bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexplained Distal Obstructive Biliary Dilatation
Authors: Zhu Yong , Jin Hailin , Mao Yingfan , Chen Jun , Qiu Yudong , Wang Zhongqiu , He Jian 
Published: September 2021

Background:
The aim was to compare the differences of clinical-radiologic characteristics between malignant and benign causes of patients with unexplained distal obstructive biliary dilatation and to develop a logistic regression model (nomogram) based on those features to predict malignant causes preoperatively.

Patients and Methods:
Clinical-radiologic characteristics of 133 patients with unexplained distal obstructive biliary dilatation were analyzed. Multivariate logistic regression analysis was performed to construct a nomogram to predict malignant causes preoperatively. The developed nomograms were externally validated by assessing their predictive accuracy in an independent set of 90 patients.

Results:
Intrahepatic bile duct diameter, enlarged gallbladder, direct bilirubin, and carbohydrate antigen19-9 differed significantly between malignant and benign group. In the training set, the logistic regression model showed the discrimination between benign and malignant causes of distal obstructive biliary dilatation with an area under the curve of 0.965, an accuracy of 0.904, a sensitivity of 0.886, a specificity of 0.913. In the validation set, the model showed an area under the curve of 0.851, an accuracy of 0.837, a sensitivity of 0.897, a specificity of 0.750.

Conclusions:
Preoperative clinical-radiologic characteristics differed significantly between malignant and benign group. Nomogram based on those features performed well in predicting the malignant causes of patients with unexplained distal obstructive biliary dilatation.
Dental Therapists in the United States
Authors: Mertz Elizabeth , Kottek Aubri , Werts Miranda , Langelier Margaret , Surdu Simona , Moore Jean 
Published: September 2021

Background:
Dental therapists (DTs) are primary care dental providers, used globally, and were introduced in the United States (US) in 2005. DTs have now been adopted in 13 states and several Tribal nations.

Objectives:
The objective of this study is to qualitatively examine the drivers and outcomes of the US dental therapy movement through a health equity lens, including community engagement, implementation and dissemination, and access to oral health care.

Methods:
The study compiled a comprehensive document library on the dental therapy movement including literature, grant documents, media and press, and gray literature. Key stakeholder interviews were conducted across the spectrum of engagement in the movement. Dedoose software was used for qualitative coding. Themes were assessed within a holistic model of oral health equity.

Findings:
Health equity is a driving force for dental therapy adoption. Community engagement has been evident in diverse statewide coalitions. National accreditation standards for education programs that can be deployed in 3 years without an advanced degree reduces educational barriers for improving workforce diversity. Safe, high-quality care, improvements in access, and patient acceptability have been well documented for DTs in practice.

Conclusion:
Having firmly taken root politically, the impact of the dental therapy movement in the US, and the long-term health impacts, will depend on the path of implementation and a sustained commitment to the health equity principle.
Catch it before it breaks!: managing metabolic bone disease of prematurity
Authors: Kehinde Folasade , Marinescu Andreea , Turchi Renee 
Published: September 2021

Purpose of review
Metabolic bone disease of prematurity, commonly referred to as osteopenia of prematurity, remains prevalent in the neonatal intensive care unit (NICU) despite recent medical advances. It is estimated that up to 60% of extreme low birth weight and 20% of very low-birth-weight infants have metabolic bone disease of prematurity. Often silent, it typically presents with poor growth, increased ventilator dependency and fractures. Clinical sequalae, such as short stature can extend into young adulthood. There is no universal consensus by neonatal intensive care unit clinicians on the screening, diagnosis, or treatment for metabolic bone disease of prematurity. The disease is often diagnosed late by radiographs or incidentally in this highly fragile population.

Recent findings
Suggest screening using DEXA (dual-energy X-ray absorptiometry) scans or ultrasound, in combination with serum markers like alkaline phosphatase, phosphorous levels, parathyroid hormone, and tubular reabsorption of phosphate, might identify at-risk babies earlier. The use of protocol-based screenings may aid in early diagnosis.

