bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychosocial risk in healthcare workers after one year of COVID-19
Authors: Moreno Martínez M , Feijoo-Cid M , Fernández-Cano M I , Llorens-Serrano C , Navarro-Giné A 
Published: December 2022

Abstract

Background
The COVID-19 pandemic overwhelmed the capacity of the healthcare system, affecting the volume of demands and the care tasks of healthcare workers.

Aims
To examine the health indicators and exposure to psychosocial risks of Spanish healthcare workers 1 year into the COVID-19 pandemic and compare them with the results of the first wave.

Methods
We conducted a cross-sectional study using an online questionnaire (April–May 2020 and 2021). The data stem from the COTS 1 project database, corresponding to the first wave of COVID-19 (n = 1989) and COTS 2 (n = 1716) corresponding to 1 year later. The samples were independent. The prevalence of exposure to psychosocial risks and adverse health indicators was estimated for every occupational group, segregating the data by sex.

Results
Professionals of all types presented worse perception of health. In general, the results were worse for women, while geriatric assistants presented the greatest exposure to psychosocial risk in COTS 2 compared to COTS 1. Sleep problems, high quantitative demands and high concern about becoming infected and spreading COVID-19 were cross-disciplinary in COTS 1, while worse perception of health, high pace of work, high work–life conflict and low development opportunities stood out in COTS 2.

Conclusions
Exposure to psychosocial risks was already high during the first wave and a significant decline in working conditions was observed. The prolongation of the pandemic exacerbated these results and seems to have multiplied the pre-existing inequalities between the axes of segregation in the labour market.
Organelle-targeted biosensors reveal distinct oxidative events during pattern-triggered immune responses
Authors: Arnaud Dominique , Deeks Michael J , Smirnoff Nicholas 
Published: December 2022

AbstractReactive oxygen species are produced in response to pathogens and pathogen-associated molecular patterns, as exemplified by the rapid extracellular oxidative burst dependent on the NADPH oxidase isoform RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) in Arabidopsis (Arabidopsis thaliana). We used the H2O2 biosensor roGFP2-Orp1 and the glutathione redox state biosensor GRX1-roGFP2 targeted to various organelles to reveal unsuspected oxidative events during the pattern-triggered immune response to flagellin (flg22) and after inoculation with Pseudomonas syringae. roGFP2-Orp1 was oxidized in a biphasic manner 1 and 6 h after treatment, with a more intense and faster response in the cytosol compared to chloroplasts, mitochondria, and peroxisomes. Peroxisomal and cytosolic GRX1-roGFP2 were also oxidized in a biphasic manner. Interestingly, our results suggested that bacterial effectors partially suppress the second phase of roGFP2-Orp1 oxidation in the cytosol. Pharmacological and genetic analyses indicated that the pathogen-associated molecular pattern-induced cytosolic oxidation required the BRI1-ASSOCIATED RECEPTOR KINASE (BAK1) and BOTRYTIS-INDUCED KINASE 1 (BIK1) signaling components involved in the immune response but was largely independent of NADPH oxidases RBOHD and RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF) and apoplastic peroxidases peroxidase 33 (PRX33) and peroxidase 34 (PRX34). The initial apoplastic oxidative burst measured with luminol was followed by a second oxidation burst, both of which preceded the two waves of cytosolic oxidation. In contrast to the cytosolic oxidation, these bursts were RBOHD-dependent. Our results reveal complex oxidative sources and dynamics during the pattern-triggered immune response, including that cytosolic oxidation is largely independent of the preceding extracellular oxidation events.
Specific suppression of long terminal repeat retrotransposon mobilization in plants
Authors: Brestovitsky Anna , Iwasaki Mayumi , Cho Jungnam , Adulyanukosol Natthawut , Paszkowski Jerzy , Catoni Marco 
Published: December 2022

