bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin Protects Against Sunitinib-induced Cardiotoxicity: Investigating the Role of AMPK
Authors: Kuburas Refik , Gharanei Mayel , Haussmann Irmgard , Maddock Helen , Sandhu Hardip 
Published: June 2022

Abstract:
Sunitinib is associated with cardiotoxicity through inhibition of AMP-protein kinase (AMPK) signaling. By contrast, the common antidiabetic agent metformin has demonstrated cardioprotection through indirect AMPK activation. In this study, we investigate the effects of metformin during sunitinib-induced cytotoxicity. Left ventricular developed pressure, coronary flow, heart rate, and infarct size were measured in Langendorff-perfused rat hearts treated with 1 µM sunitinib ±50 µM metformin ±1 µM human equilibrative nucleoside transporter inhibitor S-(4-Nitrobenzyl)-6-thioinosine (NBTI). Western blot analysis was performed for p-AMPKα levels. Primary isolated cardiac myocytes from the left ventricular tissue were used to measure live cell population levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess adjunctive treatment of and metformin in human hepatoma G2 and promyelocytic leukemia (HL-60) cells treated with 0.1–100 µM sunitinib ±50 µM metformin. In the perfused hearts, coadministration of metformin attenuated the sunitinib-induced changes to left ventricular developed pressure, infarct size, and cardiac myocyte population. Western blot analysis revealed a significant decrease in p-AMPKα during sunitinib treatment, which was attenuated after coadministration with metformin. All metformin-induced effects were attenuated, and NBTI was coadministered. The MTT assay demonstrated an increase in the EC50 value during coadministration of metformin with sunitinib compared with sunitinib monotherapy in hepatoma G2 and HL-60 cell lines, demonstrating the impact and complexity of metformin coadministration and the possible role of AMPK signaling. This study highlights the novel cardioprotective properties of metformin and AMPK activation during sunitinib-induced cardiotoxicity when administered together in the Langendorff heart model.
CFTR Suppresses Neointimal Formation Through Attenuating Proliferation and Migration of Aortic Smooth Muscle Cells
Authors: Lu Liu-Yi , Pan Ni , Huang Ze-Han , Wang Jing-Song , Tang Yong-Bo , Sun Hong-Shuo , Han Hui , Yang Han-Yan , Zhu Jun-Zhen , Guan Yong-Yuan , Zhang Bin , Li Dong-Zhi , Wang Guan-Lei 
Published: June 2022

Abstract:
Cystic fibrosis transmembrane conductance regulator (CFTR) plays important roles in arterial functions and the fate of cells. To further understand its function in vascular remodeling, we examined whether CFTR directly regulates platelet-derived growth factor-BB (PDGF-BB)-stimulated vascular smooth muscle cells (VSMCs) proliferation and migration, as well as the balloon injury–induced neointimal formation. The CFTR adenoviral gene delivery was used to evaluate the effects of CFTR on neointimal formation in a rat model of carotid artery balloon injury. The roles of CFTR in PDGF-BB–stimulated VSMC proliferation and migration were detected by mitochondrial tetrazolium assay, wound healing assay, transwell chamber method, western blot, and qPCR. We found that CFTR expression was declined in injured rat carotid arteries, while adenoviral overexpression of CFTR in vivo attenuated neointimal formation in carotid arteries. CFTR overexpression inhibited PDGF-BB–induced VSMC proliferation and migration, whereas CFTR silencing caused the opposite results. Mechanistically, CFTR suppressed the phosphorylation of PDGF receptor β, serum and glucocorticoid-inducible kinase 1, JNK, p38 and ERK induced by PDGF-BB, and the increased mRNA expression of matrix metalloproteinase-9 and MMP2 induced by PDGF-BB. In conclusion, our results indicated that CFTR may attenuate neointimal formation by suppressing PDGF-BB–induced activation of serum and glucocorticoid-inducible kinase 1 and the JNK/p38/ERK signaling pathway.
Intrascleral haptic needle fixation of 20+-year-old dislocated intraocular lenses using trailing-haptic-first modification
Authors: Kim Madeleine E. , Kim Dooho B. 
Published: June 2022

Introduction:
Repositioning and scleral fixation of 20+-year-old dislocated intraocular lenses (IOLs) was performed using the trailing-haptic-first modification of the Yamane technique.

