bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, attitude, and practice of asthma among the adults in Shendi locality, Sudan: A cross-sectional study
Authors: Elawad Sara , Saad-Omer Sabaa I. , Elawad Shaima Omer Mohamed , Elbadawi Mohamed H. , Ahmed Sahar A.A. , Bashir Sara B. , Abdelmutaleb Selma A.H. , Mohamed Sarah O. , Babiker Suad B. , Osman Sara M.S. , Fadul Mohamed A.H. , Abdalkareem Esameldeen O.M. , M. Ahmed Ahmed Balla , Galal Ali
Published: November 2024

Asthma is a chronic inflammatory condition leading to intermittent airway narrowing and obstruction. Although millions suffer from asthma globally, there is limited data from African countries, particularly Sudan. This study addresses the gap in research on asthma knowledge, attitudes, and practices among the adults in Shendi locality, Northern Sudan. This cross-sectional, community-based study was conducted in Kabushiya village, Shendi, Sudan, involving 148 participants selected through multistage random sampling. Data were collected via face-to-face interviews using a validated, structured questionnaire. Statistical analyses included Mann–Whitney, Kruskal–Wallis, Chi-square, Fisher exact tests, and multiple linear regression. Participants demonstrated high levels of knowledge, positive attitudes, and good practices regarding asthma. Knowledge scores were significantly associated with marital status, education, occupation, and income (P values: .040, .003, .000, and .006, respectively), with the highest medians among divorced individuals, those with higher education, professional workers, and people earning <50,000 SDGs (medians: 17, 16, 17, and 16, respectively). Attitude scores varied significantly by marital status, education, occupation, and family asthma history (P values: .001, .000, .003, and .016, respectively), with highest scores among divorced individuals, those with high school or higher education, professionals, and those with a first-degree relative with asthma (medians: 6, 5, 5, and 5, respectively). Patient practice scores differed by marital status and income (P values: .026 and .006, respectively), with higher scores among singles and those earning <50,000 SDGs. Co-patient practice scores were significantly influenced by occupation, personal or familial asthma experience, and family asthma status (P values: .026, .003, and .000, respectively). No significant differences were observed in co-patient practice scores between groups. The study highlights a generally good level of asthma knowledge and positive attitudes among participants, with some variability in practices based on socio-demographic factors. These findings emphasize the need for targeted education and intervention programs to improve asthma management in rural Sudan.
Current Practices for Delivering New Diagnosis Education at Children’s Oncology Group Institutions
Authors: Visungrae Narissara , Campos González Paula D. , Skipper K. Elizabeth , Li Peng , Vance David E. , Salem Adelynn J. , Herriage Teresa , Zupanec Sue , Landier Wendy
Published: November 2024

Background

The Children’s Oncology Group (COG) Nursing Discipline developed expert consensus recommendations and resources to guide the delivery of new diagnosis education across its member institutions. Current new diagnosis education practices across COG member institutions are unknown.

Objective

To understand current new diagnosis education practices across COG member institutions.

Methods

We conducted a cross-sectional survey of COG nurses between July and October 2023 to elicit current practices to deliver new diagnosis education to families across COG institutions. Data were collected and managed using REDCap electronic data capture tools. Individual responses from single institutions were averaged as a single institution-level response.

Results

Respondents included 146/227 (64.3%) COG institutions across 5 countries. Advanced practice nurses and nurse educators have primary responsibility for new diagnosis education at 28.1% and 26.7% of institutions, respectively. Less than half (42.4%) of institutions have a clearly defined process for delivering new diagnosis patient/family education. Almost all (88.2%) institutions use the COG Family Handbook; 64.7% use the COG New Diagnosis Guide, and 41.9% use the COG KidsCare app to support the delivery of new diagnosis education. More than half (61.5%) of institutions use checklists to facilitate the delivery of new diagnosis education, with 81.6% of large institutions versus 44.1% of small institutions reporting the use of checklists (P = .004).

Conclusions

There is variability in current new diagnosis education practices across COG institutions.

Implications for Practice

These findings highlight opportunities for implementing standardized approaches aligned with expert consensus recommendations for the delivery of new diagnosis education.
Acute Fluoride Toxicity Due to Intentional Ingestion of Hydrofluoric Acid Commercial Product
Authors: Macias Tatianna , Bingham Abujasen Kaileigh , Usera Phillip C. , Knight Laura D.
Published: November 2024

Hydrofluoric (HF) acid, an irritating and corrosive acid, is commonly found in cleaning supplies. Fatal HF acid ingestion has been documented, although relatively rare. We report a case of acute fluoride toxicity suicide due to the ingestion of a commercial product containing HF acid and ammonium bifluoride. To our knowledge, this is the first to describe the associated gastrointestinal histopathology in detail.

