bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide Mononucleotide Administration Triggers Macrophages Reprogramming and Alleviates Inflammation During Sepsis Induced by Experimental Peritonitis
Authors: Cros Cécile , Margier Marielle , Cannelle Hélène , Charmetant Julie , Hulo Nicolas , Laganier Laurent , Grozio Alessia , Canault Matthias 
Published: June 2022

Peritonitis and subsequent sepsis lead to high morbidity and mortality in response to uncontrolled systemic inflammation primarily mediated by macrophages. Nicotinamide adenine dinucleotide (NAD+) is an important regulator of oxidative stress and immunoinflammatory responses. However, the effects of NAD+ replenishment during inflammatory activation are still poorly defined. Hence, we investigated whether the administration of β-nicotinamide mononucleotide (β-NMN), a natural biosynthetic precursor of NAD+, could modulate the macrophage phenotype and thereby ameliorate the dysregulated inflammatory response during sepsis. For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity. β-NMN was administered for 4 days after CLP and for 3 days post thioglycolate treatment where peritoneal macrophages were subsequently analyzed. In the CLP model, administration of β-NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis. These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy. In the thioglycolate model, a significant increase in the proportion of CD206 macrophages, marker of anti-inflammatory M2 phenotype, was detected on peritoneal exudate macrophages from β-NMN-administered mice. Transcriptomic signature of these macrophages after bacterial stimulation confirmed that β-NMN administration limited the pro-inflammatory M1 phenotype and induced the expression of specific markers of M2 type macrophages. Furthermore, our data show that β-NMN treatment significantly impacts NAD + metabolism. This shift in the macrophage phenotype and metabolism was accompanied by a reduction in phagolysosome acidification and secretion of inflammatory mediators in macrophages from β-NMN-treated mice suggesting a reduced pro-inflammatory activation. In conclusion, administration of β-NMN prevented clinical deterioration and improved survival during sepsis. These effects relied on shifts in the metabolism of organs that face up an increased energy requirement caused by bacterial infection and in innate immunity response, including reprogramming of macrophages from a highly inflammatory phenotype to an anti-inflammatory/pro-resolving profile.
Computerized Working Memory Training in Remission From Major Depressive Disorder: Effects on Emotional Working Memory, Processing Speed, Executive Functions, and Associations With Symptoms
Authors: Ronold Eivind Haga , Joormann Jutta , Hammar Åsa 
Published: June 2022

IntroductionRemission from major depressive disorder (MDD) is associated with residual symptoms related to reduced functioning, quality of life, and relapse risk. Previous studies have raised questions about mechanisms involved-in and affected by cognitive training. This study investigated the associations and changes among depressive symptoms, rumination, processing speed (PS), executive functioning (EF), and emotional working memory (e-WM) pre- post computerized working memory training (CWMT).MethodTwenty-nine remitted participants were included in a pre- post pilot study of within-subject effects of online CWMT. A total of 20 participants completed the intervention and pre- post tests of EF and PS, e-WM, in addition to symptom and rumination measures. Associations between changes in symptoms and cognition were investigated pre- post. Associations between improvements in CWMT, depression history, and changes in cognition were explored. Hypotheses and statistics were preregistered before data were analyzed.ResultsManipulation of negatively valanced stimuli in e-WM showed an inverse association with rumination pre-intervention, but the association disappeared post-intervention. Cognitive functioning improved in most conditions with largest effects in EF. Symptoms did not change in the remitted sample. CWMT improvements were related to improvements in some aspects of EF and PS, but also to worse self-reported attention. Depression history was related to less improvement in EF.LimitationsSample size was small and there was dropout from the study. There was no control group, thus precluding practice and placebo effects and causal relationships.ConclusionsComputerized WM training improves cognitive functions and could influence associations between e-WM and rumination. This could counteract functional impairment following MDD.
Cochlear Implant Electrode Impedance as Potential Biomarker for Residual Hearing
Authors: Wimmer Wilhelm , Sclabas Luca , Caversaccio Marco , Weder Stefan 
Published: June 2022

