bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Obesity-Related Genetic Variants on NF-κB Signaling in Cardiovascular Disease: A Systematic Review
Authors: Shafi Viqas , Khan Nabeel Ahmad , Siddiqui Ifrah
Published: December 2024

Objective

To investigate how genetic variations in obesity-related genes (FTO, MC4R, LEP, LEPR, PCSK1, PPARG, BDNF, SIM1, TBC1D1, ADRB3, UCP1, and SH2B1) impact the NF-κB signaling pathway, exploring mechanisms of NF-κB activation, downstream inflammatory responses, and their role in cardiovascular disease (CVD) development in the context of obesity.

Background

Obesity is a leading contributor to chronic diseases, including CVD, driven in part by chronic low-grade inflammation. The NF-κB signaling pathway, a central regulator of inflammatory responses, is implicated in the pathophysiology of obesity and CVD. Genetic variations in obesity-related genes may modulate NF-κB activation and its downstream effects, exacerbating inflammation and cardiovascular risks. Understanding these mechanisms can inform therapeutic strategies to mitigate inflammation and improve health outcomes in individuals with obesity.

Methods

A systematic review of the literature was conducted using PUBMED, MEDLINE, and Google Scholar, focusing on genetic variations in the obesity-related genes FTO, MC4R, LEP, LEPR, PCSK1, PPARG, BDNF, SIM1, TBC1D1, ADRB3, UCP1, and SH2B1. Studies examining the effects of these variations on NF-κB activation, inflammatory pathways, and CVD development were included. The search was performed with no date restrictions and followed PRISMA guidelines. Articles were screened for relevance, methodological rigor, and insights into the interplay between genetic factors, inflammation, and cardiovascular pathology. Data extraction focused on key findings linking gene variants to NF-κB signaling and their downstream effects.

Results

Genetic variations in FTO, MC4R, LEP, LEPR, and SH2B1 were found to disrupt insulin and leptin signaling, resulting in enhanced NF-κB activation and chronic inflammation. Variants in PPARG and UCP1 increased oxidative stress, further amplifying NF-κB signaling. These changes promoted endothelial dysfunction, atherosclerosis, and heightened CVD risk. Interactions between these genetic factors created a pro-inflammatory state, exacerbating cardiovascular complications in obese individuals.

Conclusion

This study underscores the critical role of genetic variations in obesity-related genes in modulating NF-κB signaling, driving chronic inflammation, and increasing CVD risk. Targeting these pathways may provide therapeutic opportunities to reduce inflammation and improve cardiovascular health in obese populations.
Smell testing to identify early alpha-synucleinopathy among people with dream enactment behavior
Authors: Brown Ethan , Chahine Lana M , Videnovic Aleksandar , Marshall Micah J , Kurth Ryan , Caspell-Garcia Chelsea , Brumm Michael C , Coffey Christopher , Siderowf Andrew , Simuni Tanya , Marek Kenneth , Tanner Caroline M ,   The Parkinson’s Progression Markers Initiative
Published: December 2024

Background

REM sleep behavior disorder (RBD) is an early manifestation of alpha-synucleinopathy in many cases. Dream enactment behavior (DEB), the clinical hallmark of RBD, has many etiologies and cannot be used alone to predict underlying alpha-synucleinopathy. We compared the proportion of people with alpha-synucleinopathy, as measured by CSF alpha-synuclein seed amplification assay (CSFasynSAA), between people with polysomnographic-confirmed RBD (RBD-PSG) and people who reported DEB on a questionnaire and were further selected with smell testing and DAT-SPECT.

Methods

Participants were enrolled in the Parkinson’s Progression Marker Initiative (PPMI) and ≥60 years old without a diagnosis of Parkinson’s disease. Participants had either RBD-PSG or self-reported DEB. Self-reported DEB participants had to have hyposmia (<10thpercentile for age/sex) and at least mild DAT-SPECT abnormality (<100% age/sex-expected). We compared CSFasynSAA between RBD-PSG and self-reported DEB with hyposmia (DEB+Hypos). RBD-PSG participants also underwent smell testing and DAT-SPECT; we determined the predictive value of these tests in RBD-PSG with regards to CSFasynSAA.

Results

CSFasynSAA was positive in 171/240 (71%) of RBD-PSG and %) 180/210 (86%) of DEB+Hypos participants. Among RBD-PSG, hyposmia strongly predicted CSFasynSAA+ (PPV: 92% [95% CI 87%-97%]). Smell identification was more accurate than DAT-SPECT in predicting CSFasynSAA+ in RBD-PSG (AUC for UPSIT: 0.89 [95% CI 0.84 – 0.94]; AUC for DAT-SPECT: 0.65 [95% CI 0.58 – 0.73]).