A 56-year-old woman was found deceased near a rust remover product and a notebook containing suicide methods via chemical ingestion. Gross autopsy findings included laryngeal mucosal petechial hemorrhages; patchy esophageal mucosal denudation; and autolyzed, red-black discolored gastric mucosa. Histology of the esophagus demonstrated superficial mucosal ulceration with necrosis of the squamous mucosa, vascular congestion, and lymphoid aggregates in the lamina propria; muscularis mucosae and muscularis propria were unperturbed. The stomach showed superficial coagulative necrosis of the oxyntic crypts, with fresh microhemorrhage dissecting the glandular mucosa away from the muscularis mucosae; muscularis mucosae, submucosa, muscularis propria, and serosa were all spared.

Toxicology revealed an elevated fluoride ion concentration (20 mg/L). Death was attributed to acute fluoride toxicity due to intentional ingestion of a commercial product containing HF acid and ammonium bifluoride, and the manner was suicide.
Cardiovascular Disease in Acute Cocaine Compared to Acute Fentanyl Intoxication Deaths
Authors: Burke Olivia , Ely Susan F. , Gill James R.
Published: November 2024

Cocaine is the most common stimulant drug that causes death in Connecticut. Unlike opioid intoxication deaths, which largely correlate with dose/concentration, cocaine deaths occur more idiosyncratically, with mechanisms of death often related to underlying cardiovascular disease. We examined 78 sole acute cocaine and 306 sole acute fentanyl intoxication deaths to assess their association with cardiovascular disease. In the cocaine cohort, 87% (68/78) had atherosclerotic and/or hypertensive cardiovascular disease while 40% (122/306) in the fentanyl cohort did. Cocaine was detected in 40% of all accidental drug intoxication deaths, 41% of all accidental drug intoxication deaths involving fentanyl, and 37% of all drug intoxication deaths involving heroin. The relatively low number of sole cocaine deaths compared to the much higher proportion of cocaine/opioid deaths may be explained by the synergistic effects encountered in many mixed drug intoxications, the contributory role of cardiovascular disease in sole cocaine deaths, and/or the increased prevalence and potency of fentanyl. The high number of sole cocaine deaths in which the decedents had co-existing heart disease compared to those from sole fentanyl deaths (P < 0.001) suggests that heart disease plays a mechanistic role in sole cocaine deaths, whereas the potency of fentanyl is the dominant mechanism in fentanyl deaths.
Assessing Facility Readiness to Provide Equitable Birthing Care in New York State: A Baseline Survey
Authors: Gowani Sahar , Kellachan Jacqueline , Enwere Chiagbanwe , Kacica Marilyn
Published: November 2024

Context

Facility policies, practices, and culture contribute to inequities in maternal outcomes. In New York State (NYS), Black birthing people are 4 to 5 times more likely to experience maternal mortality than White birthing people.

Objectives

Understanding the racial, ethnic, linguistic, and gender equity policies at NYS birthing facilities can identify areas of improvement to impact care and outcomes.

Design

The design was a cross-sectional study.

Setting

The setting was NYS birthing facilities, which included hospitals and birthing centers.

Participants

Facility leadership completed self-reported surveys from December 2020 through June 2021.

Main Outcome Measure

Facility equity data were obtained across 4 domains: (1) organizational commitment to equity, (2) staff equity training and evaluation, (3) leadership and staff composition, and (4) patient data, voice, and influence.

Results

Over half of NYS birthing facilities documented a public commitment to equity in their mission, but only 15% had a written equity plan with processes for monitoring progress. Less than one-third of facilities stated that staff from underrepresented racial, ethnic, and language, gender (REaLG) groups were proportionally represented in leadership and management positions. About half of the facilities reported their staff composition reflects their patient population, but only a quarter analyzed staff REaLG demographics to serve diverse patients. Twenty-eight percent of facilities assess diversity in their board of directors, facility leadership, medical leadership, medical staff, and administrative staff. One-third required staff implicit bias training; 17% collected and used data on patient satisfaction regarding racial equity; and 12% engaged affected communities.

Conclusions

Facilities differed in their implementation of policies and practices that support equitable care. Survey data provide facilities with specific areas of improvement to focus their efforts. Equity assessments are an important step for facilities to evaluate their policies and practices and for statewide institutions to develop programming.
A key feedback loop: building electricity infrastructure and electrifying metals production
Authors: Daehn Katrin E. , Allanore Antoine , Olivetti Elsa A.
Published: November 2024

Energy infrastructure requires metals, and metals production requires energy. A transparent, physical model of the metals-energy system is presented to explore under what conditions this dependence constrains or accelerates the transition to a net-zero economy. While the mineral (as high as 340 Mt yr
−1
iron ore, 210 Mt yr
−1
limestone, 250 Mt yr
−1
bauxite and 5.5 Gt yr
−1
copper ore in the 2040–2050 decade, assuming no improvements) and total energy (up to 22 EJ yr
−1
) requirements for building low-carbon energy infrastructure are significant, it compares favourably with the current extraction and energy use supporting the fossil fuel system (15 Gt yr
−1
fossil minerals and ~38 EJ yr
−1
). There are levers to significantly reduce material use and associated impacts over time. The metals industry can play a key reinforcing role in the transition by adapting to the increasing supply of renewable electricity. Specifically, direct electrolysis can extract metal from ore close to the thermodynamic limit, to make efficient use of low-C electricity. The unique features of emerging technologies for iron extraction, molten oxide electrolysis and molten sulphide electrolysis are considered in this evolving system. Electrification enables elegant separations and provides a pathway to build out infrastructure while reducing environmental impacts, though material efficiency measures will still be crucial to meet 2050 carbon budgets.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
Current recycling innovations to utilize e-waste in sustainable green metal manufacturing
Authors: Hossain Rumana , Sahajwalla Veena
Published: November 2024

