bluuebunny/crossref_metadata_2025_split huggingface dataset:
The energy sensor AMPK orchestrates metabolic and translational adaptation in expanding T helper cells
Authors: Mayer Katharina A. , Smole Ursula , Zhu Ci , Derdak Sophia , Minervina Anastasia A. , Salnikova Maria , Witzeneder Nadine , Christamentl Anna , Boucheron Nicole , Waidhofer‐Söllner Petra , Trauner Michael , Hoermann Gregor , Schmetterer Klaus G. , Mamedov Ilgar Z. , Bilban Martin , Ellmeier Wilfried , Pickl Winfried F. , Gualdoni Guido A. , Zlabinger Gerhard J. 
Published: March 2021

AbstractThe importance of cellular metabolic adaptation in inducing robust T cell responses is well established. However, the mechanism by which T cells link information regarding nutrient supply to clonal expansion and effector function is still enigmatic. Herein, we report that the metabolic sensor adenosine monophosphate‐activated protein kinase (AMPK) is a critical link between cellular energy demand and translational activity and, thus, orchestrates optimal expansion of T cells in vivo. AMPK deficiency did not affect T cell fate decision, activation, or T effector cell generation; however, the magnitude of T cell responses in murine in vivo models of T cell activation was markedly reduced. This impairment was global, as all T helper cell subsets were similarly sensitive to loss of AMPK which resulted in reduced T cell accumulation in peripheral organs and reduced disease severity in pathophysiologically as diverse models as T cell transfer colitis and allergic airway inflammation. T cell receptor repertoire analysis confirmed similar clonotype frequencies in different lymphoid organs, thereby supporting the concept of a quantitative impairment in clonal expansion rather than a skewed qualitative immune response. In line with these findings, in‐depth metabolic analysis revealed a decrease in T cell oxidative metabolism, and gene set enrichment analysis indicated a major reduction in ribosomal biogenesis and mRNA translation in AMPK‐deficient T cells. We, thus, provide evidence that through its interference with these delicate processes, AMPK orchestrates the quantitative, but not the qualitative, manifestation of primary T cell responses in vivo.
Maternal high‐salt diet during pregnancy impairs synaptic plasticity and memory in offspring
Authors: Ge Qian , Hu Xiaoxuan , Ma Ning , Sun Meiqi , Zhang Liyun , Cai Zhenlu , Tan Ruolan , Lu Haixia 
Published: March 2021

AbstractExcess salt intake harms the brain health and cognitive functions, but whether a maternal high‐salt diet (HSD) affects the brain development and neural plasticity of offspring remains unclear. Here, using a range of behavioral tests, we reported that the offspring of maternal HSD subjects exhibited short‐ and long‐term memory deficits, especially in spatial memory in adulthood. Moreover, impairments in synaptic transmission and plasticity in the hippocampus were observed in adult offspring by using in vivo electrophysiology. Consistently, the number of astrocytes but not neurons in the hippocampus of the offspring from the HSD group were significantly decreased, and ERK and AKT signaling pathways involved in neurodevelopment were highly activated only during juvenile. In addition, the expression of synaptic proteins decreased both in juvenile and adulthood, and this effect might be involved in synaptic dysfunction. Collectively, these data demonstrated that the maternal HSD might cause adult offspring synaptic dysfunction and memory loss. It is possibly due to the reduction of astrocytes in juvenile.
Elevated HB‐EGF expression in neural stem cells causes middle age obesity by suppressing Hypocretin/Orexin expression
Authors: Xiang Jinnan , Zhang Shaoyang , Xu Ruiyao , Chu Hongshang , Biswas Soma , Yu Shuxiang , Miao Dengshun , Li Weidong , Li Shentian , Brown Andrew J. , Yang Hongyuan , Xu Yuhong , Li Baojie , Liu Huijuan 
Published: March 2021