Conclusions

Smell testing may be an effective and scalable method to identify people with alpha-synucleinopathy among those with self-reported DEB. Among individuals with RBD diagnosed by PSG, smell testing improved prediction of positive CSF alpha-synuclein biomarker.
Oropouche Virus Outbreak in Southeast, Brazil: Expanding Beyond the Amazonian Endemic Region
Authors: Delatorre Edson , de Colombo Gabriela Mendonça , Gatti Felipe Donateli , Có Anna Clara Gregório , Pereira Julia del Piero , Tavares Eric Arrivabene , Nodari Joana Zorzal , Rossi Agata , de Azevedo Suwellen Sardinha Dias , Sacchi Cláudio Tavares , Campos Karoline Rodrigues , Bugno Adriana , Alves Lyvia Neves Rebello , Bonela Lucas André Silva , Goulart Jaqueline Pegoretti , Souza Thiago de Jesus , Naveca Felipe Gomes , Ribeiro-Rodrigues Rodrigo
Published: December 2024

The Oropouche virus (OROV), historically endemic to the Amazon, has spread to nearly all Brazilian states in 2024, with Espírito Santo emerging as a significant transmission hotspot in the Atlantic Forest biome. We characterized the epidemiological factors driving OROV spread in non-endemic Southeast Brazil, analyzing environmental and agricultural conditions contributing to viral transmission. Samples from 29,000 suspected arbovirus-infected patients were tested by RT-qPCR for Dengue, Chikungunya, Zika, Mayaro, and Oropouche virus. Between March and June 2024, OROV cases in the state reached 339, demonstrating successful local transmission.

Spatial analysis revealed that most cases clustered in municipalities with tropical climates and intensive cacao, robusta coffee, coconut, and pepper cultivation. Phylogenetic analysis identified the Espírito Santo OROV strains as part of the 2022-2024 Amazonian lineage. The rapid spread of OROV outside the Amazon highlights its adaptive potential and public health threat, emphasizing the need for enhanced surveillance and targeted control measures.
Rational design of19F NMR labelling sites to probe protein structure and interactions
Authors: Streit Julian O. , Chan Sammy H.S. , Daya Saifu , Christodoulou John
Published: December 2024

Proteins are investigated in increasingly more complex biological systems, where19F NMR is proving highly advantageous due to its high gyromagnetic ratio and background-free spectra. Its application has, however, been hindered by limited chemical shift dispersions and an incomprehensive relationship between chemical shifts and protein structure. We exploit the sensitivity of19F chemical shifts to ring currents by designing labels with direct contact to a native or engineered aromatic ring. Fifty protein variants predicted by AlphaFold and molecular dynamics simulations show 80-90% success rates and direct correlations of their experimental chemical shifts with the magnitude of the engineered ring current. Our method consequently improves the chemical shift dispersion and through simple 1D experiments enables structural analyses of alternative conformational states, including ribosome-bound folding intermediates, and in-cell measurements of thermodynamics and protein-protein interactions. Our strategy thus provides a simple and sensitive tool to extract residue contact restraints from chemical shifts for previously intractable systems.
Interfamily co-transfer of sensor and helper NLRs extends immune receptor functionality between angiosperms
Authors: Du XiaoFei , Alam Maheen , Witek Kamil , Milnes Lesley , Houghton James , Lin Xiao , Zhang Yu , Cui Fuhao , Sun Wenxian , Jones Jonathan DG , Guo Hailong
Published: December 2024

Plant nucleotide-binding, leucine-rich repeat (NLR) immune receptors recognize pathogen effectors and activate defense. NLR genes can be non-functional in distantly related plants (restricted taxonomic functionality, RTF). Here, we enable Solanaceae NLR gene function in rice, soybean and Arabidopsis by co-delivering sensor NLR genes with their cognate NRC-type helper NLRs. In soybean protoplasts and in Arabidopsis plants, Solanum americanum Rpi-amr1, Rpi-amr3 and pepper Bs2 sensor NLRs confer cognate effector responsiveness if co-expressed with NRC helper NLRs. Rice carrying pepper Bs2 and NRCs recognizes the conserved effector, AvrBs2, and resists an important pathogen, Xanthomonas oryzae pv. oryzicola for which no resistance gene is available in rice. Rice lines carrying sensor and helper NLR genes otherwise resemble wild-type, with unaltered basal resistance or field fitness. Thus, interfamily co-transfer of sensor and helper NLRs can broaden utility of sensor NLRs, extending the tools available to control diseases of rice, soybean, Brassicas and other crops.
Deconstruction of a memory engram reveals distinct ensembles recruited at learning
Authors: Pouget Clément , Morier Flora , Treiber Nadja , García Pablo Fernández , Mazza Nina , Zhang Run , Reeves Isaiah , Winston Stephen , Brimble Mark A. , Kim Christina K. , Vetere Gisella
Published: December 2024

How are associative memories formed? Which cells represent a memory, and when are they engaged? By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified non-overlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented or certain mouse behaviors occurred and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the different identities of the cell ensembles active during learning, and revealed, for the first time, which ones form the core engram and are essential for memory formation and recall.
Truncated and “double-headed” derivatives of TO1-B dye for Mango-based imaging systems with increased brightness and selectivity and large Stocks shift
Authors: Svetlova Julia I. , Slushko Georgy K. , Fayzieva Anna S. , Belyaev Evgeny S. , Kamzeeva Polina N. , Aralov Andrey V.
Published: December 2024

