bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequence and 16S rRNA gene amplicon metagenomics of enhanced in-situ reductive dechlorination at a tetrachloroethene-contaminated superfund site
Authors: Reiss Rebecca A. , Guerra Peter A. , Makhnin Oleg , Kellom Matthew 
Published: June 2024

AbstractThe application of environmental DNA analysis techniques to guide the bioremediation strategy for tetrachloroethene-contaminated groundwater is exemplified by the North Railroad Avenue Plume (NRAP) Superfund site located in New Mexico, USA. Enhanced reductive dechlorination (ERD) was selected as the remedy due to the presence of tetrachloroethene biodegradation byproducts, organohalide respiring generaDehalococcoidesandDehalobacter, and associated reductive dehalogenase genes detected prior to remediation. DNA extracted from groundwater samples collected prior to remedy application and after four, 23 and 39 months was subjected to 16SrRNA gene amplicon and whole genome sequencing (WGS). The goals were to compare the potential of these methods as tools for environmental engineers and to highlight how advancements in DNA techniques can be used to understand ERD. The response of the indigenous NRAP microbiome to the injection and recirculation of electron donors and hydrogen sources is consistent with results obtained from microcosms, dechlorinating consortia, and other contaminated sites. WGS detects three times as many phyla and six times as many genera as 16S rRNA gene amplicons. Both techniques reveal abundance changes inDehalococcoidesandDehalobacterthat reflect organohalide form and availability. No methane was detected before remediation, its appearance after biostimulation corresponds to the increase in methanogenicArchaea. Assembly of WGS reads produced scaffolds containing reductive dehalogenase genes fromDehalococcoides,Dehalobacter, Dehalogenimonas, Desulfocarbo,andDesulfobacula. Anaerobic and aerobic cometabolic organohalide degrading microbes that increase in abundance at NRAP include methanogenicArchaea, methanotrophs,Dechloromonas, andXanthobacter, some of which contain hydrolytic dehalogenase genes. Aerobic cometabolism may be supported by oxygen gradients existing at the aquifer-soil interface or by microbes that have the potential to produce O2via chlorite dismutation. Results from next-generation sequencing-based methods are consistent with current hypotheses regarding syntrophy in environmental microbiomes and reveals novel taxa and genes that may contribute to ERD.
Rescuing impaired hippocampal-cortical interactions and spatial reorientation learning and memory during sleep in a mouse model of Alzheimer’s disease using hippocampal 40 Hz stimulation
Authors: Cushing Sarah D. , Moseley Shawn C. , Stimmell Alina C. , Schatschneider Christopher , Wilber Aaron A. 
Published: June 2024