Introduction and ObjectivesAmong cochlear implant candidates, an increasing number of patients are presenting with residual acoustic hearing. To monitor the postoperative course of structural and functional preservation of the cochlea, a reliable objective biomarker would be desirable. Recently, impedance telemetry has gained increasing attention in this field. The aim of this study was to investigate the postoperative course of the residual acoustic hearing and clinical impedance in patients with long electrode arrays and to explore the applicability of impedance telemetry for monitoring residual hearing.MethodsWe retrospectively analyzed records of 42 cochlear implant recipients with residual hearing covering a median postoperative follow-up of 25 months with repeated simultaneous pure tone audiometry and impedance telemetry. We used a linear mixed-effects model to estimate the relation between clinical electrode impedance and residual hearing. Besides the clinical impedance, the follow-up time, side of implantation, gender, and age at implantation were included as fixed effects. An interaction term between impedance and follow-up time, as well as subject-level random intercepts and slopes, were included.ResultsLoss of residual hearing occurred either during surgery or within the first 6 post-operative months. Electrode contacts inserted further apically (i.e., deeper) had higher impedances, independent of residual hearing. The highest impedances were measured 1 month postoperatively and gradually decreased over time. Basal electrodes were more likely to maintain higher impedance. Follow-up time was significantly associated with residual hearing. Regardless of the time, we found that a 1 kΩ increase in clinical impedance was associated with a 4.4 dB deterioration of residual hearing (p &lt; 0.001).ConclusionPure tone audiometry is the current gold standard for monitoring postoperative residual hearing. However, the association of clinical impedances with residual hearing thresholds found in our study could potentially be exploited for objective monitoring using impedance telemetry. Further analysis including near-field related impedance components could be performed for improved specificity to local immune responses.
Health Care Utilization and Anti-Cancer Drug Expenditure for Six Solid Cancers in Korea From 2007 to 2019
Authors: Park Juhee , Moon Kyeongjun , Kim Dong-Sook 
Published: June 2022

BackgroundThe burden of care continues to rise considerably worldwide and the challenge of diversity in cancer research has become important. We aimed to examine trends of cancer care utilization and anti-cancer medication among patients with six solid cancers (gastric, colorectal, liver, lung, breast, and prostate cancer) in South Korea.MethodsThis study analyzed patients diagnosed with six types of solid cancer from 2007 to 2019 using data from the National Health Insurance claims database. We analyzed the total number of cancer cases, each patient’s length of stay (LOS) in a hospital, the number of outpatient physician visits, total medical care costs, total out-of-pocket (OOP) costs, and expenditures on anti-cancer drugs.ResultsUtilization of healthcare services and spending on cancer care including anti-cancer drugs both increased in the 13-year study period. The average LOS was the highest for colorectal cancer patients at 43.5 days, and breast cancer patients had the highest average number of physician visits at 11.8. Breast cancer patients had the highest total medical costs (USD 923 million), anti-cancer drug spending (USD 156 million), and the largest increase (5 times) over the 13-year period. The anti-cancer drugs with the largest market shares were ramucirumab for gastric cancer; oxaliplatin for colorectal cancer; sorafenib for liver cancer; pembrolizumab, nivolumab, for lung cancer; trastuzumab for breast cancer; and bicalutamide for prostate cancer.ConclusionThis study was a large-scale analysis from a nationally representative database of the total population. The study also shows the pattern of cancer care in an Asian country and can provide implications for future cancer research.
Construction and Verification of a Predictive Model for Risk Factors in Children With Severe Adenoviral Pneumonia
Authors: He Yaqiong , Liu Peng , Xie Leyun , Zeng Saizhen , Lin Huashan , Zhang Bing , Liu Jianbin 
Published: June 2022

