bluuebunny/crossref_metadata_2025 huggingface dataset:
Impella compared to Venoarterial Extracorporeal Membrane Oxygenation In Cardiogenic Shock: A Systematic Review And Meta-Analysis Of Propensity Score Matched Studies
Authors: Stub Dion , Chan William , Ball Jocasta , Burell Aidan , Ihle Josh , Theng Steven , Tsintzos Stelios , Kaye David M , Seage Tahlia , Mudge Mia
Published: February 2025

Background

Veno-arterial extracorporeal membrane oxygenation (VA ECMO) and Impella, a transluminal microaxial ventricular assist device, are well-established in the management of cardiogenic shock. No randomised controlled trials (RCTs) directly compare Impella versus VA ECMO to inform their safety and efficacy in cardiogenic shock.

Purpose

This study aims to conduct a systematic review and meta-analysis of propensity score matched / adjusted studies to compare the clinical outcomes of Impella vs. VA ECMO in cardiogenic shock patients.

Methods

A systematic review was undertaken to identify comparative studies of Impella and VA ECMO in cardiogenic shock, which in the absence of RCTs, was limited to observational trials with propensity matched or adjusted outcomes to account for important confounding factors between populations. In-hospital/30-day survival and bleeding events requiring transfusion were meta-analysed using the random effects method.

Results

Five propensity score matched/adjusted studies comparing short-term survival following treatment with Impella vs. VA ECMO were included. A statistically significant difference in in-hospital/30-day mortality was detected between patients treated with Impella (39.6%) vs. VA ECMO (53.8%) (odds ratio [OR] 95% confidence interval [95% CI]: 0.57 [0.44, 0.74]; p < 0.0001). Impella was associated with significantly fewer bleeding events requiring transfusion compared with VA ECMO (19.9% vs. 28.8%, respectively) (OR = 0.61 [0.46, 0.80]; p = 0.0004).

Conclusion

In the absence of RCTs, this meta-analysis of propensity matched/adjusted observational trials represents the highest level of evidence available to date. Impella was associated with improved short-term survival and decreased bleeding events compared to VA ECMO in patients with cardiogenic shock.
Mucosal Mixed Lymphocyte Reaction Assay Using Intestinal Lymphocytes as a Biomarker for Intestinal Transplant Tolerance Development
Authors: Gunes M. Esad , Patwardhan Satyajit , Hong Julie , Manell Elin , Jordache Philip , Chauhan Ishit , Almesallmy Ahmed , Fu Jianing , Sykes Megan , Weiner Joshua
Published: February 2025

Background.

Intestinal transplantation (ITx) has the highest rate of rejection among solid organ grafts. We aimed to study the pathophysiology of rejection after ITx but lacked a tool for assessing cellular responses within the graft. Therefore, we developed a novel mixed lymphocyte reaction (MLR) assay to investigate immune responses in the graft.

Methods.

Intestinal samples were collected, decontaminated, and processed into single-cell suspensions from 9 swine and 2 patients that underwent ITx. Debris was removed using gradient centrifugation. The cells were plated with corresponding stimulator cells and incubated for 6 d before data acquisition and analysis.

Results.

Tolerant animals showed no anti-donor or anti-recipient responses in their graft mucosa but maintained strong anti–third-party responses, even after weaning immunosuppression. An animal with graft-versus-host disease displayed robust anti-recipient and anti–third-party responses but no anti-donor response. The animals with graft rejection maintained anti-donor responses at all timepoints. Finally, some tolerant animals developed “split tolerance,” with anti-donor responses in the peripheral blood but donor-specific hyporesponsiveness in the mucosal MLR, which regulatory T cells depletion suggested was attributable to local regulatory tolerance. When applied to human sample, this mucosal MLR reliably demonstrated self-tolerance with normal anti–third-party responsiveness.

Conclusions.

The novel mucosal MLR assay presented herein ± CD25 depletion serves as a useful adjunct for assessing immune responses within the intestinal graft mucosa. This could help elucidate immune responses after ITx in future studies, including our own, and could represent a promising tool for studying ITx tolerance development, guiding immunosuppression strategies, and advancing personalized transplant medicine.
Unraveling Molecular and Functional Responses Across 3 Lung Injury Models to Expand the Donor Lung Pool
Authors: Hirdman Gabriel , Stenlo Martin , Bèchet Nicholas Burdon , Niroomand Anna , Mittendorfer Margareta , Wang Qi , Edström Dag , Ghaidan Haider , Kjellström Sven , Pierre Leif , Olm Franziska , Hyllén Snejana , Lindstedt Sandra
Published: February 2025

Background.

Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries.

Methods.

Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (n = 7), aspiration-induced using endotracheal gastric content (n = 7), and injury using lavage and harmful ventilation (ventilator-induced lung injury; n = 7). Molecular and functional changes from before and after the establishment of lung injury were examined with histopathology, immunohistochemistry, cytokine levels, hemodynamics, and mass spectrometric analysis of lung tissue. The respiratory tract lining fluid was analyzed using exhaled breath particles.

Results.

