bluuebunny/crossref_metadata_2025_split huggingface dataset:
GWAS of preeclampsia and hypertensive disorders of pregnancy uncovers genes related to cardiometabolic, endothelial and placental function
Authors: Tyrmi Jaakko S. , Kaartokallio Tea , Lokki Inkeri , Jääskeläinen Tiina , Kortelainen Eija , Ruotsalainen Sanni , Karjalainen Juha , Ripatti Samuli ,   FINNPEC Study Group,   FinnGen,   Estonian Biobank Research Team, Laisk Triin , Kettunen Johannes , Pouta Anneli , Kivinen Katja , Kajantie Eero , Heinonen Seppo , Kere Juha , Laivuori Hannele 
Published: May 2022

AbstractPreeclampsia is a vascular pregnancy disorder that affects 3-5% of all pregnancies. Genetic contribution to preeclampsia susceptibility is well established, but the actual risk loci have remained largely unknown. To make further discoveries of the underlying genetic architecture, we performed a new genome-wide association study (GWAS) for maternal preeclampsia and for two other combination phenotypes encompassing maternal preeclampsia and other types of gestational hypertension disorders. We combined the data resources of the Finnish pre-eclampsia cohort ‘FINNPEC’, the Finnish FinnGen project and the Estonian Biobank to obtain cases for the three abovementioned phenotypes. In addition, we performed meta-analyses of the preeclampsia phenotype combining results with the previous largest GWAS results. The controls for each phenotype comprised all parous women in the cohorts not diagnosed with these conditions. In total, we found 18 genome-wide significant associations, of which 12 have not been associated with preeclampsia in any previous maternal GWAS for maternal preeclampsia. Seven of the novel loci were near genes previously associated with blood pressure traits – supporting the concept of pregnancy as a window to future cardiovascular health. The genetic susceptibility to cardiovascular disease may manifest for the first time during pregnancy. Alterations in the integrity of the endothelium or specifically in the glomerular filtration barrier may modify disease susceptibility. Interesting novel associations are in proximity of genes involved in the development of placenta, remodeling of uterine spiral arteries and maintenance of proteostasis in pregnancy serum. Overall, the novel associated genes shed more light on the pathophysiology of preeclampsia.
Decoding Depression Severity from Intracranial Neural Activity
Authors: Xiao Jiayang , Provenza Nicole R. , Asfouri Joseph , Myers John , Mathura Raissa K. , Metzger Brian , Adkinson Joshua A. , Allawala Anusha B. , Pirtle Victoria , Oswalt Denise , Shofty Ben , Robinson Meghan E. , Mathew Sanjay J. , Goodman Wayne K. , Pouratian Nader , Schrater Paul R. , Patel Ankit B. , Tolias Andreas S. , Bijanki Kelly R. , Pitkow Xaq , Sheth Sameer A. 
Published: May 2022

AbstractDisorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis. Here, we used intracranial neural recordings in three patients with severe depression to investigate the neural substrates of this disorder. Across prefrontal regions, we found that reduced depression severity is associated with decreased low-frequency neural activity and increased high-frequency activity. When constraining our model to decode using a single region, spectral changes in the anterior cingulate cortex best predicted depression severity in all three subjects. Relaxing this constraint revealed unique, individual-specific sets of spatio-spectral features predictive of symptom severity, reflecting the heterogeneous nature of depression. The ability to decode depression severity from neural activity increases our fundamental understanding of how depression manifests in the human brain and provides a target neural signature for personalized neuromodulation therapies.
Perturbation of the Gut Microbiome and Association with Outcomes Following Autologous Stem Cell Transplantation in Patients with Multiple Myeloma
Authors: D’Angelo Christopher , Sudakaran Sailendharan , Asimakopoulos Fotis , Hematti Peiman , El-Gamal Dalia , Safdar Nasia , Callander Natalie 
Published: May 2022