ObjectiveTo construct and validate a predictive model for risk factors in children with severe adenoviral pneumonia based on chest low-dose CT imaging and clinical features.MethodsA total of 177 patients with adenoviral pneumonia who underwent low-dose CT examination were collected between January 2019 and August 2019. The assessment criteria for severe pneumonia were divided into mild group (N = 125) and severe group (N = 52). All cases divided into training cohort (N = 125) and validation cohort (N = 52). We constructed a prediction model by drawing a nomogram and verified the predictive efficacy of the model through the ROC curve, calibration curve and decision curve analysis.ResultsThe difference was statistically significant (P &lt; 0.05) between the mild adenovirus pneumonia group and the severe adenovirus pneumonia group in gender, age, weight, body temperature, L/N ratio, LDH, ALT, AST, CK-MB, ADV DNA, bronchial inflation sign, emphysema, ground glass sign, bronchial wall thickening, bronchiectasis, pleural effusion, consolidation score, and lobular inflammation score. Multivariate logistic regression analysis showed that gender, LDH value, emphysema, consolidation score, and lobular inflammation score were severe independent risk factors for adenovirus pneumonia in children. Logistic regression was employed to construct clinical model, imaging semantic feature model, and combined model. The AUC values of the training sets of the three models were 0.85 (0.77–0.94), 0.83 (0.75–0.91), and 0.91 (0.85–0.97). The AUC of the validation set was 0.77 (0.64–0.91), 0.83 (0.71–0.94), and 0.85 (0.73–0.96), respectively. The calibration curve fit good of the three models. The clinical decision curve analysis demonstrates the clinical application value of the nomogram prediction model.ConclusionThe prediction model based on chest low-dose CT image characteristics and clinical characteristics has relatively clear predictive value in distinguishing mild adenovirus pneumonia from severe adenovirus pneumonia in children and might provide a new method for early clinical prediction of the outcome of adenovirus pneumonia in children.
Management of Primary Spontaneous Pneumothorax in a Third-Level Pediatric Surgical Center: A Retrospective Study
Authors: Spezzotto Giovanna , Boscarelli Alessandro , Giangreco Manuela , Ceschiutti Giulia , Codrich Daniela , Scarpa Maria-Grazia , Iaquinto Marianna , Olenik Damiana , Guida Edoardo , Schleef Jürgen 
Published: June 2022

IntroductionThe management of primary spontaneous pneumothorax (PSP) in pediatrics remains controversial. The aim of this study was to investigate the risk of recurrence after non-surgical treatment vs. surgery, the difference in the length of stay (LOS) between various treatment options, and the role of computed tomography (CT) in the management of PSP.Materials and MethodsWe retrospectively reviewed patients admitted to our Pediatric Surgery Unit for an episode of PSP between June 2009 and July 2020. Medical records including clinical presentation at admission, diagnostics, treatments, complications, and LOS were collected.ResultsTwenty-three patients (22 males and 1 female) were included in this study. Median age was 15.65 (range 9–18). Chest X-rays were performed in all patients and showed 5 small (22%) and 18 large (78%) PSP. Chest drain was used for large PSP (≥2 cm) if the patient was clinically unstable. Eleven patients (48%) were managed non-operatively with observation alone and a recurrence rate of 18%, chest drain was used in 11 patients with a recurrence rate of 36%, and surgery was deemed necessary as a first treatment choice in one case. Six patients (27%) had an episode of relapse after non-operative management or chest drain placement. Following surgery, a relapse occurred in 2 of the 6 patients. Chest drain insertion was associated with a longer LOS than observation alone (6.36 vs. 2.4 days), and surgery resulted in a longer LOS than other types of treatment (P = 0.001).ConclusionAccording to our experience, small PSP or clinically stable larger PSP can be treated conservatively with observation alone. Operative management should be taken into consideration in children with large symptomatic PSP, persistent air leak, and/or relapse after chest drain insertion.
Liquid Biopsy-Based Biomarkers of Inflammatory Nociception Identified in Male Rats
Authors: Merritt Christina R. , Cisneros Irma E. , Covarrubias-Zambrano Obdulia , Stutz Sonja J. , Motamedi Massoud , Bossmann Stefan H. , Cunningham Kathryn A. 
Published: June 2022

