bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis
Authors: Shu Zhaohui , Feng Jingyun , Liu Lanting , Liao Yingqin , Cao Yuhong , Zeng Zhenhua , Qiuju Huang  , Li Zhonghong , Jin Guifang , Yang Zhicheng , Xing Jieyu , Zhou Sigui
Published: February 2024

Cardiac fibrosis is considered as unbalanced extracellular matrix production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis. In vivo experiments were performed on spontaneously hypertensive rats (SHR) and SCAD-knockout mice. The cardiac tissues of hypertensive patients with cardiac fibrosis were used for the measurement of SCAD expression. In vitro experiments, with angiotensin II (Ang II), SCAD siRNA and adenovirus-SCAD were performed using cardiac fibroblasts (CFs). SCAD expression was significantly decreased in the left ventricles of SHR. Notably, swim training ameliorated cardiac fibrosis in SHR in association with the elevation of SCAD. The decrease in SCAD protein and mRNA expression levels in SHR CFs were in accordance with those in the left ventricular myocardium of SHR. In addition, SCAD expression was downregulated in CFs treated with Ang II in vitro, and SCAD siRNA interference induced the same changes in cardiac fibrosis as Ang II-treated CFs, while adenovirus-SCAD treatment significantly reduced the Ang II–induced CFs proliferation, alpha smooth muscle actin (α-SMA), and collagen expression. In SHR infected with adenovirus-SCAD, the cardiac fibrosis of the left ventricle was significantly decreased. However, cardiac fibrosis occurred in conventional SCAD-knockout mice. SCAD immunofluorescence intensity of cardiac tissue in hypertensive patients with cardiac fibrosis was lower than that of healthy subjects. Altogether, the current experimental outcomes indicate that SCAD has a negative regulatory effect on cardiac fibrosis and support its potential therapeutic target for suppressing cardiac fibrosis.
Exploring the Promise and Challenges of Artificial Intelligence in Biomedical Research and Clinical Practice
Authors: Altara Raffaele , Basson Cameron J. , Biondi-Zoccai Giuseppe , Booz George W.
Published: February 2024

Artificial intelligence (AI) is poised to revolutionize how science, and biomedical research in particular, are done. With AI, problem-solving and complex tasks using massive data sets can be performed at a much higher rate and dimensionality level compared with humans. With the ability to handle huge data sets and self-learn, AI is already being exploited in drug design, drug repurposing, toxicology, and material identification. AI could also be used in both basic and clinical research in study design, defining outcomes, analyzing data, interpreting findings, and even identifying the most appropriate areas of investigation and funding sources. State-of-the-art AI-based large language models, such as ChatGPT and Perplexity, are positioned to change forever how science is communicated and how scientists interact with one another and their profession, including postpublication appraisal and critique. Like all revolutions, upheaval will follow and not all outcomes can be predicted, necessitating guardrails at the onset, especially to minimize the untoward impact of the many drawbacks of large language models, which include lack of confidentiality, risk of hallucinations, and propagation of mainstream albeit potentially mistaken opinions and perspectives. In this review, we highlight areas of biomedical research that are already being reshaped by AI and how AI is likely to affect it further in the near future. We discuss the potential benefits of AI in biomedical research and address possible risks, some surrounding the creative process, that warrant further reflection.
Instructional Video of a Standardized Interprofessional Postsimulation Facilitator-guided Debriefing of a Fatality in Plastic Surgery
Authors: Gasteratos Konstantinos , Michalopoulos James , Nona Marven , Morsi-Yeroyiannis Antonios , Goverman Jeremy , Rakhorst Hinne , van der Hulst René R. W. J.
Published: February 2024

Background:

Postsimulation facilitator-guided debriefing (PSFGD) is the process of intentional discussion of thoughts, actions, and events that took place during simulation amongst the facilitator(s) and trainees. Despite the significance of delivering high-quality debriefings, there is a lack of evidence-based guidelines. Our study aimed to provide an instructional video demonstration of a PSFGD of a fatality.

Methods:

Fifty surgical interns participated in a burn simulation scenario in two groups. Group 1 (control, or “no exposure,” n = 25) consisted of residents who received oral postsimulation debriefing from an independent faculty member who had no exposure to our instructional video on how to debrief effectively. Group 2 (intervention, or “exposure,” n = 25) consisted of interns who were debriefed by the second faculty member who did watch our instructional video before the simulation and learned about “advocacy and inquiry” techniques. The outcome measures were the Debriefing Assessment for Simulation in Healthcare score and the postdebrief multiple-choice question (MCQ) quiz scores to assess debriefers’ performance and interns’ knowledge consolidation, respectively.

Results:

The “exposure” group presented statistically significantly higher values for the Debriefing Assessment for Simulation in Healthcare score (P < 0.001) and MCQ score (P < 0.001) compared with the “no exposure” group.