ABSTRACTThe gut microbiome is an important feature of host immunity with associations to hematologic malignancies and cellular therapy. We evaluated the gut microbiome and dietary intake in patients with multiple myeloma undergoing autologous stem cell transplantation. Thirty patients were enrolled and samples were collected at 4 timepoints: pre-transplant, engraftment, day +100 (D+100), and 9-12 months post-transplant. Microbiome analysis demonstrated a loss of alpha diversity at the engraftment timepoint driven by decreases in Blautia, Ruminococcus, and Faecalibacterium genera and related to intravenous antibiotic exposure. Higher fiber intake was associated with increased relative abundance of Blautia at the pre-transplant timepoint. Lower alpha diversity at engraftment was associated with a partial response to therapy compared to complete response (CR) or very good partial response (VGPR) (CR/VGPR vs. PR, p <0.05). We conclude that loss of bacterial diversity at engraftment may be associated with impaired response to stem cell transplantation in multiple myeloma.
Barriers to help-seeking for Malaysian women with symptoms of breast cancer: a mixed-methods, two-step cluster analysis
Authors: Rajaram Nadia , Jaganathan Maheswari , Muniandy Kavitha , Rajoo Yamuna , Zainal Hani , Rahim Norlia , Tajudeen Nurul Ain , Zainal Nur Hidayati , Khairy Azuddin Mohd , Abdul Wahab Mohamed Yusof , Teo Soo Hwang 
Published: May 2022

AbstractObjectivesImproving help-seeking behaviour is a key component of down-staging breast cancer and improving survival, but the specific challenges faced by low-income women in an Asian setting remain poorly characterized. Here, we determined the extent of help-seeking delay among Malaysian breast cancer patients and explored sub-groups of women who may face specific barriers.MethodsTime to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks.ResultsThe average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p<0.001). The most reported barrier across clusters was poor knowledge (36.3%), regardless of help-seeking behaviour (p=0.931). Unexpectedly, women with no delay (9 days average) and great delay (259 days average) were more similar to each other than to women with mild delays (58 days average). In contrast, women who experienced great delay reported poor motivation (p=0.066) and social opportunities (p=0.374) to seek help.ConclusionsDown-staging of breast cancer in Malaysia will require a multi-pronged approach aimed at alleviating culturally specific social and emotional barriers, eliminating misinformation, and instilling motivation to seek help for breast health for the women most vulnerable to help-seeking delays.
Evaluation of the ID NOW Among Symptomatic Individuals During the Omicron Wave
Authors: Stokes William , Venner Allison A. , Buss Emily , Tipples Graham , Berenger Byron M. 
Published: May 2022

ABSTRACTBACKGROUNDPoint of Care SARS-CoV-2 devices, such as the Abbott ID NOW have great potential, to help combat the COVID-19 pandemic. Starting in December, 2020, the ID NOW was implemented throughout the province of Alberta, Canada (population 4.4 million) in various settings. We aimed to assess the ID NOW performance during the BA.1 Omicron wave and compare it to previous waves.METHODSThe ID NOW was assessed in two distinct locations among symptomatic individuals: acute care (emergency room, urgent care, and hospitalized patients) and community assessment centres (AC) during the period January 5 – 18, 2022. Starting January 5, Omicron represented >95% of variants detected in our population. For every individual tested, two swabs were collected: one for ID NOW testing and the other for either reverse-transcriptase polymerase chain reaction (RT-PCR) confirmation of negative ID NOW results or for variant testing of positive ID NOW results.RESULTSA total of 3,041 paired samples were analyzed (1,139 RT-PCR positive). 1,873 samples were from 42 COVID-19 AC and 1,168 from 69 rural hospitals. ID NOW sensitivity for symptomatic individuals presenting to community AC and patients in hospital was 96.0% [95% confidence interval (CI) 94.5-97.3%, n=830 RT-PCR positive], and 91.6% (95% CI 87.9-94.4%, n=309 RT-PCR positive), respectively. SARS-CoV 2 positivity rate was very high for both populations (44.3% at AC, 26.5% in hospital).CONCLUSIONSSensitivity of ID NOW SARS-CoV-2, compared to RT-PCR, is very high during the BA.1 Omicron wave, and is significantly higher when compared to previous SARS-CoV-2 variant waves.
Medication Safety Incidents Associated with the Remote Delivery of Primary Care: A Rapid Review
Authors: Gleeson Laura L , Clyne Barbara , Barlow James W. , Ryan Benedict , Murphy Paul , Wallace Emma , De Brún Aoife , Mellon Lisa , Hanratty Marcus , Ennis Mark , Holton Alice , Pate Muriel , Kirke Ciara , Flood Michelle , Moriarty Frank 
Published: May 2022

