bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRD4 Inhibition Protects Against Myocardial Ischemia/Reperfusion Injury by Suppressing Inflammation and Oxidative Stress Through the PI3K/AKT Signaling Pathway
Authors: Wei Hongwei , Xue Qingjian , Sun Lei , Lv Jie 
Published: September 2021

Abstract:
This study aims to investigate the effect and the related mechanisms of bromodomain-containing protein 4 (BRD4) inhibition on myocardial ischemia/reperfusion (I/R) injury. In vivo and in vitro myocardial I/R models were constructed. Expression of BRD4 was examined by RT-qPCR and Western blot. I/R injury was evaluated by analyzing cardiac function and the activity of biochemical markers of myocardial injury. Inflammation and oxidative stress were determined by measuring the levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and superoxide dismutase. The activation of the PI3K/AKT signaling pathway was tested by the phosphorylation of p85 and AKT. We found BRD4 was significantly increased in the myocardial tissues after myocardial I/R injury. BRD4 inhibition suppressed the indices of cardiac function and the biochemical markers of myocardial injury. I/R-induced inflammation and oxidative stress were suppressed by shBRD4 in vivo and in vitro. In addition, BRD4 inhibition significantly increased the relative protein expression levels of p-p85, p-AKT T308, and p-AKT S473. In conclusion, this study for the first time demonstrated the protective effect of BRD4 inhibition on myocardial I/R injury in vivo and in vitro, and this effect was related to the suppression of inflammation and oxidative stress through the activation of the PI3K/AKT signaling pathway.
A Tool to Distinguish Viral From Bacterial Pneumonia
Authors: Tagarro Alfredo , Moraleda Cinta , Domínguez-Rodríguez Sara , Rodríguez Mario , Martín María Dolores , Herreros María Luisa , Jensen Julia , López Agustín , Galán Juan Carlos , Otheo Enrique 
Published: September 2021

Background:
Establishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. Most of the admitted children with CAP receive antibiotics. We aimed to build and validate a diagnostic tool combining clinical, analytical and radiographic features to differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria.

Methods:
Design—observational, multi-center, prospective cohort study was conducted in 2 phases. Settings: 24 secondary and tertiary hospitals in Spain. Patients—A total of 495 consecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. Interventions—A score with 2 sequential steps was built (training set, 70% patients, and validation set 30%). Step 1 differentiates between viral and bacterial CAP and step 2 between typical and atypical bacterial CAP. Optimal cutoff points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. Main outcome measures—Viral or bacterial etiology.

Results:
In total, 262 (53%) children (median age: 2 years, 52.3% male) had an etiologic diagnosis. In step 1, bacterial CAPs were classified with a sensitivity = 97%, a specificity = 48%, and a ROC’s area under the curve = 0.81. If a patient with CAP was classified as bacterial, he/she was assessed with step 2. Typical bacteria were classified with a sensitivity = 100%, a specificity = 64% and area under the curve = 0.90. We implemented the score into a mobile app named Pneumonia Etiology Predictor, freely available at usual app stores, that provides the probability of each etiology.

Conclusions:
This 2-steps tool can facilitate the physician’s decision to prescribe antibiotics without compromising patient safety.
Are functional outcomes and reoperation rates really better than those of cementless stems in displaced femoral neck fractures? An updated systematic review and meta-analysis of randomized controlled trials in current-generation stem designs
Authors: Fu Chun-Wei , Ma Hsuan-Hsiao , Liu Yueh-Ching , Lu Yung-Chang , Huang Tung-Fu , Chang Ming-Chau , Chen Wei-Ming 
Published: September 2021

Background:
The aim of the study was to conduct a systematic review and meta-analysis to compare the functional outcomes and reoperation rates of cemented and cementless hip arthroplasty for treating displaced femoral neck fractures in elderly patients.

Methods:
Systematic searches were conducted of literature up to December 2018 on PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials (RCTs) concerning current-generation stem designs only. Two reviewers independently determined eligibility, extracted the outcome data and assessed the risk of bias of eligible studies. The follow-up data and complication rates were pooled by using random-effects models and fixed-effects models, with mean differences and risk ratios for continuous and dichotomous variables, respectively.

Results:
Eight RCTs involving 1361 patients (1361 hips) were included in the meta-analysis. Cemented stems were associated with fewer implant-related complications (odds ratio [OR] = 0.303; 95% confidence interval [CI], 0.185%-0.496%; p < 0.001) and reoperations (OR = 0.492; 95% CI, 0.247%-0.977%; p = 0.043). There were no statistically significant differences between groups in functional outcomes, including those assessed by the EuroQol(EQ)-5D and Harris Hip Score, mortality rates, major systemic complications, minor local complications, operation times, intraoperative blood losses, and lengths of hospital stays.