Summary
We present a review of the risk factors, recent screening methods, diagnosis and management of this prevalent, clinically relevant diagnosis, as well as propose a protocol for the early screening and management of this silent disease.
Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment
Authors: Rendeiro André F. , Vorkas Charles Kyriakos , Krumsiek Jan , Singh Harjot , Kapatia Shashi , Cappelli Luca Vincenzo , Cacciapuoti Maria Teresa , Inghirami Giorgio , Elemento Olivier , Salvatore Mirella 
Published: September 2021

AbstractDeep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host’s response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.
Deep sampling of ancestral genetic diversity reveals Saccharomyces cerevisiae pre-domestication life histories
Authors: Lee Tracy J. , Liu Yu-Ching , Liu Wei-An , Lin Yu-Fei , Lee Hsin-Han , Ke Huei-Mien , Huang Jen-Pen , Lu Mei-Yeh Jade , Hsieh Chia-Lun , Chung Kuo-Fang , Liti Gianni , Tsai Isheng Jason 
Published: September 2021

AbstractThe ecology and genetic diversity of model yeast Saccharomyces cerevisiae prior to human domestication remain poorly understood. Taiwan is regarded as part of this yeast’s geographic birthplace where the most divergent natural lineage was discovered. Here, we deep sampled the broad-leaf forests across this continental island to probe the ancestral species diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages, the highest known in any region. Three lineages are endemic to Taiwan and six are widespread in Asia. Molecular dating placed the divergence of the Taiwanese and Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Extensive historical and recent admixture events were detected between natural lineages. In particular, the genetic component from a lineage associated with fruits that spanned the widest geographical range was present in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We detected prevalent purifying selection genome-wide, with lineage-specific signals of positive or directional selection independent between lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.
An individualized fMRI protocol to assess semantic congruency effects on episodic memory in an aging multilingual population
Authors: Perquin Magali , Viswanathan Shivakumar , Vaillant Michel , Risius Okka , Huiart Laetitia , Schmit Jean-Claude , Diederich Nico J. , Fink Gereon R. , Kukolja Juraj 
Published: September 2021

AbstractThe cognitive stimulation induced by multilingualism may slow down age-related memory impairment. However, a suitable neuroscientific framework to assess the influence of multilingualism on age-related memory processes is missing. We propose an experimental paradigm that assesses the effects of semantic congruency on episodic memory using functional magnetic resonance imaging (fMRI). To this end, we modified the picture-word interference (PWI) task to be suitable for the assessment of older multilingual subjects undergoing functional magnetic resonance imaging (fMRI). In particular, stimulus materials were prepared in multiple languages (French, German, Luxembourgish, English) and closely matched in semantic properties, thus enabling participants to perform the experiment in a language of their choice. This paradigm was validated in a group (n = 62) of healthy, older participants (over 64 years) who were multilingual, all practicing three or more languages. Consistent with the engagement of semantic congruency processes, we found that the encoding and recognition of semantically related vs. unrelated picture-word pairs evoked robust differences in behavior and the neural activity of parietal-temporal networks. These effects were negligibly modulated by the language used to perform the task. Based on this validation in a multilingual population, we conclude that the proposed paradigm will allow future studies to evaluate whether multilingualism aptitude engages neural systems in a manner that protects long-term memory from aging-related decline.
Unraveling the intracellular cross-talk governing the balance between TNFαmediated survival and apoptosis signaling
Authors: Biswas Sharmila , Tikader Baishakhi , Kar Sandip , Viswanathan Ganesh 
Published: September 2021

AbstractTumor necrosis factor alpha (TNFα), a pleiotropic cytokine, helps maintain a balance between proliferation and apoptosis in normal cells. This balance is often sacrificed in a diseased cell, such as that of a cancer, by preferring survival phenotype over apoptosis. Restoring this balance requires a detailed understanding of the causal intracellular mechanisms that govern TNFαstimulated apoptotic response. In this study, we use a systems biology approach to unravel the interplay between the intracellular signaling markers that orchestrate apoptosis levels. Our approach deciphered the synergism between the early intracellular markers phosphorylated JNK (pJNK) and phosphorylated AKT (pAKT) that modulate the activation of Caspase3, an important apoptotic regulator. We demonstrate that this synergism depends critically on the survival pathway signaling mediated by NFκB which plays a dominant role in controlling the extent of the overall apoptotic response. By systematic inhibition of the signaling markers, we establish that the dynamic cross-talk between the pJNK and pAKT transients directs the apoptosis phenotype via accumulated Caspase3 response. Interestingly, superposition of the semi-quantitative correlation between apoptosis and Caspase3 transient levels on the proposed TNFαnetwork model permits quantification of the dynamic apoptotic response under different stimulation conditions. Thus, the predictive model can be leveraged towards arriving at useful insights that can identify potential targeted therapeutic strategies for altering apoptotic response.
Supervised Promoter Recognition: A benchmark framework
Authors: Perez Martell Raul Ivan , Ziesel Alison , Jabbari Hosna , Stege Ulrike 
Published: September 2021

