bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancements in parabolic trough water heaters with dimpled tube–CuO deionized nanofluid: experimental and numerical investigation
Authors: Arun M , Barik Debabrata , Naik Channa Keshava , Bora Bhaskor Jyoti , Dasarathy A K , Singh Sanjay , Alqarni Sondos Abdullah , Islam Saiful , Kumar Sandeep , Pathani Ashish , Wodajo Anteneh Wogasso
Published: November 2024

The goal of this study was to improve the performance of a parabolic trough solar water heater (PTSWH) by using a dimpled texture design on the water tube and copper oxide/deionized water (CuO/DI-H2O) as a cell-side nanofluid (NF). Experimental tests will be conducted to measure and validate the thermal performance improvements using the dimpled tube–CuO NF combination. The nanoparticle (NP) concentration in the NF and the water mass flow rate (MFR) through the dimpled tube were varied for experimental and numerical analysis. The PTSWH achieved the highest efficiency of 38.25% with a CuO volume concentration (VC) of 0.3% and a water MFR of 2.5 kg/min, 12% higher than the unembellished tube with base fluid. Furthermore, the PTSWH’s overall output performance index under the same conditions was 3.56. Furthermore, at an MFR of 3.0 kg/min and a VC of 0.5%, the pressure drop was 7.24% greater. For dimple tube (computational fluid dynamics analysis), at an MFR of 3.0 kg/min, the increase in temperature [$\Delta T=({T}_O-{T}_I$)] at CuO NP VC of 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% was found to be 54°C, 56°C, 58°C, 60°C, and 62°C, respectively. These findings show that using NF and dimpled tubes to improve the performance of PTSWH systems has a high potential for a more sustainable and efficient use of solar energy.
Malaria Surveillance: A Cross-sectional Study in the Peruvian Amazon Basin, 2012–2023
Authors: Sanchez Juan F , Valdivia Hugo O , Pannebaker Danielle L
Published: November 2024

Loreto, a region located in the Amazon basin, has reported more than 80% of malaria cases in Peru. Application of diagnostic methods in remote areas is challenging; hence, the identification of factors associated with Plasmodium infection is necessary to improve malaria control. A cross-sectional study was conducted in health facilities in Loreto from 2012 to 2023. Data and blood samples for malaria diagnosis were collected. We performed an analysis to identify associated factors to malaria positivity. Among 2989 participants with malaria symptoms, the prevalence was 87.6% and Plasmodium vivax was the most prevalent species (74.0%). We identified several factors associated with malaria positivity such as age, occupation, sleeping with open windows, previous malaria episodes, number of malaria episodes in the last 12 months, and others. The high prevalence of malaria and the predominance of P. vivax highlight the relevance of P. vivax-targeted control programs to reach elimination in low-endemic areas.
The North–South Distinction: From Consensus to Contestation
Authors: Thérien Jean-Philippe
Published: November 2024

Rooted in the field of intellectual history, this article examines how the meaning of the North–South distinction has changed since its appearance in the 1960s. It explains how the largely consensual vision espoused during the early years has gradually given way to growing polarization and contestation. This evolution is unpacked by studying the genealogy of North–South narratives formulated through the ideologies of liberal internationalism and systemic reformism. The article shows that the 1960–1990 period brought about an international compromise regarding the existence of a North–South divide. Moving to the post-1990 period, the analysis then dissects the growing disagreements over the utility of the North–South terminology for interpreting the global order. While today moderate and radical reformists continue to argue that the North–South cleavage remains a structural feature of global politics, most liberals maintain that it simply fails to describe the real world. Overall, the article helps to clarify what makes the North–South distinction highly contested and nonetheless “sticky” in contemporary global affairs.
The Politics of Public Health Emergencies of International Concern
Authors: Pagotto Barbara Frossard , Eccleston-Turner Mark
Published: November 2024

The declaration of a Public Health Emergency of International Concern (PHEIC) was created by the International Health Regulations (2005) and is WHO's highest level of alert for a health emergency. PHEICs are declared by the WHO Director-General on the basis of a recommendation provided by the International Health Regulations (IHR) Emergency Committee. This paper challenges the orthodox thinking around PHEIC declarations, using a methodological approach that has not been used in this space, through a series of interviews with those involved in the PHEIC declaration process. This paper provides vital insights into the PHEIC process, allowing us to fully understand what happens “in the room” during these deliberations, something which until now, has not been possible. We argue that the PHEIC declaration, and the Emergency Committee's role in this process, is not a politically neutral technocratic one, as is commonly claimed by WHO, but a highly politicized process that is driven by a range of factors beyond the criteria set down in IHR. We show that the PHEIC is informed by health surveillance practices that operate within the colonial construction of “global health security,” which is clearly embedded within every level of the PHEIC declaration process.
Breaking up Big Tech: scissor-line suggestions for smart cuts
Authors: Schinkel Maarten Pieter , van Oosten Ruben J
Published: November 2024

