bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis HECT and RING-type E3 Ligases Promote MAPKKK18 Degradation to Regulate Abscisic Acid Signaling
Authors: Tajdel-Zielińska Małgorzata , Janicki Maciej , Marczak Małgorzata , Ludwików Agnieszka 
Published: December 2023

Abstract
Mitogen-activated protein kinase (MAPK) cascades are conserved signaling pathways that transduce extracellular signals into diverse cellular responses. Arabidopsis MAPKKK18 is a component of the MAPKKK17/18-MKK3-MPK1/2/7/14 cascades, which play critical roles in abscisic acid (ABA) signaling, drought tolerance and senescence. A very important aspect of MAP kinase signaling is both its activation and its termination, which must be tightly controlled to achieve appropriate biological responses. Recently, the ubiquitin-proteasome system (UPS) has received increasing attention as a key mechanism for maintaining the homeostasis of MAPK cascade components and other ABA signaling effectors. Previous studies have shown that the stability of MAPKKK18 is regulated by the UPS via the ABA core pathway. Here, using multiple proteomic approaches, we found that MAPKKK17/18 turnover is tightly controlled by three E3 ligases, UPL1, UPL4 and KEG. We also identified lysines 154 and 237 as critical for MAPKKK18 stability. Taken together, this study sheds new light on the mechanism that controls MAPKKK17/18 activity and function.
Serum amyloid A aggravates endotoxin‐induced ocular inflammation through the regulation of retinal microglial activation
Authors: Feng Huazhang , Zhou Wenchuan , Yang Yuan , Zhang Xuerui , Mao Ruixue , Zhou Yutong , Cheng Tongjie , Xiao Haodong , Rao Yuqing , He Jincan , Zhao Peiquan , Li Jing , Jiang Chunhui 
Published: December 2023

AbstractSerum amyloid A (SAA) are major acute‐phase response proteins which actively participate in many inflammatory diseases. This study was designed to explore the function of SAA in acute ocular inflammation and the underlying mechanism. We found that SAA3 was upregulated in endotoxin‐induced uveitis (EIU) mouse model, and it was primarily expressed in microglia. Recombinant SAA protein augmented intraocular inflammation in EIU, while the inhibition of Saa3 by siRNA effectively alleviated the inflammatory responses and rescued the retina from EIU‐induced structural and functional damage. Further study showed that the recombinant SAA protein activated microglia, causing characteristic morphological changes and driving them further to pro‐inflammatory status. The downregulation of Saa3 halted the amoeboid change of microglia, reduced the secretion of pro‐inflammatory factors, and increased the expression of tissue‐reparative genes. SAA3 also regulated the autophagic activity of microglial cells. Finally, we showed that the above effect of SAA on microglial cells was at least partially mediated through the expression and signaling of Toll‐like receptor 4 (TLR4). Collectively, our study suggested that microglial cell‐expressed SAA could be a potential target in treating acute ocular inflammation.
β-Arrestin-1 reduces acute myocardial infarction via promoting autophagy in cardiomyocytes
Authors: Liu Mengzhen , Yan Hui , Zhu Dan-Ni , Kong Ni , Cao Qi , Zhang Xiaoying , Wei Wei , Ke Ping , Chen Xiongwen , Liu Chong 
Published: December 2023

Background and purpose:
β-Arrestins are key regulators of G protein–coupled receptor (GPCR) signaling. Through their function as scaffolding proteins, β-arrestins mediate a range of cellular signaling events. However, the role of β-arrestins during myocardial ischemia remains incompletely understood. In this study, we explored the regulatory effects of β-arrestin-1 on autophagy following myocardial infarction and sought to identify the underlying mechanism.

Methods:
Acute myocardial infarction was induced by permanent left anterior descending coronary artery ligation. Cardiac function was assessed using echocardiography. β-Arrestin-1, autophagy-related 5 (ATG5), and liver kinase B1 (LKB1) were overexpressed or knocked down using lentivirus-mediated transduction of the gene or short hairpin RNA (shRNA) in cultured primary cardiomyocytes. Oxygen-glucose deprivation (OGD) in cardiomyocytes was used to simulate cardiac ischemia in vitro. Autophagy and apoptosis were assessed by western blot, flow cytometry, and transmission electron microscopy. Cell survival and lactate dehydrogenase (LDH) release were evaluated using the respective kits.