Conclusions:

Debriefers who followed the methodology as demonstrated in our instructional video were considered more competent, and the residents achieved higher MCQ scores. The quality of the debriefing ensures improved critical thinking and problem-solving skills. Safer practice and better patient outcomes are achieved by developing debriefing programs for educators.
Improving Skin Paddle Reliability and Muscle Gliding in Free Functional Gracilis Transfers
Authors: Vaile John R. , Struble Sarah L. , Patel Niki K. , Janes Lindsay E. , Park Eugene D. , Levin L. Scott , Mendenhall Shaun D.
Published: February 2024

Free functional muscle transfer is an attractive option within reconstructive surgery when seeking to restore critical muscle function. The gracilis muscle has long been utilized for this purpose due to its expendability and consistent anatomy. Historically, survival of the skin overlying the distal one-third of the myocutaneous gracilis flap has been unpredictable. To address this, the myofasciocutaneous technique was developed, with prior studies demonstrating improved distal skin paddle viability with this approach; however, the mechanism is poorly defined. This study aimed to understand what factors contribute to survival benefit in myofasciocutaneous gracilis flaps. Using cadaveric dissections followed by latex dye injections, we discuss the creation of a deep fascial sheath that contains a rich vascular network and permits adhesion-free excursion at the recipient site. This study advances our understanding of the myofasciocutaneous gracilis flap and provides wider clinical applicability in free functional muscle transfer.
Race-specific associations: inflammatory mediators and chronic low back pain
Authors: Overstreet Demario S. , Strath Larissa J. , Sorge Robert E. , Thomas Pavithra A. , He Jingui , Wiggins Asia M. , Hobson Joanna , Long D. Leann , Meints Samantha M. , Aroke Edwin N. , Goodin Burel R.
Published: February 2024

Chronic low back pain (cLBP) is a global health crisis that disproportionately burdens non-Hispanic Black (NHB) individuals, compared with those who identify as non-Hispanic White (NHW). Despite the growing personal and societal impact of cLBP, its biological underpinnings remain poorly understood. To elucidate the biological factors that underlie the racial disparities in cLBP, this study sought to determine whether inflammatory mediators associated with pain interference (PI), pain at rest (PAR), and movement-evoked pain (MEP) differ as a function of racial identity. Blood samples were collected from 156 individuals with cLBP (n = 98 NHB participants, n = 58 NHW participants). Enzyme-linked immunosorbent assay and multiplex assays were used to quantify concentrations of proinflammatory (fibrinogen, C-reactive protein [CRP], serum amyloid A, tumor necrosis factor α [TNF-α], and interleukin [IL]–1α, IL-1β, and IL-6) and anti-inflammatory markers (IL-4 and IL-13). Spearman rho correlations were used to assess associations among markers of inflammation and PI, PAR, and MEP using the Brief Pain Inventory–Short Form. Analyses revealed that for NHW patients, CRP, serum amyloid A, and IL-6 were positively associated with cLBP outcomes and IL-4 was inversely associated with PAR and MEP. However, for NHB patients, only IL-1α was positively associated with PAR. Our findings suggest that, while there are associations between inflammation and cLBP outcomes, the biomarkers that underlie the inflammation could very well differ as a function of racialized minority group. However, more research with racially inclusive samples is needed to elucidate the mechanisms that may contribute to racial disparities in cLBP.
Pulmonary infections in the returning traveler
Authors: Norman Francesca F. , Gonzalez-Sanz Marta
Published: February 2024

Purpose of review

The recent COVID-19 pandemic has shaped the epidemiology of other infectious diseases globally. International tourist arrivals are increasing and recovering to prepandemic levels. This review focuses on respiratory infections in travelers, highlighting the characteristics of the main imported viral, bacterial, fungal, and parasitic infections with pulmonary involvement.

Recent findings

A recent systematic review estimated a prevalence of respiratory symptoms in travelers of around 35%, increasing to nearly 65% in the context of mass gatherings. Common viral and bacterial pathogens account for the majority of respiratory infections with an identified cause; however, recent data focus on the need for surveillance of emerging infections such as MERS-CoV, henipaviruses and multidrug resistant bacteria, which may be spread through travel. Fungal and parasitic respiratory infections are less common, and acquisition is usually associated with specific risk factors or exposure in endemic areas. Special risk groups, such as immunocompromised travelers, may be particularly vulnerable, presenting with severe disease or reactivation of latent infections.

The next significant international epidemic could involve another new infectious agent causing respiratory disease and spreading via mobile populations. Official protocols should be adhered to, and public health interventions implemented for effective control. Continued and globally coordinated investments in research for new vaccines, therapeutic agents, disease modeling, and digital tracking strategies are essential.
Thoracic empyema: aetiology, diagnosis, treatment, and prevention
Authors: Merchant Na’im , Liu Chantal
Published: February 2024

Purpose of review

The aim of this study was to review current key points in the aetiology, diagnosis, treatment, and prevention of empyema thoracis. Early postpandemic trends have seen an increasing global incidence and evolution in the aetiology of empyema. Due to varied aetiology and typically lengthy treatment, empyema will be disproportionately affected by the rising tide of antimicrobial resistance (AMR), thus warranting attention and further research.