Physicians are challenged in treating pain patients due to the lack of quantifiable, objective methods of measuring pain in the clinic; pain sensation is multifaceted and subjective to each individual. There is a critical need for point-of-care quantification of accessible biomarkers to provide objective analyses beyond the subjective pain scales currently employed in clinical care settings. In the present study, we employed an animal model to test the hypothesis that circulating regulators of the inflammatory response directly associate with an objective behavioral response to inflammatory pain. Upon induction of localized paw inflammation, we measured the systemic protein expression of cytokines, and activity levels of matrix metalloproteinases (MMPs) that are known to participate in the inflammatory response at the site of injury and investigated their relationship to the behavioral response across a 24 h period. Intraplantar injection with 1% λ-carrageenan induced a significant increase in paw thickness across this timespan with maximal effects observed at the 8 h timepoint when locomotor activity was also impaired. Expression of the chemokines C-X-C motif chemokine ligand 1 (CXCL1) and C-C motif chemokine ligand 2 (CCL2) positively correlated with paw inflammation and negatively correlated with locomotor activity at 8 h. The ratio of MMP9 to MMP2 activity negatively correlated with paw inflammation at the 8 h timepoint. We postulate that the CXCL1 and CCL2 as well as the ratio of MMP9 to MMP2 activity may serve as predictive biomarkers for the timecourse of inflammation-associated locomotor impairment. These data define opportunities for the future development of a point-of-care device to objectively quantify biomarkers for inflammatory pain states.
Medicine shortages: Product life cycle phases and characteristics of medicines in short supply—A register study
Authors: Sarnola Kati , Kari Heini , Koskinen Hanna 
Published: June 2022

Introduction: Product life cycle refers to all phases of a product from development to active market phase and finally the phase in which products possibly exit the market. The product life cycle of medicines in short supply has not been studied in depth, although there is some indication of mature products and products with lower prices and profit margins being exposed to shortages more often. The aim of this study was to examine the product life cycle phases and characteristics of medicines in short supply as well as the features of medicine shortages in Finland from 2017 to 2019.Material and methods: Register data on medicine shortages of human medicinal products from 2017 to 2019 was combined with timely data on marketing authorizations and reimbursement status to gain data on product life cycle phases and characteristics (e.g., the age and the reimbursement status) of medicines in short supply and the features of medicine shortages. The data were analyzed in descriptive manner using appropriate statistical testing.Results: 3,526 shortages were reported during the 3-year study period and the number of shortages increased annually. The average duration of a shortage was 83 days and shortages affected 660 active pharmaceutical ingredients. Most often, shortages occurred with medicines affecting the nervous system, the cardiovascular system, and the genitourinary system. A majority of shortages (n = 2,689) was reported in the reimbursable medicines group, where shortages increased as the number of patients receiving reimbursements increased (p &lt; 0.001). In the reimbursable medicines group, shortages most commonly involved medicines aged 15–19, 20–24, and 25–29, whereas with both reimbursable and non-reimbursable products the shortages most often occurred in medicines aged 50–54. The frequency of shortages differed between the groups (p &lt; 0.001) when both age and reimbursement status were taken into account.Conclusion: Medicine shortages are common and affect commonly used medicines. Product life cycle phase has an effect on the frequency of shortages: Reimbursable medicines and medicines exposed to changes in life cycle are more likely to face a shortage. The impacts of product life cycle on the availability of medicines and medicine shortages should be studied in more detail.
Skin Dose Modeling and Measurement in a High Field In-Line MRI-Linac System
Authors: Tai Madiha , Patterson Elizabeth , Metcalfe Peter E. , Rosenfeld Anatoly , Oborn Bradley M. 
Published: June 2022