The ever-increasing market demand and the rapid uptake of the technologies of electronics create an unavoidable generation of high-volume electronic waste (e-waste). E-waste is embedded with valuable metals, alloys, precious metals and rare earth elements. A substantial portion of e-waste ends up in landfills and is incinerated due to its complex multi-material structure, creating loss of resources and often leading to environmental contamination from the release of landfill leachates and combustion gases. Conversely, due to the ongoing demand for valuable metals, global industrial and manufacturing supply chains are experiencing enormous pressure. To address this issue, researchers have put multifaceted efforts into developing viable technologies and emphasized right-scaling for e-waste reclamation. Several conventional and emerging recycling technologies have been recognized to be efficient in recovering metal alloys, precious and rare earth metals from e-waste. The recovery of valuable metals from e-waste will create an alternative source of value-added raw materials, which could become part of supply chains for manufacturing. This review discusses the urgency of metal recycling from e-waste for sustainability and economic benefit, up-to-date recycling technologies with an emphasis on their potential role in creating a circular economy in e-waste management.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
Material efficiency at the component level: how much metal can we do without?
Authors: Allwood Julian M. , Music Omer
Published: November 2024

Global production of steel and aluminium is a major driver of greenhouse gas emissions. Various processes might allow continued primary production of the two metals, but all depend on emissions-free electricity or carbon storage, and global capacity of these two key resources will be below demand for decades to come. As a result, zero-emissions steel and aluminium will mainly come from recycling, but supply will be lower than demand. This motivates demand reduction, and for the first time, this article estimates the inefficiency in current metal use by component type. The results demonstrate that around 80% of steel and 90% of aluminium liquid metal produced today may be unnecessary. Around 40% of liquid steel and 60% of liquid aluminium are never used in final components as they are removed along the supply chain of manufacturing. Of the metal that enters final service, approximately one-third could be saved by avoiding component over-specification. A further third could be saved, where the properties of metal are not used to their limits. These results point to specific opportunities for innovation in design and manufacturing technology, of which the highest priority is to re-think the use of sheet metal in construction.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
Sustainable extraction and recycling of non-ferrous metals: a review from a European perspective
Authors: Gerold Eva , Luznik Lea , Samberger Sebastian , Antrekowitsch Helmut
Published: November 2024

This review article provides a comprehensive examination of sustainable extraction and recycling methods for non-ferrous metals, which are critical to a wide range of industries including electronics, construction and renewable energy. Focusing on metals such as aluminium, copper and silicon, the study highlights the importance of recycling in conserving resources and minimizing environmental impact. It discusses the challenges posed by material diversity in recycling processes and the advances in recycling technologies that have emerged in response. Special emphasis is placed on the importance of a circular economy in maintaining a sustainable balance between consumption and conservation of metal resources. Through detailed analysis, it advocates innovative recycling practices and improved design for recyclability and highlights the role of policy, industry and consumer behaviour in achieving sustainability goals. The findings contribute to the discourse on strategic self-sufficiency in Europe through recycling, providing insights into how to improve efficiency and manage the complexity of the global material cycle. This work calls for a collaborative effort towards sustainable metallurgy and underlines the critical need for advances in recycling infrastructure and technology to ensure the long-term availability and environmental stewardship of non-ferrous metals.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
BLOC: buildable and linkable organ on a chip
Authors: Kimura Yusuke , Hamaguchi Hiroki , Oyama Kotaro , Oyama Tomoko G. , Kimura Atsushi , Ohshima Yasuhiro , Ishioka Noriko S. , Taguchi Mitsumasa
Published: November 2024

Microphysiological systems (MPSs) are attractive alternatives to animal experiments in physiology, pathophysiology, and drug development. However, conventional MPSs are designed for specific applications and have low versatility and scalability. Here, we developed a “Buildable and Linkable Organ on a Chip” (BLOC) to construct diverse MPSs. The Culture, Control, and Analysis BLOCs were standardized to the same size and linked using inlet/outlet joints for perfusion. Radiation-induced chemical reactions were used to suppress the adsorption and absorption of small hydrophobic molecules by BLOCs composed of polydimethylsiloxane. BLOCs for 2D/3D culture could also encapsulate radiation-crosslinked protein hydrogels with designed stiffness and microtopography to mimic the microenvironmentin vivo. A perfusion device connecting Culture BLOCs was designed for a toxicity assay mimicking the systemic circulation using six types of organoids. An automatic enzyme-linked immunosorbent assay device connecting Culture, Control, and Analysis BLOCs detected proteins released from organoids. BLOCs, which users can freely configure to suit their needs, is expected to become powerful tools in basic research and preclinical trials using MPSs.
The relative effects of abiotic and biotic factors in explaining the structure of soil bacterial communities at diverse taxonomic levels
Authors: Mayjonade Baptiste , Zamar Rémy , Carrere Sébastien , Roux Fabrice
Published: November 2024