Recent findings

Multiple novel biomarkers (e.g. IL-36γ) are under investigation to aid diagnosis, while oral health assessment tools are now available for prognosticating and risk-stratifying patients with thoracic empyema. There exists an ongoing lack of evidence-based guidance surrounding antibiotic treatment duration, surgical intervention indication, and prognostic scoring utility.

Understanding aetiologies in different global regions and settings is pivotal for guiding empirical treatment. Antimicrobial resistance will make thoracic empyema increasingly challenging to treat and should prompt increased awareness of prescribing practices. Novel biomarkers are under investigation which may speed up differentiation of pleural effusion types, allowing faster cohorting of patients.

Although newly identified predictors of morbidity and mortality have been suggested to be beneficial for incorporation into clinical practice, further work is required to prognosticate, risk-stratify, and standardize treatment.
Rural trauma team development training amongst medical trainees and traffic law enforcement professionals in a low-income country: a protocol for a prospective multicenter interrupted time series
Authors: Lule Herman , Mugerwa Michael , SSebuufu Robinson , Kyamanywa Patrick , Posti Jussi P. , Wilson Michael L.
Published: February 2024

Background:

Road traffic injuries and their resulting mortality disproportionately affect rural communities in low-middle-income countries (LMICs) due to limited human and infrastructural resources for postcrash care. Evidence from high-income countries show that trauma team development training could improve the efficiency, care, and outcome of injuries. A paucity of studies have evaluated the feasibility and applicability of this concept in resource constrained settings. The aim of this study protocol is to establish the feasibility of rural trauma team development and training in a cohort of medical trainees and traffic law enforcement professionals in Uganda.

Methods:

Muticenter interrupted time series of prospective interventional trainings, using the rural trauma team development course (RTTDC) model of the American College of Surgeons. A team of surgeon consultants will execute the training. A prospective cohort of participants will complete a before and after training validated trauma related multiple choice questionnaire during September 2019-November 2023. The difference in mean prepost training percentage multiple choice questionnaire scores will be compared using ANOVA-test at 95% CI. Time series regression models will be used to test for autocorrelations in performance. Acceptability and relevance of the training will be assessed using 3 and 5-point-Likert scales. All analyses will be performed using Stata 15.0. Ethical approval was obtained from Research and Ethics Committee of Mbarara University of Science and Technology (Ref: MUREC 1/7, 05/05-19) and Uganda National Council for Science and Technology (Ref: SS 5082). Retrospective registration was accomplished with Research Registry (UIN: researchregistry9490).
Optic Neuropathy and Myelopathy in a Teenager With Biotinidase Deficiency
Authors: Chodnicki Kevin D. , Aksamit Allen J. , Gavrilova Ralitza H. , Farnsworth Paul J. , McClelland Collin M.
Published: February 2024

A 19-year-old man presented with 3 years of gradually progressive, painless vision loss in both eyes. The ophthalmic examination showed bilateral diminished visual acuity, dyschromatopsia, and temporal optic nerve pallor. The neurological examination was consistent with a mild myelopathy with decreased pin-prick sensation starting at T6–T7 and descending through the lower extremities. Hyperreflexia was also present in the lower more than upper extremities. Infectious, inflammatory, and nutritional serum workup and cerebrospinal fluid analysis were both unrevealing. MRI of the brain and spinal cord showed abnormal T2 hyperintensity of the fornix, corpus callosum, optic nerves, and lateral columns of the cervical and thoracic spine, with diffusion restriction in the inferior–posterior corpus callosum and fornix. Biotinidase serum enzyme activity was tested and showed a decreased level of activity. Biotinidase gene testing showed a homozygous pathogenic variant, c.424C>A (p.P142T), confirming the diagnosis of biotinidase deficiency and prompting oral biotin supplementation. Three months after starting treatment, the patient's visual acuity, color vision, visual fields, and MRI spine abnormalities all improved significantly. Biotinidase deficiency is an important diagnostic consideration in patients with unexplained optic neuropathy and/or myelopathy.
Proposal for Prognosis-Oriented Definition of Borderline Resectable Hepatocellular Carcinoma
Authors: Haruki Koichiro , Harimoto Norifumi , Furukawa Kenei , Taniai Tomohiko , Yanagaki Mitsuru , Igarashi Yosuke , Tsunematsu Masashi , Shirai Yoshihiro , Shirabe Ken , Ikegami Toru
Published: February 2024

BACKGROUND:

Owing to advances in the multidisciplinary treatment of hepatocellular carcinoma (HCC), a conceptualization and definition for borderline resectable (BR) HCC, which carries a high risk of recurrence, is warranted. In this study, we aimed to define BR-HCC using a prognosis-oriented approach.

STUDY DESIGN:

The study included an original cohort of 221 patients and an independent validation cohort of 181 patients who had undergone primary hepatic resection for HCC. To define biological BR-HCC, we evaluated the risk factors for early recurrence beyond the Milan criteria within 1 year after hepatic resection using multivariable logistic regression models. Subsequently, we developed high-risk scores using the identified risk factors and defined BR-HCC. The utility of high-risk score was validated in the validation cohort.