Fluorogenic dyes that light up in complexes with genetically encodable RNA aptamers are increasingly used for intracellular RNA imaging. The growing toolbox of dyes and aptamers allows simultaneous or sequential monitoring of different RNAs. However, few orthogonal aptamer-dye pairs meet all the requirements of multiplex imaging in terms of brightness, contrast, etc., thus necessitating their optimization and further diversification. Here, we report new fluorogenic ligands for the Mango II aptamer, one of the most stable and widely used RNA tags. They are based on the cognate Mango ligand TO1-B, which is a thiazole orange (TO) derivative with a biotinylated tetraethylene glycol (TEG) residue attached via an amide linker, and its analogue with an isosteric triazolyl linker (TO1-triazolyl-TEG-biotin). Structural data suggested that the biotin residue might be dispensable for interactions with Mango, so we replaced it with a second TO residue or the alternative push-pull system, namely the dimethylaminophenyl (DMAP) group linked to the benzothiazolyl (BzT) group via the ethenyl linker. The resulting “double-headed” symmetric and asymmetric dyes showed reduced fluorescence in the free state due to intramolecular TO/TO or TO/DMAP-BzT interactions. The asymmetric dye exhibited intramolecular FRET in complex with Mango, resulting in a remarkably large (130 nm) Stocks shift, which may be advantageous for multiplex imaging. The main limitation of the “double-headed” dyes was their low brightness. To improve brightness, we further optimized the truncated (biotin-free) TO1-triazolyl-TEG dye by introducing a hydroxy or a methoxy group into the methylqunolinium (MQ) fragment of its push-pull system. The brightness of the methoxy-MQ derivative was increased by 40% compared to the reported TO1-triazolyl-TEG-biotin. Importantly, the methoxy-MQ derivative also showed increased selectivity for Mango over other noncanonical nucleic acids structures, making it a promising alternative to known TO-based dyes for high-contrast RNA imaging.
Rapamycin induced autophagy enhances lipid breakdown and ameliorates lipotoxicity in Atlantic salmon cells
Authors: Phadwal Kanchan , Haggarty Jennifer , Kurian Dominic , Marti Judit Aguilar , Houston Ross D. , Betancor Mónica B. , MacRae Vicky E. , Whitfield Phillip D. , Macqueen Daniel J.
Published: December 2024

Autophagy is a highly conserved cellular recycling process essential for homeostasis in all eukaryotic cells. Lipid accumulation and its regulation by autophagy are key areas of research for understanding metabolic disorders in human and model mammals. However, the role of autophagy in lipid regulation remains poorly characterised in non-model fish species of importance to food production, which could be important for managing health and welfare in aquaculture. Addressing this knowledge gap, we investigate the role of autophagy in lipid regulation using a macrophage-like cell line (SHK-1) from Atlantic salmon (Salmo salarL.), the world’s most commercially valuable farmed finfish. Multiple lines of experimental evidence reveal that the autophagic pathway responsible for lipid droplet breakdown is conserved in Atlantic salmon cells. We employed global lipidomics and proteomics analyses on SHK-1 cells subjected to lipid overload, followed by treatment with rapamycin to induce autophagy. This revealed that activating autophagy via rapamycin enhances storage of unsaturated triacylglycerols and suppresses key lipogenic proteins, including fatty acid elongase 6 and acid sphingomyelinase. Moreover, fatty acid elongase 6 was identified as cargo for autophagosomes, suggesting a critical role for autophagy in lipid metabolism in fish. Together, this study establishes a novel model of lipotoxicity and advances understanding of lipid autophagy in fish cells, with significant implications for addressing fish health issues in aquaculture.
AKR1C mediates the acquired resistance to T-Dxd in a HER-2 positive gastric cancer line
Authors: Wang Dong , Huang Qinqin , Wang Peili , Tang Feng , Han Yuhe , Wang Xiangyi , Huang Jingwei , Shi Liqi , Cao Weiqun , Zhang Zhixiang , Gu Qingyang
Published: December 2024

Trastuzumab deruxtecan (T-Dxd), an anti-HER2 antibody–drug conjugate, has significantly enhanced clinical outcomes for patients as a HER2-directed therapy compared to previous standards of care. However, acquired resistance is always a concern, necessitating further investigation into the underlying resistance mechanism. In this study, we successfully established T-Dxd-resistant cell line (N87-R) by exposing HER2-positive N87 gastric cancer cells to increasing concentrations of T-Dxd, and demonstrated its resistance phenotype bothin vitroandin vivo. While there were no changes in HER2 expression or T-Dxd binding in N87-R, a signature of drug metabolism genes were found upregulated, among which AKR1C played a critical role in the resistance mechanism. The resistance phenotype of N87-R cells was mitigated by both siRNA-mediated knockdown of AKR1C and pharmacological inhibition of its enzymatic activity. Our preclinical study underscores the critical role of AKR1C function in mediating T-Dxd resistance and suggests potential therapeutic innovation for combating T-Dxd resistance.
Protein and DNA Conformational Changes Contribute to Specificity of Cre Recombinase
Authors: Montgomery Jonathan S. , Judson Megan E. , Foster Mark P.
Published: December 2024

