bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond blood transfusions: exploring iron chelation therapies in transfusion-dependent beta-thalassemia
Authors: Talha Muhammad , Ali Mohammad Haris , Hurjkaliani Sonia , Rahmat Zainab Syyeda , Sadia Haleema , Hasibuzzaman Md. Al , Uzair Ahsan Ul Qayyum
Published: December 2024

Introduction:

Abnormal hemoglobin, or hemoglobinopathy, affects about 7% of the global population. Major hemoglobinopathies like beta-thalassemia and sickle cell disease require regular blood transfusions, leading to chronic iron overload. This review examines the efficacy and safety of deferiprone, an oral iron chelator, in managing iron overload in pediatric patients with transfusion-dependent conditions.

Methods:

Data were sourced from PubMed, Google Scholar, and relevant articles, focusing on randomized controlled trials (RCTs) published between 2010 and 2023. The search terms included “deferiprone,” “iron chelation,” “transfusion,” “iron overload,” “hemoglobinopathies,” and “thalassemia.” Three RCTs met the inclusion criteria, involving 521 pediatric patients.

Results:

The START trial demonstrated that early-start deferiprone significantly reduced iron load compared to placebo, with no severe adverse events. The DEEP-2 study found deferiprone non-inferior to deferasirox in terms of efficacy and safety. Another trial highlighted the benefits of early deferiprone therapy in delaying iron overload symptoms without serious side effects. Common adverse effects included pyrexia, nasopharyngitis, and decreased neutrophil count, but no significant differences in growth parameters, creatinine, or prolactin levels were observed.

Conclusion:

Deferiprone shows significant promise in managing iron overload in pediatric patients, with comparable effectiveness to existing therapies and a favorable safety profile. Its oral administration is advantageous for young children. However, long-term studies are needed to fully understand its safety and efficacy. Addressing challenges such as patient compliance and adverse effects through education, personalized medicine, and advanced monitoring techniques can further improve treatment outcomes for beta-thalassemia patients.
Effect of topical treatment with urea in ichthyosis, atopic dermatitis, psoriasis, and other skin conditions—a systematic review
Authors: Jawed Inshal , Umair Abdul Qadir Muhammad , Farwa Umm E. , Alam Farah , Bakhtawar Fatima Fasiha , Khan Hina , Kumar Karmani Vikash , Javaid Maham , Raja Sandesh , Khuzzaim Khan Muhammad , Raja Adarsh , Khanal Anuva
Published: December 2024

Introduction:

The urea composition has a profound effect on skin disorders, specifically xerosis, desquamation, and scaling, which are some of the main concerns of the current health industry. The application of urea is relatable and more bioactive than alternate treatments. The objective of this systematic review was to evaluate the effectiveness of topically applied urea in the treatment of ichthyosis, psoriasis, and other dermatologic conditions.

Data and sources:

Research articles were retrieved through electronic databases, including Google Scholar, PubMed, EMBASE, Elsevier, and Sage, selected based on the provision of online free literature from its inception till November 2023. The significant findings were skin dryness, transepidermal water loss (TEWL), and eczema.

Study selection:

A total of 1826 studies have been found, of which 31 were selected based on inclusion criteria. The primary reason for the exclusion of the studies was the application of urea as a control. All in vivo studies disclosed the effectiveness of urea treatment separately or in addition to another compound on skin conditions. The selected studies have reported findings related to the improvement in xerosis, erythema, scaling, and reduction in TEWL.

Conclusion:

According to the in-depth review of the research articles, the application of urea has a tremendous effect on different skin diseases. Still, its role as monotherapy is overlooked due to the presence of more susceptible alternate products that need to be addressed. However, in the future, the evaluation of the effects of treatment containing urea with antibiotics on skin diseases would be more beneficial for practical knowledge.
Advances in the diagnosis of colorectal cancer: the application of molecular biomarkers and imaging techniques: a literature review
Authors: Kwan Alicia Su Huey , Uwishema Olivier , Mshaymesh Sarah , Choudhary Karan , Salem Fatma K. , Sengar Aman Singh , Patel Raj Pravin , Kazan Zeinab , Wellington Jack
Published: December 2024

Background:

Following neoplasms of the lung and breast, colorectal cancer (CRC) is the third most frequent malignancy globally. Screening for CRC at the age of 50 years is strongly encouraged for prompt earlier diagnosis owing to prognoses being greatly correlated with time of detection and cancer staging.

Aim:

This review aimed to elucidate the most recent advancements in the detection of CRC, with an emphasis on the latest innovations in diagnostic molecular biomarkers in conjunction with radiological imaging alongside stool-based tests for CRC screening.

Methods:

A comprehensive review of the literature was performed, focusing on specific terms in different electronic databases, including that of PubMed/MEDLINE. Keywords pertaining to “colorectal cancer,” “diagnosis,” “screening,” “imaging,” and “biomarkers,” among others, were employed in the search strategy. Articles screened and evaluated were deemed relevant to the study aim and were presented in the medium of the English language.

