatial omics in improving bladder cancer diagnosis and treatment.
Variable Clinical Courses of Varicella Zoster Virus Infection–related or Vaccination-related Bone Marrow Failure
Authors: Toskov Vasil , Cseh Annamaria , Claviez Alexander , Drexler Beatrice , Rotari Natalia , Schwarz-Furlan Stephan , Braun Matthias , Bader Peter , Lang Peter , Beier Rita , Erdlenbruch Bernhard , Führer Monika , Erlacher Miriam , Niemeyer Charlotte M. , Strahm Brigitte , Yoshimi Ayami
Published: April 2024

We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two patients were treated with intravenous immunoglobulins; one had a slow hematologic recovery, and the other was rescued by allogeneic hematopoietic stem cell transplantation (HSCT). Of the 2 patients treated with immunosuppressive therapy with antithymocyte globulin and cyclosporine, one had a complete response, and the other was transplanted for nonresponse. One patient underwent a primary allograft. All patients are alive. This study demonstrated that VZV-associated BMF is a life-threatening disorder that often requires HSCT.
Factors Impacting on Patient-Centered Communication Skills and Their Opportunities to Be Involved in Decision-making From the Perspective of Patients With Cancer, Informal Caregivers, and/or Healthcare Professionals
Authors: Abu-Odah Hammoda , Chan Engle Angela , Molassiotis Alex
Published: April 2024

Background

Active participation of cancer patients and their caregivers in decision-making, along with high-quality communication, is crucial in patient-centered cancer management. Although numerous factors affecting patients’ communication and decision-making involvement have been identified, it is still unclear which ones are the most prevalent and critical.

Objective

To identify factors that contribute to high-quality patient-centered communication and decision-making participation from the perspectives of cancer patients, informal caregivers, and/or healthcare professionals.

Methods

A systematic review was conducted, using 9 databases to retrieve primary research articles published from 2010 to February 17, 2023, updated on December 13, 2023. Methodological quality was assessed using the Mixed Methods Appraisal Tool (version 18). The socioecological model of communication was utilized as analytical framework for summarizing the results.

Results

Fifty-two studies were included. The most frequently reported factors were predominantly articulated at the individual, interpersonal, and societal levels. Although the patients’ lack of knowledge and limited language proficiency were the frequent patient-level barriers, the perceived lack of knowledge and lack of training of professionals were the crucial and current professional-level barriers, as reported in studies published in 2016 onward. To circumvent these factors, it is critical to enhance professionals’ knowledge, communication skills, and patient relationships.

Conclusions

Recognizing barriers and facilitators could help in the development of strategies to overcome these barriers and enhance patient participation in clinical communication.

Implication for Practice

The findings could guide the development of programs to enhance patient-professional communication skills. Further cross-cultural studies are needed to understand culture’s impact on communication effectiveness and decision-making participation.
Reliable Method for Estimating Nerve Fiber Density in Epidermis Using Routine Histopathologic Tissue Preparation: A Promising Diagnostic Tool for Small Fiber Neuropathy
Authors: Aspegren Oskar , Pourhamidi Kaveh
Published: April 2024

Practical yet reliable diagnostic tools for small-fiber neuropathy are needed. We aimed to establish a histopathologic protocol for estimating intraepidermal nerve fiber density (eIENFD) on formalin-fixed, paraffin-embedded tissue (FFPE), evaluate its reliability through intraobserver and interobserver analyses, and provide normative reference values for clinical use. Sixty-eight healthy participants underwent nerve conduction studies and quantitative sensory testing. Skin biopsies from the distal and proximal leg were taken and processed using routine immunohistochemistry (anti-PGP9.5 antibodies) on thin 5 µm sections. eIENFD was assessed with a modified counting protocol. Interobserver and intraobserver reliabilities were excellent (ICC=0.9). eIENFD was higher in females than males (fibers/mm, 14.3±4.4 vs. 11.6±5.8, P<0.05), decreased with age (rs
=–0.47, P<0.001), and was higher proximally than distally (15.0±5.5 vs. 13.0±5.3, P=0.002). Quantile regression equations for the fifth percentile of distal and proximal eIENFD were presented: 13.125–0.161×age (y)–0.932×sex (male=1; female=0) and 17.204–0.192×age (y)–3.313×sex (male=1; female=0), respectively. This study introduces a reliable and reproducible method for estimating epidermal nerve fiber density through immunostaining on 5-µm thin FFPE tissue samples. Normative data on eIENFD is provided. Regression equations help identify abnormal decreases in small nerve fiber density.
Correction of Congenital Syndactyly of the Hand with Minimal Full-Thickness Skin Graft from the Weight-Bearing Midline Plantar Area
Authors: Woo Soo Jin , Park Kwang Hyun , Woo Sang Hyun , Nam Hyun Jae
Published: April 2024