Calls for the breakup of Big Tech, especially where behavioural remedies are cumbersome to enforce effectively, are becoming louder on both sides of the Atlantic. If there are going to be structural remedies against network companies, we propose they better be ‘smart cuts’: targeted interventions to insulate core platform functions with minimal damage to positive network effects. One major concern with dominant platforms is information bias: intentional distortion of information presented to a user to steer them away from the best matches to their query and towards content that benefits the platform instead. It can be addressed by separating a hybrid platform’s recommender system from its peripheral services with commercial tentacles in the real economy. This realigns incentives to provide users with unbiased information and invites competition on and between intermediaries. We offer scissor-line suggestions for the gatekeepers Alphabet, Amazon, and Apple. Smart cuts have a conceptual basis: they go beyond unwinding recent acquisitions and open up ecosystem structures to competition, allow for targeted flanking access regulation, and alleviate competition law enforcement.
Sustainable practice in gastroenterology: travel-related CO2 emissions for gastroenterology clinic appointments in Canada
Authors: Galts Ciarán , Anvari Sama , Kim Amy , Leontiadis Gregorios , Armstrong David
Published: November 2024

Background

Telemedicine is increasingly common in gastroenterology and may represent an opportunity for improving sustainability in medical care. The purpose of this study was to determine the carbon emissions related to travel for in-person gastroenterology clinic appointments.

Methods

We conducted a cross-sectional analysis evaluating carbon emissions associated with travel to gastroenterology appointments over a 2-week period. We determined the average number of appointments per day and used patient’s postal codes to estimate travel distances. We estimated carbon emissions based on these travel distances and completed sensitivity analyses to model methods for emissions reductions.

Results

We assessed 975 clinic appointments, of which 71 were excluded (eg, insufficient data, non-physician appointments), leaving 904 included appointments of which 75% were follow-up (678) and the remainder were new consultations (226). Sixteen different gastroenterologists had an average of 22.7 patients per clinic. The mean return distance travelled per appointment was 57.3 km which translates to 14.9 kg CO2 per patient visit. An average day at our clinic was equal to burning 146.6 L of gasoline or the annual carbon capture of 15.5 trees. By changing follow-up appointments or those with a travel distance over 100 km to telehealth, emissions were reduced by 77%.

Conclusions

We demonstrate that a relatively modest change in the number of in-person visits can save thousands of litres of gasoline emissions annually from each practicing clinician. While we cannot avoid emissions related to travel for procedure-based appointments, the use of telemedicine is one potential strategy to reduce healthcare-related emissions.
The Ordinary Soldier in Military Organization
Authors: Song Tianying
Published: November 2024

Drawing on social psychology, this article raises seemingly counterintuitive questions about international criminal law’s assumptions of human agency in a highly specific social environment. Is military institution hostile to the ‘normative individualism’ underlying international criminal law? If so, is it fair to demand individual criminal responsibility of members of a military organization in the same way as in peacetime situations? This article takes the perspective of an ordinary soldier and asks whether international criminal law is biased in describing causes of atrocities and dispensing solutions. After explicating some assumptions of individual criminal responsibility, it introduces the military organization as a total institution that subsumes individuals. It continues to examine the impact of the military mission and structure on the normative and behavioural competences of the ordinary soldier as a potential perpetrator of war crimes. It then contemplates how such a social environment undermines international criminal law’s fiction of human agency and, ultimately, its normative effect. This article not only invites further legal doctrinal reflections but also contributes to the criminological study of international crimes.
First cycle toxicity and survival in patients with rare cancers treated with checkpoint inhibitors
Authors: Othus Megan , Patel Sandip P , Chae Young Kwang , Dietrich Eliana , Streicher Howard , Sharon Elad , Kurzrock Razelle
Published: November 2024

Background

Associations between immune-related adverse events from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally funded basket trial (NCT02834013) for patients with rare cancers (n = 684) to evaluate associations between immune-related adverse events and overall survival and progression-free survival (PFS).

Methods

Patients were treated with nivolumab and ipilimumab; the trial was opened at more than 1000 sites. Landmark Cox regression models were used to assess first cycle immune-related adverse event associations with PFS and overall survival.

Results

We found that grade 1-2 treatment-related immune-related adverse events in the first cycle of therapy were associated with longer overall survival (multivariable hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.49 to 0.75; P < .001) compared with no treatment-related immune-related adverse event, while grade 3-4 immune-related adverse events were associated with shorter overall survival (HR = 1.41, 95% CI = 1.04 to 1.90; P = .025). Similar but weaker associations were observed with PFS and grade 1-2 treatment-related immune-related adverse events (HR = 0.83, 95% CI = 0.67 to 1.01; P = .067) and grade 3-4 (HR = 1.35, 95% CI = 1.02 to 1.78; P = .037) compared with no treatment-related immune-related adverse events. Grade 1-2 dermatologic toxicity was associated with improved overall survival compared with other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52 to 0.85; P = .002). There was no statistically significant overall survival difference between patients with grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other grade 1-2 toxicities.

Conclusion

In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of immune-related adverse event in the first cycle was predictive for survival.
Proinflammatory dietary pattern and risk of total and subtypes of breast cancer among US women
Authors: Romanos-Nanclares Andrea , Willett Walter C , Rosner Bernard , Stover Daniel G , Sardesai Sagar D , Holmes Michelle D , Chen Wendy Y , Tamimi Rulla M , Tabung Fred K , Eliassen A Heather
Published: November 2024

Background

Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been associated with certain cancers. Investigating whether this dietary pattern is associated with breast cancer—where the role of inflammation is less well-defined—could provide valuable insights and potentially improve strategies for preventing this cancer.

