bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-associated dementia among older people aging with HIV in the United States: a modeling study
Authors: Hyle Emily P. , Wattananimitgul Nattanicha , Mukerji Shibani S. , Foote Julia H.A. , Reddy Krishna P. , Thielking Acadia , Yu Liyang , Viswanathan Anand , Rubin Leah H. , Shebl Fatma M. , Althoff Keri N. , Freedberg Kenneth A. 
Published: February 2024

Objective:
Almost 400 000 people with HIV (PWH) in the United States are over age 55 years and at risk for age-associated dementias (AAD), including Alzheimer's disease and vascular contributions to cognitive impairment and dementia (VCID). We projected the cumulative incidence and mortality associated with AAD among PWH at least 60 years in the United States compared with the general population.

Design/methods:
Integrating the CEPAC and AgeD-Pol models, we simulated two cohorts of 60-year-old male and female individuals: PWH, and the general US population. We estimated AAD incidence and AAD-associated mortality rates. Projected outcomes included AAD cumulative incidence, life expectancy, and quality-adjusted life-years (QALYs). We performed sensitivity and scenario analyses on AAD-specific (e.g. incidence) and HIV-specific (e.g. disengagement from HIV care) parameters, as well as premature aging among PWH.

Results:
We projected that 22.1%/16.3% of 60-year-old male individuals/female individuals with HIV would develop AAD by 80 years compared with 15.9%/13.3% of male individuals/female individuals in the general population. Accounting for age-associated and dementia-associated quality of life, 60-year-old PWH would have a lower life expectancy (QALYs): 17.4 years (14.1 QALYs) and 16.8 years (13.4 QALYs) for male and female individuals, respectively, compared with the general population [male individuals, 21.7 years (18.4 QALYs); female individuals, 24.7 years (20.2 QALYs)]. AAD cumulative incidence was most sensitive to non-HIV-related mortality, engagement in HIV care, and AAD incidence rates.

Conclusion:
Projected estimates of AAD-associated morbidity, mortality, and quality of life can inform decision-makers and health systems planning as the population of PWH ages. Improved AAD prevention, treatment, and supportive care planning are critical for people aging with HIV.
Inflammatory Knee Synovitis
Authors: Feuerriegel Georg C. , Goller Sophia S. , von Deuster Constantin , Sutter Reto 
Published: February 2024

ObjectivesThe aim of this study was to assess the diagnostic value and accuracy of a deep learning (DL)–accelerated fluid attenuated inversion recovery (FLAIR) sequence with fat saturation (FS) in patients with inflammatory synovitis of the knee.Materials and MethodsPatients with suspected knee synovitis were retrospectively included between January and September 2023. All patients underwent a 3 T knee magnetic resonance imaging including a DL-accelerated noncontrast FLAIR FS sequence (acquisition time: 1 minute 38 seconds) and a contrast-enhanced (CE) T1-weighted FS sequence (acquisition time: 4 minutes 50 seconds), which served as reference standard. All knees were scored by 2 radiologists using the semiquantitative modified knee synovitis score, effusion synovitis score, and Hoffa inflammation score. Diagnostic confidence, image quality, and image artifacts were rated on separate Likert scales. Wilcoxon signed rank test was used to compare the semiquantitative scores. Interreader and intrareader reproducibility were calculated using Cohen κ.ResultsFifty-five patients (mean age, 52 ± 17 years; 28 females) were included in the study. Twenty-seven patients (49%) had mild to moderate synovitis (synovitis score 6–13), and 17 patients (31%) had severe synovitis (synovitis score >14). No signs of synovitis were detected in 11 patients (20%) (synovitis score <5). Semiquantitative assessment of the whole knee synovitis score showed no significant difference between the DL-accelerated FLAIR sequence and the CE T1-weighted sequence (mean FLAIR score: 10.69 ± 8.83, T1 turbo spin-echo FS: 10.74 ± 10.32;P= 0.521). Both interreader and intrareader reproducibility were excellent (range Cohen κ [0.82–0.96]).ConclusionsAssessment of inflammatory knee synovitis using a DL-accelerated noncontrast FLAIR FS sequence was feasible and equivalent to CE T1-weighted FS imaging.
Increased Musculoskeletal Deformities And Decreased Lung Volume In Patients After Ea/Tef Repair – A Real-Time Mri Study
Authors: Aubert Ophelia , Lacher Martin , Mayer Steffi , Frahm Jens , Voit Dirk , Rosolowski Maciej , Widenmann Anke , Hirsch Franz Wolfgang , Gräfe Daniel 
Published: February 2024

Objective:
This study aims to assess morphological and functional postoperative changes after open or minimally invasive (MIS) repair of esophageal atresia (EA) compared to healthy controls by thoracic real-time MRI.