Patient and Clinical Findings:
2 separate patients presented with late dislocation of their 3-piece IOLs, and the original surgeries were performed over 20 years ago. 1 patient had a Rezoom IOL and the other had an SI30 IOL.

Diagnosis, Intervention, and Outcomes:
The 2 patients underwent successful repositioning of the existing IOLs using the trailing-haptic-first modification of the Yamane technique. Both had good refractive outcomes without complication.

Conclusions:
To the authors' knowledge, these are the first cases reported of using 20+-year-old dislocated IOLs for successful intrascleral haptic needle fixation with the trailing-haptic-first modification of the Yamane technique. Surgeons should consider IOL repositioning with intrascleral haptic needle fixation instead of explantation for an easier and less-invasive approach.
Effects of a Novel High-Quality Protein Infant Formula on Energetic Efficiency and Tolerance: A Randomized Trial
Authors: Kuehn Devon , Zeisel Steven H. , Orenstein Diana F. , German J. Bruce , Field Catherine J. , Teerdhala Shiva , Knezevic Andrea , Patil Sujata , Donovan Sharon M. , Lönnerdal Bo 
Published: June 2022

Objectives:
Protein overfeeding in infants can have negative effects, such as diabetes and childhood obesity; key to reducing protein intake from formula is improving protein quality. The impact of a new infant formula [study formula (SF)] containing alpha-lactalbumin, lactoferrin, partially hydrolyzed whey, and whole milk on growth and tolerance compared to a commercial formula (CF) and a human milk reference arm was evaluated.

Methods:
This randomized, double-blind trial included healthy, singleton, term infants, enrollment age ≤14 days. Primary outcome was mean daily weight gain. Secondary outcomes were anthropometrics, formula intake, serum amino acids, adverse events, gastrointestinal characteristics, and general disposition.

Results:
Non-inferiority was demonstrated. There were no differences between the formula groups for z scores over time. Formula intake [−0.33 oz/kg/day, 95% confidence interval (CI): −0.66 to −0.01, P = 0.05] and mean protein intake (−0.13 g/kg/day, 95% CI: −0.26 to 0.00, P = 0.05) were lower in the SF infants, with higher serum essential amino acid concentrations (including tryptophan) compared to the CF infants. Energetic efficiency was 14.0% (95% CI: 8.3%, 19.7%), 13.0% (95% CI: 6.0%, 20.0%), and 18.1% (95% CI: 9.4%, 26.8%) higher for weight, length, and head circumference, respectively, in SF infants compared to the CF infants. SF infants had significantly fewer spit-ups and softer stool consistency than CF infants.

Conclusions:
The SF resulted in improved parent-reported gastrointestinal tolerance and more efficient growth with less daily formula and protein intake supporting that this novel formula may potentially reduce the metabolic burden of protein overfeeding associated with infant formula.
Coping Style, Insomnia, and Psychological Distress Among Persons With Gastrointestinal Cancer
Authors: Lv Gaorong , Zhao Di , Li Guopeng , Wang Qing , Zhou Miao , Gao Yiming , Zhao Xiangyu , Li Ping 
Published: June 2022

Abstract

Background
Although insomnia has been shown to play an important role in psychological distress among gastrointestinal cancer patients, little is known about the internal mechanisms underlying this relation. Coping styles have been shown to moderate the effect of sleep on emotion, and this moderating effect may be age-dependent.

Objective
To test how age and coping styles moderate the role of insomnia on psychological distress among gastrointestinal cancer patients.

