bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipose tissue insulin resistance exacerbates liver inflammation and fibrosis in a diet-induced NASH model
Authors: Hosokawa Yusei , Hosooka Tetsuya , Imamori Makoto , Yamaguchi Kanji , Itoh Yoshito , Ogawa Wataru 
Published: May 2023

Background:
Insulin regulates various biological processes in adipocytes, and adipose tissue dysfunction due to insulin resistance in this tissue plays a central role in the development of metabolic diseases, including NAFLD and NASH. However, the combined impact of adipose tissue insulin resistance and dietary factors on the pathogenesis of NAFLD-NASH has remained unknown.

Methods and Results:
3′-phosphoinositide–dependent kinase 1 (PDK1) is a serine-threonine protein kinase that mediates the metabolic actions of insulin. We recently showed that adipocyte-specific PDK1 knockout (A-PDK1KO) mice maintained on normal chow exhibit metabolic disorders, including progressive liver disease leading to NASH, in addition to reduced adipose tissue mass. We here show that maintenance of A-PDK1KO mice on the Gubra amylin NASH (GAN) diet rich in saturated fat, cholesterol, and fructose exacerbates inflammation and fibrosis in the liver. Consistent with these histological findings, RNA-sequencing analysis of the liver showed that the expression of genes related to inflammation and fibrosis was additively upregulated by adipocyte-specific PDK1 ablation and the GAN diet. Of note, the reduced adipose tissue mass of A-PDK1KO mice was not affected by the GAN diet. Our results thus indicate that adipose tissue insulin resistance and the GAN diet additively promote inflammation and fibrosis in the liver of mice.

Conclusions:
A-PDK1KO mice fed with the GAN diet, constitute a new mouse model for studies of the pathogenesis of NAFLD-NASH, especially that in lean individuals, as well as for the development of potential therapeutic strategies for this disease.
An Educational Intervention to Enhance the Performance of Peer Feedback
Authors: Haverhals Amanda 
Published: May 2023

OBJECTIVE
Offering peer feedback on a routine basis may improve nursing, patient, and organizational outcomes by addressing potentially problematic issues before they occur.

BACKGROUND
There is limited literature of specific feedback processes, although national agencies support peer feedback as a professional responsibility.

METHODS
An educational tool was used to train nurses on defining what constitutes professional peer review, reviewing ethical and professional standards, and evaluating the types of peer feedback supported by the literature along with suggestions to use when giving and receiving peer feedback.

RESULTS
The Beliefs about Peer Feedback Questionnaire was used to evaluate the nurses' perceived value and confidence when giving and receiving peer feedback before and after the implementation of the educational tool. The nonparametric Wilcoxon signed rank test demonstrated overall improvement.

CONCLUSIONS
When peer feedback educational tools were available to nurses and the environment supports professional peer review, there was a significant improvement in the level of comfort when giving and receiving peer feedback, along with increased perceived value of peer feedback given and received.
Assessing the Impact of a New Pediatric Healthcare Facility on Medication Administration
Authors: Godin Margaret R. , Nasr Annette S. 
Published: May 2023

OBJECTIVE
This observational descriptive study was designed to measure the effect a new evidence-based design (EBD) hospital has on pediatric medication safety.

BACKGROUND
Medication safety is a priority for nurse leaders. Controlling system design by increasing the understanding of the impact human factors have could improve medication delivery.

METHODS
Medication administration data from 2 studies conducted at the same hospital, 1 at an older facility in 2015 and the other at a new EBD facility in 2019, were compared using a similar research design.

RESULTS
Results indicate that rates of distractions per 100 drug administrations were all statistically significant, favoring the 2015 data regardless of the EBD. No statistically significant differences were observed in error rates of any type when comparing the data collected in the older facility versus the newer EBD facility.

