bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of long-term unmet needs and unmet rehabilitation needs on the quality of life in stroke survivors
Authors: Lee Yookyung , Kim Won-Seok , Chang Won Kee , Jung Yun Sun , Jee Sungju , Ko Sung-Hwa , Sohn Min Kyun , Shin Yong-Il , Bae Hee-Joon , Kim Beom Joon , Kim Jun Yup , Shin Dong-Ick , Yum Kyu Sun , Chae Hee-Yun , Kim Dae-Hyun , Cha Jae-Kwan , Park Man-Seok , Kim Joon-Tae , Choi Kang-Ho , Kang Jihoon , Paik Nam-Jong 
Published: March 2024

AbstractBackgroundUnmet long-term needs and rehabilitation needs are prevalent among stroke survivors and affect their quality of life. We aimed to identify the long-term unmet needs and unmet rehabilitation needs among stroke survivors in South Korea and evaluate their intercorrelations with health-related quality of life.MethodsStroke survivors who were admitted to four Regional Cardiocerebrovascular Disease Centers between January 1, 2015 and December 31, 2019 were telephonically surveyed using a computer-assisted telephone interview method. With the aim of surveying approximately 1,000 patients, 9,204 people were recruited through random sampling. Unmet needs were evaluated on the basis of Longer-term Unmet Needs after Stroke questionnaire items. Quality of life was evaluated using the EuroQoL 5-dimension, 3-level (EQ-5D-3L) questionnaire and the EQ-5D index.ResultsAmong the participants, 93.6% experienced at least one unmet need and 311 (32.6%) reported unmet rehabilitation needs. The number of unmet needs, age, modified Rankin Scale (mRS) score, and previous stroke showed significant negative correlations with the EQ-5D index (p-value < 0.05). The age-adjusted odds ratio (OR) for reporting unmet rehabilitation needs significantly increased with problems in mobility (OR, 4.96; 95% confidence interval [CI], 3.64-6.76), self-care (OR, 4.46; 95% CI, 3.32-5.98), usual activities (OR, 5.78; 95% CI, 4.21-7.93), pain/discomfort (OR, 3.76; 95% CI, 2.76-5.06), anxiety/depression (OR, 3.67; 95% CI, 2.74-4.91), higher mRS score (OR, 3.13; 95% CI, 2.29-4.28), prior hyperlipidemia (OR, 1.35; 95% CI, 1.00-1.81), and number of unmet needs (OR, 1.30; 95% CI, 1.25-1.36).ConclusionsUnmet needs were prevalent among stroke survivors and were associated with a lower quality of life and increased odds of reporting unmet rehabilitation needs. Further research is needed to investigate strategies for addressing these subjective unmet needs with the aim of improving the long-term quality of life of stroke survivors.
Methodological choices matter: A systematic comparison of TMS-EEG studies targeting the primary motor cortex
Authors: Beck Mikkel Malling , Heyl Marieke , Mejer Louise , Vinding Mikkel C. , Christiansen Lasse , Tomasevic Leo , Siebner Hartwig Roman 
Published: March 2024

AbstractBackgroundTranscranial magnetic stimulation (TMS) triggers time-locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS.MethodsHere, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared total cortical activation and specific TEP peaks and components.ResultsReporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and pre-processing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the ’prototypical’ TEP waveform of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude and latencies were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long-latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP amplitudes.ConclusionSome aspects of reporting practices could be improved in TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted.
123FASTQ: an intuitive and efficient tool for preprocessing Illumina FASTQ reads
Authors: Eidi Milad , Abdolalizadeh Samaneh , Nasirpour Mohammad Hossein , Zahiri Javad , Garshasbi Masoud 
Published: March 2024