T-cell proliferation and suppression of complement activation were unique to the gastric injury, whereas the ventilator-induced lung injury group displayed a unique activation of monocyte chemotaxis. The lipopolysaccharide injury exhibited an activation of stress response proteins. Alterations in the extracellular matrix, particularly the degradation of collagen type IV and increased elastin expression, were identified as a consistent indicator of acute lung injury. Additionally, increases in exhaled particles and differential expression of proteins in the respiratory tract lining fluid correlated with deteriorating lung function.

Conclusions.

Molecular analysis of the lung indicated distinct key differences and similarities of donor lung injury phenotypes. Analysis of various donor lung injuries suggests a heightened emphasis on the extracellular matrix for the restoration and rejuvenation of damaged donor lungs.
Simple recombinant monoclonal antibody production from
Escherichia coli
Authors: Baker Karen , Eastwood Tara A. , Garcia Esther , Lennon Chris , Mulvihill Daniel P.
Published: February 2025

Antibodies are valuable biological reagents used in a wide range of discovery research, biotechnology, diagnostic and therapeutic applications. Currently, both commercial and laboratory-scale antibody production is reliant on expression from mammalian cells, which can be time-consuming and requires the use of specialist facilities and costly growth reagents. Here, we describe a simple, rapid and cheap method for producing and isolating functional monoclonal antibodies and antibody fragments from bacterial cells that can be used in a range of laboratory applications. This simple method only requires access to basic microbial cell culture and molecular biology equipment, making scalable in-house antibody production accessible to the global diagnostics, therapeutics and molecular bioscience research communities.
Interaction of Remalan Brilliant Blue R dye with
n
-alkyltrimethylammonium chloride surfactants: conductometric and spectroscopic investigations
Authors: El-Hashani Ashraf , Kumar Sah Manish , Edbey Khaled , Ismael Rehab Gaber , Kumar Dileep , Bhattarai Ajaya
Published: February 2025

Micellization behaviour, thermodynamics and dye–surfactant interactions are the main topics of this investigation into the relationship between Remalan Brilliant Blue R (RBBR) dye and
n
-alkyltrimethylammonium chloride (C

n

TAC;
n
= 12, 14, 16 and 18) surfactants. Conductometric analysis revealed that the critical micelle concentration decreased with increasing alkyl chain length, suggesting that longer chains formed better micelles. Due to electrostatic interactions, spectrophotometric analyses revealed notable alterations in RBBR absorption following contact with C

n

TAC. Benesi–Hildebrand and Scott equations were used to compute the binding constant (
K
b
), which increased with chain length, indicating stronger dye–micelle interactions. The spontaneous interactions between RBBR and micelles were confirmed by thermodynamic analysis, which showed negative Gibbs free energy values (Δ
G
). The stability of dye–micelle complexes is attributed to hydrophobic forces, as seen by the greater negative Δ
G
that was produced by longer alkyl chains. Interestingly, increased surfactant concentrations changed equilibrium and decreased dye adsorption by breaking up pre-formed RBBR–C

n

TAC complexes. These results highlight how important the length of the alkyl chain is for micelle formation, thermodynamic parameters and dye–surfactant interactions. As the length of the chain grew, the sequence of RBBR binding strength was found to be C
12
TAC < C
14
TAC < C
16
TAC < C
18
TAC.
Dynamic kinetic resolution-mediated synthesis of C-3 hydroxylated arginine derivatives
Authors: Zheng Ye , Chen Zhenyu , Clarkson Guy J. , Marshall Stephen A. , Xiao Jianliang , Schofield Christopher J. , Wills Martin , Stachulski Andrew V.
Published: February 2025

Hydroxylated amino acids and their derivatives, including those found in proteins, are important in biology and medicinal chemistry. Incubation of N-acetyl-
l
-arginine with clavaminic acid synthase, a key oxygenase in clavulanic acid biosynthesis, affords a (3R)-hydroxylated product that is identical to material obtained by total synthesis from Boc-beta alanine. The key step employed dynamic kinetic resolution (DKR) of a β-ketoester precursor, achieved in high diastereomeric and enantiomeric excess using an (R)-SEGPHOS/Ru(II) catalyst. The results highlight the utility of DKR for the preparation of C-3 hydroxylated amino acid derivatives.
Research on characteristic properties of ASiGe nanoribbons materials for nanoelectronics and optoelectronics applications
Authors: Minh Tien Tran
Published: February 2025

This article presents the properties of armchair SiGe nanoribbon (ASiGeNR) configurations with varying ribbon widths. Using the Vienna Ab initio Simulation Package calculation program, several basic properties—such as electronic band structure, density of states, charge density distribution, real and imaginary parts of the dielectric functions, joint density of states (JDOS) and the optical absorption and reflection rates according to the energy of incident light—were investigated and evaluated. The electronic band structure was computed using both the generalized gradient approximation Perdew–Burke–Ernzerhof and HSE06 methods. The results show that the ASiGeNR configurations have a direct bandgap, ranging from a minimum of 0.0889 to a maximum of 0.7528 eV, depending on the number of atoms along the nanoribbon width, with the bandgap opening at the Γ point. There is a hybridization of sp² and sp³ orbitals in the ASiGeNRs, with the σ bonds being relatively stronger than the π bonds. ASiGeNR systems allow electromagnetic waves to pass through, primarily in the
z
-direction. The energy levels and directions in which the ASiGeNR structure absorbs or disperses the most energy occur between 2 and 4 eV in the
y
- and
z
-directions. The real part of the dielectric function varies significantly across the different structures, with the most noticeable change occurring in the
z
-direction. The ASiGeNR6 structure exhibits the highest absorption peak, which gradually decreases in the subsequent structures. The imaginary part of the dielectric function tends to peak at photon energies below 4 eV, indicating strong interaction between light and the material structures within this energy range. This suggests that changes in nanoribbon width significantly affect the optical properties of the material. The JDOS results align with the optical absorption spectrum, with peaks in JDOS corresponding to peaks in the optical absorption spectrum.
Filling ionospheric monthly medians missing data: a machine learning approach
Authors: Zossi Bruno S. , Medina Franco D. , Duran Trinidad , Fagre Mariano , de Haro Barbas Blas F. , Elias Ana G.
Published: February 2025