Background:

Traditional skin grafts for syndactyly often cause color mismatches and unsightly donor sites, whereas no–skin graft methods leave noticeable dorsal hand scars. This study presents a plantar full-thickness skin graft (FTSG) from the weight-bearing midline area for syndactyly repair, a novel approach not previously reported in the literature.

Methods:

The study included 3 groups of patients with congenital syndactyly of the hand who underwent primary operations with plantar FTSG (n = 70), groin FTSG (n = 20), and no–skin graft techniques (n = 22). Postoperative outcomes were evaluated by an assessment panel, and guardians’ satisfaction scores were measured. Color similarity between the graft and surrounding skin was assessed using a three-dimensional color space.

Results:

The plantar FTSG group demonstrated a significantly higher likelihood of receiving an excellent rating compared with the groin FTSG group, with an odds ratio of 6.30 (P < 0.001). Color difference analysis showed that plantar FTSG more closely matched surrounding skin color than groin FTSG (6.33 versus 22.57; P < 0.001). Guardians reported greater satisfaction with outcomes on the hand in the plantar FTSG group compared with the groin FTSG and no–skin graft (7.16 versus 5.05 and 4.36; P < 0.001) groups. Satisfaction with donor sites was also significantly higher in the plantar FTSG group than in the groin FTSG group (8.23 versus 6.30; P < 0.001).

Conclusion:

Correction of congenital hand syndactyly using midline plantar FTSG from the weight-bearing area can reduce scarring on the hand dorsum, ensure superior color similarity with surrounding skin, and offer inconspicuous donor sites compared with no–skin graft or groin FTSG techniques.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Body Lift with Lateral Thigh Lift: Surgical Technique and Comparison with the Inferior Body Lift
Authors: Ragonez David , Musmarra Isidoro , Barbera Federico , Couteau Claire , Aguilar Paola , Quilichini Julien
Published: April 2024

Background:

Despite its rarity, cutaneous adipose tissue excess in the trochanteric region following massive weight loss is a surgical challenge. The aim of this work is to propose a surgical technique for lifting the outer thighs by describing its indications and its limitations.

Methods:

Seventy-four patients were recruited into the study between 2018 and 2021. Two groups were identified: patients with body lift combined with lateral thigh lift (n = 20) and patients with lower body lift (n = 54). Satisfaction was determined through the BODY-Q questionnaire. The average operating time was 45 minutes longer when an outer thigh lift was performed. The median length of hospitalization was similar. The complication rate was 26% for the body lift group and 60% for the thigh lift group (P < 0.01); the most common complication was dehiscence.

Results:

Data analysis showed that the lateral thigh lift technique did not affect immediate postoperative evolution or hospitalization duration, proving its safety. There was an increase in total complications among patients who underwent the lateral thigh lift. Dehiscence was the most common complication, which can be treated on an outpatient basis. The satisfaction rate was high. Satisfaction was linked to improved quality of life.

Conclusion:

In the authors’ experience, the technique described is an effective means of treating trochanteric deformities.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
HIV care retention in three multi-month ART dispensing: a retrospective cohort study in Mozambique
Authors: Saura-Lázaro Anna , Augusto Orvalho , Fernández-Luis Sheila , López-Varela Elisa , Fuente-Soro Laura , Bila Dulce , Tovela Milagre , Macuacua Nello , Vaz Paula , Couto Aleny , Bruno Carmen , Naniche Denise
Published: April 2024

Objective:

Evaluate the effect of three multimonth dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique.

Design:

Retrospective cohort study.