Results:

There have been several innovations in the diagnostics and identification of CRC. These generally comprise molecular biomarkers, currently being studied for suitability in disease detection. Examples of these include genetic, epigenetic, and protein biomarkers. Concurrently, recent developments in CRC diagnostics highlight the advancements made in radiological imaging that offer precise insights on tumor biology in addition to morphological information. Combining these with statistical methodologies will increase the sensitivity and specificity of CRC diagnostics. However, putting these strategies into reality is hampered by several issues.

Conclusion:

Progress in diagnostic technology alongside the identification of a few prognostic predictive molecular biomarkers suggested great promise for prompt detection and management of CRC. This clearly necessitates further efforts to learn more in this specific sector.
Data analytics in pharmacy practice – current review and future directions and recommendations
Authors: Khalil Viviane
Published: December 2024

Purpose of review

Efficient application of data management is becoming vital in demonstrating value-based healthcare in health organizations more broadly as well as improving pharmacy practice capabilities.

Recent findings

The uptake of data analytics in pharmacy settings has been variable. Limited guidance and recommendations have been published on the use of data analytics in current practice and future recommendations in different pharmacy settings. Data analytics in pharmacy settings to date has been limited mostly to its use for optimization of health information for clinical decision making, standardization of processes, formulary management and tracking and measuring of performance indicators and costs.

Developing a data driven culture in pharmacy settings is important in advancing pharmacy practice and leveraging of the plethora of data available in healthcare. Possible expansion of applications of data analytics in pharmacy practice could focus on creating a data driven culture, establishing partnerships with digitally advanced departments and leveraging of their practice and expertise as well as investing in upskilling staff in digital health literacy.
Translation, cultural adaptation to Brazilian Portuguese, and validation of the Prosthetic Limb Users Survey of Mobility
Authors: Secco Milena Zavatini , Balbi Larissa Lavoura , Pinheiro Beatriz Bregantin , Pereira Maira Stéfanie de Castro , Barros Ana Regina Bavaresco , Fonseca Marisa de Cássia Registro
Published: December 2024

Background:

Several outcome measures can be performed to assess and quantify mobility after a lower limb amputation. The Prosthetic Limb Users Survey of Mobility (PLUS-M) is a self-report instrument developed to assess mobility in prosthesis users. It has already been translated into different languages but not into Brazilian Portuguese.

Objectives:

To perform the translation and cultural adaptation into Brazilian Portuguese of the PLUS-M and to assess its validity and reliability.

Study design:

Observational cross-sectional study.

Methods:

Translation and cultural adaptation were performed by following internationally recognized standards. To assess construct validity, the T-scores of PLUS-M/12-Item Short Form—Brazilian Portuguese (BR-12) item short form were correlated to the 2-Minute Walk Test and the scores from the Medical Outcomes Study 36-Short Form Health Survey domains by the Spearman correlation coefficient (ρ). A second administration of the PLUS-M/BR-12 was done by phone call to assess test-retest reliability.

Results:

Some cultural adaptations were made to improve understanding. The PLUS-M/BR-12 T-scores of 61 participants showed a strong correlation between the scores of the 2-Minute Walk Test (ρ = 0.69) and the Physical Function domain of the 36-Short Form Health Survey (ρ = 0.83), and an excellent test-retest reliability (intraclass correlation coefficient = 0.90 [IC 95% = 0.833–0.943]; F(49,49) = 19,037; P < 0.001).

Conclusions:

The PLUS-M/BR-12 demonstrated evidence of validity and reliability in assessing mobility in Brazilian adults with lower limb amputations who use a prosthetic device, and it is suitable for use in clinical care.
Undernutrition in Cleft Palate Surgery: Effects on Postoperative Fistula Formation in a Tertiary Children’s Hospital in Southern Africa
Authors: Adams Saleigh , Mahieu Amber , Verreijdt Pien M , Isaacs Samuel , Breugem Corstiaan C.
Published: December 2024

Background:

Cleft palate surgery can be complicated by fistula development. It is well known that undernutrition in general leads to more postoperative complications. However, little is known about postoperative fistula development after cleft palate surgery in low- and middle-income countries (LMIC’s).

Objective:

The aim of this study was to investigate the influence of peri-operative undernutrition on the risk of postoperative fistula formation in South African children operated on for cleft palate (CP).

Design and Setting:

Three hundred thirty-seven cleft palate patients undergoing initial cleft palate repair at Red Cross War Memorial Children’s Hospital were retrospectively reviewed.

Interventions:

Undernutrition was measured as World Health Organisation (WHO) Weight-For-Age (WFA) Z-scores, postoperative fistula was noted when the patient received revision surgery for fistula after the initial repair.

Main Outcome Measure:

Longitudinal Generalized Estimation Equations (GEE) analysis was used to examine the influence of the undernutrition Z-Score on post-operative fistula formation.

Results:

Our cohort had a mean Z-score of −0.873 (SD=1.6043). Among patients undergoing initial cleft palate repair, 21.9% were perioperatively underweight for age (Z-Score < −2), and 8.8% were severely underweight (Z-Score < −3). The cohort had a total symptomatic fistula rate of 19.9%. Decreasing perioperative WFA Z-Score (worsening undernutrition), predicts a significant increase in the odds of postoperative fistula (odds ratio = 1.233, P = 0.018).