AbstractObesity is common in the middle aged population and it increases the risks of diabetes, cardiovascular diseases, certain cancers, and dementia. Yet, its etiology remains incompletely understood. Here, we show that ectopic expression of HB‐EGF, an important regulator of neurogenesis, in Nestin+ neuroepithelial progenitors with the Cre‐LoxP system leads to development of spontaneous middle age obesity in male mice accompanied by hyperglycemia and insulin resistance. The Nestin‐HB‐EGF mice show decreases in food uptake, energy expenditure, and physical activity, suggesting that reduced energy expenditure underlies the pathogenesis of this obesity model. However, HB‐EGF expression in appetite‐controlling POMC or AgRP neurons or adipocytes fails to induce obesity. Mechanistically, HB‐EGF suppresses expression of Hypocretin/Orexin, an orexigenic neuropeptide hormone, in the hypothalamus of middle aged Nestin‐HB‐EGF mice. Hypothalamus Orexin administration alleviates the obese and hyperglycemic phenotypes in Nestin‐HB‐EGF mice. This study uncovers an important role for HB‐EGF in regulating Orexin expression and energy expenditure and establishes a midlife obesity model whose pathogenesis involves age‐dependent changes in hypothalamus neurons.
Exploration and Validation of Behavioral Pain Measures and Physiological Pain Measures Factor Structure Extracted From the Pain Assessment Tool Item Scores for Infants Admitted to Neonatal Intensive Care
Authors: Ilhan Emre , Pacey Verity , Brown Laura , Spence Kaye , Galea Claire , Adams Roger , Hush Julia M. 
Published: March 2021

Objective:
The objective of the study was to explore and then validate the factor structure of the Pain Assessment Tool (PAT).

Materials and Methods:
A retrospective medical record review was performed of all infants who were admitted to a neonatal intensive care unit between 2008 and 2018 and had 1 PAT assessment (n=2111). Scores on items of the PAT were collected. Infants were randomized to either the principal component analysis (n=1100) to explore the factor structure or confirmatory factor analysis (n=1011).

Results:
Infants in the 2 samples were demographically comparable. A 2-factor model, consisting of factors Behavioral and Physiological Pain Measures, was extracted, explaining 39.8% of the total variance. There was a low interfactor correlation (r=0.12), and both Behavioral (r=0.59) and Physiological Pain (r=0.37) Measures factor scores were correlated with nurses’ perception of pain scores. When the frequencies in the gestational age at birth categories were compared between upper and lower quartile score infants, there was more with pain at preterm than at term (χ2(3)=44.9, P<0.001) for the Physiological Pain Measures factor, whereas Behavioral Pain Measures frequency was higher at term than at preterm (χ2(3)=8.1, P<0.043). A similar pattern was observed for postmenstrual age at assessment categories: Behavioral Pain Measures (χ2(3)=41.8, P<0.001) Physiological Pain Measures (χ2(3)=46.1, P<0.001). The 2-factor correlated model performed better at explaining the observed variances: (χ2(13)=41.6, P<0.001) compared with rival models.

Discussion:
The PAT assesses both Behavioral Pain and Physiological Pain Measures, and these dimensions need to be considered separately when assessing pain in infants in the neonatal intensive care unit. Behavioral item scores may be insufficient for detecting pain in premature infants if used alone.
Hospital environmental influences and the rate of periprosthetic joint infections at a Canadian tertiary center: a retrospective chart review
Authors: Park Rosa , Wood Gavin C.A. , Hopman Wilma M. , Grant Heather J. , Yen David 
Published: March 2021

Background:
As the demand for total joint arthroplasty is expected to increase substantially in the coming years, the reported incidence of periprosthetic joint infections (PJI) after total joint arthroplasty is also expected to increase. This study investigated both patient factors and hospital factors and their relation to rates of infection for total hip arthroplasty (THA) and total knee arthroplasty (TKA). To the authors’ knowledge, this is the first paper to investigate rates of hand washing and carpet removal to PJIs.