AbstractNext-generation sequencing (NGS) has revolutionized genetic research, but preprocessing raw sequencing reads remains a crucial step. Existing tools for quality control (QC) and trimming have limitations, leading to fragmented workflows. In this article, we present 123FASTQ, a comprehensive and user-centric software solution that integrates QC analysis, trimming, and format conversion in a userfriendly interface. 123FASTQ combines the advantages of existing tools while addressing their limitations. It offers improved QC analysis with insightful visualizations, semi-automated trimming recommendations based on QC results, and various trimming options. The software also supports different file formats and provides efficient performance. By simplifying NGS data preprocessing, 123FASTQ enables researchers to utilize high-quality reads for downstream analyses. It is cross-platform and freely available athttps://sourceforge.net/projects/project-123ngs/.
HIV-1 Nef synergizes with APOL1-G1 to induce nephrocyte cell death in aDrosophilamodel of HIV-related kidney diseases
Authors: Zhu Jun-yi , Fu Yulong , van de Leemput Joyce , Yu Jing , Li Jinliang , Ray Patricio E. , Han Zhe 
Published: March 2024

ABSTRACTBackgroundPeople carrying twoAPOL1risk alleles (RA)G1orG2are at greater risk of developing HIV-associated nephropathy (HIVAN). Studies in transgenic mice showed that the expression of HIV-1 genes in podocytes, andnefin particular, led to HIVAN. However, it remains unclear whether APOL1-RA and HIV-1 Nef interact to induce podocyte cell death.MethodWe generated transgenic (Tg) flies that expressAPOL1-G1(derived from a child with HIVAN) and HIV-1nefspecifically in the nephrocytes, the fly equivalent of mammalian podocytes, and assessed their individual and combined effects on the nephrocyte filtration structure and function.ResultsWe found that HIV-1 Nef acts in synergy with APOL1-G1 resulting in nephrocyte structural and functional defects. Specifically, HIV-1 Nef itself can induce endoplasmic reticulum (ER) stress without affecting autophagy. Furthermore, Nef exacerbates the organelle acidification defects and autophagy reduction induced by APOL1-G1. The synergy between HIV-1 Nef and APOL1-G1 is built on their joint effects on elevating ER stress, triggering nephrocyte dysfunction and ultimately cell death.ConclusionsUsing a newDrosophilamodel of HIV-1-related kidney diseases, we identified ER stress as the converging point for the synergy between HIV-1 Nef and APOL1-G1 in inducing nephrocyte cell death. Given the high relevance betweenDrosophilanephrocytes and human podocytes, this finding suggests ER stress as a new therapeutic target for HIV-1 and APOL1-associated nephropathies.HIGHLIGHTSA new transgenicDrosophilamodel to study the pathogenesis of HIV-1-related kidney diseases with nephrocyte-specific expression of HIV-1nefand anAPOL1-G1risk allele derived from a patient with HIVAN.APOL1-G1 caused organelle acidification defects, reduced formation of autophagolysosomes, and reduced autophagy and protein aggregation, which culminated in ER stress.HIV-1 Nef induced ER stress through an autophagy-independent pathway. Furthermore, Nef and APOL1-G1 acted synergistically to heighten ER stress, which resulted in nephrocyte dysfunction and cell death.SIGNIFICANCE STATEMENTAPOL1risk alleles are strongly linked to HIV-associated nephropathy (HIVAN) in people of African descent, but how HIV-1 and APOL1 interact and which pathways they might converge upon is unclear. A newDrosophilamodel to study HIV-1 Nef and APOL1-G1 (a risk allele) showed that Nef can induce ER stress in nephrocytes by itself, as well as exacerbate the organelle acidification defects and reduced autophagy induced by APOL1-G1, which further stimulates ER stress to a level that could cause nephrocyte cell death. Thus, we identified ER stress as the converging point for the synergy between APOL1-G1 and HIV-1 Nef in kidney cells, providing a potential therapeutic target for HIV-1 and APOL1-associated nephropathies.
LPOR and the membranes – evolutionary pathway towards prolamellar body formation
Authors: Ogrodzińska Wiktoria , Szafran Katarzyna , Łuszczyński Mateusz , Woźnicka Olga , Gabruk Michał 
Published: March 2024