Soil microbes play pivotal roles in the multifunctioning of terrestrial ecosystems. In the context of global changes, there is an urgent need to protect soil microbial diversity, which relies on determining the abiotic and biotic factors that influence the diversity, composition, and assemblage of soil microbiota. A large number of informative studies have reported edaphic properties and climate factors as key drivers of soil bacteria microbiota. However, these studies were mainly conducted at the phylum level and based on a restricted number of non-microbial variables. In this study, we aimed to estimate the relative effects of abiotic and biotic factors in shaping soil bacterial communities at diverse taxonomic levels by focusing on 160 natural sites located in the southwest of France for which a large and unique set of non-microbial variables is available. After characterizing soil bacterial communities with the highly taxonomically resolvinggyrBgene, we identified that in addition to pH, temperature, and precipitations, soil bacterial communities at the lowest taxonomic levels appear strongly structured by soil micronutrients, notably manganese. On the other hand, soil bacterial communities at the highest taxonomic levels appear strongly structured by the interplay between descriptors of plant communities and edaphic properties. Similar to previous observations on microbial pathogens, the strong and positive associations between soil bacterial species and the presence of particular plant species suggest host specificity for soil commensal bacteria. Altogether, a deeper characterization of both abiotic and biotic factors could help fuel programs designed for protecting and restoring soil ecosystem functions.
Target-specific design of drug-like PPI inhibitors via hotspot-guided generative deep learning
Authors: Sun Heqi , Li Jiayi , Zhang Yufang , Lin Shenggeng , Chen Junwei , Tan Hong , Wang Ruixuan , Mao Xueying , Zhao Jianwei , Li Rongpei , Xiong Yi , Wei Dong-Qing
Published: November 2024

Protein–protein interactions (PPIs) are vital therapeutic targets. However, the large and flat PPI interfaces pose challenges for the development of small-molecule inhibitors. Traditional computer-aided drug design approaches typically rely on pre-existing libraries or expert knowledge, limiting the exploration of novel chemical spaces needed for effective PPI inhibition. To overcome these limitations, we introduce Hot2Mol, a deep learning framework for the de novo design of drug-like, target-specific PPI inhibitors. Hot2Mol generates small molecules by mimicking the pharmacophoric features of hot-spot residues, enabling precise targeting of PPI interfaces without the need for bioactive ligands. The framework integrates three key components: a conditional transformer for pharmacophore-guided, drug-likeness-constrained molecular generation; an E(n)-equivariant graph neural network for accurate alignment with PPI hot-spot pharmacophores; and a variational autoencoder for generating novel and diverse molecular structures. Experimental evaluations demonstrate that Hot2Mol outperforms baseline models across multiple metrics, including docking affinities, drug-likenesses, synthetic accessibility, validity, uniqueness, and novelty. Furthermore, molecular dynamics simulations confirm the good binding stability of the generated molecules. Case studies underscore Hot2Mol’s ability to design high-affinity and selective PPI inhibitors, demonstrating its potential to accelerate rational PPI drug discovery.
Cytoplasmic localization of ribonucleotide reductase is essential for genome stability
Authors: Andreadis Christos , Salguero Israel , Kearsey Stephen E.
Published: November 2024

Ribonucleotide reductase (RNR) is a major determinant of dNTP concentrations and its correct regulation is crucial for genome stability. Active RNR is cytoplasmic but the significance of this localization, away from DNA synthesis, is unclear, particularly as RNR is targeted to the nucleus after DNA damage occurs. We subverted the localization of fission yeast RNR by tagging the large (Cdc22R1) and small (Suc22R2) subunits with nuclear localization signal sequences. Directing RNR to the nucleus caused a slow S-phase and increased mutagenesis, in spite of predicted constitutive activation of RNR. Defective function of nuclear RNR is also suggested by the formation of Cdc22R1supramolecular filaments and defective RNR reoxidation. In contrast, constitutively nuclear Cdc22 or Suc22 has little effect on DNA damage repair and in fact suppressesrad3Δ-sensitivity to DNA damaging agents. We suggest that there is an inadequate flux of substrate through nuclear RNR for S phase, but nuclear targeting of RNR may facilitate DNA damage repair under some circumstances.
A CELL BIOLOGY STUDY REVEALS NEW INSIGHTS INTO THE TRANSPORT MECHANISMS OF OOMYCETE EFFECTORS
Authors: Tomczynska Iga , Stumpe Michael , Reinhardt Didier , Geisler Markus M.
Published: November 2024