Conclusions:

Worsening perioperative undernutrition in initial cleft palate surgery is associated with a significant postoperative increase in fistula formation.
Postoperative Assessment of Secondary Alveolar Bone Grafting Using a Combination of β-Tricalcium Phosphate and Chin Bone for Patients With Unilateral Cleft Alveolus
Authors: Kida-Kinoshita Kumiko , Yamanishi Tadashi , Miyagawa Kazuaki , Seikai Tetsuya , Nishio Takahiro , Otsuki Koichi , Matsushita Yutaka , Tanaka Susumu , Kogo Mikihiko
Published: December 2024

Secondary alveolar bone grafting (sABG) is crucial for the treatment of alveolar clefts. However, postoperative bone formation using a graft material comprising a mixture of beta-tricalcium phosphate (β-TCP) and chin bone has been previously evaluated only 2-dimensionally, using plain radiographic images. In this study, the authors aimed to retrospectively and 3-dimensionally assess bone formation following sABG in patients with an alveolar cleft, using a mixture of β-TCP and chin bone. Thirty-eight patients with unilateral cleft lip and alveolus (CLA, n=13) or unilateral cleft lip and palate (CLP, n=25) who underwent sABG at our hospital were recruited. The grafted material was replaced with normal bone structure within 6 months postsurgery. The authors conducted a 3-dimensional evaluation utilizing cone-beam computed tomography images taken before surgery and at 1 week, 6 months, and 12 months postsurgery. Bone survival rates inside and outside the dental arch were 56.3% and 4.6%, respectively. No patients exhibited complete resorption of the material. This combination of β-TCP and chin bone demonstrated favorable bone formation following sABG in patients with unilateral CLA and CLP.
Hepato-Pancreato-Biliary Surgery
Authors: Tsilimigras Diamantis I. , Chatzipanagiotou Odysseas , Woldesenbet Selamawit , Ruff Samantha , Cloyd Jordan M. , Pawlik Timothy M.
Published: December 2024

Objective:

To characterize the association between type of fellowship training and patient outcomes following hepatopancreatic (HP) surgery across different surgeon career stages using a national representative cohort of Medicare beneficiaries.

Background:

The current state of training in HPB surgery in North America is defined through three main pathways: the Complex General Surgical Oncology (CGSO), the Americas HPB Association fellowship, and the American Society of Transplant surgeons fellowship. Each pathway offers a unique perspective on HPB surgery with different number of training years, yet outcomes of graduates performing HP surgery relative to type of fellowship training have not been defined.

Methods:

Medicare claims were used to identify patients who underwent HP surgery for cancer between 2016-2021. The association of textbook outcomes (TO), defined as no postoperative complications, no prolonged LOS, no 90-day mortality and no 90-day readmission, relative to different fellowship pathways was examined.

Results:

Overall, 15,411 cancer operations (pancreatectomy: 11,003, 71.4%; hepatectomy: 4,408, 28.6%) were performed by 1,030 HPB surgeons. A total of 9,390 patients (60.9%) were operated on by a CGSO/SONC graduate, 2,315 patients (15.0%) by an HPB fellowship graduate and 3,706 (24.1%) by a transplant fellowship graduate. Patients who were operated on by an HPB fellowship graduate more frequently had a higher Charlson score (>5: 44.8% vs. 38.1%) and more frequently were operated on an urgent basis (7.7% vs. 6.1%) compared with individuals treated by CGSO/SONC graduates. After adjusting for patient, procedural, hospital, and surgeon related factors, the likelihood of TO following an HP operation by an HPB fellowship graduate was 47.7% versus 45.2% among CGSO (% difference 2.7%) and 42.8% among transplant fellowship graduates (% difference 4.9%, P=0.01). While the probability of TO was higher among surgeons having completed a dedicated HPB fellowship during early (1-7th year of independent practice, P=0.032) and middle (8-14th year, P<0.001) career stages, the probability of TO did not differ based on fellowship type among late career surgeons (>15th year, P=0.257)

Conclusions:

Achievement of TO following an HP procedure was higher among surgeons who had completed a dedicated HPB fellowship, especially during early and middle career stages. Further efforts should be made to enhance HP surgery exposure and training for CGSO fellows interested in a career in HPB surgery.
TRIM37 exacerbates cerebral ischemic injury by regulating the PPARγ/NF-κB pathway
Authors: Shi Guixin , Fu Linyan , Xiao Hua , Cao Fang
Published: December 2024