CONCLUSION
This study demonstrated that EBD alone does not ensure the absence of medication errors. By comparing 2 data sets, unanticipated associations were found that could impact safety. Despite the new facility's contemporary design, distractions persisted that could inform nurse leaders in developing interventions to support a safer patient care environment using a human factors approach.
Clinically Important Pharmacologic Considerations for Wide-Awake Local Anesthesia No Tourniquet Hand Surgery
Authors: Janes Lindsay , Sepehripour Sarvnaz , Lalonde Donald 
Published: May 2023

Summary:
Understanding the clinically important pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body) of medications used in surgery will help surgeons use them more safely and effectively. The goal of this article is to provide an overview of these considerations for the 2 medications used in wide-awake local anesthesia with no tourniquet upper extremity surgery (ie, lidocaine and epinephrine) to establish a better understanding of lidocaine and epinephrine in tumescent local anesthesia, as well as adverse reactions and how to manage them.
The 10-7 Facial Analysis Method for Face Lifting and Facial Rejuvenation
Authors: Jalalabadi Faryan , Rohrich Rod J. 
Published: May 2023

Summary:
Proper facial analysis is the first step toward delivering an excellent result in any face lifting or facial rejuvenating operation or procedure. Every case should be approached in a systematic and comprehensive manner, ensuring proper assessment of specific anatomic regions contributing to facial aging as well as the global facial aesthetic. Failure to do so may result in an unnatural or partially rejuvenated face. The senior author’s (R.J.R.) approach entails 10 key anatomic regions on the frontal view and 7 on the lateral view. The 10-7 facial analysis method allows the surgeon to reliably assess every patient in a detailed, top-down, structural approach when considering face lifting or facial rejuvenation.
Myocardial Perfusion Scintigraphy in a Patient With Transposition of Great Arteries Post–Atrial Switch Surgery
Authors: Mohd Radzi Aliaa , Boey Ching Yeen , Amir Hassan Siti Zarina 
Published: May 2023

Abstract
We report a case of a 33-year-old woman who underwent stress and rest myocardial perfusion scintigraphy (MPS) to exclude coronary artery disease. MPS images showed an apparent dextrocardia with a right-sided septal wall uptake. The electrocardiograph showed a right axis deviation with dominant R waves at leads aVR and V1. Upon retrieval of the patient’s medical records, she had an underlying transposition of great arteries and underwent a Senning atrial switch surgery. Hence, the MPS images demonstrated a prominent right ventricular wall due to its function as the “systemic” ventricle with minimal uptake in the “pulmonary” left ventricle.
Cerebellar Hypermetabolism in a Hodgkin Lymphoma Leads to Diagnosis of Paucisymptomatic Cryptococcus neoformans Meningitis
Authors: Vanerwegen Eef , Ahmadi Bidakhvidi Niloefar , Vergote Vibeke K. J. , Janssens Ann , Deroose Christophe M. 
Published: May 2023

AbstractMalignancy-associated cerebellar hypermetabolism on [18F]FDG PET/CT has 2 major causes: paraneoplastic autoimmune encephalitis and neoplasias (leptomeningeal/cerebellar metastases and primary cerebellar tumors). We present the case of a 33-year-old man with a newly diagnosed Hodgkin lymphoma and mere episodical headache, unexpectedly displaying intense cerebellar hypermetabolism on his staging [18F]FDG PET/CT. Both neurolymphomatosis and paraneoplastic subacute cerebellar degeneration were ruled out by clinical presentation, MR, and repeated lumbar punctures. Instead, cerebrospinal fluid analysis unveiled aCryptococcus neoformansmeningitis, highlighting the possibility of paucisymptomatic central nervous system infections as differential diagnosis in malignancy-related cerebellar hypermetabolism in addition to (para)neoplastic causes.
Orbital Radioiodine Uptake in Epithelial Conjunctival Inclusion Cyst on Scintigraphy in a Patient With Differentiated Thyroid Cancer
Authors: Makarewicz Maciej , Skierkowski Witold , Makarewicz Jacek 
Published: May 2023

Abstract
Abnormal focal accumulation of 131I is generally a reliable indicator of differentiated thyroid cancer metastases. However, many examples of false-positive 131I uptake were reported but only a few with orbital accumulation of radioiodine. We report the case of a 68-year-old woman with differentiated thyroid cancer who underwent thyroid remnants ablation with radioiodine. A focus of considerable 131I uptake corresponding to a small, periorbital tumor was detected on posttherapy whole-body 131I scan and head SPECT/CT. The tumor was surgically removed, and pathology revealed a conjunctival inclusion cyst with no features of thyroid tissue. Orbital 131I uptake was not detected on follow-up scans.
Reconstruction of Rapidly Growing Merkel Cell Carcinoma of the Cheek With Multidisciplinary Cooperation
Authors: Park Tae Jun , Ki Sae Hwi , Yoon Jin Myung 
Published: May 2023