Oomycete pathogens use dedicated effector proteins (also known as virulence factors) that manipulate the host during infection to the benefit of the pathogen. Despite extensive efforts, the understanding of how oomycete effector proteins are transported and delivered to the host is limited. Here, we show thatPhytophthora capsiciinfectingNicotiana benthamianasecretes its effectors through secretory pockets, haustoria, and from hyphae. We provide evidence that Avr3, belonging to the class of RxLR effector proteins that can be secreted and translocated to the plant cell, is found to accumulate in a distinct ring-shaped zone around the neck region of haustoria. The association with the haustorial neck is determined by an RxLR-EER motif and mutating this motif redirects Avr3 to the extrahaustorial matrix enveloping the full haustoria body. Furthermore, mass spectrometry analysis of immunoprecipitated Avr3 indicates that the RXLR motif remains intact when Avr3 is secreted from the haustorium during plant infection. We thus propose that the RXLR-EER motif determines the entry in the host cell by guiding Avr3 to the haustorial neck region, which may be a structure analogous to the Biotrophic Interfacial Complex of the fungusMagnaporthesp.
Accelerating Cell Culture Media Development Using Bayesian Optimization-Based Iterative Experimental Design
Authors: Narayanan Harini , Hinckley Joshua , Barry Rachel , Dang Brendan , Wolffe Lenna A. , Atari Adel , Tseng Yuen-Yi (Moony) , Love J. Christopher
Published: November 2024

Optimizing operational conditions for complex biological systems used in life sciences research and biotechnology is an arduous task. Here, we have applied a Bayesian Optimization-based iterative framework for experimental design to accelerate cell culture media development for two applications. First, we show this approach yields new compositions of media with cytokine supplementation to maintain the viability and distribution of PBMCs in culture. Second, we applied this framework to optimize the production of three recombinant proteins inK.phaffiicultivations. For both applications, we identified conditions with improved outcomes compared to the initial standard media using 3 to 30 times fewer experiments than other methods such as the Design of Experiments. Subsequently, we also demonstrated the extensibility of our approach to efficiently account for additional design factors through transfer learning. These examples demonstrate how coupling data collection, modeling, and optimization in this iterative paradigm, while using an exploration-exploitation tradeoff in each iteration, can reduce the time and resources for these types of optimizations.
Differential Analysis of Alternative Splicing Events in gene regions using Residual Neural Networks
Authors: Ciccolella Simone , Denti Luca , Cartes Jorge Avila , Vedova Gianluca Della , Pirola Yuri , Rizzi Raffaella , Bonizzoni Paola
Published: November 2024

Several computational methods for the differential analysis of alternative splicing (AS) events among RNA-seq samples typically rely on estimating isoform-level gene expression. However, these approaches are often error-prone due to the interplay of individual AS events, which results in different isoforms with locally similar sequences. Moreover, methods based on isoform-level quantification usually need annotated transcripts.

In this work, we leverage the ability of deep learning networks to learn features from images, to proposedeepSpecas, a novel method for event-based AS differential analysis between two RNA-seq samples. Our method does not rely on isoform abundance estimation, neither on a specific annotation.deepSpecasemploys an image embedding scheme to represent the alignments of the two samples on the same region and utilizes a residual neural network to predict the AS events possibly expressed within that region. To our knowledgedeepSpecasis the first deep learning approach for performing an event-based AS analysis of RNA-seq samples. To validatedeepSpecas, we also address the lack of high quality AS benchmark datasets. For this purpose, we manually curated a set of regions exhibiting AS events. These regions were used for training our model and for comparing our method with state-of-the-art event-based AS analysis tools. Our results highlight thatdeepSpecasachieves higher precision at the expense of a small reduction in sensitivity.

The tool and the manually curated regions are available athttps://github.com/sciccolella/deepSpecas.
Evolution of intrinsic disorder in the structural domains of viral and cellular proteomes
Authors: Mughal Fizza , Caetano-Anollés Gustavo
Published: November 2024

Intrinsically disordered regions are flexible regions that complement the typical structured regions of proteins. Little is known however about their evolution. Here we leverage a comparative and evolutionary genomics approach to analyze intrinsic disorder in the structural domains of thousands of proteomes. Our analysis revealed that viral and cellular proteomes employ similar strategies to increase disorder but achieve different goals. Viral proteomes evolve disorder for economy of genomic material and multifunctionality. On the other hand, cellular proteomes evolve disorder to advance functionality with increasing genomic complexity. Remarkably, phylogenomic analysis of intrinsic disorder showed that ancient domains were ordered and that disorder evolved as a benefit acquired later in evolution. Evolutionary chronologies of domains indexed with disorder levels and distributions across Archaea, Bacteria, Eukarya and viruses revealed six evolutionary phases, the oldest two harboring only ordered and moderate disorder domains and delimiting two universal common ancestors of life. A biphasic spectrum of disorder versus proteome makeup captured the dichotomy in the evolutionary trajectories of viral and cellular ancestors, one following reductive evolution driven by viral spread of molecular wealth and the other following expansive evolutionary trends to advance functionality through massive domain-forming co-option of disordered loop regions.