Summary Background Data:
Musculoskeletal deformities and pulmonary morbidity are common in children after EA repair. The real-time MRI is a novel technique that provides ultrafast, high-quality images during spontaneous breathing, without sedation even in young children.

Methods:
Children aged 3-18 years were prospectively examined with a 3 Tesla MRI. Musculoskeletal deformities, static thoracic cross-sectional areas (CSA) at three different levels and lung volumes, as well as dynamic right-to-left ratio of CSA of hemithoraces and lung volumes during forced breathing were evaluated.

Results:
72 children (42 open, 8 MIS, 22 controls) were recruited. In the EA group, rib fusions and adhesions (78%, P<0.01) and scoliosis (15%, P=0.32) were found after thoracotomy, but not after MIS. Mean right-to-left ratio of CSA and lung volumes were lower after EA repair compared to controls (P <0.05), indicating impaired thoracic and lung development. The number of thoracotomies was a significant risk factor for smaller thoracic volumes (P<0.05).

Conclusions:
For the first time, morphological changes and thoracic motility after EA repair were visualized by dynamic real-time MRI. Children after EA repair show decreased right-sided thoracic and lung development compared to controls. Open repair leads to significantly more musculoskeletal deformities. This study emphasizes that musculoskeletal morbidity following a thoracotomy in infancy is high.
The role of caffeine in headache disorders
Authors: Charles Andrew 
Published: February 2024

Purpose of review
Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management.

Recent findings
Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy.

Summary
There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.
State-Level Analysis of Intimate Partner Violence, Abortion Access, and Peripartum Homicide: Call for Screening and Violence Interventions for Pregnant Patients
Authors: Keegan Grace , Hoofnagle Mark , Chor Julie , Hampton David , Cone Jennifer , Khan Abid , Rowell Susan , Plackett Timothy , Benjamin Andrew , Bhardwaj Neha , Rogers Selwyn O , Zakrison Tanya L , Cirone Justin M 
Published: February 2024

BACKGROUND:
Despite representing 4% of the global population, the US has the fifth highest number of intentional homicides in the world. Peripartum people represent a unique and vulnerable subset of homicide victims. This study aimed to understand the risk factors for peripartum homicide.

STUDY DESIGN:
We used data from the 2018 to 2020 National Violent Death Reporting System to compare homicide rates of peripartum and nonperipartum people capable of becoming pregnant (12 to 50 years of age). Peripartum was defined as currently pregnant or within 1-year postpartum. We additionally compared state-level peripartum homicide rates between states categorized as restrictive, neutral, or protective of abortion. Pearson’s chi-square and Wilcoxon rank-sum tests were used.

RESULTS:
There were 496 peripartum compared with 8,644 nonperipartum homicide victims. The peripartum group was younger (27.4 ± 71 vs 33.0 ± 9.6, p < 0.001). Intimate partner violence causing the homicide was more common in the peripartum group (39.9% vs 26.4%, p < 0.001). Firearms were used in 63.4% of homicides among the peripartum group compared with 49.5% in the comparison (p < 0.001). A significant difference was observed in peripartum homicide between states based on policies regarding abortion access (protective 0.37, neutral 0.45, restrictive 0.64; p < 0.01); the same trend was not seen with male homicides.