Summary/AbstractIn preclinical Alzheimer’s disease (AD), spatial learning and memory is impaired. We reported similar impairments in 3xTg-AD mice on a virtual maze (VM) spatial-reorientation-task that requires using landmarks to navigate. Hippocampal (HPC)-cortical dysfunction during sleep (important for memory consolidation) is a potential mechanism for memory impairments in AD. We previously found deficits in HPC-cortical coordination during sleep coinciding with VM impairments the next day. Some forms of 40 Hz stimulation seem to clear AD pathology in mice, and improve functional connectivity in AD patients. Thus, we implanted a recording array targeting parietal cortex (PC) and HPC to assess HPC-PC coordination, and an optical fiber targeting HPC for 40 Hz or sham optogenetic stimulation in 3xTg/PVcremice. We assessed PC delta waves (DW) and HPC sharp wave ripples (SWRs). In sham mice, SWR-DW cross-correlations were reduced, similar to 3xTg-AD mice. In 40 Hz mice, this phase-locking was rescued, as was performance on the VM. However, rescued HPC-PC coupling no longer predicted performance as in NonTg animals. Instead, DWs and SWRs independently predicted performance in 40 Hz mice. Thus, 40 Hz stimulation of HPC rescued functional interactions in the HPC-PC network, and rescued impairments in spatial navigation, but did not rescue the correlation between HPC-PC coordination during sleep and learning and memory. Together this pattern of results could inform AD treatment timing by suggesting that despite applying 40 Hz stimulation before significant tau and amyloid aggregation, pathophysiological processes led to brain changes that were not fully reversed even though cognition was recovered.Significance StatementOne of the earliest symptoms of Alzheimer’s disease (AD) is getting lost in space or experiencing deficits in spatial navigation, which involve navigation computations as well as learning and memory. We investigated cross brain region interactions supporting memory formation as a potential causative factor of impaired spatial learning and memory in AD. To assess this relationship between AD pathophysiology, brain changes, and behavioral alterations, we used a targeted approach for clearing amyloid beta and tau to rescue functional interactions in the brain. This research strongly connects brain activity patterns during sleep to tau and amyloid accumulation, and will aid in understanding the mechanisms underlying cognitive dysfunction in AD. Furthermore, the results offer insight for improving early identification and treatment strategies.
Effect of high sensitivity C-Reactive Protein on Uric Acid-related Cardiometabolic Risk in Patients with Coronary Artery Disease— A Large Multicenter Prospective Study
Authors: Song Ying , Cai Weiting , Jiang Lin , Xu Jingjing , Yao Yi , Xu Na , Wang Xiaozeng , Liu Zhenyu , Zhang Zheng , Zhang Yongzhen , Guo Xiaogang , Wang Zhifang , Feng Yingqing , Wang Qingsheng , Li Jianxin , Zhao Xueyan , Chen Jue , Gao Runlin , Song Lei , Han Yaling , Yuan Jinqing 
Published: June 2024

AbstractAimsAlthough serum uric acid (SUA) is a risk factor for cardiometabolic outcome, but it remains unclear which patients with coronary artery disease (CAD) benefit the most from SUA lowering therapy (ULT). The association of SUA level, systemic inflammation and cardiometabolic risk is still unclear. The current study is aimed to examine whether SUA-associated cardiometabolic risk is modulated by systemic inflammation in CAD patients.Methods and ResultsA total of 16,598 CAD patients with baseline high-sensitivity C-Reactive Protein (hsCRP) and SUA available were included. Baseline and follow-up data were collected. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction and stroke. In patients with hsCRP ≥2 mg/L, increasing quintiles of SUA were significantly associated with increased rates of 2-year MACCE (adjusted p < 0.001 for trend, p = 0.037 for interaction). Each unit increase in SUA levels was associated with a 11.3% increased risk of MACCE (adjusted p < 0.001, p = 0.002 for interaction). However, in patients with hsCRP < 2mg/L, increasing quintiles of SUA were not associated with increased MACCE (adjusted p = 0.120).ConclusionElevated SUA levels are related to MACCE when hsCRP levels are 2 mg/L or more but not less than 2mg/L. This finding suggests a potential benefit of combined ULT and anti-inflammation therapy in patients with hyperuricemia and greater systemic inflammation.
Threat-Related Corticocortical Connectivity Elicited by Rapid Auditory Looms
Authors: Ignatiadis Karolina , Barumerli Roberto , Deco Gustavo , Tóth Brigitta , Baumgartner Robert 
Published: June 2024