AbstractThe tissue culture passage necessary for the generation of transgenic plants induces genome instability. This instability predominantly involves the uncontrolled mobilization of LTR retrotransposons (LTR-TEs), which are the most abundant class of mobile genetic elements in plant genomes. Here, we demonstrate that in conditions inductive for high LTR-TE mobilization, like abiotic stress in Arabidopsis (Arabidopsis thaliana) and callus culture in rice (Oryza sativa), application of the reverse transcriptase (RT) inhibitor known as Tenofovir substantially affects LTR-TE RT activity without interfering with plant development. We observed that Tenofovir reduces extrachromosomal DNA accumulation and prevents new genomic integrations of the active LTR-TE ONSEN in heat-stressed Arabidopsis seedlings, and transposons of O. sativa 17 and 19 (Tos17 and Tos19) in rice calli. In addition, Tenofovir allows the recovery of plants free from new LTR-TE insertions. We propose the use of Tenofovir as a tool for studies of LTR-TE transposition and for limiting genetic instabilities of plants derived from tissue culture.
Pediatric traumatic brain injury in a high-income developing country: experience at a level 1 neuro-trauma center
Authors: Al-Busaidi Fatma , Allawati Moosa , Al-Araimi Maryam Al-Fannah , Alhosni Asma , Al-Jubouri Yasir , Al-Mufargi Younis , Ali Mohammed , Al-Saadi Hatem , Al-Saadi Tariq 
Published: December 2022

Abstract

Background
Data on the incidence, prevalence and mortality of pediatric traumatic brain injuries (TBIs) in developing countries are not readily available or do not exist.

Aim
The aim of this study was to study the epidemiology of pediatric TBI in developing countries.

Methods
A retrospective study was conducted in a high-volume Neurosurgery Department where we reviewed pediatric cases presenting with TBI between January 2015 and December 2019. Data were collected from the electronic medical records including the patients’ demographics, neuro-vital signs, mechanism of TBI and treatment types. Radiological images were screened, and patients were classified according to the type of intracranial hemorrhage. The patient’s outcome and Glasgow Coma Scale on discharge were also recorded.

Result
Nine hundred and eighty-five cases with TBI were admitted over the period of 5 years. The average age was 53.3 months standard deviation (SD) of 39.4. Male gender accounted for 63.7% of the cases. The most common mechanisms of injuries were falls and road traffic accidents/motor vehicle collisions (63.3%, 18.3%), respectively. Nausea and vomiting followed by altered consciousness and drowsiness were the commonest presenting symptoms. Mild TBI accounted for 85.2% of the cases and the majority (92.08%) were treated conservatively (P &lt; 0.005). 93.3% of the cases were categorized as mild head injury upon discharge. The mortality rate was 1.6% in severe TBI cases.

Conclusion
Children less than 4 years of age were highly affected by TBI. This study gives emergency physicians and neurosurgeons in developing countries an expectation about TBI in pediatric cases and the immediate management to prevent further complications.
Mice harboring a R133L heterozygous mutation in LMNA exhibited ectopic lipid accumulation, aging, and mitochondrial dysfunction in adipose tissue
Authors: Qiu Ruojun , Wang Shuo , Lin Dingyi , He Yingzi , Huang Shaohan , Wu Beibei , Li Hong , Wang Min , Zheng Fenping 
Published: December 2022

AbstractThe LMNA gene encodes for the nuclear envelope proteins lamin A and C (lamin A/C). A novel R133L heterozygous mutation in the LMNA gene causes atypical progeria syndrome (APS). However, the underlying mechanism remains unclear. Here, we used transgenic mice (LmnaR133L/+ mice) that expressed a heterozygous LMNA R133L mutation and 3T3‐L1 cell lines with stable overexpression of LMNA R133L (by lentiviral transduction) as in vivo and in vitro models to investigate the mechanisms of LMNA R133L mutations that mediate the APS phenotype. We found that a heterozygous R133L mutation in LMNA induced most of the metabolic disturbances seen in patients with this mutation, including ectopic lipid accumulation, limited subcutaneous adipose tissue (SAT) expansion, and insulin resistance. Mitochondrial dysfunction and senescence promote ectopic lipid accumulation and insulin resistance. In addition, the FLAG‐mediated pull‐down capture followed by mass spectrometry assay showed that p160 Myb‐binding protein (P160 MBP; Mybbp1), the critical transcriptional repressor of PGC‐1α, was bound to lamin A/C. Increased Mybbp1 levels in tissues and greater Mybbp1‐lamin A/C binding in nuclear inhibit PGC‐1α activity and promotes mitochondrial dysfunction. Our findings confirm that the novel R133L heterozygous mutation in the LMNA gene caused APS are associated with marked mitochondrial respiratory chain impairment, which were induced by decreased PGC‐1α levels correlating with increased Mybbp1a levels in nuclear, and a senescence phenotype of the subcutaneous fat.
Liver‐specific deletion of microRNA‐34a alleviates ductular reaction and liver fibrosis during experimental cholestasis
Authors: Wan Ying , Zhou Tianhao , Slevin Elise , Koyama Sachiko , Li Xuedong , Harrison Kelly , Li Tian , Zhou Bingru , Lorenzo Sugeily Ramos , Zhang Yudian , Xu Wenjuan , Klaunig James E. , Wu Chaodong , Shetty Ashok K. , Huang Chiung‐Kuei , Meng Fanyin 
Published: December 2022