Methods

We prospectively followed 76 386 women from Nurses’ Health Study (NHS, 1984-2018) and 92 886 women from Nurses’ Health Study II (NHSII, 1991-2019). Diet was assessed by food frequency questionnaires every 4 years, starting at baseline. The inflammatory potential of diet was evaluated using the validated EDIP based on plasma C-reactive protein, interleukin-6, and tumor necrosis factor α-R2. Higher scores indicate higher dietary inflammatory potential. Hazard ratios (HRs) and 95% confidence intervals (CIs) of overall and subtypes of breast cancer were estimated using multivariable-adjusted Cox regression models.

Results

During 4 490 842 person-years of follow-up, we documented 11 026 breast cancer cases. Women in the highest compared with the lowest EDIP quintile were at higher breast cancer risk (HRQ5vsQ1 = 1.12, 95% CI = 1.05 to 1.19; Ptrend < .001). The association was stronger for estrogen receptor negative tumors (HRQ5vsQ1 = 1.29, 95% CI = 1.09 to 1.53; Ptrend = .003). Also, we observed that the association of EDIP with breast cancer risk differed by molecular subtype, with the strongest association observed with basal-like tumors (HRQ5vsQ1 = 1.80, 95% CI = 1.20 to 2.71; Ptrend = .004).

Conclusions

Higher EDIP scores were associated with a modestly increased risk of breast cancer, which was more pronounced for estrogen receptor negative and basal-like breast tumors. These results support the hypothesis that diet-related inflammation plays a role in breast cancer etiology, particularly tumors lacking hormone receptors.
Roflumilast mitigates cisplatin-induced nephrotoxicity by regulating TNF-α/TNFR1/TNFR2/Fas/Caspase mediated apoptosis and inflammatory signals
Authors: Patel Priyal , Patel Sandip , Patel Yash , Chudasama Piyush , Soni Shailesh , Patel Samir , Raval Manan
Published: November 2024

Purpose

The study aimed to evaluate the effect of roflumilast on modulating TNF-α/Caspase mediated cellular signals in cisplatin-induced nephrotoxicity in rats.

Methods

The rats (Male Wistar) were divided into five groups: normal control, disease control (cisplatin: 7 mg/kg i.p.), and cisplatin + roflumilast (0.25, 0.5, and 1 mg/kg b.w., p.o.). Cisplatin was administrated to rats on 0 day, and roflumilast treatment was started from the 6th–15th days. Blood and tissue were collected. Tissue was used to measure oxidative stress, such as malondialdehyde, superoxide dismutase, and catalase. Gene expression study involved real-time PCR of key genes linked with inflammation and apoptosis, i.e. Tnf-α, Tnfr1, Tnfr2, Fas, Nfkb, Casp3, Casp8, and Nrf2.

Findings

Cisplatin showed decreased serum creatinine and urea, high albumin, and total protein. Cisplatin elevated the malondialdehyde and reduced superoxide dismutase and catalase activity. Cisplatin also attributed an overexpression of Tnf-α, Tnfr1, Tnfr2, Nfkb, Fas, Casp3, and Casp8, and a decrease in the Nrf2 gene. Roflumilast decreased creatinine and urea and increased albumin and total protein levels. Roflumilast also downregulated the expression of Tnf-α, Tnfr1, Tnfr2, Nfkb, Fas, Casp3, and Casp8 and upregulated the Nrf2 gene expression.

Conclusion

Roflumilast manifested as a potential reno-protective agent against cisplatin-induced nephrotoxicity.
Object oriented data analysis of surface motion time series in peatland landscapes
Authors: Mitchell Emily G , Dryden Ian L , Fallaize Christopher J , Andersen Roxane , Bradley Andrew V , Large David J , Sowter Andrew
Published: November 2024

Peatlands account for 10% of UK land area, 80% of which are degraded to some degree, emitting carbon at a similar magnitude to oil refineries or landfill sites. A lack of tools for rapid and reliable assessment of peatland condition has limited monitoring of vast areas of peatland and prevented targeting areas urgently needing action to halt further degradation. Measured using interferometric synthetic aperture radar (InSAR), peatland surface motion is highly indicative of peatland condition, largely driven by the eco-hydrological change in the peatland causing swelling and shrinking of the peat substrate. The computational intensity of recent methods using InSAR time series to capture the annual functional structure of peatland surface motion becomes increasingly challenging as the sample size increases. Instead, we utilize the behaviour of the entire peatland surface motion time series using object oriented data analysis to assess peatland condition. Bayesian cluster analysis based on the functional structure of the surface motion time series finds areas indicative of soft/wet peatlands, drier/shrubby peatlands, and thin/modified peatlands. The posterior distribution of the assigned peatland types enables the scale of peatland degradation to be assessed, which will guide future cost-effective decisions for peatland restoration.
The Influence of Neck Pain and Sleep Quantity on Headache Burden in Service Members With and Without Mild Traumatic Brain Injury: An Observational Study
Authors: Reid Matthew W , Lu Lisa H , Hershaw Jamie N , Kennedy Jan E
Published: November 2024

Introduction

Headache is the most overwhelmingly reported symptom following mild traumatic brain injury (mTBI). The upper cervical spine has been implicated in headache etiology, and cervical dysfunction may result in neck pain that influences the experience of headache. Sleep problem is the second most reported symptom following mTBI. We explored the contribution of neck pain (as a potential proxy for cervical dysfunction) on headache burden along with the contribution of sleep quantity following mTBI.