Ionospheric databases, like most time series of experimental parameters, contain missing data owing to either natural or technical reasons, limiting the statistical methods that can be used to analyse these series. In this work, two machine learning (ML) techniques, gradient boosting regression (GBR) and random forest regression (RFR), are applied to estimate missing values in the hourly monthly median foF2 datasets from eight ionospheric stations, covering the period 1975–2022. Their performance is compared with that of traditional linear and multiple regressions using comparative statistical indices, which indicate that ML techniques outperform conventional methods, reaching an explained variance of 97%, and with absolute errors between 40 and 60% smaller, on average, than linear and multiple regressions. These findings highlight the efficiency of ML in reconstructing ionospheric datasets, enhancing the reliability and continuity of long-term ionospheric observations.
Equivalent local force conditions minimizing the Frank free energy for topological defect equilibria in nematic liquid crystals
Authors: Miyoshi Hiroyuki , Crowdy Darren G. , Miyazako Hiroki , Nara Takaaki
Published: February 2025

Recently, Miyoshi
et al
. (Miyoshi
et al
. 2024
Proc. R. Soc. A
480
, 20240405 (doi:
10.1098/rspa.2024.0405
)) derived analytical formulas for the Frank free energy associated with multiple topological defects in nematic liquid crystals confined to an arbitrary simply connected domain. The energy formulas, derived using an analogy with the so-called Kirchhoff–Routh path function in point vortex dynamics, required the evaluation of contour integrals involving analytical formulas associated with the crystal alignment field. Equilibria for topological defects were then obtained by finding local extrema of this Frank free energy. By contrast, in vortex dynamics, it is rare to find point vortex equilibria by minimizing the Kirchhoff–Routh path function that is a regularized kinetic energy; more commonly, a local ‘non-self-induction rule’ is used that is equivalent to each point vortex being free of net force. It is shown here that an analogous equivalent set of local force conditions can also be used to find equilibria for topological defects in nematic liquid crystals in confined domains, and without any need to evaluate the Frank free energy. This observation is significant theoretically and also because, at a technical level, the new local force conditions are easier to formulate and solve.
Effect of the Incubation Time on Blood Culture Results and Bacterial Pathogens Causing Bloodstream Infections among Children Attending Sekou Toure Regional Referral Hospital in Mwanza, Tanzania
Authors: Thomas James , Wasira Albert , Maarafu Darus , Igogo Faustin , Emmanuel Eunice , Ernest Roza , Mushi Martha F. , Mshana Stephen E.
Published: February 2025

Background: One-hour delay in initiating appropriate antimicrobial treatment increases the mortality rate of patients with bloodstream infections by 2%. This highlights the risk associated with manual blood culture methods, as they tend to have long turn-around time with initial incubation period of 18-24 hours leads to delays in obtaining diagnostic results. This study examined the impact of incubation time on blood culture results and analyzed the patterns of the pathogens causing bloodstream infections (BSIs) among children attending Sekou Toure Regional Referral Hospital, Mwanza, Tanzania
Methodology: A hospital-based, descriptive cross-sectional study was conducted at Sekou Toure Regional Referral Hospital from May to July 2024. The conventional blood culture method, using in-house prepared brain heart infusion broth with slight modifications on the initial time of the blind subculture (at 8 hours, 24 hours and 120 hours) was done to isolate the pathogens causing BSIs. Descriptive data analysis was performed using STATA software version 15.
Results: The study enrolled 302 children with clinical diagnosis of BSI. Of these, 160 (53%) were male, with a median age of 6 years (IQR: 1-7 years). Fever was the predominant clinical sign reported in 259 (85.8%) children. Microbiologically confirmed bloodstream infections were detected in 90 (29.8%) children. Among them, 51.1% (46/90) were detected through blind subculture after 8 hours of initial incubation. An additional 31 (34.4%) were detected after 24 hours, and 13 (14.4%) were identified after 120 hours of incubation.
The most frequently isolated pathogens were Klebsiella pneumoniae (25.6%, 23/90) and Staphylococcus aureus (24.4%, 22/90). Gram-negative bacteria formed the majority, (71.1% 64/90) of the isolated pathogens, with 62.5% (40/64) showing resistance to third-generation cephalosporin. Additionally, 45.5% (10/22) of the Staphylococcus aureus strains were methicillin-resistant (MRSA).
Conclusion: Blind subculture after 8 hours of initial incubation correctly detected more than half of the children with microbiological confirmed bloodstream infections. Incorporating blind subculture on MacConkey agar supplemented with cefotaxime 2µg/ml (MCA-C) after 8 hours of incubation resulted in the correct treatment of half of the children with bloodstream infections caused by Gram-negative bacteria within 24 hours. In areas with high prevalence of third-generation cephalosporin resistance, blind subculture within 8 hours should include MacConkey agar supplemented with cefotaxime 2µg/ml for appropriate treatment within 24 hours.
State of health of the gut microbiome assessed through a quantitative metabolomic-based marker panel
Authors: DeLeon Orlando , Frith Mary , Sidebottom Ashley M , Koval Jason , Lolans Karen , Ceccato Hugo D , Cham Candace M , Fei Na , Wall Elizabeth , Kupfer Sonia , Sims Arial , Pierre Joseph F , Chang Eugene B
Published: February 2025