AbstractLight-dependent protochlorophyllide oxidoreductase (LPOR) has captivated the interest of the research community for decades. One reason is the photocatalytic nature of the reaction catalyzed by the enzyme, and the other is the involvement of LPOR in the formation of a paracrystalline lattice called a prolamellar body (PLB) that disintegrates upon illumination, initiating a process of photosynthetic membrane formation.In this paper, we have integrated three traditional methods previously employed to study the properties of the enzyme to investigate how LPOR evolved and how PLB forms. We found that in cyanobacteria, LPOR activity appears to be independent of lipids, with membrane interaction primarily affecting the enzyme post-reaction, with MGDG and PG having opposite effects on SynPOR. In contrast, plant isoforms exhibit sequence alterations, rendering the enzyme effective in substrate binding mainly in the presence of anionic lipids, depending on residues at positions 122, 312, and 318. Moreover, we demonstrated that the interaction with MGDG could initially serve as enhancement of the substrate specificity towards monovinyl-protochlorophyllide (Pchlide). We have shown that the second LPOR isoforms of eudicots and monocots accumulated mutations that made these variants less and more dependent on anionic lipids, respectively. Finally, we have shown that in the presence of Pchlide, NADP+, and the lipids, plant but not cyanobacterial LPOR homolog remodel membranes into the cubic phase. The cubic phase is preserved if samples supplemented with NADP+ are enriched with NADPH.The results are discussed in the evolutionary context, and the model of PLB formation is presented.SignificanceLPOR is a unique enzyme with photocatalytic properties, developed by cyanobacteria and inherited by algae and plants. In this study, we investigated the properties of the cyanobacterial homolog, revealing that two lipids, PG and MGDG, have opposite effects on enzyme activity. Additionally, we identified mutations in plant isoforms that render the enzyme dependent on anionic lipids. Moreover, we demonstrated that in the presence of NADP+, the plant homolog remodels lipids into a cubic phase, which appears to be the initial step of prolamellar body (PLB) formation. PLB is a unique paracrystalline arrangement of lipids and proteins found in immature chloroplasts, which disintegrates upon illumination, initiating photosynthetic membrane formation.
Neuronal substance-P drives breast cancer growth and metastasisviaan extracellular RNA-TLR7 axis
Authors: Padmanaban Veena , Keller Isabel , Seltzer Ethan S. , Ostendorf Benjamin N. , Kerner Zachary , Tavazoie Sohail F. 
Published: March 2024

ABSTRACTIncreased tumour innervation is associated with adverse survival outcomes in multiple cancers1–4. To better understand the mechanisms underlying this, we studied the impact of innervation on breast cancer metastatic progression. Metastatic mammary tumours of mice were substantially more innervated than non-metastatic isogenic tumours. Three dimensional co-cultures andin vivomodels revealed that sensory dorsal root ganglion (DRG) neurons enhanced the growth, invasion, and systemic dissemination of cancer cells—thereby driving breast cancer metastasis. Byin vitroscreening of neuropeptides known to be secreted by DRG neurons, we identified substance-P (SP) as a mediator of these pro-metastatic functions. Neuronal SP signaled through tumoural tachykinin receptors (TACR1) to drive single-stranded RNA (ssRNA) secretion from cancer cells. Extracellular RNA acted on tumoural TLR7 receptors to activate an autocrine pro-metastatic gene expression program. In support of these findings, patient tumours with increased SP expression exhibited higher rates of lymph node metastasis. Additionally, this SP/ssRNA inducedTlr7gene expression signature associated with reduced breast cancer survival outcomes in two independent patient cohorts. Finally, therapeutic targeting of this neuro-cancer axis with the TACR1 antagonist aprepitant, an approved anti-nausea drug, suppressed breast cancer metastasis in multiple mouse models. Our findings reveal multiple aspects of metastatic progression to be regulated by neurons via a therapeutically targetable neuropeptide/extracellular RNA sensing axis.
Complications and treatment of hypercalciuria in patients affected by Familial Hyperkalemic Hypertension (FHHt)
Authors: D’Ambrosio Viola , Wan Elizabeth R , Hawkins-van der Cingel Gerlineke , Siew Keith , McKnight Olivia , Ferraro Pietro Manuel , Walsh Stephen B 
Published: March 2024