Methods:

We analyzed routine health data from people with HIV (PWH) aged 10 years old and older who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: ‘early enrollers’ (<6 months on ART) and ‘established enrollers’ (≥6 months on ART), and age groups: adolescents and youth (AYLHIV) (10–24 years) and adults (≥25 years).

Results:

We included 7378 PWH (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 [interquartile range (IQR): 5.7–21.6] months for AYLHIV and 10.2 (IQR: 4.8–20.9) for adults. Attrition was lower in PWH enrolled in 3MMD compared with monthly ART dispensing, in both established (aHR AYLHIV = 0.65; 95% CI: 0.54–0.78 and aHR adults = 0.50; 95% confidence interval (CI): 0.44–0.56) and early enrollers (aHR AYLHIV = 0.70; 95% CI: 0.58–0.85 and aHR adults = 0.63; 95% CI: 0.57–0.70). Among individuals in 3MMD, male gender (aHR = 1.30; 95% CI: 1.18–1.44) and receiving care in a medium-volume/low-volume healthcare facility (aHR = 1.18; 95% CI: 1.03–1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHR = 0.93; 95% CI: 0.92–0.94 per 1 month increase) and age at least 45 years (aHR = 0.77, 95% CI: 0.67–0.89) reduced risk of attrition.

Conclusion:

3MMD improves retention in care compared with monthly dispensing among established and early enrollers, although to a lesser extent among the latter.
Ruptured Baker Cyst on 18F-FDG PET/CT
Authors: de Groot Emilie Mariëtte , van Amerongen Martinus Johannes , Ploegmakers Marieke Janneke Martine , Zegers Ingrid Henrica Antonia , Arens Anne Isabelle Juliette
Published: April 2024

A 78-year-old woman with diffuse large B-cell lymphoma was referred for an 18F-FDG PET/CT to evaluate therapy response after 6 cycles of R-mini-CHOP. A new 18F-FDG accumulation was noticed medial in the upper part of the right lower leg, spreading along the medial head of the gastrocnemius muscle. The shaft-bow-looking curvature, arch sign, of 18F-FDG revealed a fluid collection on CT. This typical pattern and its specific location are indicative of a ruptured Baker’s cyst. It can manifest in 1 or both legs.
Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage
Authors: Wang Jian , Gu Diheng , Jin Ke , Shen Hualong , Qian Yaohua
Published: April 2024

Intracerebral hemorrhage (ICH) is a fatal brain injury, but the current treatments for it are inadequate to reduce the severity of secondary brain injury. Our study aims to explore the molecular mechanism of Egr1 and Phlda1 in regulating hemin-induced neuronal pyroptosis, and hope to provide novel therapeutic targets for ICH treatment. Mouse hippocampal neuron cells treated with hemin were used to simulate an in-vitro ICH model. Using qRT-PCR and western blot to evaluate mRNA and protein concentrations. MTT assay was utilized to assess cell viability. LDH levels were determined by lactate Dehydrogenase Activity Assay Kit. IL-1β and IL-18 levels were examined by ELISA. The interaction of Egr1 and Phlda1 promoter was evaluated using chromatin immunoprecipitation and dual-luciferase reporter assays. Egr1 and Phlda1 were both upregulated in HT22 cells following hemin treatment. Hemin treatment caused a significant reduction in HT22 cell viability, an increase in Nlrc4 and HT22 cell pyroptosis, and heightened inflammation. However, knocking down Egr1 neutralized hemin-induced effects on HT22 cells. Egr1 bound to the promoter of Phlda1 and transcriptionally activated Phlda1. Silencing Phlda1 significantly reduced Nlrc4-dependent neuronal pyroptosis. Conversely, overexpressing Phlda1 mitigated the inhibitory effects of Egr1 knockdown on Nlrc4 and neuronal pyroptosis during ICH. Egr1 enhanced neuronal pyroptosis mediated by Nlrc4 under ICH via transcriptionally activating Phlda1.
Evaluation of sequence-based tools to gather more insight into the positioning of rhizogenic agrobacteria within the Agrobacterium tumefaciens species complex
Authors: Vargas Ribera Pablo Roberto , Kim Nuri , Venbrux Marc , Álvarez-Pérez Sergio , Rediers Hans
Published: April 2024