Merkel cell carcinoma (MCC) is a rare and very aggressive skin cancer. An 83-year-old female presented with a 1.5 cm-sized non-tender mass on her left cheek and was diagnosed with MCC. The margin of MCC was well-defined and there was no cervical node metastasis on pre-operative computed tomography. Three weeks after the first visit, the mass rapidly increased in size. We checked the magnetic resonance imaging, a rapid-growing 2.5 cm sized nodular region and metastatic cervical lymph node were found. We performed wide excision of the MCC and neck lymph need dissection with multidisciplinary cooperation. The soft tissue defect was about 6.0×5.0 cm2 in size and reconstructed with radial forearm free flap. On permanent biopsy, the size of MCC was 3.0×2.3 cm2. There was no recurrence of MCC with radiation therapy during an 18-month follow-up. We experienced an older patient with a rapid-growing MCC and cervical lymph node metastasis in a brief time. With our experience, we discuss the evaluation and treatment plan of the rapid-growing MCC for good results.
HEART RATE VARIABILITY PARAMETERS WERE NOT ASSOCIATED WITH 30-DAY ALL-CAUSE MORTALITY IN INTENSIVE CARE UNIT PATIENTS WITH OR WITHOUT ATRIAL FIBRILLATION: A RETROSPECTIVE STUDY OF THE MIMIC-IV DATABASE
Authors: Li Sheran , Yang Qiyu , Wu Peiyu , Lu Yujing , Yang Zhengfei , Jiang Longyuan 
Published: May 2023

ABSTRACT

Objective: Our study aims to evaluate the association between heart rate variability (HRV) and short- and long-term prognosis in patients admitted to intensive care unit (ICU). Methods and Results: Adult patients continuously monitored for over 24 h in ICUs from the the American Medical Information Mart for Intensive Care (MIMIC)-IV Waveform Database were recruited in our study. Twenty HRV-related variables (8 time domain, 6 frequency domain, and 6 nonlinear variables) were calculated based on RR intervals. The association between HRV and all-cause mortality was assessed. Ninety-three patients met the inclusion criteria and were classified into atrial fibrillation (AF) and sinus rhythm (SR) groups, which were further divided into 30-day survivor group and nonsurvivor\groups based on their survival status. The 30-day all-cause mortality rates in AF and SR groups were 36.3% and 14.6%, respectively. All the time domain, frequency domain, and nonlinear HRV parameters did not differ significantly between survivors and nonsurvivors with or without AF (all P > 0.05). Presence of renal failure, malignancy, and elevated blood urea nitrogen level were associated with increased 30-day all-cause mortality in SR patients, while presence of sepsis, infection, higher platelet count, and magnesium level were associated with increased 30-day all-cause mortality in AF patients. Conclusions: Heart rate variability variables were not associated with increased 30-day all-cause mortality in ICU patients with or without AF.
Identification of secondary metabolites containing a diketopiperazine core in extracts from myxobacterial strains with growth inhibition activity against a range of prey species
Authors: Radford Emily Jade , Whitworth David , Allison Gordon 
Published: May 2023

Myxobacteria produce a variety of bioactive secondary metabolites, and with a wealth of under-researched species they hold vast potential for undiscovered compounds. With the ever-increasing need for new antibiotics, the development of novel therapeutics is vitally important. Therefore, this study aimed to extract and elucidate antimicrobial metabolites from the following myxobacteria: Myxococcus xanthus CA010 and AB022; Corallococcus exiguus DSM14696T; Myxococcus stipitatus DSM14675T; Corallococcus aberystwythensis AB050AT. Metabolite mixtures were extracted in acetone from XAD-16 resin incubated in liquid cultures and analysed using GC-MS. Bioactivity was identified using a growth inhibition assay against a panel of clinically relevant prey species including Gram-positive and Gram-negative bacteria and a fungus. The growth of Klebsiella pneumoniae and Enterococcus faecalis was most affected by the metabolite mixtures and the mixtures from AB022 and AB050AT were effective against the most prey. GC-MS analysis revealed metabolites with roles in synthesis and degradation of amino acids and fatty acids, but also identified compounds A and B with a diketopiperazine (DKP) core. With previously confirmed bioactivity of compound A, it is suggested that these DKP compounds are contributing to the antimicrobial activity observed. Furthermore, many compounds could not be identified and so these unknowns present further potential for novel bioactive compounds.
Markov State Models and Perturbation-Based Approaches Reveal Distinct Dynamic Signatures and Hidden Allosteric Pockets in the Emerging SARS-Cov-2 Spike Omicron Variants Complexes with the Host Receptor: The Interplay of Dynamics and Convergent Evolution Modulates Allostery and Functional Mechanisms
Authors: Xiao Sian , Alshahrani Mohammed , Gupta Grace , Tao Peng , Verkhivker Gennady 
Published: May 2023