Methods:
Traditional sample size calculations based on effect sizes or differences were not applicable in this observational, retrospective study. The annual rate of irrigation and debridement (I&D) at our institution was calculated. Hospital environmental influences for carpet removal and hand hygiene were obtained from hospital archives. Patient risk factors were obtained from the electronic patient charting system (PCS).

Results:
The average rate of I&D for THA was 2.8% and TKA was 1.9%. Hospital environmental influences (carpet removal and hand hygiene) were not associated with the rates of I&D.

Conclusions:
Despite rates of hand hygiene at our institution being reported as having a greater than 90% success rate, we did not find any association between successful hand hygiene practices and rates of PJI. Our study revealed that the rate of infection for THA at our institution was nearly two to three times higher than what was reported in the literature, and we believe poor patient selection played a factor.

Level of Evidence:
Level III.
Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients
Authors: Li Jun , Wu Zhao , Wang Gui-Qiang , Zhao Hong 
Published: March 2021

Abstract

Background:
Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.

Methods:
One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.

Results:
HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = −0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = −0.263, P = 0.014) and HBeAg-negative patients (r = −0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).

Conclusions:
HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.

Trial registration:
Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1
Environmental Contaminant Body Burdens and the Relationship with Blood Pressure Measures Among Indigenous Adults
Authors: Zuk Aleksandra M. , Liberda Eric N. , Tsuji Leonard J.S. 
Published: March 2021

Background:
Blood pressure (BP) increase cardiovascular disease (CVD) risk. Indigenous Canadians experience slightly higher CVD compared with nonIndigenous Canadians. This study examined the role of polychlorinated biphenyls (PCBs), other organic compound concentrations (OCs), and toxic metals on blood pressure measures among Indigenous Canadians.

Methods:
Using data from the Environment-and-Health Study, the sample was restricted to adults with valid BP measures and detectable body burden mixtures. In total, n = 759 participants were eligible, of which, n = 447(59%) were females. Principal Component Analysis (PCA) was used to reduce the complexity of the contaminant data. Orthogonal principal component (PC) variables, and sum (∑) of contaminant compounds were used as independent predictors in modified Poisson regression models with robust variance estimation, deriving prevalence ratios (PR) for hypertension, that is, systolic BP (SBP) ≥140 ml of mercury (mmHg), or diastolic BP ≥90 mm Hg. Additionally, using multivariable generalized linear regression, sex-stratified continuous SBP measure was regressed on ∑ contaminant compounds.

Results:
Two PCs were extracted from the PCA analysis. PCBs and OCs positively highly loaded on the first axis (PC-1). Lead loaded positively on the second (PC-2) axis. Hypertension was consistently associated with PC-1 across models, PR = 1.08 (95% confidence intervals = 1.003 to 1.172) fully adjusted model. Examining ∑ of contaminants, the strength of association with hypertension was strongest for ∑OCs compared with ∑PCBs. The measure of effect for continuous SBP measures with ∑ dichlorodiphenyltrichloroethane(p,p'-DDT) and dichlorodiphenyldichloroethylene(p,p’-DDE) concentrations although small was similar for both females and males, β = 0.04 (95% confidence intervals = 0.005 to 0.075) among females; however, for males the estimate is imprecise after adjusting for body mass index.

Conclusion:
This cross-sectional analysis found that PCBs and OCs were associated with associated prevalent hypertension; and exposure to OC pesticides, particularity DDT/DDE were found to be associated with prevalent SBP measures among females and not males.
Ocular Hypotension and Epiretinal Membrane as Risk Factors for Visual Deterioration Following Glaucoma Filtering Surgery
Authors: Chihara Etsuo , Chihara Tomoyuki 
Published: March 2021

Precis:
Postsurgical hypotension at 1 week and the presence of an epiretinal membrane (ERM) were significant risk factors for the deterioration of postsurgical visual acuity (VA) at 3 and 12 months, respectively.

Purpose:
The purpose of this study was to assess the effects of an ERM and postsurgical hypotension <6 mm Hg at 1 week on postsurgical VA loss.