Defining the “health” of the gut microbiome or microbial organ has been elusive and controversial. This in turn makes defining gut dysbiosis (imbalances in gut microbiota) an enigma particularly in determining what, how, and when to intervene to restore eubiosis. Taxonomical profiles of gut microbiota have typically been used but are unreliable because of highly variable interindividual taxa and arbitrary functional assignments generalized to microbial groups. We therefore developed a functional metabolomic marker panel, selected through a supervised, machine-learning approach, using a healthy adult discovery cohort. The panel’s performance and utility were evaluated individually and together using a composite Z score through; (1) two validation cohorts of self-described healthy adults, 2) a large, external inflammatory bowel disease cohort, and 3) a patient with functional bowel disease to direct dietary intervention. The findings of this study provide proof of concept that quantitative functional profiles of the gut microbiome can be useful in assessing the health of the gut microbiome and for clinical application.
A new approach to estimating HIV incidence and the size of the infected and undiagnosed population in high immigration settings
Authors: Kunkel Amber , Cazein Françoise , Lot Florence , Muzzolon Julie , Pantazis Nikos , Alioum Amadou
Published: February 2025

Most current approaches to estimating HIV incidence and the size of the undiagnosed population do not account for pre-migration infections, although these represent a substantial fraction of new diagnoses in some European countries. We propose a new approach to estimating these indicators that explicitly accounts for migration. First, we use an existing Bayesian model to estimate delays between infection and diagnosis for each newly diagnosed individual, and classify those born abroad into pre- or post-migration infections. Second, for native-born individuals and those with post-migration infections, we use a repurposed regression model to describe the global distribution of delays between infection and diagnosis, and estimate HIV incidence. For people with pre-migration infections, the same model is used to describe the delays between migration and diagnosis, and subsequently estimate the number of arriving migrants with undiagnosed HIV. Finally, these estimates are combined to estimate the number of people in the country with undiagnosed HIV. When applied to simulated data inspired by the French HIV surveillance system, the new model appropriately corrects for pre-migration HIV infections and produces estimates of HIV incidence, arrival of people with undiagnosed HIV, and the size of the undiagnosed population that are similar to the true simulated values.
Impact of a Decision aid on Perceptions of Shared Decision-Making in the Primary Care Management of Patients with Subacromial Pain Syndrome: a two-phased multi-methods study
Authors: Bengtsen Samantha C , Rathleff Michael S , Zadro Joshua R , Olesen Jens L , Foster Nadine E , Thomsen Janus L , Elwyn Glyn , Søndergaard Jens , Lyng Kristian D
Published: February 2025

Background

Subacromial pain syndrome (SAPS) is the most common shoulder pain condition in primary care). Although exercise is the recommended first-line treatment, the absence of a universally superior option underscores the need for personalized care facilitated by shared decision-making (SDM). Despite the importance of SDM is increasingly recognized, its application in SAPS care remains poorly understood. The primary aim of this study was to explore the influence of a decision aid on patient and observer perceptions of SDM in the primary care management of patients with SAPS. Furthermore, the study aimed to explore correlations between patients’ and observers’ ratings of SDM.

Methods

We conducted a multi-methods study including observations of consenting patients with SAPS in their clinical consultations with clinicians from four Danish primary care practices, using OPTION-12. Additionally, we gathered patients’ perceptions of SDM two weeks after the consultation using an online survey using the 3-item CollaboRATE questionnaire and the 9-item Shared Decision-Making Questionnaire (SDM-Q-9). We observed consultations both with and without the introduction of a decision aid tailored to support the management of patients with SAPS.

Results

Thirty-four consultations were observed (16 with the decision aid, 18 without). Without the decision aid, the mean (SD) OPTION-12 score was low 10.5 + 3.3, and the median (IQR) CollaboRATE and mean (SD) SDM-Q-9 scores were 5 (IQR = 1.3) and 22.2 + 7.5, respectively. We observed higher scores in the consultations with the decision aid; the mean (SD, range) OPTION-12 score statistically significantly increased to 22.7 (6.87, 5-32), and the median (IQR) CollaboRATE and mean (SD) SDM-Q-9 scores were 6.5 (1.4) and 30.6 + 8.4, respectively. There was a positive and statistically significant correlation between patients’ and observers’ ratings of OPTION-12 and SDM-Q-9 scores across both phases. No significant correlation was found between CollaboRATE, OPTION-12, and SDM-Q-9 in either phase.