AbstractBackground and hypothesisGordon syndrome (also pseudohypoaldosteronism type II (PHAII) or Familial Hyperkalemia with Hypertension (FHHt)) is a genetic condition characterised by hypertension, hyperkalaemia, hyperchloraemic metabolic acidosis and hypercalciuria caused by an activation of the thiazide-sensitive sodium-chloride cotransporter (NCC, encoded bySLC12A3) in the distal convoluted tubule of the kidney. Thiazides rescue the electrolyte and metabolic abnormalities however, it is not known whether they decrease urinary calcium excretion, nephrolithiasis and low bone mineral density.MethodsWe examined a cohort of 11 patients with genetically confirmed FHHt. Biochemical, radiological, and clinical data was obtained in patients before and after thiazide treatment. All patients gave informed consent.ResultsAmong the FHHt cohort 5 of the 11 patients were female. 7 patients had heterozygous pathogenic variants inKLHL3, 3 patients had variants inWNK4, and one had a variant inWNK1. At baseline, only 1 patient was hypertensive, all patients were hyperkalemic, whereas only 40% of patients had low serum bicarbonate and increased urinary calcium excretion. 50% of patients also had low bone mineral density (either osteopenia or osteoporosis) and 1 patient had bilateral nephrolithiasis. 6 patients were treated with thiazide diuretic and therefore were suitable for comparison between pre and post treatment biochemistry and imaging data.While both serum and urinary biochemistry was completely reverted after thiazide treatment, bone mineral density had a worsening trend. 1 patient presented with bilateral nephrolithiasis after thiazide treatment.ConclusionWe demonstrate that thiazide treatment normalizes serum and urinary biochemistry. Thiazide treatment therefore has clinical utility even if hypertension or hyperkalaemia are not problematic. According to our study, thiazide treatment does not seem to revert loss of bone mineral density, however, whether thiazides have an impact in nephrolithiasis is less clear and our results may require larger samples.
Structure-aware protein sequence alignment using contrastive learning
Authors: You Ronghui , Yi Yuhao , Zhu Shanfeng 
Published: March 2024

AbstractProtein alignment is a critical process in bioinformatics and molecular biology. Despite structure-based alignment methods being able to achieve desirable performance, only a very small number of structures are available among the vast of known protein sequences. Therefore, developing an efficient and effective sequence-based protein alignment method is of significant importance. In this study, we propose CLAlign, which is a structure-aware sequence-based protein alignment method by using contrastive learning. Experimental results show that CLAlign outperforms the state-of-the-art methods by at least 12.5% and 24.5% on two common benchmarks, Malidup and Malisam.
RNAinformer: Generative RNA Design With Tertiary Interactions
Authors: Patil Sharat , Runge Frederic , Franke Jörg K.H. , Hutter Frank 
Published: March 2024

AbstractThe function of an RNA molecule depends on its structure and a strong structure-to-function relationship is already achieved on the secondary structure level of RNA. Therefore, the secondary structure based design of RNAs is one of the major challenges in computational biology. A common approach to RNA design is inverse RNA folding. However, existing RNA design methods cannot invert all folding algorithms because they cannot represent all types of base interactions. In this work, we propose RNAinformer, a novel generative transformer based approach to the inverse RNA folding problem. Leveraging axial-attention, we directly model the secondary structure input represented as an adjacency matrix in a 2D latent space, which allows us to invert all existing secondary structure prediction algorithms. Consequently, RNAinformer is the first model capable of designing RNAs from secondary structures with all base interactions, including non-canonical base pairs and tertiary interactions like pseudoknots and base multiplets. We demonstrate RNAinformer’s state-of-the-art performance across different RNA design benchmarks and showcase its novelty by inverting different RNA secondary structure prediction algorithms.
Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system
Authors: Zhang Laixing , Wang Hao , Zeng Jianwei , Cao Xueli , Gao Zhengyu , Liu Zihe , Li Feixue , Wang Jiawei , Zhang Yi , Yang Maojun , Feng Yue 
Published: March 2024