AbstractWhile sounds of approaching objects are generally more salient than those of receding ones, the traditional association of this auditory looming bias with threat perception is subject to debate. Differences between looming and receding sounds may also be learned through non-threatening multisensory information, or influenced by confounding stimulus characteristics. To investigate, we analyzed corticocortical connectivity patterns from electroencephalography, examining the preferential processing of looming sounds under different attentional states. To simulate rapid distance changes we used complementary distance cues, previously studied in the looming bias literature. Notably, despite the absence of conscious threat perception, we observed crucial involvement of frontal cortical regions typically associated with threat and fear responses. Our findings suggest an underlying bias towards the ventral ‘what’ stream over the dorsal ‘where’ stream in auditory information processing, even when the participants’ task was solely focused on the discrimination of movement direction. These results support the idea, that the perceptual bias towards looming sounds reflects an auditory threat detection mechanism, while offering insights into the neural function involved in processing ecologically relevant environmental cues.
Endemic transmission and international introduction of Monkeypox virus in Southern Brazil between 2022-2023
Authors: Godinho Fernanda Marques , Bermann Thales de Lima , de Oliveira Mayara Mota , Barcellos Regina Bones , Ruivo Amanda Pellenz , de Melo Viviane Horn , Machado dos Santos Franciellen , Bauermann Milena , Selayaran Taina Machado , Soares Taina dos Santos , Sesterheim Patrícia , Baethgen Ludmila Fiorenzano , Da Rocha Fernanda Maria , Amaral Karine Medeiros , Delela Fernanda Crestina Leitenski , Mondini Renata Petzhold , Vizeu Sabrina , Gregianini Tatiana Schäffer , da Veiga Ana Beatriz Gorini , Wallau Gabriel da Luz , Salvato Richard Steiner 
Published: June 2024

AbstractMpox is a zoonotic viral disease caused by the monkeypox virus (MPXV). Human cases have been mainly restricted to the African continent until the worldwide multi-country outbreak unfolded in 2022. We reconstructed epidemiological links of MPXV infections using genomic epidemiology in Rio Grande do Sul State, southern Brazil, during 2022 and 2023. We detected five well-supported clades, three representing local transmission chains that were mostly restricted to the 2022 virus spread, one supported year-long maintenance encompassing samples from 2022 and 2023, and one new importation from Europe in 2023. Our results provide new insights into the geographic extent of community transmission and its association with viral diversity during the more pronounced 2022 mpox upsurge and during the following lower incidence endemic transmission phase. These findings highlight the power of continued genomic surveillance to uncover hidden transmission chains to understand viral dynamics and inform public health responses. The detection of sustained endemic transmission in the state is important to guide targeted control measures to curtail further community and international transmission and highlight the need for strengthening genomic surveillance.
Automatic radiotherapy treatment planning with deep functional reinforcement learning
Authors: Liu Bin , Liu Yu , Li Zhiqian , Xiao Jianghong , Yin Guosheng , Lin Huazhen 
Published: June 2024

AbstractBackground and purposeIntensity-modulated radiation therapy (IMRT) is a crucial radiotherapy technique, often formulated as an optimization problem. However, when the constraints are too tight to provide a feasible solution, human planners resort to relaxing the optimization parameters and re-evaluating until an acceptable solution is obtained. This process is laborious and time-consuming which has prompted attempts to automate radiotherapy through inverse planning studies using reinforcement learning. Unfortunately, these studies face two major limitations. Firstly, a separate sub-network must be designed for each organ, rendering them difficult to apply to patients with an inconsistent number of structures. Secondly, the low signal-to-noise inputs and discrete action space result in low training efficiency. To address these limitations, this study proposes a novel and effective model.MethodsThis study proposes an organ-sharing network calledFunctionalautomatictreatmentPlannIngNetwork (FatPIN), which contains a functional embedding layer to extract curve features of the dose-volume histogram (DVH). It outputs continuous actions that adjust the optimization parameters, thereby automating the radiotherapy planning process.ResultsExperiments were conducted on the cervical cancer dataset and the results show that the FatPIN is feasible and effective in real-world radiotherapy. With automatic iteration, FatPIN gradually increased the PTV dose, while reducing the dose levels of the OARs. Specifically, at step 50, theD95of the PTV reached 51.68 Gy, exceeding the clinical standard of 50.40 Gy, theV30,V40andV50of all OARs were within clinical requirements.ConclusionWe proposed FatPIN to implement automatic radiotherapy treatment planning. Experimental assessments conducted on cases of cervical cancer demonstrate significant improvements in patient metrics facilitated by FatPIN, thus confirming its practical applicability in clinical contexts.
Assessing CT-based Volumetric Analysis via Transfer Learning with MRI and Manual Labels for Idiopathic Normal Pressure Hydrocephalus
Authors: Srikrishna Meera , Seo Woosung , Zettergren Anna , Kern Silke , Cantré Daniel , Gessler Florian , Sotoudeh Houman , Seidlitz Jakob , Bernstock Joshua D. , Wahlund Lars-Olof , Westman Eric , Skoog Ingmar , Virhammar Johan , Fällmar David , Schöll Michael 
Published: June 2024