Methods
This was a descriptive cross-sectional study with a convenience sample. A total of 352 patients with gastrointestinal cancer from two tertiary hospitals were recruited to participate in this study. The Kessler Psychological Distress Scale (K10), Insomnia Severity Index (ISI), and Simplified Coping Style Questionnaire (SCSQ) were used to assess patients’ psychological distress, insomnia, and coping styles. We performed hierarchical multiple regression and Johnson-Neyman statistical analysis to probe the moderating effect of coping styles and age.

Results
The mean age of the participants was 58.32 years. Nearly half of the participants reported psychological distress, and many reported insomnia. Insomnia was significantly positively associated with psychological distress. Coping styles and age moderated the relationship between insomnia and distress. Specifically, positive coping buffered the effect of insomnia on psychological distress only for subjects aged 34 and younger; negative coping exacerbated the above relationship in patients aged 68 years and older while weakening the relationship in participants aged 51 years and younger.

Discussion
There are age differences in the moderating role of coping styles on the relationship between insomnia and distress among gastrointestinal cancer patients. This study provides preliminary evidence to inform tailored guidance on coping styles by age groups to attenuate the risk for psychological distress related to insomnia in the cancer population.
Overcoming Challenges of Online Research: Measures to Ensure Enrollment of Eligible Participants
Authors: Campbell Chadwick K. , Ndukwe Samuel , Dubé Karine , Sauceda John A. , Saberi Parya 
Published: June 2022

Background:
Internet-based surveys are increasingly used for health research because they offer several advantages including greater geographic reach, increased participant anonymity, and reduced financial/time burden. However, there is also a need to address inherent challenges, such as the likelihood of fraudulent responses and greater difficulty in determining eligibility.

Methods:
We conducted an online nationwide survey of 18–29 year olds living with HIV in the United States, to assess willingness to participate in HIV cure research. To ensure that respondents met age and HIV serostatus inclusion criteria, we instituted screening procedures to identify ineligible respondents using tools that were built into the survey platform (eg, reCAPTCHA, geolocation) and required documentation of age and serostatus before providing access to the incentivized study survey.

Results:
Of 1308 eligibility surveys, 569 were incomplete or ineligible because of reported age or serostatus. Of the remaining 739 potentially eligible respondents, we determined that 413 were from fraudulent, bot, or ineligible respondents. We sent individual study survey links to 326 participants (25% of all eligibility survey respondents) whose eligibility was reviewed and confirmed by our study team.

Conclusion:
Our multicomponent strategy was effective for identifying ineligible and fraudulent responses to our eligibility survey, allowing us to send the study survey link only to those whose eligibility we were able to confirm. Our findings suggest that proactive fraud prevention can be built into the screening phase of the study to prevent wasted resources related to data cleaning and unretrievable study incentives and ultimately improve the quality of data.
Impact of Perceived Stress During the SARS-CoV-2 Pandemic on Rheumatoid Arthritis Patients' Disease Activity
Authors: Pham Angela , Brook Jenny , Elashoff David A. , Ranganath Veena K. 
Published: June 2022

Introduction/Objectives
Psychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient.

Method
This was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19–related stress, RA disease activity, and demographics. For the survey responders, anti–cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19–related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3).

Results
A total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors.

Conclusions
This study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.
Micro-magnetic stimulation of primary visual cortex induces focal and sustained activation of secondary visual cortex
Authors: Lee Seung Woo , Fried Shelley I. 
Published: June 2022