Materials and Methods

Retrospective data from a repository consisting of service members recruited from primary care, with (N = 493) and without a history of mTBI (N = 63), was used for analysis. Portions of the Neurobehavioral Symptom Inventory, Pittsburgh Sleep Quality Index, and Orebro Musculoskeletal Pain Questionnaire were used for headache, sleep, and neck pain measures.

Results

Demographic and military characteristics that differed between groups were treated as covariates in analyses. Group comparisons revealed significant differences in the expected direction on all measures: mTBI > controls on headache and neck pain; controls > mTBI on sleep quantity. Regression revealed that neck pain accounted for the most variance in headache score, followed by group membership and sleep quantity. When analyzing groups separately, no difference in the pattern of results was revealed in the mTBI group. In the control group, variance in headache score was only significantly related to neck pain.

Conclusions

Amongst service members who sought service from primary care, neck pain explains more variance in headache burden than mTBI history or sleep quantity, supporting that cervical dysfunction may be a salient factor associated with headache. Neck functioning may be a potential area of intervention in the management of headaches.
ExoMol line lists – LXIV. Empirical rovibronic spectra of phosphorous mononitride (PN) covering the IR and UV regions
Authors: Semenov Mikhail , El-Kork Nayla , Yurchenko Sergei N , Tennyson Jonathan
Published: November 2024

A new phosphorous mononitride ($^{31}$P$^{14}$N and ${}^{31}$P${}^{15}$N) line list PaiN covering infrared, visible, and ultraviolet regions is presented. The PaiN line list extending to the $A\, {}^{1}\Pi$–$X\, {}^{1}\Sigma ^{+}$ vibronic band system replaces the previous YYLT ExoMol line list for PN. A thorough analysis of high-resolution experimental spectra from the literature involving the $X\, {}^{1}\Sigma ^{+}$ and $A\, {}^{1}\Pi$ states is conducted, and many perturbations to the $A\, {}^{1}\Pi$ energies are considered as part of a comprehensive MARVEL (Measured-Active-Rotational-Vibrational-Energy-Levels) study. Ab initio potential energy and coupling curves from the previous work are refined by fitting their analytical representations to 1224 empirical energy levels determined using the MARVEL procedure. The PaiN line list is compared to previously observed spectra, recorded and calculated lifetimes, and previously calculated partition functions. The ab initio transition dipole moment curve for the A–X band is scaled to match experimentally measured lifetimes. The line list is suitable for temperatures up to 5000 K and wavelengths longer than 121 nm. PaiN is available from www.exomol.com.
Digital Image Processing to Detect Adaptive Evolution
Authors: Amin Md Ruhul , Hasan Mahmudul , DeGiorgio Michael
Published: November 2024

In recent years, advances in image processing and machine learning have fueled a paradigm shift in detecting genomic regions under natural selection. Early machine learning techniques employed population-genetic summary statistics as features, which focus on specific genomic patterns expected by adaptive and neutral processes. Though such engineered features are important when training data are limited, the ease at which simulated data can now be generated has led to the recent development of approaches that take in image representations of haplotype alignments and automatically extract important features using convolutional neural networks. Digital image processing methods termed α-molecules are a class of techniques for multiscale representation of objects that can extract a diverse set of features from images. One such α-molecule method, termed wavelet decomposition, lends greater control over high-frequency components of images. Another α-molecule method, termed curvelet decomposition, is an extension of the wavelet concept that considers events occurring along curves within images. We show that application of these α-molecule techniques to extract features from image representations of haplotype alignments yield high true positive rate and accuracy to detect hard and soft selective sweep signatures from genomic data with both linear and nonlinear machine learning classifiers. Moreover, we find that such models are easy to visualize and interpret, with performance rivaling those of contemporary deep learning approaches for detecting sweeps.
Natural variation of magnesium stable isotopes in human kidney stones
Authors: Liu Jinke , Han Guilin , Tian Yu , Qu Rui , Wang Di , Shen Yanan
Published: November 2024

Kidney stones, as typical biominerals produced within the human body, pose a significant threat to human health, affecting over 12% of the global population. However, the exact mechanisms underlying their formation are not fully understood. Recent metal isotopic analysis provides a new way to study the roles of metal cations in biological processes within organisms. Here, we report the Mg isotope ratios of human kidney stones for the first time. The total range of measured values for δ26Mg in kidney stones is 1.05‰, from −1.12‰ to −0.07‰. Our data exhibit a significant 24Mg enrichment compared with the values calculated from density functional theory. We suggest that the Mg-isotopic fractionations in vivo are linked to active Mg transport mediated by proteins during intestinal absorption and preferential renal reabsorption of ionized Mg2+ via tight junctional proteins. Our results indicate that the inhibitory effect of Mg on kidney stones is related to the kink-blocking mechanism, and the incorporation of hydrated Mg lessens the extent of inhibition and the magnitude of isotope discrimination. We show that metal isotopes provide new insights into the underlying biological processes and human health.
Antisense transcription is associated with expression of metal resistance determinants in Cupriavidus metallidurans CH34
Authors: Große Cornelia , Grau Jan , Herzberg Martin , Nies Dietrich H
Published: November 2024