CONCLUSIONS:
Compared with nonperipartum peers, peripartum people are at increased risk for homicide due to intimate partner violence, specifically due to firearm violence. Increasing rates of peripartum homicide occur in states with policies that are restrictive to abortion access. There is a dire need for universal screening and interventions for peripartum patients. Research and policies to reduce violence against pregnant people must also consider the important role that abortion access plays in protecting safety.
Novel syndromic neurodevelopmental disorder caused by de novo deletion ofCHASERR, a long noncoding RNA
Authors: Ganesh Vijay S. , Riquin Kevin , Chatron Nicolas , Lamar Kay-Marie , Aziz Miriam C. , Monin Pauline , O’Leary Melanie , Goodrich Julia K. , Garimella Kiran V. , England Eleina , Yoon Esther , Weisburd Ben , Aguet Francois , Bacino Carlos A. , Murdock David R. , Dai Hongzheng , Rosenfeld Jill A. , Emrick Lisa T. , Ketkar Shamika ,   Undiagnosed Diseases Network, Sarusi Yael , Sanlaville Damien , Kayani Saima , Broadbent Brian , Isidor Bertrand , Pengam Alisée , Cogné Benjamin , MacArthur Daniel G. , Ulitsky Igor , Carvill Gemma L. , O’Donnell-Luria Anne 
Published: February 2024

Abstract/SummaryGenes encoding long non-coding RNAs (lncRNAs) comprise a large fraction of the human genome, yet haploinsufficiency of a lncRNA has not been shown to cause a Mendelian disease.CHASERRis a highly conserved human lncRNA adjacent toCHD2–a coding gene in whichde novoloss-of-function variants cause developmental and epileptic encephalopathy. Here we report three unrelated individuals each harboring an ultra-rare heterozygousde novodeletion in theCHASERRlocus. We report similarities in severe developmental delay, facial dysmorphisms, and cerebral dysmyelination in these individuals, distinguishing them from the phenotypic spectrum ofCHD2haploinsufficiency. We demonstrate reducedCHASERRmRNA expression and corresponding increasedCHD2mRNA and protein in whole blood and patient-derived cell lines–specifically increased expression of theCHD2allele inciswith theCHASERRdeletion, as predicted from a prior mouse model ofChaserrhaploinsufficiency. We show for the first time thatde novostructural variants facilitated by Alu-mediated non-allelic homologous recombination led to deletion of a non-coding element (the lncRNACHASERR) to cause a rare syndromic neurodevelopmental disorder. We also demonstrate thatCHD2has bidirectional dosage sensitivity in human disease. This work highlights the need to carefully evaluate other lncRNAs, particularly those upstream of genes associated with Mendelian disorders.
Internal Transcribed Spacers as Phylogenetic Markers Enable Species-level Metataxonomic Analysis of Ciliated Protozoa
Authors: Somasundaram Sripoorna , Yu Zhongtang 
Published: February 2024

AbstractBackgroundThe conventional morphology-based classification of ciliates is often inaccurate and time-consuming. To address this issue, sequencing, and analysis of the 18S rRNA gene of ciliates have been used as an alternative. However, this method has limitations because the highly conserved nature of this gene makes it challenging to achieve species-level resolution. This study assesses the capability of two internal transcribed spacers, ITS1 and ITS2, along with the 28S rRNA gene, to enhance the taxonomic resolution beyond that offered by the 18S rRNA gene in free-living and host-associated ciliates.ResultsWe compared sequences of ITSI, ITS2, and the 18S and the 28S rRNA genes downloaded from public databases and found that ITS1 and ITS2 are more divergent at both inter- and intra-specific levels than the 18S rRNA gene. We designed universal primers specific to the two ITS regions and the 28S rRNA gene for free-living and rumen ciliates. We then systematically evaluated these primers usingin-silicoanalysis, PCR assays, and metataxonomic or metabarcoding analysis and compared them to universal 18S rRNA gene primers. We found that the new primers are specific and inclusive, with an inclusiveness rate of over 80% based onin-silicoanalysis and confirmed their specificity using PCR evaluation. We validated the new primers with metagenomic DNA from freshwater samples and from rumen samples. Our metataxonomic analysis demonstrated that the ITS regions and the 28S rRNA gene could reveal greater ciliate diversity than the 18S rRNA gene in both environments. In particular, ITS1 detected the highest number of ciliate species, including species and genera that were not detected by the 18S rRNA gene.ConclusionsThe ITS regions, particularly ITS1, offer superior taxonomic resolution, and the NCBI ITS RefSeq database allows more species to be classified. Therefore, ITS1, and to a lesser extent ITS2, is recommended for enhancing metataxonomic analysis of ciliate communities in both freshwater and rumen environments.
Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy
Authors: Wahl Devin , Risen Sydney J. , Osburn Shelby C. , Emge Tobias , Sharma Sadhana , Gilberto Vincenzo S. , Chatterjee Anushree , Nagpal Prashant , Moreno Julie A. , LaRocca Thomas J. 
Published: February 2024

ABSTRACTNeuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer’s disease, which is characterized by the aggregation of pathological tau. One major driver of both age- and tau-associated neuroinflammation is the NF-κB and NLRP3 signaling axis. However, current treatments targeting NF-κB or NLRP3 may have adverse/systemic effects, and most have not been clinically translatable. In this study, we tested the efficacy of a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically targeting both NF-κB and NLRP3 in the brain for reducing neuroinflammation and improving cognitive function in old (aged 19 months) wildtype mice, and in rTg4510 tau pathology mice (aged 2 months). We found that 4 weeks of NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles in the brain and improved cognitive-behavioral function in both old and rTg4510 mice. These effects of NF-κB/NLRP3-targeting Nanoligomers were also associated with reduced glial cell activation and pathology, favorable changes in transcriptome signatures of glia-associated inflammation (reduced) and neuronal health (increased), and positive systemic effects. Collectively, our results provide a basis for future translational studies targeting both NF-κB and NLRP3 in the brain, perhaps using Nanoligomers, to inhibit neuroinflammation and improve cognitive function with aging and neurodegeneration.
A coarse-grained model for disordered and multi-domain proteins
Authors: Cao Fan , von Bülow Sören , Tesei Giulio , Lindorff-Larsen Kresten 
Published: February 2024

AbstractMany proteins contain more than one folded domain, and such modular multi-domain proteins help expand the functional repertoire of proteins. Because of their larger size and often substantial dynamics, it may be difficult to characterize the conformational ensembles of multi-domain proteins by simulations. Here, we present a coarse-grained model for multi-domain proteins that is both fast and provides an accurate description of the global conformational properties in solution. We show that the accuracy of a one-bead-per-residue coarse-grained model depends on how the interaction sites in the folded domains are represented. Specifically, we find excessive domain-domain interactions if the interaction sites are located at the position of the Cαatoms. We also show that if the interaction sites are located at the centre of mass of the residue, we obtain good agreement between simulations and experiments across a wide range of proteins. We then optimize our previously described CALVADOS model using this centre-of-mass representation, and validate the resulting model using independent data. Finally, we use our revised model to simulate phase separation of both disordered and multi-domain proteins, and to examine how the stability of folded domains may differ between the dilute and dense phases. Our results provide a starting point for understanding interactions between folded and disordered regions in proteins, and how these regions affect the propensity of proteins to self-associate and undergo phase separation.
Alterations of Pleiotropic Neuropeptide-Receptor gene couples in Cetacea
Authors: Valente Raul , Cordeiro Miguel , Pinto Bernardo , Machado André , Alves Filipe , Sousa-Pinto Isabel , Ruivo Raquel , Castro L. Filipe C. 
Published: February 2024

AbstractBackgroundHabitat transitions have considerable consequences in organism homeostasis, as they require the adjustment of several concurrent physiological compartments to maintain stability and adapt to a changing environment. Within the range of molecules with a crucial role in the regulation of different physiological processes, neuropeptides are key agents. Here, we examined the coding status of several neuropeptides and their receptors with pleiotropic activity in Cetacea.ResultsAnalysis of 202 mammalian genomes, including 41 species of Cetacea, exposed an intricate mutational landscape compatible with gene sequence modification and loss. Specifically for Cetacea, in the twelve genes analysed we have determined patterns of loss ranging from species-specific disruptive mutations (e.g., Neuropeptide FF-Amide Peptide Precursor;NPFF) to complete erosion of the gene across the cetacean stem lineage (e.g., Somatostatin Receptor 4;SSTR4).ConclusionsImpairment of some of these neuromodulators, may have contributed to the unique energetic metabolism, circadian rhythmicity and diving response displayed by this group of iconic mammals.
Multiple plastid losses within photosynthetic stramenopiles revealed by comprehensive phylogenomics
Authors: Terpis Kristina X. , Salomaki Eric D. , Barcytė Dovilė , Pánek Tomáš , Verbruggen Heroen , Kolisko Martin , Bailey J. Craig , Eliáš Marek , Lane Christopher E 
Published: February 2024