AbstractPrimary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammatory responses and fibrotic scar formation leading to cholestasis. Ductular reaction and liver fibrosis are typical liver changes seen in human PSC and cholestasis patients. The current study aimed to clarify the role of liver‐specific microRNA‐34a in the cholestasis‐associated ductular reaction and liver fibrosis. We demonstrated that miR‐34a expression was significantly increased in human PSC livers along with the enhanced ductular reaction, cellular senescence, and liver fibrosis. A liver‐specific miR‐34a knockout mouse was established by crossing floxed miR‐34a mice with albumin‐promoter‐driven Cre mice. Bile duct ligation (BDL) induced liver injury characterized by necrosis, fibrosis, and immune cell infiltration. In contrast, liver‐specific miR‐34a knockout in BDL mice resulted in decreased biliary ductular pathology associated with the reduced cholangiocyte senescence and fibrotic responses. The miR‐34a‐mediated ductular reactions may be functioning through Sirt‐1‐mediated senescence and fibrosis. The hepatocyte‐derived conditioned medium promoted LPS‐induced fibrotic responses and senescence in cholangiocytes, and miR‐34a inhibitor suppressed these effects, further supporting the involvement of paracrine regulation. In conclusion, we demonstrated that liver‐specific miR‐34a plays an important role in ductular reaction and fibrotic responses in a BDL mouse model of cholestatic liver disease.
Innately expressed estrogen‐related receptors in the skeletal muscle are indispensable for exercise fitness
Authors: Sopariwala Danesh H. , Rios Andrea S. , Pei Guangsheng , Roy Anirban , Tomaz da Silva Meiricris , Thi Thu Nguyen Hao , Saley Addison , Van Drunen Rachel , Kralli Anastasia , Mahan Kristin , Zhao Zhongming , Kumar Ashok , Narkar Vihang A. 
Published: December 2022

AbstractTranscriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how exercise improves fitness. Here, we have elucidated the role of nuclear receptors, estrogen‐related receptor alpha and gamma (ERRα/γ) in regulating myofibrillar composition, contractility, and exercise capacity in skeletal muscle. We used muscle‐specific single or double (DKO) ERRα/γ knockout mice to investigate the effect of ERRα/γ deletion on muscle and exercise parameters. Individual knockout of ERRα/γ did not have a significant impact on the skeletal muscle. On the other hand, DKO mice exhibit pale muscles compared to wild‐type (WT) littermates. RNA‐seq analysis revealed a predominant decrease in expression of genes linked to mitochondrial and oxidative metabolism in DKO versus WT muscles. DKO muscles exhibit marked repression of oxidative enzymatic capacity, as well as mitochondrial number and size compared to WT muscles. Mitochondrial function is also impaired in single myofibers isolated from DKO versus WT muscles. In addition, mutant muscles exhibit reduced angiogenic gene expression and decreased capillarity. Consequently, DKO mice have a significantly reduced exercise capacity, further reflected in poor fatigue resistance of DKO mice in in vivo contraction assays. These results show that ERRα and ERRγ together are a critical link between muscle aerobic capacity and exercise tolerance. The ERRα/γ mutant mice could be valuable for understanding the long‐term impact of impaired mitochondria and vascular supply on the pathogenesis of muscle‐linked disorders.
Effect of intravenous antihypertensives on outcomes of severe hypertension in hospitalized patients without acute target organ damage
Authors: Ghazi Lama , Li Fan , Simonov Michael , Yamamoto Yu , Nugent James T. , Greenberg Jason H. , Bakhoum Christine Y. , Peixoto Aldo J. , Wilson F. Perry 
Published: December 2022

Background:
Treatment of severe inpatient hypertension (HTN) that develops during hospitalization is not informed by guidelines. Intravenous (i.v.) antihypertensives are used to manage severe HTN even in the absence of acute target organ damage; however they may result in unpredictable blood pressure (BP) reduction and cardiovascular events. Our goal was to assess the association between i.v. antihypertensives and clinical outcomes in this population.