Results:
β-Arrestin-1 knockout (KO) increased myocardial infarction size, an effect that was associated with decreased autophagy and deterioration of cardiac function. The overexpression of β-arrestin-1 significantly increased autophagy levels and decreased cell apoptosis in cardiomyocytes exposed to OGD, whereas the knockdown of β-arrestin-1 exerted the opposite effect. The protective effect of β-arrestin-1 overexpression was abrogated by ATG5 knockdown. β-Arrestin-1 KO attenuated the myocardial infarction–induced phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). In cultured myocytes, the blockade of AMPK or the knockdown of LKB1 inhibited the β-arrestin-1–induced increase in the LC3-II/LC3-I ratio and beclin 1 expression levels and attenuated β-arrestin-1–mediated cardioprotective effects.

Conclusions:
Collectively, our findings suggested that β-arrestin-1 promotes cardiomyocyte survival under ischemic conditions via the regulation of LKB1/AMPK-dependent autophagy. These findings may be helpful in designing novel therapeutic strategies for myocardial ischemia.
Localized Cutaneous Argyria at the Site of a Prior Melanoma Excision Confirmed by Scanning Electron Microscopy With Energy Dispersive X-ray Analysis
Authors: McTighe Shane P. , Taylor Elizabeth A. , Allbritton Jill , Lewin-Smith Michael R. 
Published: December 2023

Abstract
Localized cutaneous argyria is a rare condition caused by the accumulation of silver particles in the skin, leading to blue–gray discoloration. Argyria may mimic melanoma and lead to misdiagnosis. We present a patient with a history of melanoma that developed a blue–gray nodule at a prior melanoma graft. The diagnosis was confirmed using scanning electron microscopy and energy dispersive x-ray analysis. These techniques differentiate argyria from melanoma and can be performed on formalin-fixed, paraffin-embedded, tissue sections. Health care providers should be alert that argyria may mimic recurrent melanoma in patients unaware of silver exposure.
Wellness Program Participation and its Association With Illness-Related Absenteeism and Turnover
Authors: Jenkins Kristi Rahrig 
Published: December 2023

Objective
The aim of the study is to evaluate the possible association between health and wellness initiative (HWI) participation and illness related absenteeism (IRA) and turnover overtime.

Methods
The IRA (2016–2019) and turnover (2016–2020) analysis consisted of a time-series design. The IRA analysis used a comparison group with propensity score matching based on select demographics and linear mixed-effects regression modeling. Logistic regression was used to measure the relationship between 2016 participation in the HWI on 2017–2020 turnover.

Results
The percent increase when comparing 2016 and 2019 IRA is lower for participants (15.8%) than nonparticipants (50.0%, P > 0.001). The results also show that participating in the HWI in 2016 is associated with lower odds of subsequent turnover (odds ratio = 0.90).

Conclusions
Employers may consider implementing a comprehensive health and wellness program as part of their strategy to assist in lower IRA increases and turnover overtime.
Productivity Loss Among Opioid and Benzodiazepine Users in the United States
Authors: Thornton J. Douglas , Varisco Tyler , Bhatt, M.Econ. Prachet , Olateju Olajumoke , Shrestha Mina , Shen Chan 
Published: December 2023

Objective
The aim of the study is to estimate the association between productivity losses and the use of prescription opioids and benzodiazepines among employed US adults with painful conditions.

Methods
Using Medical Expenditures Panel Survey (2010–2019), we used two-part (logistic regression and generalized linear model with zero-truncated negative binomial link) model to compare missed workdays due to illness or injury among employed adults with a painful condition.

Results
Of the eligible sample of 57,413 working US individuals, 14.65% were prescription opioid users, 2.95% were benzodiazepine users, and 1.59% were both opioid and benzodiazepine users. The predicted missed workdays were 5.75 (95% Confidence Limit [CL]: 5.58–5.92) days for benzodiazepine users, 13.06 (95% CL: 12.88–13.23) days among opioid users, and 15.18 (95% CL: 14.46–15.90) days for opioid and benzodiazepine concomitant users.