AbstractDeep learning has become a prevalent method in identifying genomic regulatory sequences such as promoters. In a number of recent papers, the performance of deep learning models have continually been reported as an improvement over alternatives for sequence-based promoter recognition. However, the performance improvements in these models do not account for the different datasets that models are being evaluated on. The lack of a consensus dataset and procedure for benchmarking purposes has made the comparison of each model’s true performance difficult to assess.We present a framework called Supervised Promoter Recognition Framework (‘SUPR REF’) capable of streamlining the complete process of training, validating, testing, and comparing promoter recognition models in a systematic manner. SUPR REF includes the creation of biologically relevant benchmark datasets to be used in the evaluation process of deep learning promoter recognition models. We showcase this framework by comparing the models’ performance on alternative datasets, and properly evaluate previously published models on new benchmark datasets. Our results show that the reliability of deep learning ab initio promoter recognition models on eukaryotic genomic sequences is still not at a sufficient level, as precision is severely lacking. Furthermore, given the observational nature of these data, cross-validation results from small datasets need to be interpreted with caution.AvailabilitySource code and documentation of the framework is available online at https://github.com/ivanpmartell/suprref
Identification of a stress-sensitive anorexigenic neurocircuit from medial prefrontal cortex to lateral hypothalamus
Authors: Clarke Rachel E , Voigt Katharina , Reichenbach Alex , Stark Romana , Bharania Urvi , Dempsey Harry , Lockie Sarah H , Mequinion Mathieu , Lemus Moyra , Wei Bowen , Reed Felicia , Rawlinson Sasha , Nunez-Iglesias Juan , Foldi Claire J. , Kravitz Alexxai V. , Verdejo-Garcia Antonio , Andrews Zane B. 
Published: September 2021

AbstractBy modeling neural network dynamics related to homeostatic state and BMI, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans. We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice. In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under non-stressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose-seeking in mice. These studies identify a glutamatergic mPFC-LH as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.
EEG-Based Spectral Analysis Showing Brainwave Changes Related to Modulating Progressive Fatigue During a Prolonged Intermittent Motor Task
Authors: Suviseshamuthu Easter S. , Handiru Vikram Shenoy , Allexandre Didier , Hoxha Armand , Saleh Soha , Yue Guang H. 
Published: September 2021

ABSTRACTRepeatedly performing a submaximal motor task for a prolonged period of time leads to muscle fatigue comprising a central and peripheral component, which demands a gradually increasing effort. However, the brain contribution to the enhancement of effort to cope with progressing fatigue lacks a complete understanding. The intermittent motor tasks (IMTs) closely resemble many activities of daily living (ADL), thus remaining physiologically relevant to study fatigue. The scope of this study is therefore to investigate the EEG-based brain activation patterns in healthy subjects performing IMT until self-perceived exhaustion. Fourteen participants (median age 51.5 years; age range 26-72 years; 5 males) repeated elbow flexion contractions at 40% maximum voluntary contraction by following visual cues displayed on an oscilloscope screen until subjective exhaustion. Each contraction lasted for approximately 5 s with a 2-s rest between trials. The force, EEG, and surface EMG (from elbow joint muscles) data were simultaneously collected. After preprocessing, we selected a subset of trials at the beginning, middle, and end of the study session representing brain activities germane to mild, moderate, and severe fatigue conditions, respectively, to compare and contrast the changes in the EEG time-frequency (TF) characteristics across the conditions. The outcome of channel- and source-level TF analyses reveals that the theta, alpha, and beta power spectral densities vary in proportion to fatigue levels in cortical motor areas. We observed a statistically significant change in the band-specific spectral power in relation to the graded fatigue from both the steady- and post-contraction EEG data. The findings would enhance our understanding on the etiology and physiology of voluntary motor-action-related fatigue and provide pointers to counteract the perception of muscle weakness and lack of motor endurance associated with ADL. The study outcome would help rationalize why certain patients experience exacerbated fatigue while carrying out mundane tasks, evaluate how clinical conditions such as neurological disorders and cancer treatment alter neural mechanisms underlying fatigue in future studies, and develop therapeutic strategies for restoring the patients’ ability to participate in ADL by mitigating the central and muscle fatigue.
The vacuolar iron transporter mediates iron detoxification inToxoplasma gondii
Authors: Aghabi Dana , Sloan Megan , Dou Zhicheng , Guerra Alfredo J. , Harding Clare R. 
Published: September 2021