Patients and Methods:
A total of 69 patients (69 eyes) who underwent trabeculectomy with adjunctive mitomycin C between 2017 and 2019 (mean follow-up period: 22.8 mo) were enrolled, and 14 parameters that could be associated with the deterioration of VA at 3 and 12 months were studied.

Results:
There was a significant association between VA loss at 3 months and postsurgical intraocular pressure at 1 week (P=0.006 by multiple regression) and hypotony maculopathy (P=0.024 by Fisher exact test). However, this association was lost at 12 months. Instead of postsurgical hypotension, the presence of an ERM was significantly associated with VA loss at 12 months (P=0.035 by Fisher exact test, and P=0.023 by logistic regression).

Conclusions:
Postsurgical hypotension at 1 week was significantly associated with mid-term, but not long-term, postsurgical VA loss. The presence of an ERM, which was not a risk factor for mid-term acuity loss, was a significant risk factor for VA loss at 12 months.
Adherence to recent antibiotic guidelines for acute uncomplicated cystitis
Authors: Amayun Ira 
Published: March 2021

ABSTRACT

Background:
In 2017, the Centers for Disease Control and Prevention (CDC) published guidelines for treating acute uncomplicated cystitis (AUC) with nitrofurantoin (NTF), sulfamethoxazole-trimethoprim (SMX-TMP), or fosfomycin (FM) as appropriate first-line agents.

Objective:
To evaluate whether provider adherence to prescribing NTF, SMX-TMP, or FM has improved since the 2017 CDC guidelines were released, and to examine outcomes relative to the use of prescribing guidelines.

Data source:
A literature review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and a systematic search for articles was conducted in the PubMed and Cochrane search engines using Boolean operators (AND, OR). The searches resulted in 56 published studies. After application of exclusion criteria, 11 peer-reviewed articles were ultimately included in this review.

Conclusion:
The review showed prescribers' increasing efforts to adhering to antibiotic prescription guidelines for treating AUC, such as the 2017 CDC guidelines. The studies presented strong evidence that NTF, SMX-TMP, and FM are equally efficacious and cost-effective for treating AUC without concern for antibiotic resistance. Studies that referenced prescription guidelines and local antibiotic resistance yielded desired patient outcomes in bacterial and symptom resolution and cost-effectiveness.

Implications for practice:
This article provides evidence and a platform for nurse practitioners to initiate collaborative efforts for structured AUC treatment guidelines in primary health care. To increase prescription adherence, electronic health records could be designed that would prompt prescribers to use updated local antibiotic resistance information and to use NTF, SMT-TMX, and FM as first-line agents.
An initiative to increase opioid overdose education and naloxone distribution for homeless veterans residing in contracted housing facilities
Authors: Rife Tessa , Tat Christina , Jones Jennifer , Pennington David L. 
Published: March 2021

ABSTRACT

Background:
Up to 35% of veterans with opioid use disorder (OUD) are homeless, and veterans with OUD are nearly 29 times higher risk for homelessness; however, few are prescribed naloxone, an evidence-based intervention to reverse life-threatening opioid overdose.

Local problem:
Many housing facilities for homeless veterans contracted with the San Francisco Veterans Affairs Health Care System are located in neighborhoods with high rates of opioid overdose. No systematic interventions have been implemented to provide opioid overdose education and naloxone kits to veterans and staff at these facilities. This quality improvement (QI) initiative aimed to increase provision of opioid overdose education and naloxone for veterans and staff at contracted housing facilities.

Methods:
This was a prospective single-arm cohort QI intervention. All contracted veteran housing programs were included. Descriptive statistics evaluated results.

Interventions:
A total of 18 contracted veteran housing programs were contacted from July 2019 through January 2020 to schedule training.

Results:
Of those, 13 programs responded to outreach and 10 visits were completed at 8 housing facilities. Training was provided by pharmacist and nurse practitioner trainers to 26 staff members and 59 veterans. Naloxone was prescribed to 37 veterans.