Conclusions
Concomitant use of prescription opioids and benzodiazepines was significantly associated with having more missed workdays among employed adults with documented painful conditions.
Antibiotic cement nails manufactured with threaded rods or cannulated intramedullary nails are better than those made with guidewires and do not debond
Authors: Bray Ryan , Zalikha Abdul K. , Ren Emily , Nasr Kerellos , Vaidya Rahul 
Published: December 2023

Purpose:
The purpose of this study was to comparatively evaluate cement debonding at the time of removal of antibiotic cemented coated nails (ABNs) with cores made with a guidewire ($120), a regular intramedullary nail ($1100) or a threaded rod from a circular frame external fixator set ($60).

Methods:
A retrospective study was performed on 32 ABNs that had been implanted for long bone infections after intramedullary nailing. All ABNs were manufactured intraoperatively by the treating surgeon using 2 grams of vancomycin and single package of Tobramycin Simplex Cement (Stryker, Kalamazoo, MI). The powder, antibiotics, and polymer were mixed and then injected into an ABN cement mold (Bonesetter Holdings USA). Debonding was assessed at time of removal by the operating surgeon. Rates of cement debonding between the 3 groups were statistically compared.

Results:
Debonding occurred in 0/12 of the cement nails manufactured with an intramedullary nail, 0/7 threaded rod ABNs, and 6/13 guidewire ABNs. There was a significant difference in the rate of debonding between the 3 groups (P < 0.01). Removal of the remnant cement was accomplished with thin osteotomes, long pituitary rongeurs, or reamers. The canal was visualized using an arthroscope to ensure complete removal of the cement.

Conclusion:
ABNs fabricated with standard intramedullary nails or threaded rods did not lead to any debonding. Debonding of the cement from the inner core of an antibiotic nail often requires significant effort to remove the remnant cement. Given that threaded rods are often cheaper than guidewires, we recommend that ABNs be fabricated with either threaded rods or interlocking nails, but not guidewires, depending on the level of stability required.
Medical Errors Among Postgraduate Medical Students Joining The Iraqi and Arab Councils For Medical Specializations - Medical City Complex
Authors: Mahmood Deema Thamer , Kareem Niam Kamal , Abed Mays Mohammed , Al-mothaffar Ali M.J. 
Published: December 2023

ABSTRACTBackgroundAll humans make mistakes. Unintentional medical mistakes affect patients and their families, but they can also have a negative behavioral, psychological and emotional impact on the involved healthcare practitioner or providers. These could include emotional distress, fear, feeling guilt and even depression.AimThis study aims to describe the events contributing to medical errors and the impact of these errors on behavior among postgraduate medical students joining the Iraqi and Arabic councils for medical specialty.Subjects and MethodsA cross-sectional study was conducted in Medical city complex, Baghdad, Iraq, by convenient sampling. Data were collected by a self-administered questionnaire form, which was given to all participants and retrieved at the same day. The questionnaire contains three sections (13 items), in the first section it mainly asks about personal information of the participant and their specialty, Second section contains the main question of the study which is whether they have been involved in a medical error or not, and the third section asks about the events and behavior that are related to those errors like the time of the error, the most important contributing factor, the strongest feeling that they felt after this error and the most obvious behavioral response after the error.ResultsThe total number of participants was 200 individuals. 111 of them were juniors and 89 were senior doctors. Gender (p-value< 0.0001) was significantly associated with medical errors, notably males tended to be involved in medical errors more than females with a number of 46 (40.7%) compared to 21 (24.13%) respectively. there is statistically significant association between decreased navigation of social media applications during work hours for non-work and medical error (P value < 0.0001). Furthermore, specialty was significantly associated with medical errors (P value < 0.0001) as surgical specialty tended to be involve in medical errors more than medical specialty with a number of 34 (38.2%) compared to 33(29.7%) respectively.ConclusionDistraction of attention was the most contributing factor behind medical errors. Emotional distress was the most common feeling experienced by participants. Increasing vigilance was the most behavioral response among participants following their involvement in medical errors. Furthermore, male doctors tend to be involved in medical errors more than female doctors. Surgical specialty tends to be involved in medical errors more than medical specialty.
A Tale of Two Parasites: A Glimpse into the RNA Methylome of Patient-derivedP. falciparumandP. vivaxisolates
Authors: Roy Priyanka , Gujarati Sukriti , Gupta Pallavi , Gupta Ishaan , Mahapatra Tanmaya , Gupta Dinesh , Kochar Sanjay Kumar , Kochar Dhanpat Kumar , Das Ashis 
Published: December 2023