RESULTS:

In the original cohort (hepatitis B virus:hepatitis C virus = 20%:29%), recurrence beyond the Milan criteria within 1 year was observed in 28 patients (13%), with a 5-year survival rate of 25%. Multivariable analysis identified risk factors for recurrence beyond the Milan criteria within 1 year, including serum alpha-fetoprotein levels of 12 ng/mL or more (p = 0.02), tumor diameters less than 5 cm (p = 0.02), tumor number 3 or more (p = 0.001), and macrovascular invasion (p = 0.04). BR-HCC was defined as a tumor with 2 or more identified risk factors, and 42 patients (19%) were diagnosed with BR-HCC, with a 5-year survival rate of 51%. In the validation cohort, 45 (25%) patients had BR-HCC, with a 5-year survival rate of 42%.

CONCLUSIONS:

The prognosis-oriented definition of BR-HCC enabled us to identify patients who are susceptible to early unresectable recurrence and have poor survival after hepatic resection for HCC. For patients with BR-HCC, preoperative systemic therapy may be a viable option to improve postresection outcomes.
Determination of
ω
-end functionalities in tailored poly(2-alkyl-2-oxazoline)s by liquid chromatography and mass spectrometry
Authors: Engel Nora , Dirauf Michael , Czaplewska Justyna A. , Nischang Ivo , Gottschaldt Michael , Schubert Ulrich S.
Published: February 2024

The in-depth analytical characterization of polymers, in particular regarding intended biomedical applications, is becoming increasingly important to elucidate their structure–property relationships. Specifically, end group analysis of e.g. polymers featuring a ‘stealth effect’ towards the immune system is of particular importance because of their use in coupling reactions to bioactive compounds. Herein, we established a liquid chromatography (LC) protocol to analyse bicyclo[6.1.0]nonyne-functionalized poly(2-alkyl-2–oxazoline)s (POx)s as promising functional polymers that can be applied in strain-promoted click reactions. This work involved the synthesis of poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx) by living cationic ring-opening polymerization (CROP) with different molar masses ranging from 2 up to 17.5 kDa and, to our knowledge, the first liquid chromatographic analysis of PMeOx. The developed analytical protocol enables the quantitative determination of post-polymerization reaction sequences with respect to the conversion of the
ω
-end groups. All synthesized polymers were straightforwardly analysed on a C18-derivatized silica monolithic column under reversed-phase chromatographic conditions with a binary mobile phase gradient comprising a mixture of acetonitrile and water. Subsequent mass spectrometry of collected elution fractions enabled the confirmation of the desired
ω
-end group functionalities and the identification of synthetic by-products.
The effect of model structure and data availability on Usutu virus dynamics at three biological scales
Authors: Heitzman-Breen Nora , Liyanage Yuganthi R. , Duggal Nisha , Tuncer Necibe , Ciupe Stanca M.
Published: February 2024

Understanding the epidemiology of emerging pathogens, such as Usutu virus (USUV) infections, requires systems investigation at each scale involved in the host–virus transmission cycle, from individual bird infections, to bird-to-vector transmissions, and to USUV incidence in bird and vector populations. For new pathogens field data are sparse, and predictions can be aided by the use of laboratory-type inoculation and transmission experiments combined with dynamical mathematical modelling. In this study, we investigated the dynamics of two strains of USUV by constructing mathematical models for the within-host scale, bird-to-vector transmission scale and vector-borne epidemiological scale. We used individual within-host infectious virus data and per cent mosquito infection data to predict USUV incidence in birds and mosquitoes. We addressed the dependence of predictions on model structure, data uncertainty and experimental design. We found that uncertainty in predictions at one scale change predicted results at another scale. We proposedin silicoexperiments that showed that sampling every 12 hours ensures practical identifiability of the within-host scale model. At the same time, we showed that practical identifiability of the transmission scale functions can only be improved under unrealistically high sampling regimes. Instead, we proposed optimal experimental designs and suggested the types of experiments that can ensure identifiability at the transmission scale and, hence, induce robustness in predictions at the epidemiological scale.
Measuring semantic memory using associative and dissociative retrieval tasks
Authors: Marko Martin , Michalko Drahomír , Kubinec Adam , Riečanský Igor
Published: February 2024

Recent theoretical advances highlighted the need for novel means of assessing semantic cognition. Here, we introduce the associative-dissociative retrieval task (ADT), positing a novel way to test inhibitory control over semantic memory retrieval by contrasting the efficacy of associative (automatic) and dissociative (controlled) retrieval on a standard set of verbal stimuli. All ADT measures achieved excellent reliability, homogeneity, and short-term temporal stability. Moreover, in-depth stimulus level analyses showed that the associative retrieval is easier for words evoking few but strong associates, yet such propensity hampers the inhibition. Finally, we provided critical support for the construct validity of the ADT measures, demonstrating reliable correlations with domain-specific measures of semantic memory functioning (semantic fluency and associative combination) but negligible correlations with domain-general capacities (processing speed and working memory). Together, we show that ADT provides simple yet potent and psychometrically sound measures of semantic memory retrieval and offers noteworthy advantages over the currently available assessment methods.
The moral machine experiment on large language models
Authors: Takemoto Kazuhiro
Published: February 2024