Methods:
This is a multihospital retrospective study of adults admitted for reasons other than HTN who develop severe HTN during hospitalization without acute target end organ damage. We defined severe HTN as BP elevation of systolic >180 or diastolic >110 mmHg. Treatment was defined as receiving i.v. antihypertensives within 3 h of BP elevation. We used overlap propensity score weighted Cox models to study the association between treatment and clinical outcomes during index hospitalization.

Results:
Of 224 265 unique, nonintensive care unit hospitalizations, 20 383 (9%) developed severe HTN, of which 5% received i.v. antihypertensives and 79% were untreated within 3 h of severe BP elevation. In the overlap propensity weighted population, patients who received i.v. antihypertensives were more likely to develop myocardial injury (5.9% in treated versus 3.6% in untreated; hazard ratio [HR]: 1.6 [1.13, 2.24]). Treatment was not associated with increased risk of stroke (HR: 0.7 [0.3, 1.62]), acute kidney injury (HR: 0.97 [0.81, 1.17]), or death (HR: 0.86 [0.49, 1.51]).

Conclusions:
Intravenous antihypertensives were associated with increased risk of myocardial injury in patients who develop severe HTN during hospitalization. These results suggest that i.v. antihypertensives should be used with caution in patients without acute target organ damage.
Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes
Authors: Agarwal Rajiv , Ruilope Luis M. , Ruiz-Hurtado Gema , Haller Hermann , Schmieder Roland E. , Anker Stefan D. , Filippatos Gerasimos , Pitt Bertram , Rossing Peter , Lambelet Marc , Nowack Christina , Kolkhof Peter , Joseph Amer , Bakris George L 
Published: December 2022

Objective:
Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist with a short half-life. Its effects on cardiorenal outcomes were thought to be mediated primarily via nonhemodynamic pathways, but office blood pressure (BP) measurements were insufficient to fully assess hemodynamic effects. This analysis assessed the effects of finerenone on 24-h ambulatory BP in patients with chronic kidney disease and type 2 diabetes.

Methods:
ARTS-DN (NCT01874431) was a phase 2b trial that randomized 823 patients with type 2 diabetes and chronic kidney disease, with urine albumin-to-creatinine ratio ≥30 mg/g and estimated glomerular filtration rate of 30–90 ml/min per 1.73 m2 to placebo or finerenone (1.25–20 mg once daily in the morning) administered over 90 days. Ambulatory BP monitoring (ABPM) over 24 h was performed in a subset of 240 patients at screening, Day 60, and Day 90.

Results:
Placebo-adjusted change in 24-h ABPM systolic BP (SBP) at Day 90 was –8.3 mmHg (95% confidence interval [CI], –16.6 to 0.1) for finerenone 10 mg (n = 27), –11.2 mmHg (95% CI, –18.8 to –3.6) for finerenone 15 mg (n = 34), and –9.9 mmHg (95% CI, –17.7 to –2.0) for finerenone 20 mg (n = 31). Mean daytime and night-time SBP recordings were similarly reduced and finerenone did not increase the incidence of SBP dipping. Finerenone produced a persistent reduction in SBP over the entire 24-h interval.

Conclusions:
Finerenone reduced 24-h, daytime, and night-time SBP. Despite a short half-life, changes in BP were persistent over 24 h with once-daily dosing in the morning.
Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia
Authors: Cuomo Alessandro , Aguglia Eugenio , Biagini Stefano , Carano Alessandro , Clerici Massimo , D'Agostino Armando , De Filippis Sergio , De Giorgi Serafino , Goracci Arianna , Libri Claudia , Lombardi Francesco , Lupi Matteo , Maina Giuseppe , Martinotti Giovanni , Nigro Pietro , Pettorruso Mauro , Ricci Valerio , Rossi Eros , Russo Felicia , Fagiolini Andrea ,   The Italian Clinical Psychopharmacology Working Group
Published: December 2022

Abstract

Purpose/Background
Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients.