AbstractBackgroundThe COVID-19 pandemic triggered rapid, fundamental changes in how healthcare is delivered in communities, notably increased remote delivery of primary care. While the impact of these changes on medication safety are not yet fully understood, research conducted before the pandemic may provide evidence for possible consequences. This rapid review examines the published literature on medication safety incidents associated with the remote delivery of primary care.Objective(s)To examine the published literature on medication safety incidents associated with the remote delivery of primary care, with a focus on telemedicine and electronic prescribing.MethodsA rapid review was conducted according to the Cochrane Rapid Reviews Methods Group guidance. An electronic search was carried out on Embase and Medline (via PubMed) using key search terms “medication error”, “electronic prescribing”, “telemedicine” and “primary care”. Identified studies were synthesised narratively; reported medication safety incidents were categorised according to the WHO Conceptual Framework for the International Classification for Patient Safety.ResultsFifteen studies were deemed eligible for inclusion in this review. All fifteen studies reported medication incidents associated with electronic prescribing; no studies were identified that reported medication safety incidents associated with telemedicine. The most commonly reported medication safety incidents were ‘wrong label/instruction’ and ‘wrong dose/strength/frequency’. The frequency of medication safety incidents ranged from 0.89 to 81.98 incidents per 100 electronic prescriptions analysed.ConclusionsTo our knowledge, this is the first review to examine the literature on medication safety incidents associated with the remote delivery of primary care. Common incident types associated with electronic prescriptions were identified. There was wide variation in reported frequencies of medication safety incidents associated with electronic prescriptions. A gap in the literature was identified regarding medication safety incidents associated with telemedicine. Further research is required to determine the impact of the COVID-19 pandemic on medication safety in primary care.
Goat kid recognition of their mothers’ calls is not impacted by changes in source-filter parameters
Authors: Perroux Tania , McElligott Alan G. , Briefer Elodie F. 
Published: May 2022

AbstractFeatures varying more between than within individuals are usually considered as potential cues for individual recognition. According to the source-filter theory of vocal production, the fundamental frequency of mammal’s vocalisations depends on the characteristics of the vocal folds, while formants are determined by the characteristics of the vocal tract. Goat mothers and their kids (Capra hircus) display mutual recognition, and both source-related parameters (F0) and filter-related ones (formants) have been shown to be individualised in their vocalisations. Here, we aimed to identify if these parameters (source-related parameters (F0) and/or filter vocal parameters) are used by goat kids to recognise their mother’s vocalisations. To this aim, we used an algorithm to modify either F0 or formants of the calls of goat mothers to different degrees (within or exceeding the range of natural intra-individual variability), and we played back these modified calls to their kids. We did not observe any difference in the kid reactions to the modified maternal vocalisations and to the natural calls. We suggest that either: (i) fundamental frequency and formants are not involved in maternal recognition in goats; (ii) goat kids have a tolerance for variation when recognising their mother’s calls that exceeds the shifts we performed; (iii) goat maternal recognition is based on other vocal features than those tested here, or (iv) goat kid maternal recognition is based on a combination of different features and might be more flexible than previously thought, such that when one main feature is modified, kids focus on other features.
Succinct k-mer Sets Using Subset Rank Queries on the Spectral Burrows-Wheeler Transform *
Authors: Alanko Jarno N. , Puglisi Simon J. , Vuohtoniemi Jaakko 
Published: May 2022