Cupriavidus metallidurans is able to thrive in metal-rich environments but also survives metal starvation. Expression of metal resistance determinants in C. metallidurans was investigated on a global scale. Cupriavidus metallidurans was challenged with a MultiTox metal mix specifically designed for the wildtype strain CH34 and its plasmid-free derivative AE104, including treatment with ethylenediamintetraacetate (EDTA), or without challenge. The sense and antisense transcripts were analyzed in both strains and under all three conditions by RNASeq. A total of 10 757 antisense transcripts (ASTs) were assigned to sense signals from genes and untranslated regions, and 1 319 of these ASTs were expressed and were longer than 50 bases. Most of these (82%) were dual-use transcripts that contained antisense and sense regions, but ASTs (16%) were also observed that had no sense regions. Especially in metal-treated cells of strains CH34 and AE104, up- or down-regulated sense transcripts were accompanied by antisense transcription activities that were also regulated. The presence of selected asRNAs was verified by reverse transcription polymerase chain reaction (RT-PCR). Following metal stress, expression of genes encoding components of the respiratory chain, motility, transcription, translation, and protein export were down-regulated. This should also affect the integration of the metal efflux pumps into the membrane and the supply of the energy required to operate them. To solve this dilemma, transcripts for the metal efflux pumps may be stabilized by interactions with ASTs to allow their translation and import into the membrane. Alternatively, metal stress possibly causes recruitment of RNA polymerase from housekeeping genes for preferential expression of metal resistance determinants.
ECOD: integrating classifications of protein domains from experimental and predicted structures
Authors: Schaeffer R Dustin , Medvedev Kirill E , Andreeva Antonina , Chuguransky Sara Rocio , Pinto Beatriz Lazaro , Zhang Jing , Cong Qian , Bateman Alex , Grishin Nick V
Published: November 2024

The evolutionary classification of protein domains (ECOD) classifies protein domains using a combination of sequence and structural data (http://prodata.swmed.edu/ecod). Here we present the culmination of our previous efforts at classifying domains from predicted structures, principally from the AlphaFold Database (AFDB), by integrating these domains with our existing classification of PDB structures. This combined classification includes both domains from our previous, purely experimental, classification of domains as well as domains from our provisional classification of 48 proteomes in AFDB predicted from model organisms and organisms of concern to global health. ECOD classifies over 1.8 M domains from over 1000 000 proteins collectively deposited in the PDB and AFDB. Additionally, we have changed the F-group classification reference used for ECOD, deprecating our original ECODf library and instead relying on direct collaboration with the Pfam sequence family database to inform our classification. Pfam provides similar coverage of ECOD with family classification while being more accurate and less redundant. By eliminating duplication of effort, we can improve both classifications. Finally, we discuss the initial deployment of DrugDomain, a database of domain-ligand interactions, on ECOD and discuss future plans.
Harmonizome 3.0: integrated knowledge about genes and proteins from diverse multi-omics resources
Authors: Diamant Ido , Clarke Daniel J B , Evangelista John Erol , Lingam Nathania , Ma’ayan Avi
Published: November 2024

By processing and abstracting diverse omics datasets into associations between genes and their attributes, the Harmonizome database enables researchers to explore and integrate knowledge about human genes from many central omics resources. Here, we introduce Harmonizome 3.0, a significant upgrade to the original Harmonizome database. The upgrade adds 26 datasets that contribute nearly 12 million associations between genes and various attribute types such as cells and tissues, diseases, and pathways. The upgrade has a dataset crossing feature to identify gene modules that are shared across datasets. To further explain significantly high gene set overlap between dataset pairs, a large language model (LLM) composes a paragraph that speculates about the reasons behind the high overlap. The upgrade also adds more data formats and visualization options. Datasets are downloadable as knowledge graph (KG) assertions and visualized with Uniform Manifold Approximation and Projection (UMAP) plots. The KG assertions can be explored via a user interface that visualizes gene–attribute associations as ball-and-stick diagrams. Overall, Harmonizome 3.0 is a rich resource of processed omics datasets that are provided in several AI-ready formats. Harmonizome 3.0 is available at https://maayanlab.cloud/Harmonizome/.
InterPro: the protein sequence classification resource in 2025
Authors: Blum Matthias , Andreeva Antonina , Florentino Laise Cavalcanti , Chuguransky Sara Rocio , Grego Tiago , Hobbs Emma , Pinto Beatriz Lazaro , Orr Ailsa , Paysan-Lafosse Typhaine , Ponamareva Irina , Salazar Gustavo A , Bordin Nicola , Bork Peer , Bridge Alan , Colwell Lucy , Gough Julian , Haft Daniel H , Letunic Ivica , Llinares-López Felipe , Marchler-Bauer Aron , Meng-Papaxanthos Laetitia , Mi Huaiyu , Natale Darren A , Orengo Christine A , Pandurangan Arun P , Piovesan Damiano , Rivoire Catherine , Sigrist Christian J A , Thanki Narmada , Thibaud-Nissen Françoise , Thomas Paul D , Tosatto Silvio C E , Wu Cathy H , Bateman Alex
Published: November 2024