Conclusions:
A pharmacist-led and nurse practitioner–led initiative was effective in increasing veteran and staff access to opioid overdose education and naloxone at >44% contracted veteran housing facilities. Challenges included lack of response from housing programs, low veteran turn out, and inability to provide naloxone to veterans not enrolled/ineligible for health care. Future initiatives should examine strategies to standardize access in homeless veterans' programs.
Experimentally evoked pain in Alzheimer's disease
Authors: Anderson Alison R. , Iversen W. Larkin , Carter Michael A. , Moss Karen O. , Cowan Ronald L. , Monroe Todd B. 
Published: March 2021

ABSTRACT

Background:
Pain continues to be underrecognized and undertreated in Alzheimer's disease (AD) while existing guidance about pain assessment and management in dementia is not widespread. Brain regions involved in pain processing and modulation are damaged during AD, and the pain experience in AD is not well understood. Experimental pain studies using psychophysics can further our understanding of the pain experience in AD, which may lead to improved assessment and management of pain in people living with AD.

Objective:
A systematic review was conducted to explicate the current understanding of experimentally evoked pain in AD from primary research using psychophysical methods.

Data Sources:
Peer-reviewed publications were found via PubMed, CINAHL, and PsycINFO. A total of 18 primary research, peer-reviewed full articles that met inclusion criteria were included, representing 929 total participants.

Conclusions:
Experimentally evoked pain in people with AD demonstrates that despite cognitive impairment and a reduced ability to effectively communicate, individuals with AD experience pain similar to or more unpleasant than cognitively intact older adults. This may mean amplified pain unpleasantness in people with AD.

Implications for practice:
Our current best practices need to be widely disseminated and put into clinical practice. Self-report of pain continues to be the gold standard, but it is ineffective for noncommunicative patients and those unable to understand pain scales or instructions because of memory/cognitive impairment. Instead, pain treatment should be ethically initiated based on patient reports and behaviors, caregiver/surrogate reports, review of the medical record for painful conditions, analgesic trials, and regular reassessments.
Lung Navigation Ventilation Protocol to Optimize Biopsy of Peripheral Lung Lesions
Authors: Bhadra Krish , Setser Randolph M. , Condra William , Pritchett Michael A. 
Published: March 2021

Background:
Computed tomography-to-body divergence caused by respiratory motion, atelectasis, diaphragmatic motion and other factors is an obstacle to peripheral lung biopsies. We examined a conventional ventilation strategy versus a lung navigation ventilation protocol (LNVP) optimized for intraprocedural 3-dimensional image acquisition and bronchoscopic biopsy of peripheral lung nodules.

Methods:
A retrospective, single center study was conducted in consecutive subjects with peripheral lung lesions measuring <30 mm. Effects of ventilation strategies including atelectasis and tool-in-lesion confirmation were assessed using cone beam computed tomography images. Diagnostic yield was also evaluated. Complications were assessed through 7 days.

Results:
Fifty subjects were included (25 per group) with 27 nodules in the conventional group and 25 nodules in the LNVP group. Atelectasis was assessed by 2 blinded readers: [reader 1 (R1) and reader 2 (R2)]. Atelectasis was more prevalent in the conventional ventilation group, both for dependent atelectasis (R1: 64% and R2: 68% vs. R1: 36% and R2: 16%, P=0.00014) and sublobar/lobar atelectasis (R1: 48% and R2: 56% vs. R1: 20% and R2: 32%, P=0.01). Similarly, the target lesion was obscured due to atelectasis more often in the conventional ventilation group (R1: 36% and R2: 36% vs. R1: 4% and R2: 8%, P=0.01). Diagnostic yield was 70% for conventional ventilation and 92% for LNVP (P=0.08).

Conclusion:
LNVP demonstrated markedly reduced dependent and sublobar/lobar atelectasis and lesions either partially or completely obscured by atelectasis compared with conventional ventilation. Future prospective studies are necessary to understand the impact of protocolized ventilation strategies for bronchoscopic biopsy of peripheral lung lesions.