Conclusion:
In treating displaced femoral neck fracture in elderly patients with hip arthroplasty with current-generation stems, cemented stems were found to have fewer implant-related complications and reoperations than those of cementless stems. Functional outcomes and mortality rates were similar between the groups.
Increased incidence of neurogenic bladder after radical hysterectomy for cervical cancer: A nationwide population-based cohort study
Authors: Chou Meng-Han , Meng En , Wu Sheng-Tang , Cha Tai-Lung , Sun Guang-Huan , Yu Dah-Shyong , Chung Chi-Hsiang , Chien Wu-Chien 
Published: September 2021

Background:
The effect of radical hysterectomy for patients with cervical cancer on voiding function remains controversial. The purpose of this study was to examine the association between radical hysterectomy for patients with cervical cancer and the odds of developing neurogenic bladder by using data from the National Health Insurance Research Database (NHIRD) in Taiwan.

Methods:
We identified 17 936 patients who underwent radical hysterectomy for cervical cancer between 2000 and 2013 among inpatients registered in the Longitudinal Health Insurance Database in Taiwan. Of the patients, those diagnosed as having cervical cancer without radical hysterectomy were selected and compared as a matched control group. Patients diagnosed as having cervical cancer before the index date, those with neurogenic bladder dysfunction before tracking, and those aged <20 years were excluded. The hazard ratios (HRs) of neurogenic bladder and other variants of interest were further calculated using a multivariate Cox regression analysis. The cutoff p value of <0.05 was regarded as statistically significant.

Results:
The adjusted HR (aHR) of subsequent neurogenic bladder was higher in the hysterectomy group (aHR = 1.205; 95% CI, 1.086-1.440; p = 0.029) than in the control group during the follow-up period. As to the age subgroups, the patients aged 20 to 44 years (aHR = 3.321, p = 0.001) had a significantly increased risk of developing neurogenic bladder after radical hysterectomy as compared with those aged 45 to 64 years (aHR = 1.193, p = 0.012).

Conclusion:
Patients with cervical cancer undergoing radical hysterectomy have an increased risk of neurogenic bladder, which may result from nerve denervation caused by the operation. These patients should be informed of the potential risk of voiding dysfunction during discussion of the subsequent management for cervical cancer.
Effect of epidural analgesia on long-term outcomes after curative surgery for pancreatic cancer: A single-center cohort study in Taiwan
Authors: Lin Kuan-Ju , Hsu Fu-Kai , Shyr Yi-Ming , Ni Yu-Wei , Tsou Mei-Yung , Chang Kuang-Yi 
Published: September 2021

Background:
Whether epidural anesthesia and analgesia (EA) improves long-term outcomes after pancreatic cancer surgery remains controversial. We conducted this retrospective cohort study to investigate the influence of EA on cancer recurrence and overall survival after surgery for pancreatic cancer.

Methods:
We conducted an electronic medical chart review of patients with pancreatic cancer who underwent curative resection at our hospital from 2008 to 2017 and were followed up until December 2019. Patient demographics, anesthetic and surgical characteristics, and pathologic features were also collected. The effects of EA on postoperative cancer recurrence and overall survival were evaluated using proportional hazards regression models with inverse probability of treatment weighting (IPTW) based on propensity scores to balance unequal distributions of observed covariates. For sensitivity analysis, multivariable regression modeling and quintile-stratified propensity adjustments were also used.

Results:
Among the 252 included patients, the median follow-up period was 15.9 months (interquartile range 6.8–28.2 months), and 88 (35%) received EA after pancreatic cancer surgery. EA was not associated with greater cancer recurrence (IPTW adjusted HR: 0.98; 95% CI, 0.78%-1.24%; p = 0.87) or all-cause mortality (IPTW adjusted HR: 1.02; 95% CI, 0.82%-1.27%; p = 0.85) after pancreatic cancer resection. In sensitivity analysis, both the multivariable and stratified Cox regression analyses failed to demonstrate significant effects of EA on cancer recurrence and survival after surgery.

Conclusion:
There were no significant associations between EA and cancer recurrence and overall survival after curative surgery for pancreatic cancer. Prospective studies should be considered to elucidate the relationship between EA and cancer outcomes after pancreatic cancer surgery.
Physician Prescribing and Referral Patterns in Children with Cerebral Visual Impairment
Authors: Rice Melissa L. , Sandoval Monica A. , Castleberry Katherine M. , Schwartz Terry L. 
Published: September 2021

SIGNIFICANCE
Cerebral visual impairment (CVI) is the leading cause of visual impairment in the developed world. Providing children with CVI with the appropriate treatment ensures the best possible visual outcome and potentially improves quality of life.

PURPOSE
The purpose of this study was to determine physician prescribing and visual rehabilitation referral patterns in children with CVI.