Conclusion

A decision aid significantly improved observer- and patient-rated SDM in primary care consultations for patients with SAPS. Observer-rated SDM scores more than doubled with the decision aid, and patients reported higher levels of SDM. These findings highlight the potential of decision aids to enhance SDM in SAPS care.
Aedes albopictusis rapidly invading its climatic niche in France: wider implications for biting nuisance and arbovirus control in Western Europe
Authors: Radici Andrea , Hammami Pachka , Cannet Arnaud , L’Ambert Grégory , Lacour Guillaume , Fournet Florence , Garros Claire , Guis Hélène , Fontenille Didier , Caminade Cyril
Published: February 2025

The Asian tiger mosquito,Aedes albopictus,is a competent vector of arboviruses, such as dengue. After its introduction into southern Europe, this invasive species has been rapidly spreading as well as causing autochthonous cases of arboviral diseases. BothAe. albopictuspresence and potential to transmit arboviruses are facilitated at warm temperatures, hence global warming is expected to favor their presence in temperate regions.

We use a climate- and environmental-driven mechanistic modelling framework to investigate the impact of recent climate change onAe. albopictusrange expansion and its potential to transmit dengue in Western Europe. We simulate climatic suitability, adult density and dengue transmission risk which we compare with a large ensemble of entomological and epidemiological observations over the past 20 years. Most importantly, we analyze a novel dataset about colonization of French municipalities to estimate the spread rate ofAe. albopictusand compare it with model predictions. Lastly, we analyze the sensitivity of entomological and epidemiological risk to changes in temperature, rainfall and human density.

Distribution of both simulated mosquito populations and dengue transmission risk satisfactorily match entomological and dengue observations for Western Europe (AUC = 0.90 and 0.75 respectively). While lowlands in southern Europe were already climatically suitable for hostingAe. albopictusaround 2010, Western France, together with large populated cities such as London, Zagreb and Vienna, have only become suitable recently. Importantly, the accelerating colonization ofAe. albopictusin France may be approaching its theoretical climatic suitability limit, which could determine future expansion. Area at risk of local dengue transmission has recently expanded from the Mediterranean coasts over northern Spain and Western France. The sensitivity analysis suggests that climate change may expose medium-sized cities to the highest epidemiological risk; this finding is consistent with recently reported dengue outbreaks in Italy and southern France.
Benchmarking long-read genome assemblers for three sequencing protocols and three agricultural species
Authors: Birbes Clément , Dréau Andreea , Milan Denis , Iampietro Carole , Gaspin Christine , Donnadieu Cécile , Zytnicki Matthias , Klopp Christophe
Published: February 2025

Today, long read technologies make it possible to produce telomere-to-telomere genome assemblies. These assemblies permit more accurate whole genome analyses, including on repeated regions.

The genome assembly process can chain several steps such as read correction, contigs assembly, contig polishing, scaffolding and gap filling, among others. Each step usually requires at least one software package, and input sequences. For the end user, it is not necessarily clear which combination of tools, together with read types, will work best for a given genome.

In this work, we will focus on contig production, which is a central and complex task of the assembly process. It aims at producing the longest, errorless, sequences, calledcontigs, from reads. While it is possible to produce contigs from short reads, long reads are now widely preferred, since they produce much longer contigs.

In this work, we evaluate several contig producing software packages (usually namedassemblers), on long reads generated by two sequencers using three protocols, for three eukaryotic, complex species with different characteristics. Our aim is twofold. First, we would like to give readers insight on the impact of sequencing technology and assembler combinations, in order to help them make their choice for a given genome. Second, we would like to present different assembly metrics and provide a critical view on their interpretation.
Nano formulation development and antibacterial activity ofcinnamon bark extract-chitosancomposites againstburkholderia glumae, the causative agent ofbacterial panicle blightin rice
Authors: Mohammed-Naji Qamar , Zulperi Dzarifah , Ahmad Khairulmazmi , Hata Erneeza Mohd
Published: February 2025

Bacterial panicle blight (BPB) disease, caused byBurkholderia glumae, poses a significant threat to rice production. Conventional chemical control methods contribute to environmental concerns and resistance issues, necessitating the development of sustainable alternatives. This study aimed to formulate and evaluate cinnamon bark extract-chitosan (CBE-CS) nano formulations for antibacterial efficacy againstBurkholderia glumae. First, the antibacterial activity of cinnamon bark extract (CBE) was assessed, revealing a minimum inhibitory concentration (MIC) of 6.25 μg/mL and a minimum bactericidal concentration (MBC) of 12.5 μg/mL. Morphological analysis using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and transmission electron microscopy (TEM) showed significant bacterial cell wall damage, cytoplasmic leakage, and structural degradation after treatment. Chemical characterization of CBE using gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FTIR) identified key active compounds, with (Z)-3-phenylacryldehyde as the major component (51.24%). Next, nano formulations of CBE-CS were developed, and their physicochemical properties were characterized, including particle size, zeta potential, encapsulation efficiency (33.9%), and loading capacity (48.78%). Antibacterial assessments demonstrated that the nano formulations effectively inhibitedBurkholderia. glumae. Finally, greenhouse trials on rice seedlings confirmed the efficacy of these nano formulations in controlling BPB disease, showing significant bacterial suppression and improved plant health. These findings suggest that CBE-CS nanoparticles offer a promising, eco-friendly alternative for managing bacterial blight in rice, providing both effective antibacterial activity and enhanced plant protection.
NeuroDISK: An AI Approach to Automate Continuous Inquiry-Driven Discoveries in Neuroimaging Genetics
Authors: Garijo Daniel , Yang Qifan , Vargas Hernán , Gadewar Shruti P. , Low Kevin , Ratnakar Varun , Osorio Maximiliano , Zhu Alyssa H. , McMahon Agnes , Gil Yolanda , Jahanshad Neda
Published: February 2025