As large language models (LLMs) have become more deeply integrated into various sectors, understanding how they make moral judgements has become crucial, particularly in the realm of autonomous driving. This study used the moral machine framework to investigate the ethical decision-making tendencies of prominent LLMs, including GPT-3.5, GPT-4, PaLM 2 and Llama 2, to compare their responses with human preferences. While LLMs' and humans' preferences such as prioritizing humans over pets and favouring saving more lives are broadly aligned, PaLM 2 and Llama 2, especially, evidence distinct deviations. Additionally, despite the qualitative similarities between the LLM and human preferences, there are significant quantitative disparities, suggesting that LLMs might lean toward more uncompromising decisions, compared with the milder inclinations of humans. These insights elucidate the ethical frameworks of LLMs and their potential implications for autonomous driving.
Locomotion and the early Mesozoic success of Archosauromorpha
Authors: Shipley Amy E. , Elsler Armin , Singh Suresh A. , Stubbs Thomas L. , Benton Michael J.
Published: February 2024

The Triassic was a time of ecological upheaval as life recovered from the Permian-Triassic mass extinction. Archosauromorphs were a key component of the recovery, diversifying substantially during the Triassic and encompassing the origins of dinosaurs, pterosaurs and crocodylomorphs. Here, we explore the evolution of locomotion in Archosauromorpha to test whether dinosaurs show any distinctive locomotory features that might explain their success. We implement geometric morphometrics on limb bone shapes and use limb ratios to calculate bipedality and cursoriality metrics. We find that the Avemetatarsalia (dinosaurs, pterosaurs and relatives) exhibit more variable limb form and limb ratios than any other group, indicating a wider range of locomotory modes. The earliest avemetatarsalians were bipedal and cursorial, and their range of form increased through the Triassic with notable diversification shifts following extinction events. This is especially true of dinosaurs, even though these changes cannot be discriminated from a stochastic process. By contrast, the Pseudosuchia (crocodilians and relatives) were more restricted in limb form and locomotor mode with disparity decreasing through time, suggesting more limited locomotor adaptation and vulnerability to extinction. Perhaps the greater locomotor plasticity of dinosaurs gave them a competitive advantage in the changing climates of the Late Triassic.
Role of electromagnetic energy and momentum in the Aharonov–Bohm effect
Authors: Kholmetskii Alexander L. , Missevitch Oleg V. , Yarman Tolga
Published: February 2024

We analyse the physical meaning of the Aharonov–Bohm (AB) phase based on its representation through electromagnetic (EM) potentials as a sum of four components, which, in addition to the known electric and magnetic phase components, contains two more terms recently disclosed by our team in the analysis of quantum phase effects for dipoles and charges, and which we named the complementary electric AB phase and the complementary magnetic AB phase. Using the complete expression for the AB phase, we reveal that the phase component, explicitly depending on time, is determined by the interactional electric energy, while the phase component, explicitly depending on the velocity of charge, is determined by the interactional EM momentum for an isolated system ‘source of EM field and charge’. These findings shed new light on the origin of the AB phase and, in particular, allow us to generalize the de Broglie relationship and the Heisenberg uncertainty relations for a charged particle in an EM field.
Unifying temperature definition in atomistic and field representations of conservation laws
Authors: Chen Youping
Published: February 2024

In this work, a field representation of the conservation law of linear momentum is derived from the atomistic, using the theory of distributions as the mathematical tool, and expressed in terms of temperature field by defining temperature as a derived quantity as that in molecular kinetic theory and atomistic simulations. The formulation leads to a unified atomistic and continuum description of temperature and a new linear momentum equation that, supplemented by an interatomic potential, completely governs thermal and mechanical processes across scales from the atomic to the continuum. The conservation equation can be used to solve atomistic trajectories for systems at finite temperatures, as well as the evolution of field quantities in space and time, with atomic or multiscale resolution. Four sets of numerical examples are presented to demonstrate the efficacy of the formulation in capturing the effect of temperature and thermal fluctuations, including phonon density of states, thermally activated dislocation motion, dislocation formation during epitaxial processes, and attenuation of longitudinal acoustic waves as a result of their interaction with thermal phonons.
Multi-fidelity reduced-order surrogate modelling
Authors: Conti Paolo , Guo Mengwu , Manzoni Andrea , Frangi Attilio , Brunton Steven L. , Nathan Kutz J.
Published: February 2024