AbstractThe k-spectrum of a string is the set of all distinct substrings of length k occurring in the string. This is a lossy but computationally convenient representation of the information in the string, with many applications in high-throughput bioinformatics. In this work, we define the notion of the Spectral Burrows-Wheeler Transform (SBWT), which is a sequence of subsets of the alphabet of the string encoding the k-spectrum of the string. The SBWT is a distillation of the ideas found in the BOSS and Wheeler graph data structures. We explore multiple different approaches to index the SBWT for membership queries on the underlying k-spectrum. We identify subset rank queries as the essential subproblem, and propose four succinct index structures to solve it. One of the approaches essentially leads to the known BOSS data structure, while the other three offer attractive time-space trade-offs and support simpler query algorithms that rely only on fast rank queries. The most general approach involves a novel data structure we call the subset wavelet tree, which we find to be of independent interest. All of the approaches are also amendable to entropy compression, which leads to good space bounds on the sizes of the data structures. Using entropy compression, we show that the SBWT can support membership queries on the k-spectrum of a single string in O(k) time and (n + k)(log σ + 1/ ln 2) + o((n + k)σ) bits of space, where n is the number of distinct substrings of length k in the input and σ is the size of the alphabet. This improves from the time O(k log σ) achieved by the BOSS data structure. We show, via experiments on a range of genomic data sets, that the simplicity of our new indexes translates into large performance gains in practice over prior art.
Changes in ProteinN-Glycosylation Regulation Occur in the Human Parkinsonian Brain in a Region-Specific Manner
Authors: Lúcia Rebelo Ana , Drake Richard R. , Marchetti-Deschmann Martina , Saldova Radka , Pandit Abhay 
Published: May 2022

SummaryParkinson’s Disease (PD) associated state of neuroinflammation due to the aggregation of aberrant proteins is widely reported. One type of post-translational modification involved in protein stability is glycosylation. Here, we aimed to characterise the human Parkinsonian nigro-striatalN-glycome, and related transcriptome/proteome, and its correlation with endoplasmic reticulum stress and unfolded protein response (UPR), providing a comprehensive characterisation of the PD molecular signature. Significant changes were seen upon PD: 3% increase in sialylation and 5% increase in fucosylation in both regions, and 2% increase in oligomannosylatedN-glycans in the substantia nigra. In the latter, a decrease in the mRNA expression of sialidases and an upregulation in the UPR pathway were also seen. To show the correlation between these, we also describe anin vitrofunctional study where changes in specific glycosylation trait enzymes (inhibition of sialyltransferases) led to impairments in cell mitochondrial activity, changes in glyco-profile and upregulation in UPR pathways. This complete characterisation of the human nigro-striatalN-glycome provides an insight into the glycomic profile of PD through a transversal approach while combining the other PD “omics” pieces, which can potentially assist in the development of glyco-focused therapeutics.
Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii
Authors: Yin Deqi , Jiang Ning , Cheng Chang , Sang Xiaoyu , Feng Ying , Chen Ran , Chen Qijun 
Published: May 2022

AbstractThe biology of Toxoplasma gondii, the causative pathogen of one of the most wide-spread parasitic diseases remains poorly understood. Lactate, which is derived from glucose metabolic pathways, is considered to be not only an energy source in a variety of organisms including Toxoplasma gondii, but also a regulatory molecule that participates in gene activation and protein functioning. Lysine lactylation is a type of posttranslational modifications (PTMs) that was recently associated with chromatin remodeling, but lysine lactylation of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and found 1964 lactylation sites on 955 proteins in the T. gondii RH strain. The lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and multiple signaling pathways. We also performed chromatin immunoprecipitation sequencing (ChIP-seq) analysis with a lactylation specific antibody, the results revealed that histone H4K12la and H3K14la were enriched in the promoter and exon regions of Toxoplasma gondii genes associated with microtubule-based movement and cell invasion. We further confirmed the de-lactylase activity of histone deacetylase TgHDACs 2, 3, and 4, and that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in the parasites. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissection of the functional biology of Toxoplasma gondii.
Parieto-frontal Oscillations Show Hand Specific Interactions with Top-Down Movement Plans
Authors: Blohm G. , Cheyne D.O. , Crawford J.D. 
Published: May 2022