Collaborative and multi-site neuroimaging studies have greatly accelerated the rate at which new and existing data can be aggregated to answer a neuroscientific question. New research initiatives are continuously collecting more data, allowing opportunities to refine previous published findings through continuous and dynamic updates. Yet, we lack a practical framework for researchers to systematically, automatically, and continuously update published findings. We developed NeuroDISK, an automated artificial intelligence based framework that: 1) performs automated and inquiry-driven analyses, and 2) continuously updates these analyses as new data becomes available. NeuroDISK was evaluated using published results from the ENIGMA consortium’s work on the genetic architecture of the cerebral cortex. We incorporate both meta-analysis and meta-regression options to showcase our framework on the effect of specific genotypes and moderators on select brain regions. Initial NeuroDISK meta-analysis results replicate the original publication, and we show result updates after adding new data. The NeuroDISK framework can be generalized for users to define question(s), run corresponding workflow(s) and access results interactively and continuously.
How Much Time Do Surgeons Spend Operating?
Authors: Andrade Nicholas S.
Published: February 2025

Background

Although surgeons participate in various clinical activities, performing surgery is their unique specialized function. Despite this, the fundamental metric of time spent operating remains unexplored.

Methods

We retrospectively analyzed operating room cases performed by surgeons who worked full-time for a full calendar year in two general hospitals. The operating time (from start to stop of the procedure) was extracted from electronic medical records for all cases from 2021 to 2024.

Results

263 surgeon-years were analyzed across 14 specialties. Surgeons spent a median of 451 hours operating annually (range 52-1160 hours) and performed a median of 414 cases (49-1381 cases). Annual operating time varied tenfold across specialties, from Cardiothoracic surgery (856 hours) to Podiatry (87 hours).

Conclusion

Surgeons spend about a quarter of their work time performing their uniquely trained function. The substantial variation within and between specialties suggests opportunities to optimize surgical workforce utilization. Understanding the determinants of operating time and sustainable surgical workload could improve healthcare system efficiency and surgical care delivery.
Genomewide Screen Identifies Peroxisomal Role in APOL1 Podocytopathy
Authors: Kim Jiyoung , Karel Isaac Z , Song Huijuan , Dewalt Megan , Orwick Shelley , Buelow Daelynn R. , Lee Kendyll , Brodsky Sergey V , Blissett Angie , Cocucci Ema , Baker Sharyn D. , Lin Pei-Hui , Pabla Navjot S. , Madhavan Sethu M
Published: February 2025

The G1 and G2 variants of the APOL1 gene increase the risk of chronic kidney disease (CKD) in individuals of African descent. In the presence of secondary stressors such as inflammation and hypoxia, these gain-of-function variants can induce podocyte dysfunction and cell death through mechanisms that are not fully understood. To identify genes that influence the cytotoxic effects of APOL1 variants under hypoxic conditions, we conducted a comprehensive whole-genome RNA interference (RNAi) screen. We found that silencing several peroxisomal (PEX) genes significantly intensified the cytotoxicity associated with the G1 and G2 variants, revealing the previously unknown role of peroxisomes in APOL1-related cytotoxicity. Importantly, enhancing peroxisomal function through both genetic and pharmacological approaches led to a significant reduction in cytotoxicity linked to these variants. We also identified a peroxisomal targeting signal at the C-terminus of APOL1 that facilitates its translocation to peroxisomes during hypoxia, and mutations in this signal were found to reduce the cytotoxic effects of the variants. Collectively, our findings underscore the importance of peroxisomal function in the pathogenesis of CKD associated with APOL1 variants and suggest that targeting peroxisomes may represent an effective therapeutic strategy to mitigate CKD risk in vulnerable populations.

TRANSLATIONAL STATEMENT

Peroxisomal function is necessary to protect from APOL1 (kidney risk variant) KRV-mediated cytotoxicity in the presence of hypoxia, and targeting peroxisomes may represent an effective therapeutic strategy to mitigate CKD risk.
Neurology Training in Italy: A Survey on Italian Residency Programmes and Compliance with European Training Standards
Authors: Farè Matteo , Angelini Luca , Nuredini Andi , Nucera Bruna , Fiume Giulia , Bombaci Alessandro , Cartella Sandy Maria
Published: February 2025

Background

Since 2005, the European Union of Medical Specialists – Section of Neurology and the European Board of Neurology have outlined a comprehensive curriculum, the European Training Requirements in Neurology (ETRN), which defines the essential clinical knowledge, practical skills, and research competencies that European neurology training programmes should encompass. Despite these standards, notable differences in training quality and resources persist among Italian residency programmes. This survey, conducted by the Italian Section of Young Neurologists, aimed to assess the alignment of Italian neurology residency programmes with ETRN standards and to evaluate residents’ and early-career neurologists’ self-reported knowledge, practical skills, and access to specialised training opportunities.