High-fidelity numerical simulations of partial differential equations (PDEs) given a restricted computational budget can significantly limit the number of parameter configurations considered and/or time window evaluated. Multi-fidelity surrogate modelling aims to leverage less accurate, lower-fidelity models that are computationally inexpensive in order to enhance predictive accuracy when high-fidelity data are scarce. However, low-fidelity models, while often displaying the qualitative solution behaviour, fail to accurately capture fine spatio-temporal and dynamic features of high-fidelity models. To address this shortcoming, we present a data-driven strategy that combines dimensionality reduction with multi-fidelity neural network surrogates. The key idea is to generate a spatial basis by applying proper orthogonal decomposition (POD) to high-fidelity solution snapshots, and approximate the dynamics of the reduced states—time-parameter-dependent expansion coefficients of the POD basis—using a multi-fidelity
long short-term memory
network. By mapping low-fidelity reduced states to their high-fidelity counterpart, the proposed reduced-order surrogate model enables the efficient recovery of full solution fields over time and parameter variations in a non-intrusive manner. The generality of this method is demonstrated by a collection of PDE problems where the low-fidelity model can be defined by coarser meshes and/or time stepping, as well as by misspecified physical features.
Supply chain loss from easing COVID-19 restrictions: an evolutionary economic-epidemiological modelling study
Authors: Ye Yang , Cao Zhidong , Dajun Zeng Daniel , Zhang Qingpeng
Published: February 2024

Since the start of the COVID-19 pandemic, many firms have been shifting their supply chains away from countries with stringent control measures to mitigate supply-chain disruption. Nowadays, the global economy has reopened from the COVID-19 pandemic at various paces in different countries. Understanding how the global supply network evolves during and after the pandemic is necessary for determining the timing and speed of reopening. By harnessing the real-world and real-time global human movement and the latest macroeconomic data, we propose an evolutionary economic-epidemiological model to explore the evolutionary dynamics of the global supply network under various global reopening scenarios. We find that, for highly restrictive countries, the delay in reopening has limited public health benefits in the long run but leads to significant supply-chain loss. A longer duration of stringent control measures substantially hurts the profitability of firms in highly restrictive countries, leading to slower supply-chain recovery in 5 years. This research presents the first data-driven evidence of supply chain loss due to the timing and speed of reopening and sheds light on the post-pandemic supply-chain reformation and recovery. Insights learned from COVID-19 will also be a valuable policymaking reference for combating future infectious disease epidemics and geopolitical changes.
The source of microbial transmission influences niche colonization and microbiome development
Authors: Tanger Isabel S. , Stefanschitz Julia , Schwert Yannick , Roth Olivia
Published: February 2024

Early life microbial colonizers shape and support the immature vertebrate immune system. Microbial colonization relies on the vertical route via parental provisioning and the horizontal route via environmental contribution. Vertical transmission is mostly a maternal trait making it hard to determine the source of microbial colonization in order to gain insight into the establishment of the microbial community during crucial development stages. The evolution of unique male pregnancy in pipefishes and seahorses enables the disentanglement of both horizontal and vertical transmission, but also facilitates the differentiation of maternal versus paternal provisioning ranging from egg development, to male pregnancy and early juvenile development. Using 16S rRNA amplicon sequencing and source-tracker analyses, we revealed how the distinct origins of transmission (maternal, paternal and horizontal) shaped the juvenile internal and external microbiome establishment in the broad-nosed pipefish
Syngnathus typhle
. Our data suggest that transovarial maternal microbial contribution influences the establishment of the juvenile gut microbiome whereas paternal provisioning mainly shapes the juvenile external microbiome. The identification of juvenile key microbes reveals crucial temporal shifts in microbial development and enhances our understanding of microbial transmission routes, colonization dynamics and their impact on lifestyle evolution.
A cretaceous frog with eggs from northwestern China provides fossil evidence for sexual maturity preceding skeletal maturity in anurans
Authors: Du Baoxia , Zhang Jing , Gómez Raúl Orencio , Dong Liping , Zhang Mingzhen , Lei Xiangtong , Li Aijing , Dai Shuang
Published: February 2024

Mesozoic fossils of frogs are rare in the palaeontological record, particularly those exhibiting soft tissues that offer limited insights into early life-history characteristics. Here we report on a skeletally immature frog from the Lower Cretaceous of northwest China, with egg masses in the body and eggs in the oviduct, indicative of a gravid female. CT reconstruction of the specimen allows referral toGansubatrachus qilianensisand we assign it as a paratype complementing the diagnosis of the type species.The new fossil, which might represent a younger individual than the holotype ofGansubatrachus, shows that sexual maturation occurred before full adulthood in this frog and provides evidence of death linked to mating behaviour. We also discuss other potential sources of variation and life-history traits ofGansubatrachus. The new finding represents the oldest Early Cretaceous frog preservingin situeggs and provides a glimpse into ancient anuran development during Mesozoic times.
Organic compounds drive growth in phytoplankton taxa from different functional groups
Authors: Martens Nele , Ehlert Emilia , Putri Widhi , Sibbertsen Martje , Schaum C.-Elisa
Published: February 2024