AbstractThe new generation of SARS-CoV-2 Omicron variants displayed a significant growth advantage and the increased viral fitness by acquiring convergent mutations, suggesting that the immune pressure can promote convergent evolution leading to the sudden acceleration of SARS-CoV-2 evolution. In the current study, we combined structural modeling, extensive microsecond MD simulations and Markov state models to characterize conformational landscapes and identify specific dynamic signatures of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the recently emerged highly transmissible XBB.1, XBB.1.5, BQ.1, and BQ.1.1 Omicron variants. Microsecond simulations and Markovian modeling provided a detailed characterization of the conformational landscapes and revealed the increased thermodynamic stabilization of the XBB.1.5 subvariant which is contrasted to more dynamic BQ.1 and BQ.1.1 subvariants. Despite considerable structural similarities, Omicron mutations can induce unique dynamic signatures and specific distributions of conformational states. The results suggested that variant-specific changes of conformational mobility in the functional interfacial loops of the spike receptor binding domain can be fine-tuned through cross-talk between convergent mutations thereby providing an evolutionary path for modulation of immune escape. By combining atomistic simulations and Markovian modeling analysis with perturbation-based approaches, we determined important complementary roles of convergent mutation sites as effectors and receivers of allosteric signaling involved in modulating conformational plasticity at the binding interface and regulating allosteric responses. This study also characterized the dynamics-induced evolution of allosteric pockets in the Omicron complexes that revealed hidden allosteric pockets and suggested that convergent mutation sites could control evolution and distribution of allosteric pockets through modulation of conformational plasticity in the flexible adaptable regions. Through integrative computational approaches, this investigation provides a systematic analysis and comparison of the effects of Omicron subvariants on conformational dynamics and allosteric signaling in the complexes with the ACE2 receptor.For Table of Contents Use Only
Discovery of new deaminase functions by structure-based protein clustering
Authors: Huang Jiaying , Lin Qiupeng , Fei Hongyuan , He Zixin , Xu Hu , Li Yunjia , Qu Kunli , Han Peng , Gao Qiang , Li Boshu , Liu Guanwen , Zhang Lixiao , Hu Jiacheng , Zhang Rui , Zuo Erwei , Luo Yonglun , Ran Yidong , Qiu Jin-Long , Zhao Kevin Tianmeng , Gao Caixia 
Published: May 2023

SummaryThe elucidation of protein function and its exploitation in bioengineering have greatly contributed to the development of the life sciences. Existing protein mining efforts generally rely on amino acid sequences rather than protein structures due to technical difficulties in structural elucidation. We describe here for the use of AlphaFold2 to predict and subsequently cluster an entire protein family based on predicted structure similarities. We selected the deaminase family of proteins to analyze and through this approach identified many previously unknown deaminase properties. We applied these new deaminases to the development of new cytosine base editors with distinct features. Although we found many new double-stranded DNA deaminases from the DddA-like protein clade, we were surprised to find that most of the proteins in this family were not actually double-stranded DNA cytidine deaminases. From this protein clade, we engineered the smallest single-strand specific cytidine deaminase, which facilitates the first efficient cytosine base editor to be packaged into a single AAV vector. Importantly, we also profiled a deaminase from this clade that edits robustly in soybean plants, which previously suffered from poor editing by cytosine base editors. These newly discovered deaminases based on AI-assisted structural predictions greatly expand the utility of base editors for therapeutic and agricultural applications.
High-resolution kinetics of herbivore-induced plant volatile transfer reveal clocked response patterns in neighboring plants
Authors: Waterman Jamie M. , Cofer Tristan M. , Wang Lei , Glauser Gaétan , Erb Matthias 
Published: May 2023