Rhizogenic Agrobacterium, the causative agent of hairy root disease (HRD), is known for its high phenotypic and genetic diversity. The taxonomy of rhizogenic agrobacteria has undergone several changes in the past and is still somewhat controversial. While the classification of Agrobacterium strains was initially mainly based on phenotypic properties and the symptoms they induced on plants, more and more genetic information has been used along the years to infer Agrobacterium taxonomy. This has led to the definition of the so-called Agrobacteriumtumefaciens species complex (Atsc), which comprises several genomospecies. Interestingly, the rhizogenic Agrobacterium strains are found in several of these genomospecies. Nevertheless, even up until today Agrobacterium strains, and in particular rhizogenic agrobacteria, are prone to misclassification and considerable confusion in literature. In this study, we evaluated different phylogenetic analysis approaches for their use to improve Agrobacterium taxonomy and tried to gain more insight in the classification of strains into this complex genus, with a particular focus on rhizogenic agrobacteria. The genome sequence analysis of 579 assemblies, comprising Agrobacterium, Allorhizobium and Rhizobium strains demonstrated that phylogenies based on single marker genes, such as the commonly used 16S rRNA and recA gene, do not provide sufficient resolution for proper delineation of the different genomospecies within the Atsc. Our results revealed that (in silico) multi-locus sequences analysis (MLSA) in combination with average nucleotide identity (ANIb) at a 94.0% threshold delineates genomospecies accurately and efficiently. Additionally, this latter approach permitted the identification of two new candidate genomospecies.
Machine Learning-driven Histotype Diagnosis of Ovarian Carcinoma: Insights from the OCEAN AI Challenge
Authors: Asadi-Aghbolaghi Maryam , Farahani Hossein , Zhang Allen , Akbari Ardalan , Kim Sirim , Chow Ashley , Dane Sohier ,   OCEAN Challenge Consortium,   OTTA Consortium, Huntsman David G , Gilks C Blake , Ramus Susan , Köbel Martin , Karnezis Anthony N , Bashashati Ali
Published: April 2024

Ovarian cancer poses a significant health burden as one of the deadliest malignancies affecting women globally. Histotype assignment of epithelial ovarian cancers can be challenging due to morphologic overlap, inter-observer variability, and the lack of ancillary diagnostic techniques in some areas of the world. Moreover, rare cancers can pose particular diagnostic difficulties because of a relative lack of familiarity with them, underscoring the necessity for robust diagnostic methodologies. The emergence of Artificial Intelligence (AI) has brought promising prospects to the realm of ovarian cancer diagnosis. While various studies have underscored AI’s promise, its validation across multiple healthcare centers and hospitals has been limited. Inspired by innovations in medical imaging driven by public competitions, we initiated the Ovarian Cancer subtypE clAssification and outlier detectioN (OCEAN) challenge — the most extensive histopathology competition to date.
Connecting Transcriptomics with Computational Modeling to Reveal Developmental Adaptations in the Human Pediatric Myocardium
Authors: Salameh Shatha , Guerrelli Devon , Miller Jacob A. , Desai Manan , Moise Nicolae , Yerebakan Can , Bruce Alisa , Sinha Pranava , d’Udekem Yves , Weinberg Seth H. , Posnack Nikki Gillum
Published: April 2024

Background

Nearly 1% or 1.3 million babies are born with congenital heart disease (CHD) globally each year – many of whom will require palliative or corrective heart surgery within the first few years of life. A detailed understanding of cardiac maturation can help to expand our knowledge on cardiac diseases that develop during gestation, identify age-appropriate cardiovascular drug therapies, and inform clinical care decisions related to surgical repair, myocardial preservation, or postoperative management. Yet, to date, our knowledge of the temporal changes that cardiomyocytes undergo during postnatal development is largely limited to animal models.

Methods

Right atrial tissue samples were collected from n=117 neonatal, infant, and pediatric patients undergoing correct surgery due to (acyanotic) CHD. Patients were stratified into five age groups: neonate (0-30 days), infant (31-364 days), toddler to preschool (1-5 years), school age (6-11 years), and adolescent to young adults (12-32 years). We measured age-dependent adaptations in cardiac gene expression, and used computational modeling to simulate action potential and calcium transients.