Phytoplankton are usually considered autotrophs, but an increasing number of studies show that many taxa are able also to use organic carbon. Acquiring nutrients and energy from different sources might enable an efficient uptake of required substances and provide a strategy to deal with varying resource availability, especially in highly dynamic ecosystems such as estuaries. In our study, we investigated the effects of 31 organic carbon sources on the growth (proxied by differences in cell counts after 24 h exposure) of 17 phytoplankton strains from the Elbe estuary spanning four functional groups. All of our strains were able to make use of at least 1 and up to 26 organic compounds for growth. Pico-sized green algae such as
Mychonastes
, as well as the nano-sized green alga
Monoraphidium
in particular were positively affected by a high variety of substances. Reduced light availability, typically appearing in turbid estuaries and similar habitats, resulted in an overall poorer ability to use organic substances for growth, indicating that organic carbon acquisition was not primarily a strategy to deal with darkness. Our results give further evidence for mixotrophy being a ubiquitous ability of phytoplankton and highlight the importance to consider this trophic strategy in research.
Consequences of kelp forest ecosystem shifts and predictors of persistence through multiple stressors
Authors: Smith Joshua G. , Malone Daniel , Carr Mark H.
Published: February 2024

Ecological communities can be stable over multiple generations, or rapidly shift into structurally and functionally different configurations. In kelp forest ecosystems, overgrazing by sea urchins can abruptly shift forests into alternative states that are void of macroalgae and primarily dominated by actively grazing sea urchins. Beginning in 2014, a sea urchin outbreak along the central coast of California resulted in a patchy mosaic of remnant forests interspersed with sea urchin barrens. In this study, we used a 14-year subtidal monitoring dataset of invertebrates, algae, and fishes to explore changes in community structure associated with the loss of forests. We found that the spatial mosaic of barrens and forests resulted in a region-wide shift in community structure. However, the magnitude of kelp forest loss and taxonomic-level consequences were spatially heterogeneous. Taxonomic diversity declined across the region, but there were no declines in richness for any group, suggesting compositional redistribution. Baseline ecological and environmental conditions, and sea urchin behaviour, explained the persistence of forests through multiple stressors. These results indicate that spatial heterogeneity in preexisting ecological and environmental conditions can explain patterns of community change.
A HOSPITAL BASED OBSERVATIONAL STUDY ON HIV-TB COINFECTION
Authors: Soni Akansha , Jain Parul , Venkatesh Vimala , JAIN AMITA , HIMANSHU D , GUPTA NEETU , TANDON RITU
Published: February 2024

ABSTRACT
 
 
BACKGROUND:
HIV is the leading cause of failure to reach TB control targets in high-HIV settings. TB on the other hand enhances progression of HIV infection to AIDS.
MATERIAL AND METHODS :
An observational study was conducted in which a total of 573 newly diagnosed HIV-positive patients enrolled at ART center, KGMU, Lucknow between May 2021 to June 2022 were taken of which 80 patients had newly diagnosed TB. These HIV-TB co-infected patients were analyzed for demographic factors. Also, CD4 counts were done at the time of enrolment on ART and then about six to eight months later. For comparision, of the 493 HIV only patients, 50 age and sex matched consecutive patients for whom baseline and follow up CD4 counts were available were enrolled as controls. The change from baseline CD4 count was calculated using paired t-test and Wilcoxon signed rank test.
RESULTS :
In present study,among HIV-TB coinfected patients, baseline CD4 levels were 194.52±162.27, and follow up CD4 levels were 285.09±170.33. An increment of 90.57±165.60 in mean CD4 levels was observed which was statistically significant(t=4.019; p<0.001 ).
CONCLUSION :
Significant rise in CD4 counts was observed in HIV-TB coinfected patients started on ART and ATT.
Assessing NGS-based computational methods for predicting transcriptional regulators with query gene sets
Authors: Lu Zeyu , Xiao Xue , Zheng Qiang , Wang Xinlei , Xu Lin
Published: February 2024

This article provides an in-depth review of computational methods for predicting transcriptional regulators with query gene sets. Identification of transcriptional regulators is of utmost importance in many biological applications, including but not limited to elucidating biological development mechanisms, identifying key disease genes, and predicting therapeutic targets. Various computational methods based on next-generation sequencing (NGS) data have been developed in the past decade, yet no systematic evaluation of NGS-based methods has been offered. We classified these methods into two categories based on shared characteristics, namely library-based and region-based methods. We further conducted benchmark studies to evaluate the accuracy, sensitivity, coverage, and usability of NGS-based methods with molecular experimental datasets. Results show that BART, ChIP-Atlas, and Lisa have relatively better performance. Besides, we point out the limitations of NGS-based methods and explore potential directions for further improvement.

Key points

An introduction to available computational methods for predicting functional TRs from a query gene set.

A detailed walk-through along with practical concerns and limitations.

A systematic benchmark of NGS-based methods in terms of accuracy, sensitivity, coverage, and usability, using 570 TR perturbation-derived gene sets.