Ischemic stroke is the primary cause of mortality for individuals with disability worldwide. Tripartite motif 37 (TRIM37) plays multiple regulatory roles in various cellular processes. Our research aimed to investigate the effects of TRIM37 on the progression of ischemic stroke and its related mechanisms. Primary rat brain microvascular endothelial cells (BMECs) were treated with oxygen-glucose deprivation and reoxygenation (OGD/R) and then transduced with pShuttle-H1-TRIM37 shRNA plasmid, pShuttle-CMV-TRIM37 plasmid, or corresponding negative controls. The effects of TRIM37 were also explored in middle cerebral artery occlusion surgery-induced rat brain damage in vivo. Factor VIII staining showed the successful isolation of the primary BMECs. The OGD/R procedure significantly inhibited the cell viability and upregulated the TRIM37 expression in a time-dependent manner. In addition, OGD/R evidently increased the cell permeability, elevated the tumor necrosis factor alpha and intercellular adhesion molecule 1 levels, and upregulated the nuclear expression of nuclear factor (NF)-κB, but downregulated the peroxisome proliferator-activated receptors γ (PPARγ), zonula occludens-1, and cytoplasmic NF-κB expressions, which were reversed by TRIM37 knockdown. Furthermore, TRIM37 interacted with PPARγ and promoted its ubiquitination. The effects on cell permeability and inflammation induced by TRIM37 overexpression were reversed by PPARγ agonist. TRIM37 knockdown also inhibited middle cerebral artery occlusion-induced rat brain damage in vitro. TRIM37 may be a potential therapeutic target for ischemic stroke, and the knockdown of TRIM37 may improve brain injury by regulating the PPARγ/NF-κB pathway to modulate the inflammatory response.
Preventive effect of aminocaproic acid combined with nimodipine on short-term rebleeding in patients with aneurysmal subarachnoid hemorrhage
Authors: Zhao Qiong , Liu Zhongyang , Yang Qingcheng
Published: December 2024

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening and life-limiting disease with high mortality and disability rates. Herein, we aim to explore the preventive effect of aminocaproic acid combined with nimodipine on short-term rebleeding in patients with aSAH. Retrospectively, the medical data of patients with aSAH (n = 256) were collected. According to different treatment methods, patients were categorized into the aminocaproic acid + nimodipine group (n = 152) and the nimodipine group (n = 104), and were treated for 1 week. Baseline characteristics, incidence of rebleeding, average velocity of cerebral artery blood flow, cerebral vasospasm index, vascular endothelial function, complications, and adverse events were analyzed between the two groups. After 1-week treatment, compared to the nimodipine group, the aminocaproic acid + nimodipine group exhibited lower incidence of rebleeding, notable decreases in average velocity of cerebral artery blood flow and the cerebral vasospasm index, and downregulation of endothelin-1 and vascular endothelial growth factor (P < 0.05). There were no significant differences about complications and adverse events between the two groups. Aminocaproic acid combined with nimodipine is superior to nimodipine alone in preventing the short-term rebleeding in patients with aSAH, and has good safety.
Uncertainty in COVID-19 transmission could undermine our ability to predict long COVID
Authors: Beams Alexander B. , Earn David J. D. , Colijn Caroline
Published: December 2024

As SARS-CoV-2 has transitioned from a novel pandemic-causing pathogen into an established seasonal respiratory virus, focus has shifted to post-acute sequelae of COVID-19 (PASC, colloquially ‘long COVID’). We use compartmental mathematical models simulating emergence of new variants to help identify key sources of uncertainty in PASC trajectories. Some parameters (such as the duration and equilibrium prevalence of infection, as well as the fraction of infections that develop PASC) matter more than others (such as the duration of immunity and secondary vaccine efficacy against PASC). Even if newer variants carry the same risk of PASC as older types, the dynamics of selection can give rise to greater PASC prevalence. However, identifying plausible PASC prevalence trajectories requires accurate knowledge of the transmission potential of COVID-19 variants in the endemic phase. Precise estimates for secondary vaccine efficacy and duration of immunity will not greatly improve forecasts for PASC prevalence. Researchers involved with Living Evidence Synthesis, or other similar initiatives focused on PASC, are well advised to ascertain primary efficacy against infection, duration of infection and prevalence of active infection in order to facilitate predictions.
Social organization of necrophoresis: insights into disease risk management in ant societies
Authors: Avanzi Quentin , Lisart Léon , Detrain Claire
Published: December 2024

Insect societies, which are at a high risk of disease outbreaks, have evolved sanitary strategies that contribute to their social immunity. Here, we investigated in the red ant
Myrmica rubra,
how the discarding of nestmate cadavers is socially organized depending on the associated pathogenicity. We examined whether necrophoresis is carried out by a specific functional group of workers or by any nestmates that may become short-term specialists. By observing the behavioural profiles of tagged individuals, we assigned half of the colony members to functional groups (foragers, intermittent-foragers, domestics, nurses and inactives). Following the introduction of uninfected or sporulating corpses into the nest, intermittent-foragers were the functional group most involved in necrophoresis, as they touched, moved and discarded more cadavers. Interestingly, sporulating corpses induced a more generalized response in workers from all functional groups, thereby accelerating their rejection from the nest. The individuals contacting corpses were also prophylactically engaged in more grooming behaviour, suggesting the existence of hygienist workers within ant colonies. These findings raise questions about a trade-off existing between concentrating health risks on a few workers who are highly specialized in necrophoresis and exposing a larger population of nestmates who cooperate to speed up nest sanitization.
Stability of state-dependent switched systems under hybrid delayed impulsive control
Authors: Cui Qian , Cao Jinde , Abdel-Aty Mahmoud
Published: December 2024