AbstractVolatiles emitted by herbivore-attacked plants (senders) can enhance defenses in neighboring plants (receivers), with important consequences for community dynamics. However, the temporal dynamics of this phenomenon remain poorly studied. Using a custom-built, high- throughput proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) system, we explored temporal patterns of volatile transfer and responses between herbivore-attacked and undamaged maize plants. We found that continuous exposure to natural blends of herbivore-induced volatiles results in clocked temporal response patterns in neighboring plants, characterized by an induced terpene burst at the onset of the second day of exposure. This delayed burst is not explained by terpene accumulation during the night, but coincides with delayed jasmonate accumulation in receiver plants. The delayed burst occurs independent of day : night light transitions and cannot be fully explained by sender volatile dynamics. Instead, it is the result of a stress memory from volatile exposure during the first day and secondary exposure to bioactive volatiles on the second day. Our study reveals that prolonged exposure to natural blends of stress-induced volatiles results in a response that integrates priming and direct induction into a distinct and predictable temporal response pattern. This provides an answer to the long-standing question of whether stress volatiles predominantly induce or prime plant defenses in neighboring plants, by revealing that they can do both in sequence.
Physiological Responses of The Leaves of a High-Altitude PlantPicrorhiza kurroato Cold Stress
Authors: Agrawal Shreya , Saklani Pooja 
Published: May 2023

ABSTRACTThere are various plants that grow in high elevations and experience various environmental stresses, cold stress being the most prevalent one. Plants undergo biochemical, metabolic, molecular, and physiological changes under cold stress hence, they adopt various mechanisms to tolerate it. The antioxidant defense system, osmotic regulators and photosynthetic pigments in the plant provide them stress tolerance. The present study is conducted on a high-altitude plant,Picrorhiza kurroawhich grows in such environmental conditions, to study the physiological parameters that provides it the coping mechanism against the cold stress. For this study, the leaves were collected from Pothivasa (2200 m asl) and Tungnath (3600 m asl) in Rudraprayag, Uttarakhand, India. The photosynthetic pigments, lipid peroxidation, antioxidant enzymes, and osmoprotectants present in the leaves were determined to visualize the impact of cold stress. It was revealed that the concentration of chlorophyll a, chlorophyll b, and carotenoids increased with increase in elevation. The activity of SOD, CAT, POD, APOX and GR were analyzed and they were observed to decrease with altitude. The MDA concentration which is an indicator of lipid peroxidation is higher in Pothivasa (2.214 μmol L-1) and lower in Tungnath (1.697 μmol L-1). There is a significant increase in the total protein content, total soluble sugar content and total proline content along the altitudinal gradient. Therefore, the leaves from both the sampling locations revealed the physiological changes occurred in them to adapt to the cold stress conditions.
Machine-learning guided Venom Induced Dermonecrosis Analysis tooL: VIDAL
Authors: Laprade William , Bartlett Keirah E. , Christensen Charlotte R. , Kazandjian Taline D. , Patel Rohit N. , Crittenden Edouard , Dawson Charlotte A. , Mansourvar Marjan , Wolff Darian S. , Fryer Thomas J. , Laustsen Andreas H. , Casewell Nicholas R. , Gutiérrez José María , Hall Steven R. , Jenkins Timothy P. 
Published: May 2023

AbstractSnakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations of envenomings vary depending on the snake’s venom, with paralysis, haemorrhage, and necrosis being the most common and medically relevant effects. To assess the efficacy of antivenoms against dermonecrosis, a preclinical testing approach involvesin vivomouse models that mimic local tissue effects of cytotoxic snakebites in humans. However, current methods for assessing necrosis severity are time-consuming and susceptible to human error. To address this, we present the Venom Induced Dermonecrosis Analysis tool (VIDAL), a machine-learning-guided image-based solution that can automatically identify dermonecrotic lesions in mice, adjust for lighting biases, scale the image, extract lesion area and discolouration, and calculate the severity of dermonecrosis. We also introduce a new unit, the dermonecrotic unit (DnU), to better capture the complexity of dermonecrosis severity. Our tool is comparable to the performance of state-of-the-art histopathological analysis, making it an accessible, accurate, and reproducible method for assessing dermonecrosis. Given the urgent need to address the neglected tropical disease that is snakebite, high-throughput technologies such as VIDAL are crucial in developing and validating new and existing therapeutics for this debilitating disease.