NGS-based methods outperform motif-based methods. Among NGS methods, those utilizing larger databases and adopting region-centric approaches demonstrate favorable performance. BART, ChIP-Atlas, and Lisa are recommended as these methods have overall better performance in evaluated scenarios.
Persistent tailoring of MSC activation through genetic priming
Authors: Beauregard Michael A. , Bedford Guy C. , Brenner Daniel A. , Sanchez Solis Leonardo D. , Nishiguchi Tomoki , Abhimanyu  , Carrero Longlax Santiago , Mahata Barun , Veiseh Omid , Wenzel Pamela L. , DiNardo Andrew R. , Hilton Isaac B. , Diehl Michael R.
Published: February 2024

Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce expression of pro-inflammatory effectors that can potentiate immunogenicity. Here, we describe a ‘genetic priming’ method that can both selectively and sustainably boost MSC potency via the controlled expression of the inflammatory-stimulus-responsive transcription factor IRF1 (interferon response factor 1). MSCs engineered to hyper-express IRF1 recapitulate many core responses that are accessed by biochemical priming using the proinflammatory cytokine interferon-γ (IFNγ). This includes the upregulation of anti-inflammatory effector molecules and the potentiation of MSC capacities to suppress T cell activation. However, we show that IRF1-mediated genetic priming is much more persistent than biochemical priming and can circumvent IFNγ-dependent expression of immunogenic MHC class II molecules. Together, the ability to sustainably activate and selectively tailor MSC priming responses creates the possibility of programming MSC activation more comprehensively for therapeutic applications.

GRAPHICAL ABSTRACT
Cell Cycle-Dependent TICRR/TRESLIN and MTBP Chromatin Binding Mechanisms and Patterns
Authors: Noble Tyler D. , Sansam Courtney G. , Wittig Kimberlie A. , Majchrzycka Blanka , Sansam Christopher L.
Published: February 2024

The selection of replication origins is a defining characteristic of DNA replication in eukaryotes, yet its mechanism in humans has not been well-defined. In this study, we use Cut&Run to examine genomic binding locations for TICRR/TRESLIN and MTBP, the human orthologs for the yeast DNA replication initiation factors Sld3 and Sld7. We mapped TRESLIN and MTBP binding in HCT116 colorectal cancer cells using asynchronous and G1 synchronized populations. Our data show that TRESLIN and MTBP binding patterns are more defined in a G1 synchronized population compared to asynchronously cycling cells. We also examined whether TRESLIN and MTBP are dependent on one another for binding. Our data suggest MTBP is dependent on TRESLIN for proper association with chromatin during G1 but not S phase. Finally, we asked whether TRESLIN and MTBP binding to chromatin requires licensed origins. Using cell lines with a non-degradable inducible Geminin to inhibit licensing, we show TRESLIN and MTBP binding does not require loaded MCMs. Altogether, our Cut&Run data provides evidence for a chromatin binding mechanism of TRESLIN-MTBP during G1 that is dependent on TRESLIN and does not require interactions with licensed origins.
A ZBP1 isoform blocks ZBP1-mediated cell death
Authors: Cai Zhi-Yu , Wu Puqi , Mo Wei , Yang Zhang-Hua
Published: February 2024

ZBP1 is an interferon-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA), a type of left-handed nucleic acid. More than that, the binding of ZBP1 with Z-NA promotes cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppresser of the inflammatory signaling mediated by full-length ZBP1. Compared with ZBP1, ZBP1-S protein has Zα domains but no RHIM domains. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Rip1D325A/D325A) with Cleavage-resistant RIP1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-depedent cell death. Intriguingly,Rip1D325A/D325Acells go death spontaneously when ZBP1-S was deleted, indicating the cell death driven by ZPB1 is under the check of ZBP1-S. Thus, our findings reveal that alternative splicing ofZbp1represents an autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against auto-inflammations.

Highlight

ZBP1-short isoform is expressed synchronously with ZBP1.

ZBP1-short isoform counteracts ZBP1 mediated cell death.

ZBP1-S suppresses ZBP1 signaling in an Zα-domain dependent manner.

ZBP1-S prevents the autoactivation of ZBP1 inRip1D325A/D325Acells.
Meiotic drive against chromosome fusions in butterfly hybrids
Authors: Boman Jesper , Wiklund Christer , Vila Roger , Backström Niclas
Published: February 2024

Species frequently differ in karyotype, but heterokaryotypic individuals may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can thus serve as a mechanism for speciation between incipient lineages but their evolution poses a paradox. How does underdominant rearrangements evolve? One solution is the fixation of underdominant chromosomal rearrangements through genetic drift. However, this requires small and isolated populations. Fixation is more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate transmission ratio distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover a transmission bias favoring the fused state at chromosome with unknown polarization in one experiment and a transmission bias favoring the unfused state of derived fusions in both experiments. The latter result support a scenario where chromosome fusions can fix in populations despite counteracting effects of meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that this transmission bias can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why derived fusions may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.