In this paper, a novel state-dependent switching (SDS) method for switched systems with hybrid delayed impulses is proposed, which is different from the conventional approach of pre-setting the switching instants. First, for the SDS method involving delayed impulses, two preconditions, namely, coverage and overlap, are guaranteed. Then, by the Lyapunov stability theory and the proposed SDS strategy, the unified stability criteria of the switched systems under hybrid delayed impulsive control are obtained. Moreover, we discover that the impulsive delay has a double effect, that is, undermining and promoting system stability, which is contingent on the stability of the original systems. To validate the effectiveness of our results, we provide illustrative examples involving circuit switched networks.
Emergence of Sparse Coding, Balance and Decorrelation from a Biologically-Grounded Spiking Neural Network Model of Learning in the Primary Visual Cortex
Authors: Ruslim Marko A. , Spencer Martin J. , Hogendoorn Hinze , Meffin Hamish , Lian Yanbo , Burkitt Anthony N.
Published: December 2024

1

Many computational studies attempt to address the question of information representation in biological neural networks using an explicit optimization based on an objective function. These approaches begin with principles of information representation that are expected to be found in the network and from which learning rules can be derived.

This study approaches the question from the opposite direction; beginning with a model built upon the experimentally observed properties of neural responses, homeostasis, and synaptic plasticity. The known properties of information representation are then expected to emerge from this substrate.

A spiking neural model of the primary visual cortex (V1) was investigated. Populations of both inhibitory and excitatory leaky integrate-and-fire neurons with recurrent connections were provided with spiking input from simulated ON and OFF neurons of the lateral geniculate nucleus. This network was provided with natural image stimuli as input. All synapses underwent learning using spike-timing-dependent plasticity learning rules. A homeostatic rule adjusted the weights and thresholds of each neuron based on target homeostatic spiking rates and mean synaptic input values.

These experimentally grounded rules resulted in a number of the expected properties of information representation. The network showed a temporally sparse spikeresponseto inputs and this was associated with a sparsecodewith Gabor-like receptive fields. The network was balanced at both slow and fast time scales; increased excitatory input was balanced by increased inhibition. This balance was associated with decorrelated firing that was observed as population sparseness. This population sparseness was both the cause and result of the decorrelation of receptive fields. These observed emergent properties (balance, temporal sparseness, population sparseness, and decorrelation) indicate that the network is implementing expected principles of information processing: efficient coding, information maximization (’infomax’), and a lateral or single-layer form of predictive coding.

These emergent features of the network were shown to be robust to randomized jitter of the values of key simulation parameters.
Advances and applications of the closest-tree algorithm and Hadamard conjugation in phylogenetic inference
Authors: González Ernesto Álvarez , Balám-Narváez Ricardo , Angulo Diego F. , Duchen Pablo
Published: December 2024

In phylogenetic inference Hadamard methods and the closest-tree algorithm have been a promising alternative to likelihood-based methods. However, applications to actual biological problems have been limited so far. In the early nineties, Hendy and Penny (1993) developed the two-state closest-tree algorithm for estimating the optimal branch lengths of a phylogenetic tree, whose parameters correspond to the Cavender’s molecular evolution model (CFN). Steel et al. (1992) then developed the four-state version of this method, whose parameters correspond to the Kimura 3ST’s molecular evolution model (K3ST). In both cases, formulas for solving the optimization problems were provided. Here, we do not only contribute with proofs for these formulas, but we also adapt this methodology to the orchid genusLophiarella, whose phylogenetic relationships remain unclear. With this biological application, we show the efficacy of the closest-tree algorithm coupled with Hadamard conjugation, phylogenetic invariants and edge-parameter inequalities (in Fourier coordinates) in jointly inferring the tree topology and the molecular evolution model that best explains the data. Finally, we reconcile this phylogeny with biogeographical and morphological aspects within this genus.
Parallelization of particle-based reaction-diffusion simulations using MPI
Authors: Guo Sikao , Korolija Nenad , Milfeld Kent , Jhaveri Adip , Sang Mankun , Ying Yue Moon , Johnson Margaret E
Published: December 2024

Particle-based reaction-diffusion models offer a high-resolution alternative to the continuum reaction-diffusion approach, capturing the discrete and volume-excluding nature of molecules undergoing stochastic dynamics. These methods are thus uniquely capable of simulating explicit self-assembly of particles into higher-order structures like filaments, spherical cages, or heterogeneous macromolecular complexes, which are ubiquitous across living systems and in materials design. The disadvantage of these high-resolution methods is their increased computational cost. Here we present a parallel implementation of the particle-based NERDSS software using the Message Passing Interface (MPI) and spatial domain decomposition, achieving close to linear scaling for up to 96 processors in the largest simulation systems. The scalability of parallel NERDSS is evaluated for bimolecular reactions in 3D and 2D, for self-assembly of trimeric and hexameric complexes, and for protein lattice assembly from 3D to 2D, with all parallel test cases producing accurate solutions. We demonstrate how parallel efficiency depends on the system size, the reaction network, and the limiting timescales of the system, showing optimal scaling only for smaller assemblies with slower timescales. The formation of very large assemblies represents a challenge in evaluating reaction updates across processors, and here we restrict assembly sizes to below the spatial decomposition size. We provide the parallel NERDSS code open source, with detailed documentation for developers and extension to other particle-based reaction-diffusion software.
The Functional Connectome Mediating Circadian Synchrony in the Suprachiasmatic Nucleus
Authors: Nikhil K.L. , Singhal Bharat , Granados-Fuentes Daniel , Li Jr-Shin , Kiss István Z. , Herzog Erik D.
Published: December 2024