METHODS
A retrospective chart review was completed on children with CVI examined at Cincinnati Children's Hospital Medical Center from January 1, 2008, to March 1, 2018. Significant refractive error warranting correction was determined using the American Academy of Ophthalmology Preferred Guidelines and the American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee Guidelines. The CVI Range was used as a surrogate to categorize CVI severity.

RESULTS
A total of 194 children were included. Sixty-eight (35%) had refractive error warranting correction and were prescribed glasses (group RC), 99 (51%) did not have refractive error warranting correction and were not prescribed glasses (group NRNC), 20 (10%) had refractive error warranting correction but were not prescribed glasses (group RNC), and 7 (4%) did not have refractive error warranting correction but were prescribed glasses (group NRC). There was greater than one-line Snellen equivalent difference between group RC (20/156) and group RNC (20/221). There was greater than six-line Snellen equivalent difference between group NRNC (20/149) and group NRC (20/35). Mean CVI Range score 2 values for each group were 5.9, 4.6, 4.8, and 7.1.

CONCLUSIONS
Children with less severe CVI were less likely to have significant refractive error but given glasses. Despite significant refractive error, children with more severe CVI were not prescribed glasses. Children with very low visual function were not prescribed glasses as frequently, possibly limiting their visual rehabilitation. Providers should ensure that all children with CVI are correctly prescribed glasses to provide the best possible visual outcome.
The Interplay Between Stress and Fullness in Patients With Functional Dyspepsia and Healthy Controls: An Exploratory Experience Sampling Method Study
Authors: Klaassen Tim , Vork Lisa , Smeets Fabiënne G.M. , Troost Freddy J. , Kruimel Joanna W. , Leue Carsten , Masclee Ad A.M. , Keszthelyi Daniel 
Published: September 2021

ABSTRACT

Objective
Fullness is a cardinal symptom in functional dyspepsia (FD). The use of real-time symptom assessment might provide more insight into factors, such as daily stress, that can influence fullness. Therefore, this study aimed to use the experience sampling method (a real-time, repeated-measurement method making use of repeated questionnaires available at random moments for a limited amount of time) to assess the association between stress and fullness in patients with FD and healthy controls (HCs).

Methods
Thirty-five patients with FD (25 female, mean age = 44.7 years) and 34 HCs (24 female, mean age = 44.1 years) completed the experience sampling method (a maximum of 10 random moments per day) for 7 consecutive days. Stress and fullness were rated on an 11-point Numeric Rating Scale. Data between patients with FD and HCs were statistically compared using a Student samples t test and linear mixed-effects models with repeated measures (level 1) nested within participants (level 2).

Results
Average fullness scores were 2.23 (standard error = 0.37) points higher in patients with FD compared with HCs (p < .001). Average stress scores were 1.37 (standard error = 0.30) points higher in patients with FD compared with HCs (p = .002).
In FD, fullness scores increased with 0.14 for every 1-point increase in concurrent stress scores (p = .010). Fullness scores at t = 0 increased with 0.12 for every 1-point increase in stress scores at t = −1 (p = .019). T = 0 stress scores were not associated with change in t = −1 fullness scores. No associations between concurrent symptom scores were found for HCs.

Conclusions
Concurrent and preceding stress scores are positively associated with fullness scores in patients with FD, but not in HCs. These findings indicate that increased levels of stress may precede feelings of fullness in patients with FD.

Trial registration
ClinicalTrials.gov identifier NCT04204421.
Prediction Model for Tumor Volume Nadir in EGFR-mutant NSCLC Patients Treated With EGFR Tyrosine Kinase Inhibitors
Authors: Nishino Mizuki , Lu Junwei , Hino Takuya , Vokes Natalie I. , Jänne Pasi A. , Hatabu Hiroto , Johnson Bruce E. 
Published: September 2021

Purpose:
In patients with advanced non–small cell lung cancer (NSCLC) and oncogenic driver mutations treated with effective targeted therapy, a characteristic pattern of tumor volume dynamics with an initial regression, nadir, and subsequent regrowth is observed on serial computed tomography (CT) scans. We developed and validated a linear model to predict the tumor volume nadir in EGFR-mutant advanced NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKI).

Materials and Methods:
Patients with EGFR-mutant advanced NSCLC treated with EGFR-TKI as their first EGFR-directed therapy were studied for CT tumor volume kinetics during therapy, using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir in a training cohort of 34 patients, and then was validated in an independent cohort of 84 patients.

Results:
The linear model for tumor nadir prediction was obtained in the training cohort of 34 patients, which utilizes the baseline tumor volume before initiating therapy (V0) to predict the volume decrease (mm3) when the nadir volume (Vp) was reached: V0−Vp=0.717×V0−1347 (P=2×10−16; R
2=0.916). The model was tested in the validation cohort, resulting in the R
2 value of 0.953, indicating that the prediction model generalizes well to another cohort of EGFR-mutant patients treated with EGFR-TKI. Clinical variables were not significant predictors of tumor volume nadir.