Cre, a conservative site-specific tyrosine recombinase, is a powerful gene editing tool in the laboratory. Expanded applications in human health are hindered by lack of understanding of the mechanism by which Cre selectively binds and recombines its cognateloxPsequences. This knowledge is essential for retargeting the enzyme to new sites and for mitigating effects of off-target recombination. Prior studies have suggested that in addition to a few base-specific contacts to cognateloxPDNA, specificity is enhanced by (1) autoinhibition involving a conformational change in the C-terminal helix of Cre, and (2) indirect readout via binding-coupled conformational changes in the target DNA. We used isothermal titration calorimetry (ITC), circular dichroism (CD) and heteronuclear NMR spectroscopy to investigate DNA site recognition by wild-type Cre and a deletion mutant lacking the C-terminal helix. ITC of Cre and a C-terminal deletion variant against cognate and non-cognate DNA recombinase binding elements (RBEs) reveal that the C-terminus reduces DNA binding affinity by six-fold towards cognate DNA. Additionally, ITC revealed highly unfavorable binding enthalpy, which when combined with evidence from CD and NMR of structural differences between cognate and non-cognate complexes support a model in which binding-coupled DNA bending provides a unique structure-thermodynamic signature of cognate complexes. Together, these findings advance our understanding of site-recognition by Cre recombinase.
RNA encodes physical information
Authors: Seim Ian , Zhang Vita , Jalihal Ameya P. , Stormo Benjamin M. , Cole Sierra J. , Ekena Joanne , Nguyen Hung T. , Thirumalai D. , Gladfelter Amy S.
Published: December 2024

Most amino acids are encoded by multiple codons, making the genetic code degenerate. Synonymous mutations affect protein translation and folding, but their impact on RNA itself is often neglected. We developed a genetic algorithm that introduces synonymous mutations to control the diversity of structures sampled by an mRNA. The behavior of the designed mRNAs reveals a physical code layered in the genetic code. We find that mRNA conformational heterogeneity directs physical properties and functional outputs of RNA-protein complexes and biomolecular condensates. The role of structure and disorder of proteins in biomolecular condensates is well appreciated, but we find that RNA conformational heterogeneity is equally important. This feature of RNA enables both evolution and engineers to build cellular structures with specific material and responsive properties.
Regimen comprising clarithromycin, clofazimine and bedaquiline is more efficacious than monotherapy in a mouse model of chronicMycobacterium aviumlung infection
Authors: Rimal Binayak , Howe Ruth A. , Panthi Chandra , Lamichhane Gyanu
Published: December 2024

Mycobacterium avium, a leading non-tuberculous mycobacterium (NTM) pathogen, causes chronic pulmonary infections, particularly in individuals with underlying lung conditions or immunosuppression. Current treatments involve prolonged multi-drug regimens with poor outcomes and significant side effects, highlighting the urgent need for improved therapies. Using a BALB/c mouse model of chronicM. aviumpulmonary disease, we evaluated the efficacy of individual antibiotics— clarithromycin, clofazimine, and rifabutin—and combination regimens including clarithromycin+bedaquiline and clarithromycin+clofazimine+bedaquiline. Clarithromycin demonstrated potent bactericidal activity, reducing lung bacterial burden by 2.2 log10CFU, while clofazimine transitioned from bacteriostatic to bactericidal, achieving a 1.7 log10CFU reduction. Rifabutin was bacteriostatic againstM. aviumMAC 101 but ineffective against MAC 104. The triple-drug regimen of clarithromycin+clofazimine+bedaquiline was the most effective, achieving a 3.3 log10CFU reduction in bacterial load, with 98% clearance within the first week and continued efficacy over eight weeks. Gross pathology confirmed these results, with granulomatous lesions observed only in untreated or rifabutin-treated mice. Combination therapy demonstrated enhanced efficacy compared to monotherapy. The findings underscore the potential of oral clarithromycin+clofazimine+bedaquiline or clarithromycin+clofazimine regimen as a promising therapeutic strategy forM. aviumpulmonary disease.
Vibrio choleraeO1 El Tor A1552 encodes two functional ornithine lipid synthases and induces ornithine lipid formation under low phosphate and under low salinity growth conditions
Authors: Vences-Guzmán Miguel Ángel , Olea-Ozuna Roberto Jhonatan , Martínez-Méndez Raquel , Escobedo-Hinojosa Wendy Itzel , Castro-Santillán Marlene , Guan Ziqiang , Zamorano-Sánchez David , Sohlenkamp Christian
Published: December 2024

Ornithine lipids (OLs) are phosphorus-free membrane lipids that can be formed by a wide range of bacteria. The presence of OLs is frequently related to the resistance to abiotic stress conditions, and its synthesis is often induced as part of various stress responses. Two different pathways for synthesizing OLs are currently known: the OlsBA pathway first described inSinorhizobium meliloti, and the OlsF pathway first described inSerratia proteamaculans. We identified in the genome ofVibrio choleraeO1 El Tor A1552 two genes encoding OlsF homologs, VC0489 is located on chromosome 1, whereas VCA0646 is located on chromosome 2. Both synthases, when expressed inEscherichia coli, caused the synthesis of OLs. Single mutants deficient in each of the OL synthases, double mutants deficient in both OL synthases, and mutants deficient in the transcriptional regulator PhoB were constructed and characterized. We corroborated that VC0489 is solely responsible for the synthesis of OLs under phosphate-limitation. The deletion of VC0489 reduced the growth velocity compared to the wildtype under phosphate-limiting conditions but not under phosphate-replete conditions. The expression of VCA0646 is favored under low salt growth conditions, and its deletion abrogates OL synthesis at low salinities. The absence of VCA0646 and, therefore, the lack of OLs under low salt conditions makes the respective mutant more susceptible to polymyxin than OL-forming strains. None of the mutants was affected in biofilm formation, swimming, or virulence assays usingCaenorhabditis elegansorGalleria mellonella. Here, we describe two functional OL synthases present in a single bacterium for the first time, and we show evidence that OLs have an important function during theV. choleraelifecycle.
In-depth Characterization of S-Glutathionylation in Ventricular Myosin Light Chain 1 Across Species by Top-Down Proteomics
Authors: Chapman Emily A. , Rogers Holden T. , Gao Zhan , Chan Hsin-Ju , Alvarado Francisco J. , Ge Ying
Published: December 2024