Circadian rhythms in mammals arise from the spatiotemporal synchronization of ∼20,000 neuronal clocks in the Suprachiasmatic Nucleus (SCN). While anatomical, molecular, and genetic approaches have revealed diverse cell types and signaling mechanisms, the network wiring that enables SCN cells to communicate and synchronize remains unclear. To overcome the challenges of revealing functional connectivity from fixed tissue, we developed MITE (Mutual Information & Transfer Entropy), an information theory approach that infers directed cell-cell connections with high fidelity. By analyzing 3447 hours of continuously recorded clock gene expression from 9011 cells in 17 mice, we found that the functional connectome of SCN was highly conserved bilaterally and across mice, sparse, and organized into a dorsomedial and a ventrolateral module. While most connections were local, we discovered long-range connections from ventral cells to cells in both the ventral and dorsal SCN. Based on their functional connectivity, SCN cells can be characterized as circadian signal generators, broadcasters, sinks, or bridges. For example, a subset of VIP neurons acts as hubs that generate circadian signals critical to synchronize daily rhythms across the SCN neural network. Simulations of the experimentally inferred SCN networks recapitulated the stereotypical dorsal-to-ventral wave of daily PER2 expression and ability to spontaneously synchronize, revealing that SCN emergent dynamics are sculpted by cell-cell connectivity. We conclude that MITE provides a powerful method to infer functional connectomes, and that the conserved architecture of cell-cell connections mediates circadian synchrony across space and time in the mammalian SCN.

Highlights

We developed MITE, an information theory method, to accurately infer directed functional connectivity among circadian cells.

SCN cell types with conserved connectivity patterns spatially organize into two regions and function as generators, broadcasters, sinks, or bridges of circadian information.

One-third of VIP neurons serve as hubs that drive circadian synchrony across the SCN.

Key connectivity features mediate the generation and maintenance of intercellular synchrony and daily waves of clock gene expression across the SCN.
Fine-Tuned Deep Transfer Learning Models for Large Screenings of Safer Drugs Targeting Class A GPCRs
Authors: Provasi Davide , Filizola Marta
Published: December 2024

G protein-coupled receptors (GPCRs) remain a focal point of research due to their critical roles in cell signaling and their prominence as drug targets. However, directly linking drug efficacy to receptor-mediated activation of specific intracellular transducers and the resulting physiological outcomes remains challenging. It is unclear whether the enhanced therapeutic window of certain drugs — defined as the dose range that provides effective therapy with minimal side effects — stems from their low intrinsic efficacy across all signaling pathways or ligand bias, wherein specific transducer subtypes are preferentially activated in a given cellular system compared to a reference ligand. Accurately predicting safer compounds, whether through low intrinsic efficacy or ligand bias, would greatly advance drug development. While AI models hold promise for such predictions, the development of deep learning models capable of reliably forecasting GPCR ligands with defined bioactivities remains challenging, largely due to the limited availability of high-quality data. To address this, we pre-trained a model on receptor sequences and ligand datasets across all class A GPCRs, and then refined it to predict low-efficacy compounds or biased agonists for individual class A GPCRs. This was achieved using transfer learning and a neural network incorporating natural language processing of target sequences and receptor mutation effects on signaling. These two fine-tuned models—one for low-efficacy agonists and one for biased agonists—are available on demand for each class A GPCR and enable virtual screening of large chemical libraries, thereby facilitating the discovery of compounds with potentially improved safety profiles.
Kolmogorov-Arnold Networks for Genomic Tasks
Authors: Cherednichenko Oleksandr , Poptsova Maria
Published: December 2024

Kolmogorov-Arnold Networks (KANs) emerged as a promising alternative for multilayer perceptrons in dense fully connected networks. Multiple attempts have been made to integrate KANs into various deep learning architectures in the domains of computer vision and natural language processing. Integrating KANs into deep learning models for genomic tasks has not been explored. Here, we tested linear KANs (LKANs) and convolutional KANs (CKANs) as replacement for MLP in baseline deep learning architectures for classification and generation of genomic sequences. We used three genomic benchmark datasets: Genomic Benchmarks, Genome Understanding Evaluation, and Flipon Benchmark. We demonstrated that LKANs outperformed both baseline and CK-ANs on almost all datasets. CKANs can achieve comparable results but struggle with scaling over large number of parameters. Ablation analysis demonstrated that the number of KAN layers correlates with the model performance. Overall, linear KANs show promising results in improving the performance of deep learning models with relatively small number of parameters. Unleashing KAN potential in different SOTA deep learning architectures currently used in genomics requires further research.
Cluster-Specific Urban Contexts Associated with High Levels of Sleep Impairment and Daytime Sleepiness: Findings from the Urbasan Collaborative Study
Authors: Voruz Philippe , Ruas Marco Vieira , Fellay Noé , Romano Noemi , Mussini Michelangelo , Saubade Mathieu , Faivre Vincent , Gremeaux Vincent , Jeanneret Ophélia , Tonnerre Quentin , Beetschen Patrick , Domon-Aubort Marie-Noëlle , Spini Dario , Kayser Bengt , Rappo Daniel , Joost Stéphane
Published: December 2024

Introduction

Impaired sleep is a global health concern. However, the environmental factors contributing to sleep impairment in urban settings are still not well understood.