ABSTRACTUnderstanding the molecular mechanisms of the malarial parasites in hosts is crucial for developing effective treatments. Epitranscriptomic research on pathogens has unveiled the significance of RNA methylation in gene regulation and pathogenesis. We present the first report investigating methylation patterns determined using Nanopore Direct RNA Sequencing, to single-base resolution across RNA of P. falciparum and P. vivax from Malaria patients with hepatic dysfunction. Distinct RNA methylation profiles of N6-methyladenosine and 5-methylcytosine in the parasites suggest species-specific regulatory mechanisms. These modifications are unevenly present in the annotated regions of the mRNA, potentially influencing mRNA export and translation. Methylated antisense transcripts, splicing events and modified transcripts originating from apicoplast and mitochondrial genomes have been detected. We observe a striking overlap of differential methylation of isoforms with either of the modifications in both species. The correlation of these regulatory layers will decipher the post-transcriptional environment of malaria parasites in vivo and elucidate their inherent proteome plasticity.
SIK2: A novel negative feedback regulator of FGF signaling
Authors: Kuser-Abali Gamze , Ugurlu-Bayarslan Asli , Yilmaz Yeliz , Ozcan Ferruh , Karaer Funda , Bugra Kuyas 
Published: December 2023

AbstractA wide range of cells respond to FGF2 by proliferation via activation of the Ras/ERK pathway. In this study we explored the potential involvement of serine/threonine kinase SIK2 in this cascade within retinal Müller glia. We found that SIK2 phosphorylation status and activity is modulated in an FGF2-dependent manner, possibly via ERK. With SIK2 downregulation we observed enhanced ERK activation with delayed attenuation and increased cell proliferation, while SIK2 overexpression hampered FGF-dependent ERK activation. In vitro kinase and site directed mutagenesis studies indicated that SIK2 targets the pathway element Gab1 on Ser266. This phosphorylation event weakens Gab1 interactions with its partners Grb2 and Shp2. Collectively, our results suggest that during FGF dependent proliferation process ERK-mediated activation of SIK2 targets Gab1, resulting in downregulation of the Ras/ERK cascade in a feedback loop.
A computational account of joint SSRI and anti-inflammatory treatment
Authors: Reneaux Melissa , Mayberg Helen , Friston Karl , Pinotsis Dimitris A. 
Published: December 2023

AbstractWe present a computational model that elucidates the interplay between inflammation, serotonin levels, and brain activity. The model delineates how inflammation impacts extracellular serotonin, while cerebral activity reciprocally influences serotonin concentration. Understanding the reciprocal interplay between the immune system and brain dynamics is important, as unabated inflammation can lead to relapsing depression. The model predicts dynamics within the prefrontal cortex (PFC) and subcallosal cingulate cortex (SCC), mirroring patterns observed in depressive conditions. It also accommodates pharmaceutical interventions that encompass anti-inflammatory and antidepressant agents, concurrently evaluating their efficacy with regard to the severity of depressive symptoms.
Chemical probes to interrogate the extreme environment of mosquito larval guts
Authors: Guzmán Lindsay E. , Wijetunge Anjalee N. , Riske Brendan F. , Massani Brooke B. , Riehle Michael A. , Jewett John C. 
Published: December 2023

AbstractMosquito control methods are vital for the spread of life-threatening illnesses such as dengue fever, malaria, and yellow fever. Vector control technologies must be selective to minimize deleterious effects to our ecosystem. Successful methods that control mosquito larva populations utilize the uniquely high alkaline nature of the midgut. Here, we present novel protected triazabutadienes (pTBD) which are deprotected under basic conditions of the larval midgut, releasing an aryl diazonium ion (ADI) that results in protein modification. The probes contain a bioorthogonal terminal alkyne handle, enabling a selective Cu-click reaction with an azido-fluorophore for quantification by SDS PAGE and visualization using fluorescence microscopy. A control TBD, unable to release an ADI, did not label the midgut. We envision our chemical probes will aid in the development of new selective mosquito control methods thus preventing the spread of mosquito-borne illnesses with minimal impact on other organisms in the ecosystem.
Preclinical studies with ground germinated barley (GGB) for oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice
Authors: Martiniuk Frank , Mack Adra , Martiniuk Justin , Meinke Peter , Schoser Benedikt , Hu Gongshe , Kambitsis Angelo , Arvanitopoulos John , Arvanitopoulos Elena , Tchou-Wong Kam-Meng 
Published: December 2023