S-glutathionylation (SSG) is increasingly recognized as a critical signaling mechanism in the heart, yet SSG modifications in cardiac sarcomeric proteins remain understudied. Here we identified SSG of the ventricular isoform of myosin light chain 1 (MLC-1v) in human, swine, and mouse cardiac tissues using top-down mass spectrometry (MS)-based proteomics. Our results enabled the accurate identification, quantification, and site-specific localization of SSG in MLC-1v across different species. Notably, the endogenous SSG of MLC-1v was observed in human and swine cardiac tissues but not in mice. Treating non-reduced cardiac tissue lysates with GSSG elevated MLC-1v SSG levels across all three species.
Temperature-sensitive cortical condensation modulates mechano-response at Tricellular Junctions
Authors: Zheng Qi-hong , Zhang Chengge , Wang Ming-Xin , Xiang Xiaoxiang , Zhang Shaohong , Wang Yaru , Yu Huapeng H.
Published: December 2024

A general mechanism to maintain epithelial integrity during cell movements is to couple adhesion strength with mechanical force. Mechanosensitive proteins are recruited to adhesion sites to reinforce cell-cell or cell-matrix linkage in response to elevated tension. However, subcellular mechanisms for highly dynamic protein transport into and out of tension-bearing structures remain elusive. Furthermore, it is still unknown whether mechanosensitivity can be modulated by physiological signals in vivo. Here we revealed a direct edge-to-vertex route of Canoe/Afadin transport to tricellular junctions under tension, which relies on an obligatory binding partner Mbt/PAK. Without Mbt/PAK, Canoe/Afadin becomes insensitive to cytoskeletal tension and forms tactoid-shaped condensates directly at bicellular junctions. Remarkably, a temporary increase in temperature within the physiological range dissolves these condensates, allowing Canoe/Afadin to regain mechanosensitivity and enrichment at tricellular junctions. Functionally, the localization of Mbt/PAK at cell junctions oscillates during synchronous cell division within embryonic mitotic domains, enabling dynamic adjustments of Canoe/Afadin mechanosensitivity to preserve epithelial integrity in rapidly dividing tissues. Collectively, our findings suggest a physiological process in which the state of protein condensation, regulated by biochemical inputs, can supersede mechanical signals to modulate adhesion strength during cell division.
Mental health and weight loss in men: an exploratory mixed methods study of the Game of Stones trial
Authors: Torrens Claire E , Turner Katrina , Swingler James , O’Dolan Catriona , MacLean Alice , Macaulay Lisa , Dombrowski Stephan U , Avenell Alison , Cotton Seonaidh , McKinley Michelle C , Hunt Kate , Gray Cindy , Kee Frank , MacLennan Graeme , Hoddinott Pat
Published: December 2024

Objective

Weight management interventions can affect mental health. Mental health can affect engagement with weight loss interventions or services. This study explored mental health and wellbeing outcomes, retention and participant experiences of mental health within the Game of Stones trial.

Methods

Mixed methods process evaluation within a 3-group randomised controlled trial: behavioural text messages with financial incentives, texts alone, and waiting list control, for 585 men with obesity. Secondary outcomes analysed descriptively included: Warwick-Edinburgh Mental Wellbeing Scale, Weight Self-Stigma Questionnaire, EQ-5D-5L, EQ-5D-5L anxiety and depression subscale, Patient Health Questionniare-4, and retention. Three categories of participants were compared: ever diagnosed with a mental health condition (n=146; 25.0%), latent mental health condition (n=142; 24.3%) no mental health condition (n=295; 50.6%). Semi-structured interviews (n=54) were conducted after 12 months and analysed using Framework method.

Results

A higher proportion of men who self-reported ever having a mental health condition had a disability, multiple long-term conditions, were under financial strain and were single compared to those with those with a latent mental health condition and no mental health condition. Improvements from baseline were shown for weight stigma, wellbeing and PHQ-4 at 12 months for men in intervention groups with a mental health condition and latent mental health condition. EQ-5D-5L Visual Analogue Scale scores improved across all mental health categories and trial groups, but EQ-5D-5L and EQ-5D-5L-AD scores were inconsistent. Retention at 12 months was 76.0% (mental health condition), 70.4% (latent mental health condition) and 72.5% (no mental health condition). The qualitative evidence indicated that stress, anxiety and depression were experienced in different ways by men during the programme. Mental health difficulties were unique to the individual, could be episodic, recurrent, cyclical or ongoing and were a barrier to behaviour change for some but not for others.