Methodology

This study involved 179 participants from a Swiss municipality (Yverdon-les-Bains), where sleep quality and diurnal sleepiness were measured using validated questionnaires, alongside environmental and geo-referenced data.

Results

The findings revealed a high prevalence of sleep disorders across diverse demographic groups (respectively 15.6% for diurnal sleepiness and 91.1% for significantly altered sleep quality). Additionally, sleep disorders were associated with both environmental and socio-demographic factors. Geospatial analysis identified clusters of sleep disturbances in specific neighborhoods, with distinct associations to specific sub-scores (factors) of the sleep evaluation.

Conclusion

Assessing sleep in urban environments is crucial, as it is linked to elevated levels of sleepiness. Environmental and socio-demographic variables play significant roles in these disturbances. The incorporation of geospatial analyses allows for a more precise identification of patterns within the city, offering opportunities for tailored interventions to address the different patterns of sleep disorders.
Semilichen - an unjustly neglected symbiotic system between green biofilms and true lichens
Authors: Vondrák Jan , Svoboda Stanislav , Říha Pavel , Kantnerová Veronika , Škaloud Pavel , Kubásek Jiří
Published: December 2024

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Symbiotic systems of photosynthetic microorganisms and fungi are widespread in terrestrial biomes and lichens are probably the most advanced and complex. Conversely, the least complex systems are “green biofilms” with a completely unexplored mycobiome. We describe here a new system intermediate between green biofilms and lichens – semilichens.

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Light and fluorescence microscopy, eDNA sequencing, molecular phylogeny, Chlorophyllafluorescence and13C labelling/metabolomics were used to study algal and fungal identity, morphology and physiology of the symbiosis.

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Tight contact between algae and a single predominant fungus (mycobiont) is revealed in semilichens. The algae are from the symbiotic lineages of Trebouxiophyceae and Ulvophyceae, the fungi belong to Arthoniomycetes, Dothideomycetes, Eurotiomycetes, Lecanoromycetes and Lichinomycetes. Algae are alive and perform substantial photosynthetic activity.13C labelled photosynthates are partially converted into specific fungal polyols (arabitol, mannitol) demonstrating the C-flow from algae to fungi.

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The new symbiotic system was defined and compared with other terrestrial algal-fungal symbioses. It is characterized by minimalist environmental requirements and extremely low production of biomass. As a result, it also inhabits environments unfavourable for lichens. Our research supports the hypothesis that the long-term existence of algae and fungi in terrestrial conditions affected by frequent and repeated drying is likely dependent on their mutual coexistence.
Longitudinal cellular and humoral immune responses following Covid-19 BNT162b2-mRNA-based booster vaccination of craft and manual workers in Qatar.
Authors: Thomas Remy , Zaqout Ahmed , Meqbel Bakhita , Jafar Umar , Vaikath Nishant , Aldushain Abdullah , Naik Adviti , Shaath Hibah , Al-Akl Neyla S , Adam Abdi , Ali Moussa Houda Y , Shin Kyung Chul , Taha Rowaida Z , Abukhattab Mohammed , Almaslamani Muna A , Alajez Nehad M , Arredouani Abdelilah , Park Yongsoo , Abdulla Sara A , El-Agnaf Omar MA , Omrani Ali S , Decock Julie
Published: December 2024

Introduction: In March 2020, the rapid spread of SARS-CoV-2 prompted global vaccination campaigns to mitigate COVID-19 disease severity and mortality. The 2-dose BNT162b2-mRNA vaccine effectively reduced infection and mortality rates, however, waning vaccine effectiveness necessitated the introduction of a third vaccine dose or booster. To assess the magnitude and longevity of booster-induced immunity, we conducted a longitudinal study of SARS-CoV-2 specific cellular and humoral immune responses among Qatar's vulnerable craft and manual worker community. We also investigated the impact of prior naturally acquired immunity on booster vaccination efficacy. Methods: Seventy healthy participants were enrolled in the study, of whom half had prior SARS-CoV-2 infection. Blood samples were collected before and after booster vaccination to evaluate immune responses through SARS-CoV-2 specific ELISpots, IgG ELISA, neutralization assays, and flow cytometric immunophenotyping. Results: T cell analysis revealed increased Th1 cellular responses, marked by enhanced IFN-γ release, in recently infected participants, which was further enhanced by booster vaccination for up to 6-months. Furthermore, booster vaccination stimulated cytotoxic T cell responses in infection-naïve participants, characterized by granzyme B production. Both natural SARS-CoV-2 infection and booster vaccination induced robust and durable SARS-CoV-2 specific humoral immune responses, with high neutralizing antibody levels. Prior natural infection was also linked to an increased number of class-switched B cells prior to booster vaccination. Conclusion: These findings underscore the importance of booster vaccination in enhancing anti-viral immunity across both infection-naïve and previously infected individuals, enhancing distinct arms of the anti-viral immune response and prolonging naturally acquired immunity.
Simulating two-dimensional topological quantum phase transitions on a digital quantum computer
Authors: Liu Yu-Jie , Shtengel Kirill , Pollmann Frank
Published: December 2024