ABSTRACTGenetic deficiency of lysosomal acid maltase or acid α-glucosidase (GAA) results in the orphan disease known as glycogen storage disease type II or acid maltase deficiency (AMD) or Pompe disease (PD), encompassing at least four clinical subtypes of varying severity. PD results from mutations in theGAAgene and deficient GAA activity, resulting in the accumulation of glycogen in tissues (primarily muscle) and characterized by progressive skeletal muscle weakness and respiratory insufficiency. The current approved enzyme replacement therapy (ERT) for PD is via intravenous infusion of a recombinant human GAA (rhGAA) secreted by CHO cells (Myozyme, Sanofi-Genzyme) given once every 2 weeks and has shown varying efficacy in patients. Although the current ERT has proven to be very efficient in rescuing cardiac abnormalities and extending the life span of infants, the response in skeletal muscle is variable. In late-onset patients, only mild improvements in motor and respiratory functions have been achieved and the current ERT is unsatisfactory in the reversal of skeletal muscle pathology. Additional challenges for ERT include insufficient targeting/uptake of enzyme into disease-relevant tissues, poor tolerability due to severe ERT-mediated anaphylactic and immunologic reactions and the prohibitively high cost of lifelong ERT ($250-500K/year adult patient). A consensus at a Nov.-2019 US Acid Maltase Deficiency Association conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment. Our objective is to develop an innovative and affordable approach via barley GAA (bGAA) from ground germinated barley (GGB) or liquid GGB (L-GGB) for Oral-ERT for PD or as a daily supplement to Myozyme. To this end, we hypothesize that a bGAA produced in germinated barley can be ingested daily that allows the maintenance of a therapeutic level of enzyme. We have shown in extensive preliminary data thatGGBorL-GGBwas (1) enzymatically active, (2) was taken up by GAA KO mice and human WBCs to reverse the enzyme defect that was blocked by mannose-6-phosphate, (3) hydrolyzed glycogen, (4) increased significant changes in the clinical phenotype towards the WT levels in GAA KO mice dose-dependently, (5) taken up by PD myoblasts, lymphoid/fibroblasts cells to reverse the defect, (6) bGAA was ∼70kD, (7) Km, Vmax, pH optima, inhibitors and kinetics was similar to human placental GAA and an rhGAA and (8) was strain specific.
The relationship of job characteristics with in-role and extra-role performance: the mediating effect of job crafting
Authors: Mihalca Loredana , Ratiu Lucia , Helm Christoph , Brendea Gabriela , Metz Daniel 
Published: December 2023

PurposeDrawing upon the job demands-resources model, the purpose of this study is to investigate the differential relevance of contextual antecedents for job crafting dimensions (i.e. increasing structural and social job resources) and consequently for various aspects of work performance (in-role and extra-role performance). Despite considerable research on the role of job autonomy and social support in predicting job crafting, little attention has been paid to how problem-solving, a knowledge job characteristic, relates to job crafting dimensions.Design/methodology/approachSurvey data were collected from 282 employees belonging to different information technology companies in Romania. Structural equation modeling was used to examine the hypothesized relations.FindingsProblem-solving was positively related to both job crafting dimensions, whereas social support was positively related only to increasing social job resources. Unexpectedly, job autonomy predicted increasing structural resources only when social support was high, as the post-hoc analysis indicated. Furthermore, increasing structural job resources fully mediated the relationship of problem-solving with in-role performance and different types of extra-role behaviors, whereas increasing social resources did not act as a mediator.Originality/valueThe current study is the first to show that problem-solving is an important predictor for job crafting. Furthermore, this study contributes to the literature by revealing that crafting structural resources represents an important mechanism that explains the positive relationship between work design (i.e. problem-solving) and different performance facets.