Results

Enrichment of differentially expressed genes (DEG) was explored, revealing age-dependent changes in several key biological processes (cell cycle, cell division, mitosis), cardiac ion channels, and calcium handling genes. Gene-associated changes in ionic currents exhibited both linear trends and sudden shifts across developmental stages, with changes in calcium handling (INCX) and repolarization (IK1) most strongly associated with an age-dependent decrease in the action potential plateau potential and increase in triangulation, respectively. We also note a shift in repolarization reserve, with lowerIKrexpression in younger patients, a finding likely tied to the increased amplitude ofIKstriggered by elevated sympathetic activation in pediatric patients.

Conclusion

This study provides valuable insights into age-dependent changes in human cardiac gene expression and electrophysiology among patients with CHD, shedding light on molecular mechanisms underlying cardiac development and function across different developmental stages.
Sexual dimorphism in the tardigradeParamacrobiotus metropolitanustranscriptome
Authors: Sugiura Kenta , Yoshida Yuki , Hayashi Kohei , Arakawa Kazuharu , Kunieda Takekazu , Matsumoto Midori
Published: April 2024

Background

In gonochoristic animals, the sex determination pathway induces different morphological and behavioral features that can be observed between sexes, a condition known as sexual dimorphism. While many components of this sex differentiation cascade shows high levels of diversity, factors such as the Doublesex-Mab-3-related transcription factor (DMRT) are highly conserved throughout animals. Species of the phylum Tardigrada exhibits remarkable diversity in morphology and behavior between sexes, suggesting a pathway regulating such dimorphism. Despite the wealth of genomic and zoological knowledge accumulated in recent studies, the sexual differences in tardigrades genomes have not been identified. In this study, we focused on the gonochoristic speciesParamacrobiotus metropolitanusand employed omics analyses to unravel the molecular basis of sexual dimorphism.

Results

Transcriptome analysis between sex identified numerous differentially expressed genes, of which approximately 2,000 male-biased genes were focused on 29 non-male-specific genomic loci. From these regions, we identified two Macrobiotidae family specificDMRTparalogs, which were significantly upregulated in males and lacked sex specific splicing variants. Furthermore, phylogenetic analysis indicated all tardigrade genomes lacks thedoublesexortholog, suggestingdoublesexemerged after the divergence of Tardigrada. In contrast to sex-specific expression, no evidence of genomic difference between the sexes were found. We also identified several anhydrobiosis genes exhibiting sex-biased expression, possibly suggesting a mechanism for protection of sex specific tissues against extreme stress.

Conclusions

This study provides a comprehensive analysis for analyzing the genetic differences between sexes in tardigrades. The existence of male-biased, but not male-specific, genomic loci and identification of the family specific male-biasedDMRTsubfamily would provide the foundation for understanding the sex determination cascade. In addition, sex-biased expression of several tardigrade-specific genes which are involved their stress tolerance suggests a potential role in protecting sex-specific tissue and gametes.
Food touch limits lifespan through bioamine and neuroendocrine signaling
Authors: Kitto Elizabeth S. , Beydoun Safa , Leiser Scott F.
Published: April 2024

In multicellular organisms, sensory perception affects many aspects of behavior and physiology. Sensory cues are frequently perceived by the nervous system, which in turn coordinates systemic changes that can modulate health. Here we find that the sense of touch interacts with nutritional state to modulate lifespan inC. elegans. Worms subjected to dietary restriction are shorter-lived when they perceive tactile stimuli that mimic bacterial food and protective soil. Touch modulation of dietary restriction requires primary mechanoreceptors, the neurotransmitters dopamine and tyramine/adrenaline, and the neuropeptides insulin and GnRH. Ultimately, the touch circuit regulates the longevity effectors DAF-2/IGF1R and FMO-2/FMO5. These results establish a physiological touch circuit and connect neural reward pathways to the growth and reproductive axes. Finding that gentle touch can modulate longevity suggests a role for physical comfort in healthspan and lifespan.
Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity
Authors: Dublin-Ryan Leeran B. , Bhadra Ankan K. , True Heather L.
Published: April 2024