Teaser

Comparative and evolutionary genomic analyses of the intrinsic disorder of structural domains in thousands of proteomes reveal proteomes increase disorder as a benefit acquired later in evolution to support viral economy and multifunctionality or advanced cellular functionality.
Robustness in Hopfield neural networks with biased memory patterns
Authors: Montazeri Ali , Schmidt Robert
Published: November 2024

Biological neural networks are able to store and retrieve patterns in the presence of different types of noise. Hopfield neural networks have been inspired by biological neural networks and provide a model for auto-associative memory patterns. An important parameter in these networks is the pattern bias, i.e. the mean activity level of the network, which is closely related to the degree of sparseness in the coding scheme. Here we studied the relation between robustness against different types of biologically-motivated noise and pattern bias. To do so, we developed performance and robustness measures, which are applicable to varying degrees of sparseness of the memory representations, using analytically-optimized thresholds and corruption tolerances adjusted by mutual information. We then applied these tools in numerical simulations and found that, for different types of noise, the pattern load, i.e. the number of patterns that the network has to store, determined which pattern bias is most robust. Across different types of noise, the higher the pattern load was, the more biased was the most robust performing pattern representation. Given the variation in the sparseness level in different brain regions, our findings suggest that memory pattern encoding schemes (i.e. degree of sparseness) in different brain regions might be adapted to the expected memory load in order to best mitigate the adverse effects of disruptions.
ADAT2/3-mediated tRNA editing promotes cancer cell growth and tumorigenicity
Authors: Ramirez-Moya Julia , Antika Titi Rindi , Liu Qi , Xiong Xushen , Ali Raja , Gutierrez Alejandro , Gregory Richard I.
Published: November 2024

Transfer RNAs (tRNAs) are subject to various chemical modifications that influence their stability or function. Adenosine to Inosine (A-to-I) editing in the tRNA anticodon at position A34 is an important modification that expands anticodon-codon recognition at the wobble position and is required for normal mRNA translation. The relevance of tRNA editing in cancer remains unexplored. Here we show that the genes encoding the ADAT2/3 deaminase complex, responsible for A-to-I tRNA editing in humans, are commonly amplified and/or overexpressed in several tumor types including liposarcoma (LPS). We find that knockdown of the ADAT complex suppresses LPS cell growth and tumorigenicity. Mechanistically, we find that decreased tRNA editing upon ADAT2 depletion leads to defective translation of a subset of mRNAs. Thus, ADAT-mediated tRNA modification promotes oncogenesis by enhancing the translation of growth promoting mRNAs that are enriched in NNC codons that lack cognate tRNAs and therefore depend on A-I tRNA editing for decoding and mRNA translation. Our results uncover an oncogenic role of tRNA editing and identify ADAT2/3 as a potential new cancer therapeutic target.
First attempt to validate multiplex PCR with sex markers SSM4 and ALLWSex2 in long-term stored blood samples of eastern North American shortnose sturgeon (Acipenser brevirostrum)
Authors: Tabatabaei Pozveh Hajar Sadat , Dorafshan Salar , Benfey Tillmann J. , Addison Jason A. , Litvak Matthew K.
Published: November 2024

Sex-specific information is crucial for sturgeon culture, conservation, and fisheries management. However, identifying the sex of sturgeon is difficult, especially for immature individuals. Two recent studies identified two female-specific loci (AllWSex2 and SSM4) that are conserved among many Acipenserid species, but they have not been validated for all species within this family. The objectives of this study were to 1) determine whether SSM4 can be used to sex shortnose sturgeon; 2) develop and test a multiplex PCR technique using both ALLWSex2 and SSM4 for sexing shortnose sturgeon; 3) determine if long-term storage of blood samples can be used to sex shortnose sturgeon; and 4) test the effect of storage temperature on DNA degradation. DNA was extracted from frozen RBC samples from 36 fish which had previously been sexed. A multiplex PCR was set up using three pairs of primers: AllWSex2 and SSM4, as female-specific loci, and mtDNA as an internal control which were all run on a 2 % agarose gel. AllWSex2 and SSM4 allowed for perfect discrimination of sex. While there was DNA degradation, as a result of long-term storage and temperature, the signal was still strong enough after 8 years of cold storage to delineate sex. This suggests that researchers now have the ability to reexamine archived/frozen samples to determine sex of their fish.
Phylogenetic and functional compositional shifts associated with selective logging and forest regrowth in tropical rainforests of the Congo Basin
Authors: Depecker Jonas , Asimonyio Justin A. , Hatangi Yves , Honnay Olivier , Janssens Steven B. , Kambale Jean-Léon , Vandelook Filip , Carta Angelino
Published: November 2024

Background and aims

Tropical rainforests constitute a globally important biome severely threatened by anthropogenic activities. Accounting for the phylogenetic and functional dimensions can provide insights into how anthropogenic activities affect tree species community assembly. Here, we aimed to assess the effects of selective logging and forest regrowth on the tree composition in the Yangambi region (Democratic Republic of the Congo), as compared to reference undisturbed old-growth forest by incorporating phylogenetic and functional information.