Conclusion

The trial was able to engage and retain men regardless of mental health category. Behavioural text messages with or without incentives helped some men lose weight, but not others. Observed heterogeneity for mental health and wellbeing measures is problematic for weight management trials with men.
Remote Real Time Digital Monitoring fills a Critical Gap in the Management of Parkinson’s disease
Authors: Negi Aarushi S. , Karjagi Shreesh , Parisi Laura , Daley Kerry W. , Abay Annie K. , Gala Aryaman S. , Wilkins Kevin B. , Hoffman Shannon L. , Ferris Margaret S. , Zahed Hengameh , Chattree Gaurav , Palushaj Bianca , Bronte-Stewart Helen M.
Published: December 2024

Background and Objectives

People with Parkinson’s disease (PWP) face significant gaps in care. Limited neurologist access, infrequent clinic visits, and inadequate symptom measurement culminate in suboptimal therapy and high morbidity. Quantitative Digitography (QDG) addresses these care gaps by providing validated, quantitative metrics of all motor signs in Parkinson’s disease (PD) in real-time through a 30-second repetitive alternating finger tapping (RAFT) task. We investigated the feasibility and clinical relevance of remote QDG monitoring in individuals with movement disorders.

Methods

In this prospective cohort study, participants with suspected or clinically established PD were referred by neurologists from Stanford Movement Disorders Clinic, with one participant recruited outside Stanford. Participants were asked to complete at-home QDG-RAFT for 30 days and were administered usability and quality-of-life questionnaires throughout testing; descriptive statistics summarized compliance and questionnaire responses, and a Spearman correlation assessed the relationship between QDG Mobility Score and MDS-UPDRS Part II scores. The primary outcome was compliance with once-daily testing for at least 16/30 days of remote monitoring.

Results

30 participants (24 with clinically diagnosed and 6 with suspected PD at time of referral) were included. 100% of participants demonstrated compliance with once-daily testing for at least 16/30 days. Adherence rates for once-daily and twice-daily testing were 96.2% and 82.2%, respectively, with 96% of participants rating once-daily testing as easy. The QDG Mobility Score correlated strongly with patients’ self-reported impact of motor symptoms on Activities of Daily Living (ADLs) per the MDS-UPDRS II (ρ=-0.61 [−0.88, −0.16], p=0.004). QDG-RAFT documented motor asymmetry and impairment from 1-month pre-diagnosis to 20-years duration of PD. The QDG Mobility Score reflected motor improvement and deterioration after adding or removing respectively a single tablet of carbidopa/levodopa.

Discussion

Participants showed excellent compliance with remote QDG monitoring and found the system easy to use. The QDG Mobility Score was highly correlated with ADLs, captured motor complexities across a broad disease duration range, and detected responses to minor therapy adjustments. A pivotal advancement in PD care, QDG offers providers an accessible, comprehensive tool to remotely monitor motor symptoms, optimize treatment regimens, and bridge care gaps created by infrequent clinic visits and subjective symptom assessment.
The association between body roundness index and kidney stones in a diabetic population: NHANES 2011–2018
Authors: Cui Chongsong , Peng You , Zhao Ying , Chan Feiin , Ren Qiqi , Liu Zhenjie
Published: December 2024

Background

Predominantly attributed to metabolic disruptions, individuals with diabetes are more prone to kidney stones than the general population. The Body Rounds Index (BRI), a new measure of obesity and health risks, has been shown to have a positive correlation with the risk of developing kidney stones. Our study sets out to explore the correlation between BRI and kidney stones specifically within the diabetic population.

Methods

Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018, this cross-sectional study probed the link between BRI and kidney stones among diabetic individuals. We conducted a logistic regression analysis to investigate the relationship between BRI and kidney stones, with adjustments for various covariates. To further explore the association trends between different BRI levels and the incidence of kidney stones, we categorized BRI into four levels, thereby enhancing the robustness of our results. Additionally, subgroup and sensitivity analyses were performed to ensure the reliability and consistency of our findings.

Results

A total of 3,558 diabetic patients were included in this study, of whom 546 (15.3%) had kidney stones. After adjusting for some and all confounders, we observed that the prevalence of kidney stones in diabetic patients increased by 7% and 5% for each unit increase in BRI in Models 2 and 3, respectively (Model 2: OR=1.07, 95% CI: 1.03-1.11; Model 3: OR=1.05, 95% CI: 1.00-1.09).This association remained statistically significant when the BRI was divided into quartiles, the prevalence of kidney stones in the highest quartile of BRI (Q4) was 50% greater than in the lowest quartile (Q1) (OR=1.50, 95% CI: 1.14-1.98; P<0.05).

Conclusions

Our research indicates a positive correlation between BRI and the incidence of kidney stones among diabetics. We believe that BRI may be an effective indicator for assessing the risk of kidney stones in diabetic patients.
Association of healthcare fragmentation and overall survival in patients with kidney transplant in Colombia
Authors: Barrera Luis Manuel , Sánchez-Santiesteban Daniela , Buitrago Giancarlo
Published: December 2024

Objective

Kidney transplantation requires a multidisciplinary approach to achieve optimal outcomes. Healthcare fragmentation can negatively impact clinical outcomes; however, this issue remains understudied in low- and middle-income countries (LMICs). This study aimed to assess healthcare fragmentation in kidney transplant patients during their first post-transplant year and evaluate its association with three-year survival among patients enrolled in Colombia’s contributory healthcare scheme.

Methods

A retrospective cohort study was conducted using administrative data from Colombia’s contributory healthcare scheme. The cohort included kidney transplant recipients (2012–2016) who survived the first post-transplant year. Healthcare fragmentation was measured by the number of unique providers involved in the first year. Patients were categorised into high- and low-fragmentation groups based on the 75th percentile of provider distribution. The primary outcome was three-year survival, analysed using multivariate Cox regression to estimate hazard ratios (HRs), adjusted for age, sex, Charlson Comorbidity Index (CCI), insurer, region, and transplant year.