Cortical visual prostheses that aim to restore sight to the blind require the ability to create neural activity in the visual cortex. Electric stimulation delivered via microelectrodes implanted in the primary visual cortex (V1) has been the most common approach, although conventional electrodes may not effectively confine activation to focal regions and thus the acuity they create may be limited. Magnetic stimulation from microcoils confines activation to single cortical columns of V1 and thus may prove to be more effective than conventional microelectrodes, but the ability of microcoils to drive synaptic connections has not been explored. Here, we show that magnetic stimulation of V1 using microcoils induces spatially confined activation in the secondary visual cortex (V2) in mouse brain slices. Single-loop microcoils were fabricated using platinum–iridium flat microwires, and their effectiveness was evaluated using calcium imaging and compared with that of monopolar and bipolar electrodes. Our results show that compared to the electrodes, the microcoils better confined activation to a small region in V1. In addition, they produced more precise and sustained activation in V2. The finding that microcoil-based stimulation propagates to higher visual centres raises the possibility that complex visual perception, e.g. that requiring sustained synaptic inputs, may be achievable.This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.
Spatio-temporal feature extraction in sensory electroneurographic signals
Authors: Silveira C. , Khushaba R. N. , Brunton E. , Nazarpour K. 
Published: June 2022

The recording and analysis of peripheral neural signal can provide insight for various prosthetic and bioelectronics medicine applications. However, there are few studies that investigate how informative features can be extracted from population activity electroneurographic (ENG) signals. In this study, five feature extraction frameworks were implemented on sensory ENG datasets and their classification performance was compared. The datasets were collected in acute rat experiments where multi-channel nerve cuffs recorded from the sciatic nerve in response to proprioceptive stimulation of the hindlimb. A novel feature extraction framework, which incorporates spatio-temporal focus and dynamic time warping, achieved classification accuracies above 90% while keeping a low computational cost. This framework outperformed the remaining frameworks tested in this study and has improved the discrimination accuracy of the sensory signals. Thus, this study has extended the tools available to extract features from sensory population activity ENG signals.
This article is part of the theme issue ‘Advanced neurotechnologies: translating innovation for health and well-being’.
bHLH heterodimer complex variations shape meristems in Arabidopsis thaliana by affecting target gene specificity
Authors: Mor Eliana , Pernisová Markéta , Minne Max , Cerutti Guillaume , Ripper Dagmar , Nolf Jonah , Andres Jennifer , Ragni Laura , Zurbriggen Matias D. , Rybel Bert De , Vernoux Teva 
Published: June 2022

ABSTRACTThe main regions of cell proliferation in plants are the root and shoot apical meristems during primary growth and the vascular cambia as lateral meristems during secondary thickening. A number of unique regulators have been described in each of these meristems, suggesting that these different meristems might have independently evolved dedicated transcriptional networks to balance cell proliferation. Here, we show that the basic Helix Loop Helix (bHLH) transcription factor complexes formed by TARGET OF MONOPTEROS5 (TMO5), LONESOME HIGHWAY (LHW) and their close homologs are broadly expressed throughout plant development and operate as general regulators of cell proliferation in all meristems. Yet, genetic and expression analyses indicate that these complexes have specific functions in distinct meristems mediated by heterodimer complex variations between members of the TMO5 and LHW subclades. We determine that this is primarily due to their expression domains limiting the possible combinations of heterodimer complexes within a certain meristem, and to a certain extent to the absence of some members in a given meristem. We further demonstrate target gene specificity for heterodimer complexes, suggesting that spatial differences in transcriptional responses through heterodimer diversification allow a common bHLH heterodimer complex module to contribute to the control of cell proliferation in multiple meristems.
Health Care Utilization of US Medicare Beneficiaries Living with Parkinson’s Disease
Authors: Pearson Caroline , Hartzman Alex , Munevar Dianne , Feeney Megan , Dolhun Rachel , Todaro Veronica , Rosenfeld Sheera , Willis Allison , Beck James 
Published: June 2022