InterPro (https://www.ebi.ac.uk/interpro) is a freely accessible resource for the classification of protein sequences into families. It integrates predictive models, known as signatures, from multiple member databases to classify sequences into families and predict the presence of domains and significant sites. The InterPro database provides annotations for over 200 million sequences, ensuring extensive coverage of UniProtKB, the standard repository of protein sequences, and includes mappings to several other major resources, such as Gene Ontology (GO), Protein Data Bank in Europe (PDBe) and the AlphaFold Protein Structure Database. In this publication, we report on the status of InterPro (version 101.0), detailing new developments in the database, associated web interface and software. Notable updates include the increased integration of structures predicted by AlphaFold and the enhanced description of protein families using artificial intelligence. Over the past two years, more than 5000 new InterPro entries have been created. The InterPro website now offers access to 85 000 protein families and domains from its member databases and serves as a long-term archive for retired databases. InterPro data, software and tools are freely available.
CATH v4.4: major expansion of CATH by experimental and predicted structural data
Authors: Waman Vaishali P , Bordin Nicola , Lau Andy , Kandathil Shaun , Wells Jude , Miller David , Velankar Sameer , Jones David T , Sillitoe Ian , Orengo Christine
Published: November 2024

CATH (https://www.cathdb.info) is a structural classification database that assigns domains to the structures in the Protein Data Bank (PDB) and AlphaFold Protein Structure Database (AFDB) and adds layers of biological information, including homology and functional annotation. This article covers developments in the CATH classification since 2021. We report the significant expansion of structural information (180-fold) for CATH superfamilies through classification of PDB domains and predicted domain structures from the Encyclopedia of Domains (TED) resource. TED provides information on predicted domains in AFDB. CATH v4.4 represents an expansion of ∼64 844 experimentally determined domain structures from PDB. We also present a mapping of ∼90 million predicted domains from TED to CATH superfamilies. New PDB and TED data increases the number of superfamilies from 5841 to 6573, folds from 1349 to 2078 and architectures from 41 to 77. TED data comprises predicted structures, so these new folds and architectures remain hypothetical until experimentally confirmed. CATH also classifies domains into functional families (FunFams) within a superfamily. We have updated sequences in FunFams by scanning FunFam-HMMs against UniProt release 2024_02, giving a 276% increase in FunFams coverage. The mapping of TED structural domains has resulted in a 4-fold increase in FunFams with structural information.
The PLSDB 2025 update: enhanced annotations and improved functionality for comprehensive plasmid research
Authors: Molano Leidy-Alejandra G , Hirsch Pascal , Hannig Matthias , Müller Rolf , Keller Andreas
Published: November 2024

Plasmids are extrachromosomal DNA molecules in bacteria and archaea, playing critical roles in horizontal gene transfer, antibiotic resistance, and pathogenicity. Since its first release in 2018, our database on plasmids, PLSDB, has significantly grown and enhanced its content and scope. From 34 513 records contained in the 2021 version, PLSDB now hosts 72 360 entries. Designed to provide life scientists with convenient access to extensive plasmid data and to support computer scientists by offering curated datasets for artificial intelligence (AI) development, this latest update brings more comprehensive and accurate information for plasmid research, with interactive visualization options. We enriched PLSDB by refining the identification and classification of plasmid host ecosystems and host diseases. Additionally, we incorporated annotations for new functional structures, including protein-coding genes and biosynthetic gene clusters. Further, we enhanced existing annotations, such as antimicrobial resistance genes and mobility typing. To accommodate these improvements and to host the increase plasmid sets, the webserver architecture and underlying data structures of PLSDB have been re-reconstructed, resulting in decreased response times and enhanced visualization of features while ensuring that users have access to a more efficient and user-friendly interface. The latest release of PLSDB is freely accessible at https://www.ccb.uni-saarland.de/plsdb2025.
PWAS Hub: exploring gene-based associations of complex diseases with sex dependency
Authors: Zucker Roei , Kelman Guy , Linial Michal
Published: November 2024

The Proteome-Wide Association Study (PWAS) is a protein-based genetic association approach designed to complement traditional variant-based methods like GWAS. PWAS operates in two stages: first, machine learning models predict the impact of genetic variants on protein-coding genes, generating effect scores. These scores are then aggregated into a gene-damaging score for each individual. This score is then used in case-control statistical tests to significantly link to specific phenotypes. PWAS Hub (v1.2) is a user-friendly platform that facilitates the exploration of gene-disease associations using clinical and genetic data from the UK Biobank (UKB), encompassing 500k individuals. PWAS Hub reports on 819 diseases and phenotypes determined by PheCode and ICD-10 clinical codes, each with a minimum of 400 affected individuals. PWAS-derived gene associations were reported for 72% of the tested phenotypes. The PWAS Hub also analyzes gene associations separately for males and females, considering sex-specific genetic effects, inheritance patterns (dominant and recessive), and gene pleiotropy. We illustrated the utility of the PWAS Hub for primary (essential) hypertension (I10), type 2 diabetes mellitus (E11), and specified haematuria (R31) that showed sex-dependent genetic signals. The PWAS Hub, available at pwas.huji.ac.il, is a valuable resource for studying genetic contributions to common diseases and sex-specific effects.
[SNG2], a prion form of Cut4/Apc1, confers non-Mendelian inheritance of heterochromatin silencing defect in fission yeast
Authors: Sharma Suman , Srivastava Suchita , Dubey Rudra Narayan , Mishra Poonam , Singh Jagmohan
Published: November 2024