Results

The cohort comprised 2,028 kidney transplant patients, with a mean age of 47.7 years (SD: 13.4), 38.7% female, and 68.7% presenting a CCI≤3. Healthcare fragmentation ranged from 1 to 34 providers, with a mean of 8.94 (SD: 6.77). High fragmentation (≥11 providers) was observed in 30.2% of patients. Three-year mortality was significantly higher in the high-fragmentation group (18%) compared to the low-fragmentation group (12%) (p=0.04). High fragmentation was associated with a 49% increased mortality risk (adjusted HR: 1.49; 95% CI: 1.12–1.97; p=0.01).

Conclusion

Healthcare fragmentation significantly reduces three-year overall survival in kidney transplant recipients in Colombia. These findings underscore the importance of integrated care models and improved coordination among providers to enhance patient outcomes, particularly in resource-limited settings.
Engineering a ribozyme with aminoacyl-tRNA synthetase activity
Authors: Gan Gary , Chen Ji , Manuel Gerald , Corn Robert M. , Luptak Andrej , Golden Barbara L.
Published: December 2024

A ribozyme that can charge a tRNA with amino acids and discriminate between cognate and non-cognate tRNAs is of interest because a RNA with this ability may have been a critical for translation in the transition from the RNA world. In addition, it could provide a tool for incorporating non-canonical amino acids for biotechnology applications. Here, we rationally engineer a ribozyme by fusing a tRNA binding module (a T-box riboswitch) with a catalytic module (a flexizyme) to generate a ribozyme that can amino acylate a target tRNA. We demonstrate that this ribozyme be readily redesigned to alter tRNA specificity. This ribozyme is compatible with an in vitro translation system and could be used to recode a protein sequence to site-specifically incomporate a non-canonical amino acid.
The probability and duration of immigration in microbial communities
Authors: Curtis Thomas P , Allen Ben , Brown Mathew , Bell Amy , Swan Donna , Davenport Russel , Sloan William
Published: December 2024

Immigration is a fundamental feature of microbial communities. We propose a method to determine the probability (Pi)thata number of immigrants (i) can attain an abundanceNusing the ratio of the probabilities of deathqand division or “birth”pand the gambler’s ruin equation:Pi= (1-(q/p)i/(1-(q/p)N). We estimate the probability of successful bioaugmentation or transplantation, the fate of a mutation infection and extinction. For example, an inoculum of 108bacteria with aq/pof 1.00000001 has a 10-43chance of attaining an abundance of 1010. The immigration parameter used in neutral models,mis1/(1-q/p). We calculated the long-term average value of m andq/pin a wastewater treatment plant. The value ofmvaries by >5 orders of magnitude, with a curious bimodal distribution. However, all the values ofq/pare very close to, but greater than,1. We expect the long-term average value ofq/pto be ∼1 in all stable microbial communities. In the absence of migration, bacterial populations with aq/p≥1 will go extinct with probability 1. The link betweenq/pand infectious dose is known and we demonstrate that, in principle, the gambler’s ruin equation can estimate the infectious dose in naturally occurring infections, usingVibrio cholerae“carriers” to illustrate the point. We use the ratioq/pto estimate the time (measured in events or solar time) for a given change in abundance to happen. Whenq/p=1, extinction in even a small microbial population will take thousands of years.
Vancomycin-resistantEnterococcuscolonise the antibiotic-treated intestine by occupying distinct nutrient- and metabolite-defined intestinal niches
Authors: King Olivia G. , Yip Alexander Y. G. , Horrocks Victoria , Blanco Jesús Miguéns , Marchesi Julian R. , Mullish Benjamin H. , Clarke Thomas B. , McDonald Julie A. K.
Published: December 2024

Antibiotic treatment significantly disrupts the gut microbiome and promotes vancomycin-resistantEnterococcus(VRE) intestinal colonisation. These disruptions lead to the intestine acting as a reservoir for VRE that seed difficult-to-treat infections. Patients would benefit from new treatments that prevent or treat VRE intestinal colonisation. However, the factors that drive VRE growth in the gut are poorly understood. We demonstrated that multiple antibiotics that promote VRE intestinal colonisation increased the concentration of a wide range of nutrients and decreased the concentration of a wide range of microbial metabolites. We demonstrated that specific short chain fatty acids and branched chain fatty acids found in healthy gut microbiomes inhibited VRE growth, however inhibition was incomplete at physiologically relevant concentrations. We also showed that VRE could use most nutrients increased in antibiotic-treated faecal microbiomes as carbon or nitrogen sources to support their growth, where growth was higher in the presence of oxygen.Enterococcus faeciumandEnterococcus faecalishad some common and some distinct preferences for use of specific nutrients that were enriched in antibiotic-treated faecal microbiomes. Finally, we showed thatE. faeciumandE. faecalisoccupied overlapping but distinct nutrient-defined intestinal niches that promoted high growth when cultured with each other and when cultured with carbapenem-resistantEnterobacteriaceae(another group of multidrug-resistant pathogens). Our results demonstrated that VRE occupy distinct intestinal niches in the antibiotic-treated intestine, defined by their abilities to utilise specific enriched nutrients and their abilities to grow with reduced concentrations of microbial metabolites.
Metabolic regulation in adult and aging skeletal muscle stem cells
Authors: Sartorelli Vittorio , Ciuffoli Veronica
Published: December 2024