Methods

An anonymous, online survey was distributed to neurology residents and recently qualified neurologists across Italy in November 2023. The survey included 39 items across four sections: demographics, residency programme structure, learning objectives, and out-of-network internship opportunities. Responses were evaluated using descriptive statistics and comparative analyses across institution sizes and training years.

Results

Of 248 respondents (45.2% female, mean age 28.9 years), only 70.5% of ETRN’s basic training objectives were met, with lower compliance observed for advanced competencies. Practical skills like lumbar puncture and history-taking were widely acquired, but advanced diagnostic techniques (e.g., EMG, neuro-sonography) and subspecialty training (e.g., neuro-oncology, palliative care) showed limited availability. Out-of-network internship participation was low (21.7%), mainly due to institutional constraints and lack of financial support, limiting exposure to diverse clinical environments.

Conclusions

Italian neurology training programmes align reasonably well with ETRN standards at the basic level, though significant gaps remain in advanced training, diagnostic techniques, and interdisciplinary skills. Enhanced standardisation, improved funding for extra-network internships, and focused efforts on advanced training are essential to elevate Italian neurology residency programmes to meet European standards more fully.
Cancer risks forMSH6pathogenic variant carriers
Authors: van der Werf – ‘t Lam A.S. , Dowty J.G. , Italia M. , Bakker A.C. , Koops F. , Bleeker F. , Gomez – Garcia E. , van Hest L.P. , Gille H.J.P. , Cornips M.C. , de Jong M.M. , Letteboer T.G.W. , Duijkers F.A.M. , Wagner A. , Eikenboom E.L. , van Asperen C.J. , Bajwa – ten Broeke S.W. , Win A.K. , Jenkins M.A. , Nielsen M.
Published: February 2025

Introduction

Lynch syndrome (LS) is a hereditary cancer syndrome caused by (likely) pathogenic variants (LP/P) in DNA mismatch repair genes, includingMSH6. It is associated with elevated lifetime risks for colorectal cancer (CRC), endometrial cancer (EC), and other malignancies. However, cancer risks specific toMSH6-associated LS, particularly for non-colorectal cancers, remain poorly defined. This study aims to provide refined cancer risk estimates for individuals withMSH6LP/P.

Methods

We conducted a retrospective cohort study of 360 families with 1117 knownMSH6LP/P carriers identified in the Netherlands between 1995 and 2020. Pedigree data were collected from multiple clinical centers, and cancer diagnoses were confirmed through medical records. Age- and sex-specific hazard ratios (HRs) and cumulative risks (CRs) were estimated using segregation analysis, appropriately adjusted for ascertainment.

Results

CR by age 80 forMSH6LP/P carriers were 36% in males (95% CI:25–48%) and 21% in females (95% CI 13–32%) for CRC, and 23% in females (95% CI:15–43%) for EC. Elevated risks were observed for ovarian cancer (OC) (6.4%, 95% CI:3–14.8%; HR 5.58, p=0.00037), urinary tract cancers (10.1% in males, 4.1% in females; HR 2.52, p=0.012), and biliary tract cancers (4.9% in males, 4.2% in females; HR 2.76, p=0.031). No increased risks were identified for prostate or breast cancer.

Conclusion

This study refines cancer risk estimates for MSH6 LP/P carriers, suggesting the need for delayed CRC screening in males and females and proactive discussions regarding prophylactic surgery for females to address elevated risks for EC and OC.
A Systematic Review of Psychological Resilience in the COVID-19 Responses: Current Research and Future Directions
Authors: Pasha Atena , Inusah Abdul-Hanan , Nayem Jannatun , Li Xiaoming , Qiao Shan
Published: February 2025

The COVID-19 pandemic has highlighted the importance of psychological resilience for well-being. However, no systematic review has been synthesizing global literature on this topic. This review examines psychological resilience across diverse populations, focusing on measurement, associated factors, and future public health preparedness strategies. Guided by the PRISMA, a thorough search of PsycINFO, PubMed, ScienceDirect, and Web of Science was conducted in February 2024 including empirical studies considering psychological resilience during the COVID-19 pandemic published in peer-reviewed English journals from 2020 to 2024, using search terms relevant to psychological resilience and COVID-19. Sixty-eight studies included, mostly using CD-RISC to measure psychological resilience. Multiple factors at various socio-ecological levels were associated with psychological resilience. Effective strategies in promoting resilience included promoting social connectedness through government policies and health communication campaigns and implementing personalized interventions such as telehealth services, resilience-training programs, and mindfulness-based interventions. For preparedness for future public health crises, long-term strategies emphasized investments in mental health services, resilience-building activities, and providing robust support for mental health across diverse populations. Community and educational initiatives should focus on mental health promotion programs in colleges and schools and life skills training to improve interpersonal skills and job crafting. Technological solutions like remote consultations, mHealth applications, and telehealth were also recommended. This review suggests that improving preparedness for future public health crises requires prioritizing investments in mental health services, resilience-building activities, and mHealth applications. These insights provide a foundational resource for research, policy, and interventions to strengthen resilience globally at individual, community, and structural levels.
Extending scope and power of circular RNA research with circtools 2.0
Authors: Kulkarni Shubhada R. , Dieterich Christoph , Jakobi Tobias
Published: February 2025