AbstractTo generate a hand-specific reach plan, the brain must integrate hand-specific signals with the desired movement strategy. Although various neurophysiology / imaging studies have investigated hand-target interactions in simple reach-to-target tasks, the whole-brain timing and distribution of this process remain unclear, especially for more complex, instruction-dependent motor strategies. Previously, we showed that a pro/anti-pointing instruction influences magnetoencephalographic (MEG) signals in frontal cortex that then propagate recurrently through parietal cortex (Blohm et al., 2019). Here, we contrasted left versus right hand pointing in the same task to investigate 1) which cortical regions of interest show hand specificity, and 2) which of those areas interact with the instructed motor plan. Eight bilateral areas – the parietooccipital junction (POJ), superior parietooccipital cortex (SPOC), supramarginal gyrus (SMG), middle / anterior interparietal sulcus (mIPS/aIPS), primary somatosensory / motor cortex (S1/M1), and dorsal premotor cortex (PMd) – showed hand-specific changes in beta band power, with four of these (M1, S1, SMG, aIPS) showing robust activation before movement onset. M1, SMG, SPOC, and aIPS showed significant interactions between contralateral hand specificity and the instructed motor plan, but not with bottom-up target signals. Separate hand / motor signals emerged relatively early and lasted through execution, whereas hand-motor interactions only occurred close to movement onset. Taken together with our previous results, these findings show that instruction-dependent motor plans emerge in frontal cortex and interact recurrently with hand-specific parietofrontal signals before movement onset to produce hand-specific motor behaviors.Impact StatementThe brain must generate different motor signals, depending which hand is used. The distribution and timing of hand use / instructed motor plan integration is not understood at the whole-brain level. Using whole-brain MEG recordings we show that different sub-networks involved in action planning code for hand usage (alpha and beta frequencies) and integrating hand use information into a hand-specific motor plan (beta band). The timing of these signals indicates that frontal cortex first creates a general motor plan and then integrates hand-specific frontoparietal information to produce a hand-specific motor plan.
Mechanosensor Piezo1 Mediates Bimodal Patterns of Intracellular Signaling
Authors: Pan Yijia , Shi Linda Zhixia , Preece Daryl , Gomez-Godinez Veronica , Yoon Chi Woo , Lu Shaoying , Carmona Christopher , Woo Seung-Hyun , Chien Shu , Berns Michael W. , Liu Longwei , Wang Yingxiao 
Published: May 2022

AbstractPiezo1 belongs to mechano-activatable cation channels serving as biological force sensors. However, the molecular events downstream of Piezo1 activation remain unclear. In this study, we used biosensors based on fluorescence resonance energy transfer (FRET) to investigate the dynamic modes of Piezo1-mediated signaling and revealed a bimodal pattern of Piezo1-induced intracellular calcium signaling. Laser-induced shockwaves (LIS) and its associated shear stress can mechanically activate Piezo1 to induce transient intracellular calcium (Ca[i]) elevation, accompanied by an increase in FAK activity. Interestingly, multiple pulses of shockwave stimulation caused a more sustained calcium increase and a decrease of FAK activity. Similarly, tuning the degree of Piezo1 activation by titrating either the dosage of Piezo1 ligand Yoda1 or the expression level of Piezo1, produced a similar bimodal pattern of FAK responses. Specifically, a low degree of Piezo1 activation (transient mode) leads to a transient Ca[i] response with FAK activation, whereas a high degree of Piezo1 activation (sustained mode) causes a sustained Ca[i] response with FAK suppression. Further investigation revealed that SHP2 serves as an intermediate regulator mediating this bimodal pattern in Piezo1 sensing and signaling. These results suggest that the degrees of Piezo1 activation induced by both mechanical LIS and chemical ligand stimulation may determine downstream signaling characteristics.