The Australian MRI-Linac prototype radiotherapy system has been shown to generate significant entry skin or surface dose increases. This arises from electron contamination focusing toward the isocenter caused by the 1 T MRI field being in-line with the x-ray beam. The aim of this study is to present accurate Monte Carlo modeling of these skin dose changes and to compare them with previous experimental measurements. Accurate skin dose modeling will improve confidence in the pathway forward to treatment planning for clinical trials. A COMSOL Multiphysics model of the Australian MRI-Linac system was used to generate a 3D magnetic field map to be used in corresponding Geant4 Monte Carlo simulations. The Geant4 simulations included the x-ray source (6 MV Linac), multileaf collimators (MLCs), and a 30 cm × 30 cm × 30 cm water phantom located with its front surface at the beam isocenter. Simulations were performed with a source to surface distance (SSD) of 1,819 mm for nominal field sizes 2 cm × 2 cm, 6 cm × 6 cm, and 10 cm × 10 cm. Central axis percentage depth dose (PDD) and surface (or skin) doses at 70 μm depth were calculated by using high-resolution scoring voxels of 10 μm thickness. The results were compared with corresponding experimental data collected using MOSkin™ on the Australian MRI-Linac prototype system. The accurate modeling provides great detail into how the electron contamination is heavily confined and focused toward the beam central axis due to the presence of in-line magnetic field. This concentration significantly increases the skin dose up to 320% for the field size of 10 cm × 10 cm. For 2 cm × 2 cm and 6 cm × 6 cm, the surface skin dose is 128% and 217%, respectively, as compared to the skin dose in the absence of the magnetic field. The simulation results are in generally good agreement, ±10%, with previously collected experimental data for the same nominal field sizes. For the first time, detailed Geant4 Monte Carlo simulations of the electron contamination in the Australian MRI-Linac system have been performed and confirmed to be sufficiently accurate. These simulations will provide a solid framework for estimating the skin dose changes in more clinically relevant treatment plan scenarios that are envisaged in the near future.
Effect of Plyometric Jump Training on Skeletal Muscle Hypertrophy in Healthy Individuals: A Systematic Review With Multilevel Meta-Analysis
Authors: Arntz F. , Mkaouer B. , Markov A. , Schoenfeld B. J. , Moran J. , Ramirez-Campillo R. , Behrens M. , Baumert P. , Erskine R. M. , Hauser L. , Chaabene H. 
Published: June 2022

Objective: To examine the effect of plyometric jump training on skeletal muscle hypertrophy in healthy individuals.Methods: A systematic literature search was conducted in the databases PubMed, SPORTDiscus, Web of Science, and Cochrane Library up to September 2021.Results: Fifteen studies met the inclusion criteria. The main overall finding (44 effect sizes across 15 clusters median = 2, range = 1–15 effects per cluster) indicated that plyometric jump training had small to moderate effects [standardised mean difference (SMD) = 0.47 (95% CIs = 0.23–0.71); p &lt; 0.001] on skeletal muscle hypertrophy. Subgroup analyses for training experience revealed trivial to large effects in non-athletes [SMD = 0.55 (95% CIs = 0.18–0.93); p = 0.007] and trivial to moderate effects in athletes [SMD = 0.33 (95% CIs = 0.16–0.51); p = 0.001]. Regarding muscle groups, results showed moderate effects for the knee extensors [SMD = 0.72 (95% CIs = 0.66–0.78), p &lt; 0.001] and equivocal effects for the plantar flexors [SMD = 0.65 (95% CIs = −0.25–1.55); p = 0.143]. As to the assessment methods of skeletal muscle hypertrophy, findings indicated trivial to small effects for prediction equations [SMD = 0.29 (95% CIs = 0.16–0.42); p &lt; 0.001] and moderate-to-large effects for ultrasound imaging [SMD = 0.74 (95% CIs = 0.59–0.89); p &lt; 0.001]. Meta-regression analysis indicated that the weekly session frequency moderates the effect of plyometric jump training on skeletal muscle hypertrophy, with a higher weekly session frequency inducing larger hypertrophic gains [β = 0.3233 (95% CIs = 0.2041–0.4425); p &lt; 0.001]. We found no clear evidence that age, sex, total training period, single session duration, or the number of jumps per week moderate the effect of plyometric jump training on skeletal muscle hypertrophy [β = −0.0133 to 0.0433 (95% CIs = −0.0387 to 0.1215); p = 0.101–0.751].Conclusion: Plyometric jump training can induce skeletal muscle hypertrophy, regardless of age and sex. There is evidence for relatively larger effects in non-athletes compared with athletes. Further, the weekly session frequency seems to moderate the effect of plyometric jump training on skeletal muscle hypertrophy, whereby more frequent weekly plyometric jump training sessions elicit larger hypertrophic adaptations.