AbstractIron is essential to living cells, acting as a cofactor in a number of essential enzymes in metabolism; however, iron requires proper storage or it can be dangerous to the cell. In both yeast and plants, iron is stored in a vacuole through the action of a vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including inToxoplasma gondii, a pathogen of medical and veterinary importance. Here, we assess the role of VIT inT. gondii. We show that deletion of VIT causes a slight growth defectin vitro, however leads to hypersensitivity in the presence of excess iron, confirming its essential role in iron detoxification in the parasite. In the absence of VIT, parasites contain less iron and are at a growth disadvantage when moving into an iron-depleted environment. We show parasite VIT expression is regulated by environmental iron levels at both the transcript and protein level, and by altering the distribution of VIT within the cell. In the absence of VIT, we find that theT. gondiiresponds by altering expression of genes with a role in iron metabolism and by increasing the activity of the antioxidant protein catalase. We also show that iron detoxification has an important role both in parasite survival within macrophages and in pathogenesis in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification inT. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.
In vitroFunctional Analysis of pgRNA Sites Regulating Assembly of Hepatitis B Virus
Authors: Patel Nikesh , Clark Sam , Weiß Eva U. , Mata Carlos P. , Bohon Jen , Farquhar Erik R. , Maskell Daniel P. , Ranson Neil A. , Twarock Reidun , Stockley Peter G. 
Published: September 2021

AbstractThe roles of RNA sequence/structure motifs, Packaging Signals (PSs), for regulating assembly of an HBV genome transcript have been investigated in an efficientin vitroassay containing only core protein (Cp) and RNA. Variants of three conserved PSs, within the genome of a strain not used previously, preventing correct presentation of a Cp-recognition loop motif are differentially deleterious for assembly of nucleocapsid-like particles (NCPs). Cryo-electron microscopy reconstruction of theT=4 NCPs formed with the wild-type gRNA transcript, reveal that the interior of the Cp shell is in contact with lower resolution density, potentially encompassing the arginine-rich protein domains and gRNA. Symmetry-relaxation of this reconstruction reveals that such contacts are made at every symmetry axis. We infer from their regulation of assembly that some of these contacts would involve gRNA PSs, and confirmed this by X-ray RNA footprinting. Mutation of the ε stem-loop in the gRNA, where polymerase bindsin vivo, produces a poor RNA assembly substrate with Cp alone, largely due to alterations in its conformation. The results show that RNA PSs regulate assembly of HBV genomic transcriptsin vitro, and therefore may play similar rolesin vivo,in concert with other molecular factors.
Land Use Cover changes in the western escarpment of Rift Valley in the Gamo Zone, Southern Ethiopia
Authors: Dingamo Temesgen , Takele Serekebirhan , Demissew Sebsebe , Woldu Zerihun 
Published: September 2021

AbstractLULC changes are caused by natural and human alterations of the landscape that could largely affect forest biodiversity and the environment. The aim of the study was to analyzed LULC change dynamics in the western escarpment of the rift valley of the Gamo Zone, Southern Ethiopia. Digital satellite images downloaded from USGS were analyzed using ERDAS Imagine (14) and Arc GIS 10.2 software and supervised image classification was used to generate LULC classification, accuracy assessment and Normalized Difference Vegetation Index (NDVI). Drivers of LULC change were identified and analyzed. Four land classes were identified such as forest, farmland, settlement and water-wetland. Settlement and farmlands have increased by 7.83% and 5.88%, respectively. On the other hand, both forest and water bodies and wetland decreased by aerial coverage of 11.03% and 2.68%, respectively. The overall accuracy of the study area was 92.86%, 94.22% and 94.3% with a kappa value of 0.902, 0.92 and 0.922, respectively. NDVI values ranged between -0.42 to 0.73. Agricultural expansion (31.4%), expansion of settlement (25.7%) and Fuelwood collection and Charcoal production (22.9%) were the main driving forces that jeopardize forest biodiversity of the study area. Integrated land use and policy to protect biodiversity loss, forest degradation and climate changes are deemed necessary.