Adult stem cells maintain homeostasis and enable regeneration of most tissues. Quiescence, proliferation, and differentiation of stem cells and their progenitors are tightly regulated processes governed by dynamic transcriptional, epigenetic, and metabolic programs. Previously thought to merely reflect a cell's energy state, metabolism is now recognized for its critical regulatory functions, controlling not only energy and biomass production but also the cell's transcriptome and epigenome. In this review, we explore how metabolic pathways, metabolites, and transcriptional and epigenetic regulators are functionally interlinked in adult and aging skeletal muscle stem cells.
Influence of magnetic field-induced anisotropic gluon pressure during pre-equilibrium in heavy-ion collisions: A faster road toward isotropization
Authors: Ayala Alejandro , Mizher Ana Julia
Published: December 2024

Magnetic fields of a large intensity can be generated in peripheral high-energy heavy-ion collisions. Although their intensity drops fast and, moreover, it is not clear whether these fields last long enough to induce a magnetization during the quark-gluon plasma phase, most of the models and simulations predict a significant intensity that lasts up to proper times of order 1 fm after the beginning of the reaction, which is a typical time for the hydrodynamical phase to start. This interval of time is referred to as the pre-equilibrium stage. The evolution of the reaction during pre-equilibrium is thus likely to be influenced by these fields. In this work we adopt a strong field approximation to study the effects of the magnetic field-induced anisotropy on the gluon pressure. We include this anisotropy within the description obtained by means of effective kinetic theory and explore the consequences to reach isotropization at proper times of order 1 fm. We show that when including the magnetic field effects, isotropization is achieved faster.

Published by the American Physical Society
2024
Semianalytical model of optothermal fluidics in a confinement
Authors: Tsuji Tetsuro , Saito Shun , Taguchi Satoshi
Published: December 2024

In this paper, we provide the semianalytical solution of the temperature and flow fields of a fluid confined in a narrow space between two parallel plates. The temperature increase is triggered by photothermal effects of fluids and/or boundaries due to the absorption of a focused Gaussian beam irradiated perpendicular to the fluid film, and then the temperature variation induces the flow fields through a buoyancy force and/or thermo-osmotic slip. The semianalytical solution to this optothermal fluidic system is validated by comparing with the results of numerical simulation, and is applied to typical optothermal fluidic problems. In particular, the optothermal trap of nanoparticles observed in our previous experiment [Tsuji , ] is investigated in terms of thermophoretic force and flow drag that are obtained semianalytically. The semianalytical solution can be shared through open-source codes that are available to researchers without the background of fluid mechanics.

Published by the American Physical Society
2024
Crystal structure and Hirshfeld surface analysis of the layered hybrid metal halide poly[bis(2-iodoethylammonium) [di-μ-iodido-diiodidogermanate(II)]]
Authors: Kucheriv Olesia I. , Apostu Mircea-Odin , Prysiazhna Olena , Potaskalov Vadim A. , Malinkin Sergey O.
Published: December 2024

The title compound is a germanium-based hybrid metal halide that represents a less-toxic alternative to more popular lead-based analogues in optoelectronic applications. {(2-IC2H4NH3)2[GeI4]}
n
is composed of infinite inorganic layers that are formed by [GeI6]4− octahedra connected in a corner-sharing manner with four equatorial I atoms. The organic (2-IC2H4NH3)+ cations interleave the inorganic layers. There are two types of 2-iodoethylammonium cations, with synclinal and antiperiplanar conformations. The organic cations interact with the inorganic layers through hydrogen bonds and I...I contacts. The crystal under investigation was twinned by a 180° rotation around [100].
Crystal structure of catena-poly[bis(N,O-dimethylhydroxylammonium) [di-μ-bromido-dibromidostannate(II)]]
Authors: Sirenko Valerii Y. , Apostu Mircea-Odin , Golenya Irina A. , Naumova Dina D. , Partsevska Sofiia V.
Published: December 2024

The title compound, {(C2H8NO)2[SnBr4]}
n
, is a layered hybrid perovskite crystallizing in the monoclinic space group C2/c. The asymmetric unit consists of one H3C—O—NH2
+—CH3 cation (Me2HA+), one SnII atom located on a twofold rotation axis, and two Br atoms. The SnII atom has a distorted octahedral coordination environment formed by the bromido ligands. The {SnBr6} units corner-share their equatorial Br atoms, forming infinite mono-layers that extend parallel to the ab plane. These inorganic layers are sandwiched by the organic Me2HA+ cations organized in double-layers; stacking of the layers is along the c-axis direction. Consecutive inorganic layers, separated by the organic cations, are shifted relative to each other along the b-axis direction. Specifically, the SnII atom in one inorganic layer is offset by 3.148 Å along the b axis relative to the SnII atom in an adjacent inorganic layer. The N,O-dimethylhydroxylammonium cation forms two hydrogen bonds with the axial bromide anions of the inorganic layers as acceptors, and leads to the cohesion of the crystal structure. According to Hirshfeld surface analysis, the highest contributions to the crystal packing are from H...H (46.2%), Br...H (38.5%), and H...O (14.8%) contacts.