Prions represent epigenetic regulator proteins that can self-propagate their structure and confer their misfolded structure and function on normally folded proteins. Like the mammalian prion PrPSc, prions also occur in fungi. While a few prions, like Swi1, affect gene expression, none are shown to affect heterochromatin structure and function. In fission yeast and metazoans, histone methyltransferase Clr4/Suv39 causes H3-Lys9 methylation, which is bound by the chromodomain protein Swi6/HP1 to assemble heterochromatin. Earlier, we showed that sng2-1 mutation in the Cut4 subunit of anaphase-promoting complex abrogates heterochromatin structure due to defective binding and recruitment of Swi6. Here, we demonstrate that the Cut4p forms a non-canonical prion form, designated as [SNG2], which abrogates heterochromatin silencing. [SNG2] exhibits various prion-like properties, e.g. non-Mendelian inheritance, requirement of Hsp proteins for its propagation, de novo generation upon cut4 overexpression, reversible curing by guanidine, cytoplasmic inheritance and formation of infectious protein aggregates, which are dissolved upon overexpression of hsp genes. Interestingly, [SNG2] prion imparts an enhanced tolerance to stress conditions, supporting its role in promoting cell survival under environmental stress during evolution.
Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity
Authors: Baniulyte Gabriele , McCann Abby A , Woodstock Dana L , Sammons Morgan A
Published: November 2024

The p53 family of transcription factors (p53, p63 and p73) regulate diverse organismal processes including tumor suppression, maintenance of genome integrity and the development of skin and limbs. Crosstalk between transcription factors with highly similar DNA binding profiles, like those in the p53 family, can dramatically alter gene regulation. While p53 is primarily associated with transcriptional activation, p63 mediates both activation and repression. The specific mechanisms controlling p63-dependent gene regulatory activity are not well understood. Here, we use massively parallel reporter assays (MPRA) to investigate how local DNA sequence context influences p63-dependent transcriptional activity. Most regulatory elements with a p63 response element motif (p63RE) activate transcription, although binding of the p63 paralog, p53, drives a substantial proportion of that activity. p63RE sequence content and co-enrichment with other known activating and repressing transcription factors, including lineage-specific factors, correlates with differential p63RE-mediated activities. p63 isoforms dramatically alter transcriptional behavior, primarily shifting inactive regulatory elements towards high p63-dependent activity. Our analysis provides novel insight into how local sequence and cellular context influences p63-dependent behaviors and highlights the key, yet still understudied, role of transcription factor paralogs and isoforms in controlling gene regulatory element activity.
Genetic testing in a national cohort of adults with chronic kidney disease of unknown origin
Authors: de Haan Amber , Eijgelsheim Mark , Vogt Liffert , Hoorn Ewout J , Rotmans Joris I , Fortrie Gijs , Marsman Roos F J , Rothuizen Tonia C , Spijker H Siebe , Claus Laura R , Konings Constantijn J A M , Waanders Femke , Doornebal Joan , Kramer Andrea B , Adema Aaltje Y , van der Zwaag Bert , van Eerde Albertien M , Knoers Nine V A M , de Borst Martin H
Published: November 2024

Background

Chronic kidney disease (CKD) remains unexplained in at least 20% of patients. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, but prospective data from routine clinical practice are limited. We aimed to determine the diagnostic yield and relevance of MPS-based gene panel testing in patients with unexplained CKD in a real-world context. We additionally examined barriers to implementation of genetic testing.

Methods

In this prospective cohort study, we recruited patients with unexplained CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 without underlying clinical diagnosis) with onset at <50 years of age who underwent MPS-based multigene panel testing from 11 academic and non-academic hospitals across the Netherlands. In patients with a (likely) pathogenic variant, we verified that the variant likely explained the clinical phenotype. A nationwide online survey was sent to all Dutch nephrologists and residents to investigate potential barriers for gene panel testing.

Results

A diagnostic variant was identified in 59/340 participants (17%). Most common diagnostic variants were in NPHP1 (13 patients), COL4A3 (12 patients), COL4A4 (5 patients), COL4A5 (6 patients) and PAX2 (5 patients). A genetic diagnosis led to at least one clinical consequence in 73% of patients. Main barriers reported by Dutch nephrologists (N = 71) included genetic illiteracy (53%), difficulties with test selection (51%) and a lack of time (43%).