AbstractCRISPR-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements, which function in three stages: adaptation, expression and interference. Interestingly, phages were also found to encode CRISPR-Cas systems to antagonize their hosts and establish infection. TheVibrio cholerae-infecting ICP1 phage was the first discovered phage with a functional CRISPR-Cas system against an antiphage region in the host genome. Nevertheless, this system lacks a domain essential for recruitment of helicase-nuclease Cas2/3 during target DNA cleavage, and how this system accomplishes the interference stage remains unknown. Here, surprisingly, we found that Cas1, a highly conserved component known to exclusively work in the adaptation stage, also mediates the interference stage through connecting Cas2/3 to the DNA bound-Cascade (Csy) complex of the ICP1 CRISPR-Cas system. A series of structures of Csy, Csy-dsDNA, Cas1-Cas2/3 and Csy-dsDNA-Cas1-Cas2/3 complexes collectively reveal the whole process of Cas1-mediated target DNA cleavage by the ICP1 CRISPR-Cas system. Together, these data support an unprecedented model in which Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system and also shed light on a unique model of primed adaptation.
GutEggerthella lentapromotes the efficacy of resveratrol through reductive metabolism
Authors: Dong Zhixiang , Yu Peijun , Zhou Hui , Li Rui , Sun Qiang , Yang Yunpeng , Gu Yang , Jiang Weihong 
Published: March 2024

AbstractResveratrol (RSV) is a plant-derived natural product with diverse biological activities. It has attracted considerable attention for its notable efficacy in nutritional health and disease treatment. The physiological impact of RSV in the human body is closely connected to the gut microbiota; however, the primary gut microorganisms responsible for RSV metabolism and the underlying mechanisms remain unclear. Here, based on theex vivoculturing of the gut microbiota from human feces, we isolated a bacterium capable of efficiently metabolizing RSV, namelyEggerthella lentaJ01. Through the induced enrichment transcriptomics and bioinformatic analyses, we further identified a resveratrol reductase (RER) fromE. lentaJ01, which specifically catalyzes the hydrogenation of the C9–C10 double bond of RSV and initiates RSV’s in vivo metabolism. RER and its homologs represent a novel class of ene-reductases. The abundance of RER in the gut microbiota of healthy individuals was significantly higher than that in patients with inflammatory bowel disease, suggesting its crucial physiological function. Cell culture experiments and animal studies showed that dihydroresveratrol (DHR), a metabolite of RSV catalyzed by RER, exhibited stronger biological activity in inhibiting the growth of colon cancer cells and alleviating symptoms of enteritis in mouse models. Our results expand the understanding of gut microbial metabolism of RSV and its medicinal functions, providing possible guidance for optimizing RSV bioavailability in the human body.
Stromal DUF760-1 and DUF760-2 proteins are degraded by the chloroplast Clp protease system but have very different half-lives
Authors: Yuan Bingjian , van Wijk Klaas J. 
Published: March 2024

ABSTRACTThe chloroplast AAA+ chaperone CLPC1 aids to select, unfold and deliver hundreds of proteins to the stromal CLP protease core complex for degradation. Throughin vivoCLPC1 trapping we previously identified dozens of trapped proteins that are substrate adaptors (e.g.CLPS1 and CLPF), other chaperones (CLPC2 and CLPD) or (potential) substrates (e.g.RH3) for the CLP chaperone-protease system. Here we show that two of these highly trapped proteins, DUF760-1 and DUF760-2, are substrates for the chloroplast CLP protease system.In plantaBiFC and yeast-2-hybrid analyses show that both DUF760 proteins can directly interact with the N-domain of CLPC1. Immunoblotting and confocal microscopy analysis demonstrates that both DUF760 proteins are highly enriched inclpc1-1andclpr2-1loss-of function mutants.In vivocycloheximide chase assays in different genetic backgrounds show that DUF760-1 and 2 are both degraded by the chloroplast CLP protease. The half-life of DUF760-1 is 4-6 hours, whereas DUF760-2 is so unstable that it is very hard to detect unless degradation is inhibited in CLP loss-of-function alleles. Null mutants for DUF760-1 and DUF760-2 show weak but differential pigment phenotypes and differential sensitivity of protein translation inhibitors. The functions of these DUF760 proteins are unknown; the lack of shared mRNA co-expressors and the large difference in half-life and protein abundance, suggest that they play different roles within the chloroplast. Taken together, our results demonstrate that DUF760-1 and 2 are newly discovered substrates of CLP chaperone-protease system.