Circular RNAs (circRNAs) play a pivotal role in gene regulation, acting as transcriptional modulators at various cellular levels and exhibit remarkable specificity across cell types and developmental stages. Detecting circRNAs from high-throughput RNA-seq data presents significant challenges, as it requires specialized tools to identify back-splice junctions (BSJ) in raw sequencing data. To address this need, we previously developedcirctools, a robust and user-friendly software for circRNA detection, downstream analysis, and wet-lab integration. Building on this foundation, we now introducecirctools 2.0, a significantly enhanced framework designed to advance computational and support experimental analysis for circular RNA research. Novel key features ofcirctools 2.0include: (1) an ensemble approach to circRNA detection with improved recall rates, (2) a module for automated design of circRNA padlock probes for the Xenium spatial trancriptomics platform, (3) circRNA conservation analysis across animal model species, and (4) support for the Oxford Nanopore sequencing platform for full-length circRNA detection.

Availability

circtools 2.0 is available atgithub.com/jakobilab/circtoolsand licensed under GPLv3.0.

Contact

tjakobi@arizona.edu
Pamrevlumab did not meet its primary endpoint for ambulatory patients with Duchenne Muscular Dystrophy: the LELANTOS-2 trial
Authors: Wong Brenda L. , Phan Han C. , Péréon Yann , De Lucia Silvana , Dai Yi , Chen Ziyi , Campbell Craig , Sansone Valeria A. , Delstanche Stéphanie , Wang Steven , Gambetti Olga V. , Brandsema John F. , Carrier Ewa ,   LELANTOS-2 study investigators
Published: February 2025

Background

In Duchenne muscular dystrophy (DMD), fibrosis is linked to connective tissue growth factor (CTGF) overexpression. Pamrevlumab, a fully human monoclonal antibody that inhibits CTGF activity, showed promise as a DMD treatment in a phase 2 trial.

Objective

LELANTOS-2 (NCT04632940) was a global phase 3 study of the safety and efficacy of pamrevlumab for ambulatory males 6 to <12 years old with DMD.

Methods

Patients were randomized 1:1 to pamrevlumab 35 mg/kg every 2 weeks for 52 weeks or placebo. All received a stable corticosteroid regimen (deflazacort or prednisone/prednisolone). Primary endpoint was change in North Star Ambulatory Assessment (NSAA) total score from baseline to Week 52. Treatment-emergent adverse events (TEAEs) were noted. Patients who completed the main study period were eligible to enroll in the open-label extension (OLE).

Results

Seventy-three patients enrolled (mean [SD] age, 9.0 [1.5] years; pamrevlumab [n=37], placebo [n=36]). Between-group baseline characteristics were similar. The difference in change in NSAA score was not significant (least squares [LS] mean [SE]: pamrevlumab, –3.022 [0.5505] vs placebo, –2.494 [0.6962];p=0.5553). Across all secondary endpoints, there were no significant differences between patients treated with pamrevlumab or placebo. Nearly all patients (pamrevlumab, n=35 [97.2%]; placebo, n=35 [97.2%]) experienced TEAEs (most mild/moderate). Sixty-eight (34 from each original treatment group) patients enrolled in and received pamrevlumab during the OLE. OLE efficacy and safety were consistent with the main study period. No deaths occurred.

Conclusions

Pamrevlumab failed to meet its primary endpoint. Its future as a DMD treatment is uncertain.
Dynamic Prediction of Mortality Risk Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Spohr Philipp , Fröhlich Rebecca C. , Scharf Sebastian , Rommerskirchen Anna , Bobak Jonathan , Schweier Sarah , Jäger Paul , Kobbe Guido , Dietrich Sascha , Dilthey Alexander T. , Henrich Birgit , Pfeffer Klaus , Haas Rainer , Klau Gunnar W.
Published: February 2025

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for high-risk hematological malignancies, but early mortality within 100 days remains a significant challenge, affecting approximately 18% of patients. Identifying high-risk patients early is critical for timely interventions. While static risk scores like the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) and Endothelial Activation and Stress Index (EASIX) are valuable, they do not adapt to patients’ clinical trajectories. Leveraging the increasing availability of digital medical datasets, we developed a dynamic risk stratification system based on a random forest approach to continuously predict mortality risk from day 0 to day 30 post-transplantation.

Analyzing data from 847 patients undergoing alloHSCT between 2004 and 2019, our model achieved high classification performance, with AUROC scores continuously exceeding 0.8 from day 17, and effectively stratified patients into high, moderate, and low-risk groups. Feature importance analysis revealed a shift over time, with early predictions utilizing diverse variables and later stages relying more on inflammation-related bloodwork parameters. This dynamic approach surpasses static methods, demonstrating improved predictive performance and adaptability across treatment phases. To promote reproducibility and broader application, we provide open access to the software and accompanying bloodwork time-series dataset.