Conclusions

MPS-based multigene panel testing yielded a genetic diagnosis in 17% of patients with unexplained CKD. Our findings support the relevance of MPS in the diagnostic workup of adults with unexplained CKD with onset at <50 years of age. Additionally, our results underline the need to improve genetic education among nephrologists to better the implementation of MPS-based diagnostic testing in clinical practice.
Generating Campaign Awareness With Digital Media: Exploring Factors Associated With Awareness of and Receptivity to FDA’s Fresh Empire Tobacco Prevention Campaign
Authors: Henes Amy , Curry Laurel , Farrelly Matthew , Guillory Jamie , Crichton Andrew , Saunders McKinley , MacMonegle Anna , Mekos Debra , Zhao Xiaoquan , Nonnemaker James , Guo Merrybelle , Wagner Dana E
Published: November 2024

Introduction

We explore factors that were associated with awareness of and receptivity to U.S. Food and Drug Administration’s Fresh Empire tobacco public education campaign.

Aims and Methods

Evaluation data were 10 674 survey responses from 5129 unique respondents who identified with the Hip Hop peer crowd between 2016 and 2019. The sample was predominantly non-Hispanic Black and Hispanic youth. We assessed the outcomes of brand awareness, ad awareness, and perceived ad effectiveness. We used panel regression models to test which demographic and other characteristics—including potential campaign exposure, as measured by impressions assigned to respondents based on their media market of residence and survey completion date—were associated with these outcomes.

Results

Black, non-Hispanic youth; Hispanic youth; and youth with additional non-Hispanic or multiracial identities were more likely to be aware of the Fresh Empire brand and reported higher ad awareness and perceived effectiveness scores than White, non-Hispanic respondents. Among the full sample, respondents with higher Hip Hop scores—indicating greater identification with the Hip Hop peer crowd—reported higher ad awareness. Compared with nonsusceptible never smokers, youth susceptible to smoking reported lower ad awareness and perceived effectiveness scores. Higher potential exposure to campaign broadcast and digital media were both associated with higher ad awareness.

Conclusions

Fresh Empire reached and appealed to a racially and ethnically diverse group of Hip Hop youth. Our findings highlight the ability of digital media to generate campaign awareness among specific youth audiences.

Implications

Understanding factors that contribute to awareness of and positive reactions to the Fresh Empire campaign can inform the development and implementation of future campaigns focused on Hip Hop youth, youth of color, and other underrepresented audiences. Fresh Empire’s success in reaching its audience using primarily digital media demonstrates the potential of digital media campaigns to be effective at reaching specific audiences with tobacco prevention messages.
Unlocking the Cardiovascular Benefits of Walnuts: Insights on Molecular Mechanism From Animal Studies
Authors: Tepavčević Snežana , Zec Manja , Stojiljković Mojca , Bošković Maja , Ćulafić Tijana , Stanković Aleksandra , Romić Snježana , Živković Maja , Korićanac Goran
Published: November 2024

The health-promoting benefits of walnut consumption are substantially ascribed to its fatty acid (FA) profile, which is rich in polyunsaturated FA with an exceptionally high n-3 to n-6 ratio. There are also phytonutrients in walnuts that are linked to health welfare. This review article integrates all studies on the effects of walnuts on the cardiovascular system performed on experimental animals, and thus is a source of data on the mechanisms underlying the observed effects. These studies, which are very diverse in experimental design, indicate that a diet enriched with walnuts or treating animals with walnut extract or chemical constituents of walnuts, has many favorable effects on heart and vascular system function. The cardiovascular effect of walnuts depends on the metabolic status of the organism. Among the cardiovascular effects of walnuts is that they improve the FA profile in the circulation and heart in favor of n-3 polyunsaturated FAs. In addition, a favorable effect on triglyceride and cholesterol status, which reduces cardiovascular disease risk, is observed. Intake of walnuts promotes FA catabolism and has anti-inflammatory, antioxidant, and antiarrhythmic effects. Walnuts also have a beneficial effect on vascular tone, accompanied by a decrease in blood pressure and reduced risk for atherosclerosis. In conclusion, studies on experimental animals encourage the consumption of walnuts as a simple, convenient approach to improve cardiovascular health.
Occupational health: the case for return on investment
Authors: Anselmi Lorenzo , Pattani Shriti , Greenberg Neil , Pahl Nick
Published: November 2024

This editorial delves into the complexities of economic evaluations in occupational health, examining a wide range of interventions and their potential return on investment. From mental health programmes to ergonomic improvements, the article explores the evidence supporting these initiatives and the challenges of quantifying their economic benefits.
Decoding spatial orientation in planar materials
Authors: Rawal Angela , Kulachenko Artem , Rawal Amit
Published: November 2024

Structural disorder induces energetic fluctuations, leading to variations in energy levels across different scales, with the spatial orientation of structural units playing a pivotal role in shaping the resulting structure-property relationships. In this communication, we derive expressions for higher-order nematic orientation parameters for planar materials analogous to the Hermans orientation parameter used for axially symmetric materials. The measure of anisotropy has been analyzed by integrating the widely used probability density functions representing the orientation distributions in nematic order parameters. These higher-order nematic orientation parameters are essential for accurately determining the ‘true’ orientation distribution function of macromolecules and understanding structure-property relationships in complex planar systems.