Methods

We measured the phylogenetic and functional alpha-diversity and dissimilarity of undisturbed old-growth, disturbed old-growth, and regrowth rainforests by sampling species abundances and key traits related to usefulness (wood density), vegetative (specific leaf area), and reproductive (fruit type) functions. Then, we evaluated the association between phylogenetic and functional dissimilarity to unravel potential drivers underlying changes in the community composition.

Key results

Phylogenetic and functional dissimilarities resulted in a consistent compositional separation of the disturbed old-growth forests and regrowth forests from the undisturbed old-growth forests, with this separation clearly associated with key functional traits.

Compared to undisturbed old-growth forests, disturbed old-growth forests subjected to selective logging did not diverge in terms of both phylogenetic and functional diversity and structure. However, regrowth forests displayed increased levels of phylogenetic diversity and comparable functional diversity as undisturbed old-growth forests.

Conclusions

Selective logging and forest regrowth have not led to an overdispersion or clustering of phylogenetic lineages nor functional traits in the tropical rainforests in the Congo Basin, rather, these anthropogenic activities brought an altered phylogenetic and functional community composition which may have serious implications for the stability of these ecosystems.
Tunability of calcium dynamics by signaling inputs and cell-cell communication in pancreatic beta cells
Authors: Shang Xingbo , Levchenko Andre
Published: November 2024

In addition to frequently occurring stable all-or-none responses, live cells can display more complex response dynamics, e.g., oscillations in the activity/concentration of biomolecules. While the emergence and function of oscillatory dynamics have been heavily investigated, fewer efforts have been spent on whether cells can fine-tune different aspects of an oscillatory signal (e.g., peakwidth, duty cycle, and frequency) and whether this fine-tuning can allow oscillatory signals to convey different information. In this study, we investigate glucose-induced calcium (Ca2+) oscillation in MIN6 cells, finding that the spontaneous or induced changes in the phosphatidylinositol 4,5-bisphosphate (PIP2) level during Ca2+oscillation can modulate the peakwidth of individual Ca2+spikes. Additionally, using a combination of optogenetics and Ca2+imaging, we demonstrate that variation of the widths and frequencies of Ca2+spikes can exert strong influence on coupling between neighboring MIN6 cells.
Modeling American Kestrel Decline Using Spatiotemporal Subsampling to Improve eBird Data Reliability
Authors: Sharma Archith , Bednarz James C. , Kwon Junhyeon
Published: November 2024

American Kestrel (Falco sparverius) numbers have plummeted over 40% since 1980, despite many other raptor species, including the closely related Merlin (Falco columbarius) rebounding in the same period, post the ban on the use of DDT. One plausible reason for this decline is the increase in Cooper’s Hawks (Astur cooperii), a predatory species. To model the impact of Cooper’s Hawk on American Kestrels, one can use citizen science data such as eBird. However, eBird contains a heavy sampling bias towards recent data in large cities as it has gained popularity over time. A novel framework testing different spatiotemporal subsampling resolutions was employed in seeing how to make the data more reliable and to enjoy a finer time resolution compared to the Breeding Bird Survey (BBS) standard. The ecological relationship between two species is then modeled using a time-series framework that accounts for both current and past interactions, with the model order determined based on criteria such as BIC. The creation and analysis of synthetic data are also tested to verify that our framework reflects the ground truth of the bird abundance trend. Immediate forecast results based on the eBird data suggests a decline of American Kestrels at the current pace.
Constitutive neural networks for main pulmonary arteries: Discovering the undiscovered
Authors: Vervenne Thibault , Peirlinck Mathias , Famaey Nele , Kuhl Ellen
Published: November 2024

Accurate modeling of cardiovascular tissues is crucial for understanding and predicting their behavior in various physiological and pathological conditions. In this study, we specifically focus on the pulmonary artery in the context of the Ross procedure, using neural networks to discover the most suitable material model. The Ross procedure is a complex cardiac surgery where the patient’s own pulmonary valve is used to replace the diseased aortic valve. Ensuring the successful long-term outcomes of this intervention requires a detailed understanding of the mechanical properties of pulmonary tissue. Constitutive artificial neural networks offer a novel approach to capture such complex stressstrain relationships. Here we design and train different constitutive neural networks to characterize the hyperelastic, anisotropic behavior of the main pulmonary artery. Informed by experimental biaxial testing data under various axial-circumferential loading ratios, these networks automatically discover the inherent material behavior, without the limitations of predefined mathematical models. We regularize the model discovery using cross-sample feature selection and explore its sensitivity to the collagen fiber distribution. Strikingly, we uniformly discover an isotropic exponential first-invariant term and an anisotropic quadratic fifth-invariant term. We show that constitutive models with both these terms can reliably predict arterial responses under diverse loading conditions. Our results provide crucial improvements in experimental data agreement, and enhance our understanding into the biomechanical properties of pulmonary tissue. The model outcomes can be used in a variety of computational frameworks of autograft adaptation, ultimately improving the surgical outcomes after the Ross procedure.
Normalized Dynamic Time Warping Increases Sensitivity In Differentiating Functional Network Connectivity In Schizophrenia
Authors: Wiafe Sir-Lord , Kinsey Spencer , Iraji Armin , Miller Robyn , Calhoun Vince D.
Published: November 2024