AbstractOchrophyta is a vast and morphologically diverse group of algae with complex plastids, including familiar taxa with fundamental ecological importance (diatoms or kelp), and a wealth of lesser-known and obscure organisms. The sheer diversity of ochrophytes poses a challenge for reconstructing their phylogeny, with major gaps in sampling and an unsettled placement of particular taxa yet to be tackled. We sequenced transcriptomes from 25 strategically selected representatives and used these data to build the most taxonomically comprehensive ochrophyte-centered phylogenomic supermatrix to date. We employed a combination of approaches to reconstruct and critically evaluate the relationships among ochrophytes. While generally congruent with previous analyses, the updated ochrophyte phylogenomic tree resolved the position of several taxa with previously uncertain placement, and supported a redefinition of the class Synchromophyceae. Our results indicated that the heterotrophic plastid-lacking heliozoanActinophrys solis not a sister lineage of ochrophytes, as proposed recently, but rather phylogenetically nested among them. In addition, we foundPicophagus flagellatusto be a secondarily heterotrophic ochrophyte lacking all hallmark plastid genes, yet exhibiting mitochondrial proteins that seem to be genetic footprints of lost plastid organelle. We thus document, for the first time, plastid loss in two separate ochrophyte lineages. Altogether, our study provides a new framework for reconstructing trait evolution in ochrophytes and demonstrates that plastid loss is more common than previously thought.Issue Section:Discoveries
Broad de-regulated U2AF1 splicing is prognostic and augments leukemic transformation via protein arginine methyltransferase activation
Authors: Venkatasubramanian Meenakshi , Schwartz Leya , Ramachandra Nandini , Bennett Joshua , Subramanian Krithika R. , Chen Xiaoting , Gordon-Mitchell Shanisha , Fromowitz Ariel , Pradhan Kith , Shechter David , Sahu Srabani , Heiser Diane , Scherle Peggy , Chetal Kashish , Kulkarni Aishwarya , Myers Kasiani C. , Weirauch Matthew T. , Grimes H. Leighton , Starczynowski Daniel T. , Verma Amit , Salomonis Nathan 
Published: February 2024

ABSTRACTThe role of splicing dysregulation in cancer is underscored by splicing factor mutations; however, its impact in the absence of such rare mutations is poorly understood. To reveal complex patient subtypes and putative regulators of pathogenic splicing in Acute Myeloid Leukemia (AML), we developed a new approach called OncoSplice. Among diverse new subtypes, OncoSplice identified a biphasic poor prognosis signature that partially phenocopiesU2AF1-mutant splicing, impacting thousands of genes in over 40% of adult and pediatric AML cases.U2AF1-like splicing co-opted a healthy circadian splicing program, was stable over time and induced a leukemia stem cell (LSC) program. Pharmacological inhibition of the implicatedU2AF1-like splicing regulator, PRMT5, rescued leukemia mis-splicing and inhibited leukemic cell growth. Genetic deletion of IRAK4, a common target ofU2AF1-like and PRMT5 treated cells, blocked leukemia development in xenograft models and induced differentiation. These analyses reveal a new prognostic alternative-splicing mechanism in malignancy, independent of splicing-factor mutations.Statement of significanceUsing a new in silico strategy we reveal counteracting determinants of patient survival in Acute Myeloid Leukemia that co-opt well-defined mutation-dependent splicing programs. Broad poor-prognosis splicing and leukemia stem cell survival could be rescued through pharmacological inhibition (PRMT5) or target deletion (IRAK4), opening the door for new precision therapies.Competing InterestsConflict-of-interest disclosure: DTS. serves on the scientific advisory board at Kurome Therapeutics; is a consultant for and/or received funding from Kurome Therapeutics, Captor Therapeutics, Treeline Biosciences, and Tolero Therapeutics; and has equity in Kurome Therapeutics. AV has received research funding from GlaxoSmithKline, BMS, Jannsen, Incyte, MedPacto, Celgene, Novartis, Curis, Prelude and Eli Lilly and Company, has received compensation as a scientific advisor to Novartis, Stelexis Therapeutics, Acceleron Pharma, and Celgene, and has equity ownership in Throws Exception and Stelexis Therapeutics.