The nascent polypeptide-associate complex (NAC) is a heterodimeric chaperone complex that binds near the ribosome exit tunnel and is the first point of chaperone contact for newly synthesized proteins. Deletion of the NAC induces embryonic lethality in many multi-cellular organisms. Previous work has shown that the deletion of the NAC rescues cells from prion-induced cytotoxicity. This counterintuitive result led us to hypothesize that NAC disruption would improve viability in cells expressing human misfolding proteins. Here, we show that NAC disruption improves viability in cells expressing expanded polyglutamine and also leads to delayed and reduced aggregation of expanded polyglutamine and changes in polyglutamine aggregate morphology. Moreover, we show that NAC disruption leads to changes inde novoyeast prion induction. These results indicate that the NAC plays a critical role in aggregate organization as a potential therapeutic target in neurodegenerative disorders.
Rigid, bivalent CTLA-4 binding to CD80 is required to disrupt thecisCD80 / PD-L1 interaction
Authors: Robinson Maximillian A , Kennedy Alan , Orozco Carolina T , Chen Hung-Chang , Waters Erin , Giovacchini Dalisay , Yeung Kay , Filer Lily , Hinze Claudia , Lloyd Christopher , Dovedi Simon J , Sansom David M
Published: April 2024

The CTLA-4 and PD-1 checkpoints control immune responses to self-antigens and are key targets in cancer immunotherapy. Both pathways are connected via a cis interaction between CD80 and PD-L1, the ligands for CTLA-4 and PD-1 respectively. This cis interaction prevents PD-1 binding to PD-L1 but is reversed by CTLA-4 trans-endocytosis of CD80. However, the mechanism by which CTLA-4 selectively removes CD80 but not PD-L1 is unclear. Here we show that CTLA-4 – CD80 interactions are unimpeded by PD-L1 and that CTLA-4 binding with CD80 does not displace PD-L1 per se. Rather, both the rigidity and bivalency of the WT CTLA-4 molecule is required to orientate CD80 such that PD-L1 interactions are no longer permissible. Moreover, soluble CTLA-4 released PD-L1 only at specific expression levels of CD80 and PD-L1, whereas CTLA-4 trans-endocytosis released PD-L1 in all conditions. These data show that PD-L1 release from CD80 is driven by biophysical factors associated with orientation and bivalent cross-linking of proteins in the cell membrane and that trans-endocytosis of CD80 efficiently promotes PD-L1 availability.
Delta-5 elongase knockout reduces DHA and TAG synthesis coupled with an increase of heat sensitivity in a marine diatom
Authors: Zhu Junkai , Li Shuangqing , Chen Weizhong , Xu Xinde , Wang Xiaoping , Wang Xinwei , Han Jichang , Jouhet Juliette , Amato Alberto , Maréchal Eric , Hu Hanhua , Allen Andrew E. , Gong Yangmin , Jiang Haibo
Published: April 2024

Recent global marine lipidomic analysis reveals a strong relationship in the ocean between temperature and phytoplanktonic abundance of omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential for human nutrition and primarily from phytoplankton in marine food webs. In phytoplanktonic organisms, EPA may play a major role in regulating the phase transition temperature of membranes, while the function of DHA remains to be explored. In the oleaginous diatomPhaeodactylum tricornutum, DHA is distributed mainly on extraplastidial phospholipids, which is very different from the EPA enriched in thylakoid lipids. Here, CRISPR/Cas9-mediated knockout ofptELO5a, which encodes a delta-5 elongase catalyzing the elongation of EPA to synthesize DHA, led to a substantial interruption of DHA synthesis inP. tricornutum. TheptELO5amutants show significant alterations in transcriptome and glycerolipidomes including membrane lipids and triacylglycerols under normal temperature (22°C), and are more sensitive to elevated temperature (28°C) than wild type. We conclude that the PtELO5a-mediated synthesis of small amounts of DHA has indispensable functions in regulating the membrane lipid, and indirectly contributing storage lipid accumulation and maintaining thermomorphogenesis inP. tricornutum. This study also highlights the significance of DHA synthesis and lipid composition for environmental adaptation ofP. tricornutum.