Methods/Procedures
We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers.

Findings/Results
Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects.

Implications/Conclusions
The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.
Real-World Clinical Practice Among Patients With Bipolar Disorder and Chronic Kidney Disease on Long-term Lithium Therapy
Authors: Kumar Rakesh , Joseph Boney , Pazdernik Vanessa M. , Geske Jennifer , Nuñez Nicolas A. , Pahwa Mehak , Kashani Kianoush B. , Veldic Marin , Betcher Hannah K. , Moore Katherine M. , Croarkin Paul E. , Ozerdem Aysegul , Cuellar-Barboza Alfredo B. , McElroy Susan L. , Biernacka Joanna M. , Frye Mark A. , Singh Balwinder 
Published: December 2022

Abstract

Purpose
Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design.

Methods
Adult BD patients on LTLT for ≥1 year who enrolled in the Mayo Clinic Bipolar Disorder Biobank and developed CKD (stage 3) were included, and our study was approved by the Mayo Clinic Institutional Review Board. The primary outcome was the time to the first mood episode after CKD diagnosis among the lithium (Li) continuers and discontinuers. Cox proportional hazards models were used to estimate the time to the first mood episode. We tested for differences in other medication changes between the Li continuers and discontinuers group using Mantel-Haenszel χ2 tests (linear associations).

Results
Of 38 BD patients who developed CKD, 18 (47%) discontinued Li, and the remainder continued (n = 20). The median age of the cohort was 56 years (interquartile range [IQR], 48–67 years), 63.2% were female, and 97.4% were White. As compared with continuers, discontinuers had more psychotropic medication trials (6 [IQR, 4–6] vs 3 [IQR, 2–5], P = 0.02), a higher rate of 1 or more mood episodes (61% vs 10%, P = 0.002), and a higher risk of a mood episode after CKD diagnoses (Hazard Ratio, 8.38; 95% confidence interval, 1.85–38.0 [log-rank P = 0.001]].

Conclusions
Bipolar disorder patients on LTLT who discontinued Li had a higher risk for relapse and a shorter time to the first mood episode, suggesting a need for more thorough discussion before Li discontinuation after the CKD diagnosis.
α-Lipoic Acid as Adjunctive Treatment for Schizophrenia
Authors: De Lima David Nunes , Costa Filho Carlos Winston Luz , Frota Ilgner Justa , de Oliveira Alissandra Lima Barbosa , Menezes Carlos Eduardo de Souza , Chaves Filho Adriano José Maia , Viana Glautemberg de Almeida , Campos Eugênio de Moura , Collares Mônica , de Queiroz Maria Goretti Rodrigues , da Cruz Fonseca Said Gonçalvez , Vasconcelos Silvânia Maria Mendes , Macêdo Danielle S. , Sanders Lia Lira Olivier 
Published: December 2022

Abstract

Background/Purpose
There is evidence for low endogenous antioxidant levels and oxidative imbalance in patients with schizophrenia. A previous open-label study with α-lipoic acid (ALA), a potent antioxidant, improved patients' negative and cognitive symptoms and markers of lipid peroxidation. Here we report the results of a randomized double-blind, placebo-controlled study to verify the response of patients with schizophrenia to adjunctive treatment with ALA (100 mg/d) in a 4-month follow-up.

Methods
We conducted a 16-week, double-blind, placebo-controlled study of ALA at 100 mg/d dosages. We compared negative and positive symptoms, cognitive function, extrapyramidal symptoms, body mass index, and oxidative/inflammatory parameters between placebo and control groups.

Results
We found no significant improvement in body mass index, cognition, psychopathology, antipsychotic adverse effects, or oxidative stress and inflammation in the experimental group compared with placebo. The whole group of patients improved in several measures, indicating a strong placebo effect in this population. A surprising finding was a significant decrease in red blood cells, white blood cells, and platelets in the group treated with ALA.

Conclusions
The decrease in red blood cells, white blood cells, and platelet counts requires further investigation and attention when prescribing ALA for patients with schizophrenia.