AbstractThe number of people living with Parkinson’s disease (PD) is expected to rise in the coming years. This study analyzed health care utilization patterns of Medicare beneficiaries with a PD diagnosis (ICD-10 code G20) who were enrolled in 2019. Utilization analysis included PD-related specialists and primary care physicians, therapy services, and mental health services. We found 685,116 (1.2%) Medicare beneficiaries had PD (56.3% male, 77.9% over age 70, 85.3% White, and 16.0% rural residents). Few Medicare beneficiaries with PD sought care from a movement disorder specialist (MDS) (9.1%); another 50.9% visited a general neurologist. Results reveal low utilization rates for therapy and even lower rates for mental health services. Overall healthcare utilization varied significantly by demographic group with women, people of color, and rural residents being less likely to access specialist care. Our findings emphasize the need for further research on population-specific barriers to accessing PD-related health care.
Enhanced surveillance of monkeypox in Bas-Uélé, Democratic Republic of Congo: the limitations of symptom-based case definitions
Authors: Mande Gaspard , Akonda Innocent , De Weggheleire Anja , Brosius Isabel , Liesenborghs Laurens , Bottieau Emmanuel , Ross Noam , Gembu Guy -Crispin , Colebunders Robert , Verheyen Erik , Dauly Ngonda , Leirs Herwig , Laudisoit Anne 
Published: June 2022

AbstractBackgroundFollowing an outbreak of cases of vesicular-pustular rash with fever evocative of human monkeypox in Bas-Uélé province, Democratic Republic of Congo, surveillance was strengthened.MethodsHouseholds with at least one active generalized vesicular-pustular rash case were visited, and contact and clinical history information was collected from all household members. Whenever possible, skin lesion were screened by PCR for the monkeypox virus, followed by the varicella-zoster virus when negative for the former.ResultsPCR results were obtained for 77 suspect cases distributed in 138 households, of which 27.3% were positive for monkeypox, 58.4% for chickenpox, and 14.3% negative for both. Confirmed monkeypox cases presented more often with monomorphic skin lesions, on palms of hands, and on soles of feet. Integrating these three features into the case definition raised the specificity to 85%, but would miss 50% of true monkeypox cases. A predictive model fit on patient demographics and symptoms had 97% specificity and 80% sensitivity, but only 80% and 33% in predicting out-of-sample cases.ConclusionFew discriminating features were identified and the performance of clinical case definitions was suboptimal. Rapid field diagnostics are needed to optimize worldwide early detection and surveillance of monkeypox.
On the origin of Omicron’s unique Spike gene insertion
Authors: Venkatakrishnan A.J. , Anand Praveen , Lenehan Patrick J. , Suratekar Rohit , Raghunathan Bharathwaj , Niesen Michiel J.M. , Soundararajan Venky 
Published: June 2022

AbstractThe emergence of a heavily mutated SARS-CoV-2 variant (Omicron; B.1.1.529/BA.1/BA.2) and its rapid spread globally created public health alarms. Characterizing the mutational profile of Omicron is necessary to interpret its shared or distinctive clinical phenotypes with other SARS-CoV-2 variants. We compared the mutations of Omicron with prior variants of concern (Alpha, Beta, Gamma, Delta), variants of interest (Lambda, Mu, Eta, Iota and Kappa), and ∼1500 SARS-CoV-2 lineages constituting ∼5.8 million SARS-CoV-2 genomes. Omicron’s Spike protein has 26 amino acid mutations (23 substitutions, two deletions and one insertion) that are distinct compared to other variants of concern. Whereas the substitution and deletion mutations have appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) has not been previously observed in any other SARS-CoV-2 lineage. Here, we discuss various mechanisms through which the nucleotide sequence encoding for ins214EPE could have been acquired and highlight the plausibility of template switching via either the human transcriptome or prior viral genomes. Analysis of homology of the inserted nucleotide sequence and flanking regions suggests that this template switching event could have involved the genomes of SARS-CoV-2 variants (e.g. B.1.1 strain), other human coronaviruses that infect the same host cells as SARS-CoV-2 (e.g. HCoV-OC43 or HCoV-229E), or a human transcript expressed in a host cell that was infected by the Omicron precursor. Whether ins214EPE impacts the epidemiological or clinical properties of Omicron (e.g. transmissibility) warrants further investigation. There is also a need to understand whether human host cells are being exploited by SARS-CoV-2 as an ‘evolutionary sandbox’ for inter-viral or host-virus genomic interplay to produce new SARS-CoV-2 variants.