Efficient preparation of many-body ground states is key to harnessing the power of quantum computers in studying quantum many-body systems. In this work, we propose a simple method to design exact linear-depth parameterized quantum circuits which prepare a family of ground states across topological quantum phase transitions in 2D. We achieve this by constructing ground states represented by isometric tensor networks (isoTNS), which form a subclass of tensor network states that are efficiently preparable. By continuously tuning a parameter in the wavefunction, the many-body ground state undergoes quantum phase transitions, exhibiting distinct 2D quantum phases. We illustrate this by constructing an isoTNS path with bond dimension D=2 interpolating between distinct symmetry-enriched topological (SET) phases. At the transition point, the wavefunction is related to a gapless point in the classical six-vertex model. Furthermore, the critical wavefunction supports a power-law correlation along one spatial direction while remaining long-range ordered in the other spatial direction. We provide an explicit parametrized local quantum circuit for the path and show that the 2D isoTNS can also be efficiently simulated by a holographic quantum algorithm requiring only an 1D array of qubits.

Published by the American Physical Society
2024
Temporal networks with node-specific memory: Unbiased inference of transition probabilities, relaxation times, and structural breaks
Authors: Clemente Giulio Virginio , Tessone Claudio J. , Garlaschelli Diego
Published: December 2024

One of the main challenges in the study of time-varying networks is the interplay of memory effects with structural heterogeneity. In particular, different nodes and dyads can have very different statistical properties in terms of both link formation and link persistence, leading to a superposition of typical timescales, suboptimal parametrizations, and substantial estimation biases. Here we develop an unbiased maximum-entropy framework to study empirical network trajectories by controlling for the observed structural heterogeneity and local link persistence simultaneously. An exact mapping to a heterogeneous version of the one-dimensional Ising model leads to an analytic solution that rigorously disentangles the hidden variables that jointly determine both static and temporal properties. Additionally, model selection via likelihood maximization identifies the most parsimonious structural level (either global, node specific, or dyadic) accounting for memory effects. As we illustrate on real-world social networks, this method enables an improved estimation of dyadic transition probabilities, relaxation times, and structural breaks between dynamical regimes. In the resulting picture, the graph follows a generalized configuration model with given degrees and given time-persisting degrees, undergoing transitions between empirically identifiable stationary regimes.

Published by the American Physical Society
2024
From laminar to chaotic flow via stochastic resonance in viscoelastic channel flow
Authors: Li Yuke , Steinberg Victor
Published: December 2024

Recent research indicates that low-inertia viscoelastic channel flow experiences supercritical nonnormal mode elastic instability from laminar to sustained chaotic flow due to finite-size perturbations. The challenge of this paper is to elucidate a realization of such a pathway when the intensity of the elastic wave is too low to amplify vortex fluctuations above the instability onset. The study identifies two subregions in the transition flow regime at Weissenberg number Wi>Wic, the instability onset. In the lower subregion at Wic≤Wi≤300, we discover periodic spikes in the streamwise velocity time series u(t) that appear in the chaotic power spectrum as low-frequency, high-intensity peaks resembling stochastic resonance (SR). In contrast, the spanwise velocity power spectrum, Ew, remains flat and with low-intensity, noisy, and broad elastic wave peaks. The spikes significantly distort the probability density function of u and initiate and amplify random streaks and wall-normal vorticity fluctuations. The condition for the SR emergence is similar to that of a dynamical system where the presence of a chaotic attractor, limit cycle, and external white noise are necessary. This similarity is confirmed by presenting a phase portrait in two subregions of the transition regime. In the upper subregion at Wi>400, the periodic spikes disappear and Ew becomes chaotic with a large intensity elastic wave sufficient to self-organize and synchronize the streaks into cycles and to amplify the wall normal vorticity, according to a recently proposed mechanism of vortex-wave interactions.

Published by the American Physical Society
2024
Impact pathways: improving medicine access through cross-national stockpiling
Authors: De Vries Harwin , Lemmens Stef , Breugem Thomas , Olivier Max
Published: December 2024

Purpose

Pressure to address drug shortages is increasing, and calls for cross-national stockpiling solutions are on the rise. This paper argues that cross-national stockpiling presents an important opportunity for operations and supply chain management (OSCM) research to help improve medicine access in the short- and long-term.

Design/methodology/approach

To substantiate our claims for future research, we conducted an empirical analysis of shortage co-occurrence on twelve EU member-states, reviewed practice reports and academic literature, and held extensive discussions with pharmaceutical supply chain stakeholders.

Findings

We show that the potential for cross-national stockpiling is unmistakably there and that, although OSCM research has touched upon important facets of cross-national stockpiling, many open questions still require novel research.

Originality/value

We present opportunities for impactful research along various dimensions, including understanding barriers and stakeholder behavior, quantifying cost-effectiveness and potential knock-on effects, analyzing the positive and negative implications of product standardization and determining novel equitable mechanisms for allocation and financing cross-national stockpiles.