Our study advances the application of dynamic time warping (DTW) as a functional connectivity measure by introducing a normalization technique which enhances the detection of schizophrenia effects in comparison to both standard DTW and traditional correlation methods. By rigorously examining the statistical validity of DTW and our proposed normalized DTW measure, we show that it effectively captures interdependencies between fMRI signals beyond linear correlation, offering a more robust, complementary and informative approach to functional connectivity analysis. Through comprehensive evaluations, we demonstrate that normalized DTW is more sensitive to differences in functional brain network connections between schizophrenia and controls, highlighting its potential to provide deeper insights into clinical research.
Health benefits of a five-day at-home modified fasting program: a randomised controlled trial
Authors: Grundler Franziska , Ducarmon Quinten R. , Holley Alfred , Knufinke Marie , Strathmeyer Selina , Heelemann Steffen , Geyer Roland , Martinez Tellez Borja , MacArthur Michael R , Zeller Georg , Wilhelmi de Toledo Françoise , Mesnage Robin
Published: November 2024

Background

Fasting has been shown to be one of the most cost-effective methods to improve cardiometabolic health. We studied a 5-day hypocaloric (∼600 kcal/day) and ketogenic, modified fasting program (MFP) for at-home interventions. We hypothesised that this MFP induces metabolic changes comparable to 5 days of prolonged fasting (75-250kcal/day).

Methods

We tested the MFP in a two-arm randomised controlled trial where sixty-four healthy subjects were randomised to MFP or control group. Serum biochemistry analyses and questionnaires allowed for determining effects on cardiometabolic risk factors. Emotional well-being, possible side effects and physical activity were assessed with questionnaires. Biological pathways and metabolic processes were explored with nuclear magnetic resonance blood metabolomics and gut metagenomics analyses.

Results

MFP participants (n=32) experienced weight loss (−3.1 ± 1.1 kg) persisting one month after the intervention. The MFP induced significant, but transient reductions, in systolic (−6.4 ± 11.5 mmHg) and diastolic (−4.4 ± 7.7 mmHg) blood pressure, glucose levels, HbA1c and coagulation factors. The MFP led to greater reductions in BMI (p=0.006), diastolic pressure (p = 0.009), cholesterol (p = 0.02), and LDL (p = 0.02) in individuals at risk of cardiometabolic diseases compared to healthy individuals. Total cholesterol, LDL-C and HDL-C levels continued decreasing during food reintroduction. The MFP also increased emotional and physical well-being. Blood metabolomics revealed a significant decrease in chronic inflammation markers. Shotgun metagenomics of the gut microbiome showed trends in the changes in relative abundance of the majority of bacterial species and their genomic repertoire of carbohydrate-active enzymes (CAZymes). This reflected a decrease in families metabolising dietary fibre substrates and an increase in families metabolising host-derived glycan substrates. Comparing MFP effects with a previous cohort’s 5-day prolonged fasting showed similar metabolic changes.

Conclusion

This MFP is safe and effectively improves cardiometabolic health and emotional well-being in healthy individuals. It offers comparable metabolic benefits to those observed during 5-day prolonged fasting in a clinic. It is safe to be practised at home, widely accessible and compatible with individuals’ everyday life.
Development and characterization of bioinks for 3D bioprinting of in vitro skeletal muscle constructs
Authors: Kado Abdalkader Rodi , Yamauchi Kosei , Konishi Satoshi , Fujita Takuya
Published: November 2024

The use of 3D bioprinting to constructin vitroskeletal muscle models presents a promising approach; however, selecting an optimal bioink remains a common challenge. This study focuses on the development and characterization of bioinks for extrusion-based 3D bioprinting, specifically targeting the creation of accurate skeletal muscle models. By exploring various compositions of alginate, gelatin, fibrinogen, and nanofiber cellulose, we evaluate these formulations based on printability and their support for the growth and differentiation of C2C12 myoblast cells.

While alginate provided a strong, stable matrix for printing scaffolds embedded with C2C12 cells, it did not effectively promote cell growth and differentiation. The addition of fibrinogen to alginate enhanced cell growth and differentiation but was limited mainly to the scaffold surfaces, even with the inclusion of gelatin as a sacrificial ink. Notably, replacing alginate with nanofiber cellulose (NFC) alongside fibrinogen significantly improved cell growth and differentiation, leading to the formation of mature myotubes. Cell distribution was observed both inside and on the surfaces of the scaffolds, indicating effective spatial cell distribution. Furthermore, the scaffolds were tailored to form skeletal muscle bundles anchored between PDMS pillars for contractility testing. Upon exposure to electrical stimulation, the cells displayed measurable displacement, demonstrating contractile function.

These findings offer valuable insights into optimizing bioink formulations that promote myoblast growth and differentiation into skeletal musclein vitro, with potential applications in future neuromuscular disease modeling.