AbstractBackgroundBrain computed tomography (CT) is an accessible and commonly utilized technique for assessing brain structure. In cases of idiopathic normal pressure hydrocephalus (iNPH), the presence of ventriculomegaly is often neuroradiologically evaluated by visual rating and manually measuring each image. Previously, we have developed and tested a deep-learning-model that utilizes transfer learning from magnetic resonance imaging (MRI) for CT-based intracranial tissue segmentation. Accordingly, herein we aimed to enhance the segmentation of ventricular cerebrospinal fluid (VCSF) in brain CT scans and assess the performance of automated brain CT volumetrics in iNPH patient diagnostics.MethodsThe development of the model used a two-stage approach. Initially, a 2D U-Net model was trained to predict VCSF segmentations from CT scans, using paired MR-VCSF labels from healthy controls. This model was subsequently refined by incorporating manually segmented lateral CT-VCSF labels from iNPH patients, building on the features learned from the initial U-Net model. The training dataset included 734 CT datasets from healthy controls paired with T1-weighted MRI scans from the Gothenburg H70 Birth Cohort Studies and 62 CT scans from iNPH patients at Uppsala University Hospital. To validate the model’s performance across diverse patient populations, external clinical images including scans of 11 iNPH patients from the Universitätsmedizin Rostock, Germany, and 30 iNPH patients from the University of Alabama at Birmingham, United States were used. Further, we obtained three CT-based volumetric measures (CTVMs) related to iNPH.ResultsOur analyses demonstrated strong volumetric correlations (ρ=0.91, p<0.001) between automatically and manually derived CT-VCSF measurements in iNPH patients. The CTVMs exhibited high accuracy in differentiating iNPH patients from controls in external clinical datasets with an AUC of 0.97 and in the Uppsala University Hospital datasets with an AUC of 0.99.DiscussionCTVMs derived through deep learning, show potential for assessing and quantifying morphological features in hydrocephalus. Critically, these measures performed comparably to gold-standard neuroradiology assessments in distinguishing iNPH from healthy controls, even in the presence of intraventricular shunt catheters. Accordingly, such an approach may serve to improve the radiological evaluation of iNPH diagnosis/monitoring (i.e., treatment responses). Since CT is much more widely available than MRI, our results have considerable clinical impact.
The Regular Consumption of a Food Supplement Containing Miraculin Can Contribute to Reducing Biomarkers of Inflammation and Cachexia in Malnourished Patients with Cancer and Taste Disorders: The CLINMIR Pilot Study
Authors: Álvarez-Mercado Ana Isabel , López Plaza Bricia , Plaza-Diaz Julio , Arcos Castellanos Lucía , Ruiz-Ojeda Francisco Javier , Brandimonte-Hernández Marco , Feliú-Batlle Jaime , Hummel Thomas , Palma Milla Samara , Gil Ángel 
Published: June 2024