Conclusion:
The linear model was built to predict the tumor volume nadir in EGFR-mutant advanced NSCLC patients treated with EGFR-TKIs, which provide an important metrics in treatment monitoring and therapeutic decisions at nadir such as additional local abrasive therapy.
Antibody response to a fourth mRNA Covid-19 vaccine boost in weak responder kidney transplant recipients
Authors: Caillard Sophie , Thaunat Olivier , Benotmane Ilies , Masset Christophe , Blancho Gilles 
Published: September 2021

AbstractThe US FDA has recently authorized immunocompromised people to receive a third dose of mRNA Covid-19 vaccine following the two-doses regimen to further boost protection. Unfortunately, a non-negligible proportion of people treated with immunosuppressive drugs either do not respond or show only a weak response after a third boost and should, therefore, still be considered at risk of severe Covid-19. As of June 2021, we were granted the opportunity to offer a fourth vaccine dose to French solid organ transplant recipients who still showed a weak antibody response after the third dose. In this multicenter study, we demonstrate that that the protection conferred by a fourth dose is adequate for the majority of kidney transplant recipients.
Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications
Authors: Stone Mars , Grebe Eduard , Sulaeman Hasan , Di Germanio Clara , Dave Honey , Kelly Kathleen , Biggerstaff Brad , Crews Bridgit O. , Tran Nam , Jerome Keith R. , Denny Thomas N. , Hogema Boris , Destree Mark , Jones Jefferson M. , Thornburg Natalie , Simmons Graham , Krajden Mel , Kleinman Steve , Dumont Larry J. , Busch Michael P. 
Published: September 2021

AbstractSARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.
Microsaccades as a marker not a cause for attention-related modulation
Authors: Yu Gongchen , Herman James P. , Katz Leor N. , Krauzlis Richard J. 
Published: September 2021

AbstractRecent evidence suggests that microsaccades are causally linked to the attention-related modulation of neurons – specifically, that microsaccades towards the attended location are required for the subsequent changes in firing rate. These findings have raised questions about whether attention-related modulation is due to different states of attention as traditionally assumed or might instead be a secondary effect of microsaccades. Here, in two rhesus macaques, we tested the relationship between microsaccades and attention-related modulation in the superior colliculus, a brain structure crucial for allocating attention. We found that attention-related modulation emerged even in the absence of microsaccades, was already present prior to microsaccades towards the cued stimulus, and persisted through the suppression of activity that accompanied all microsaccades. Nonetheless, consistent with previous findings, we also found significant attention-related modulation when microsaccades were directed towards, rather than away from, the cued location. Thus, in contrast to the prevailing hypothesis, microsaccades are not necessary for attention-related modulation, at least not in the superior colliculus. They do, however, provide an additional marker for the state of attention, especially at times when attention is shifting from one location to another.
Aggressive but not reproductive boldness in male green anole lizards correlates with baseline vasopressin activity
Authors: Kabelik David , Julien Allison R. , Waddell Brandon R. , Batschelett Mitchell A. , O’Connell Lauren A. 
Published: September 2021

AbstractAcross species, individuals within a population differ in their level of boldness in social encounters with conspecifics. This boldness phenotype is often stable across both time and social context (e.g., reproductive versus agonistic encounters). Various neural and hormonal mechanisms have been suggested as underlying these stable phenotypic differences, which are often also described as syndromes, personalities, and coping styles. Most studies examining the neuroendocrine mechanisms associated with boldness examine subjects after they have engaged in a social interaction, whereas baseline neural activity that may predispose behavioral variation is understudied. The present study tests the hypotheses that physical characteristics, steroid hormone levels, and baseline variation in Ile3-vasopressin (VP, a.k.a., Arg8-vasotocin) signaling predispose boldness during social encounters. Boldness in agonistic and reproductive contexts was extensively quantified in male green anole lizards (Anolis carolinensis), an established research organism for social behavior research that provides a crucial comparison group to investigations of birds and mammals. We found high stability of boldness across time, and between agonistic and reproductive contexts. Next, immunofluorescence was used to colocalize VP neurons with phosphorylated ribosomal protein S6 (pS6), a proxy marker of neural activity. Vasopressin-pS6 colocalization within the paraventricular and supraoptic nuclei of the hypothalamus was inversely correlated with boldness of aggressive behaviors, but not of reproductive behaviors. Our findings suggest that baseline vasopressin release, rather than solely context-dependent release, plays a role in predisposing individuals toward stable levels of displayed aggression toward conspecifics by inhibiting behavioral output in these contexts.