AbstractBackgroundTaste disorders are common in patients with cancer undergoing systemic therapy, persist during treatment and are associated with reduced food intake, increasing the risk of malnutrition. Cachectic syndrome, which is common in these patients and characterized by marked weight loss, anorexia, asthenia and anemia, is linked to the presence and growth of the tumor and leads to systemic inflammation.Synsepalum dulcificumis a plant whose berries contain miraculin, a glycoprotein that transforms sour tastes into sweet ones and could serve to ameliorate taste disorders in patients with cancer.ObjectiveTo evaluate the effect of the regular intake of Dried Miracle Berries (DMB), a novel food containing miraculin, on several biomarkers of inflammation and cachexia in malnourished patients with cancer and taste disorders receiving systemic antineoplastic therapy.Materials and methodsTriple-blind, randomized, placebo-controlled clinical trial. Thirty-one patients with cancer of various etiologies receiving chemotherapy were enrolled in a pilot study and divided into three groups. The first group received a tablet containing 150 mg of DMB (standard dose); the high-dose group received a tablet of 300 mg of DMB, and the third group received a tablet with 300 mg of the placebo for three months before each main meal. Plasma levels of several molecules associated with inflammation and cancer cachexia were measured using the X-MAP Luminex multiplexing platform.ResultsThe three groups showed a decrease in the plasma levels of IL-6, IL-1β, TNF-α, and PIF throughout the intervention, although the percentage change from baseline was greater in patients receiving a standard dose of DMB. In contrast, the CNTF concentration only decreased in the DMB standard-dose group. This group also presented the greatest reduction in the IL-6/ IL-10 ratio, while IL-15 and IL-10 increased in the groups treated with DMB but not in the placebo. Regardless of DMB consumption, sTNFR-II tended to decrease with treatment in patients who responsed well to the antineoplastic treatment. We did not find significant correlations between cytokines and sensory variables or dietary and nutritional status.ConclusionsThe regular consumption of a standard dose of the food supplement DMB containing miraculin along with a systemic antineoplastic treatment can contribute to reducing biomarkers of inflammation and cachexia in malnourished patients with cancer exhibiting taste disorders.
Epigenetic factors in the 22q11.2 deletion syndrome in relation to stress and schizophrenia
Authors: Jiao Chuan , Demars Fanny , Iftimovici Anton , He Qin , Kebir Oussama , Tripathi Anushree , Turbé Hugo , Demily Caroline , Krebs Marie-Odile , Jay Thérèse M , Chaumette Boris 
Published: June 2024

Abstract22q11.2 deletion syndrome (22q11.2DS) stands out as one of the most significant risk factors for schizophrenia (SCZ), with approximately 40% of individuals with 22q11.2DS experiencing psychosis. The presence of discordant phenotypes among monozygotic twins, along with the involvement of environmental factors in the multiple-hit model hypothesis for psychosis onset, underscores the potential role of epigenetic modifications in the development of neuropsychiatric disorders among individuals with 22q11.2DS. To gain a deeper understanding of the underlying biological mechanisms, we conducted a translational study using three datasets: a genome-wide methylation dataset from peripheral blood of individuals with 22q11.2DS with or without SCZ, a microRNA expression dataset from the same cohort, and a second genome-wide methylation dataset obtained from a mouse model exploring gene-environment interactions. Human recruitment was carried out at a specialized center focusing on rare psychiatric disorders and included one pair of monozygotic twins discordant for SCZ. In the animal model, DNA extraction was performed from the prefrontal cortex among four groups : wild-type and Df(h22q11)/+ mice, with or without exposure to acute stress. This study identified alterations in DNA methylation and microRNA expression linked to the 22q11.2 deletion as well as SCZ within the context of the deletion in humans. The results were then compared to the effects of the corresponding deletion and stress in the mouse model. Notably, four genes (ZBTB20, SHANK3, GRAMD1B, XKR4) overlapped across all comparisons. Pathway analysis evealed epigenetic differences in the Wnt pathway associated with stress and SCZ within the context of the deletion. These findings support the hypothesis that the onset of SCZ in individuals with 22q11.2DS may be influenced by epigenetic mechanisms, both within and outside the implicated region, under the influence of environmental stressors. If replicated, these findings could be used to develop biomarkers for early diagnosis in del22q11 carriers and to explore new targeted therapeutic strategies.