bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐Level Tragus Stimulation Modulates Atrial Alternans and Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation
Authors: Kulkarni Kanchan , Singh Jagmeet P. , Parks Kimberly A. , Katritsis Demosthenes G. , Stavrakis Stavros , Armoundas Antonis A. 
Published: June 2021

Background
Low‐level tragus stimulation (LLTS) has been shown to significantly reduce atrial fibrillation (AF) burden in patients with paroxysmal AF. P‐wave alternans (PWA) is believed to be generated by the same substrate responsible for AF. Hence, PWA may serve as a marker in guiding LLTS therapy. We investigated the utility of PWA in guiding LLTS therapy in patients with AF.

Methods and Results

Twenty‐eight patients with AF were randomized to either active LLTS or sham (earlobe stimulation). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 μs, frequency 20 Hz, amplitude 10–50 mA), for 1 hour daily over a 6‐month period. AF burden over 2‐week periods was assessed by noninvasive continuous ECG monitoring at baseline, 3 months, and 6 months. A 5‐minute control ECG for PWA analysis was recorded during all 3 follow‐up visits. Following the control ECG, an additional 5‐minute ECG was recorded during active LLTS in all patients. At baseline, acute LLTS led to a significant rise in PWA burden. However, active patients receiving chronic LLTS demonstrated a significant reduction in both PWA and AF burden after 6 months (
P
<0.05). Active patients who demonstrated an increase in PWA burden with acute LLTS showed a significant drop in AF burden after 6 months of chronic LLTS.

Conclusions
Chronic, intermittent LLTS resulted in lower PWA and AF burden than did sham control stimulation. Our results support the use of PWA as a potential marker for guiding LLTS treatment of paroxysmal AF.
Manganese (II) chloride leads to dopaminergic neurotoxicity by promoting mitophagy through BNIP3-mediated oxidative stress in SH-SY5Y cells
Authors: Huang Yanning , Wen Qiaolin , Huang Jinfeng , Luo Man , Xiao Yousheng , Mo Ruikang , Wang Jin 
Published: June 2021

Abstract
Background
Manganese overexposure can induce neurotoxicity, lead to manganism and result in clinical manifestations similar to those of parkinsonism. However, the underlying molecular mechanism is still unclear. This study demonstrated that MnCl2 induces mitophagy and leads to neurotoxicity by promoting BNIP3-mediated reactive oxygen species (ROS) generation.

Methods
Human neuroblastoma SH-SY5Y cells were used throughout our experiments. Cell viability was detected by cell proliferation/toxicity test kits. Mitochondrial membrane potential was measured by flow cytometry. ROS generation was detected using a microplate reader. Protein levels were evaluated by Western blot. Transmission electron microscopy was used to evaluate mitochondrial morphology. Co-immunoprecipitation was used to verify the interaction between BNIP3 and LC3.

Results
MnCl2 led to loss of mitochondrial membrane potential and apoptosis of SH-SY5Y cells by enhancing expression of BNIP3 and conversion of LC3-I to LC3-II. Moreover, MnCl2 reduced expression of the mitochondrial marker protein TOMM20 and promoted interaction between BNIP3 and LC3. The results also indicated that a decrease in BNIP3 expression reduced the mitochondrial membrane potential loss, attenuated apoptosis and reduced mitochondrial autophagosome formation in SH-SY5Y cells after MnCl2 treatment. Finally, we found that manganese-induced ROS generation could be reversed by the antioxidant N-acetyl cysteine (NAC) or silencing BNIP3 expression.

Conclusions
BNIP3 mediates MnCl2-induced mitophagy and neurotoxicity in dopaminergic SH-SY5Y cells through ROS. Thus, BNIP3 contributes to manganese-induced neurotoxicity by functioning as a mitophagy receptor protein.
Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data
Authors: Schwarz Simon , Gildemeister Daniela , Hein Arne , Schröder Patrick , Bachmann Jean 
Published: June 2021

AbstractHuman pharmaceuticals are extensively studied and assessed before marketing approval. Since 2006, this also includes an assessment of environmental risks. In the European Union, this is based on the guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00 corr 2), which is currently under revision. For Germany, the German Environment Agency (UBA) is tasked with the evaluation of environmental risks of human pharmaceuticals. Applicants seeking approval of medicinal products need to submit fate and effect data, in case predicted environmental concentrations (PECs) exceed 10 ng/L in surface waters, or the substance is of specific concern through its mode of action or physico-chemical characteristics.Over the last decade, this regulatory work resulted in an internal agency database containing effect data on approximately 300 active pharmaceutical ingredients (APIs). A considerable part of this data is currently not publicly available due to property rights held by the respective applicants. The database was evaluated to draw conclusions on how the current assessment approach may be improved.The evaluation of aquatic effect data shows considerable variation in ecotoxic effect concentrations, but supports the current use of 10 ng/L as PEC action limit. For endocrine-active substances and antibiotics, a clear sensitivity profile was observed, which allows a more targeted assessment in the future. The conclusions drawn from terrestrial effect data are less clear, as the database itself is biased because information is only available for substances with high sorption. Further adaptations of the terrestrial assessment strategy, including action triggers, appear necessary. Fate data show a high persistence of many APIs: approximately 43% of all APIs are classified as very persistent; 12% of these show DT50 values in a range where abiotic or biotic degradation is not expected.Overall, the evaluation has shown that improvements of the current guideline are possible.
The reduced genome of a heritable symbiont from an ectoparasitic feather feeding louse
Authors: Alickovic Leila , Johnson Kevin P. , Boyd Bret M. 
Published: June 2021

AbstractBackgroundFeather feeding lice are abundant and diverse ectoparasites that complete their entire life cycle on an avian host. The principal or sole source of nutrition for these lice is feathers. Feathers appear to lack four amino acids that the lice would require to complete development and reproduce. Several insect groups have acquired heritable and intracellular bacteria that can synthesize metabolites absent in an insect’s diet, allowing insects to feed exclusively on nutrient-poor resources. Multiple species of feather feeding lice have been shown to harbor heritable and intracellular bacteria. We expected that these bacteria augment the louse’s diet with amino acids and facilitated the evolution of these diverse and specialized parasites. Heritable symbionts of insects often have small genomes that contain a minimal set of genes needed to maintain essential cell functions and synthesize metabolites absent in the host insect’s diet. Therefore, we expected the genome of a bacterial endosymbiont in feather lice would be small, but encode pathways for biosynthesis of amino acids.ResultsWe sequenced the genome of a bacterial symbiont from a feather feeding louse (Columbicola wolffhuegeli) that parasitizes the Pied Imperial Pigeon (Ducula bicolor) and used its genome to predict metabolism of amino acids based on the presence or absence of genes. We found that this bacterial symbiont has a small genome, similar to the genomes of heritable symbionts described in other insect groups. However, we failed to identify many of the genes that we expected would support metabolism of amino acids in the symbiont genome. We also evaluated other gene pathways and features of the highly reduced genome of this symbiotic bacterium.ConclusionsBased on the data collected in this study, it does not appear that this bacterial symbiont can synthesize amino acids needed to complement the diet of a feather feeding louse. Our results raise additional questions about the biology of feather chewing lice and the roles of symbiotic bacteria in evolution of diverse avian parasites.
Increased expression of transient receptor potential channels and neurogenic factors associates with cough severity in a guinea pig model
Authors: Guan Mengyue , Ying Sun , Wang Yuguang 
Published: June 2021

Abstract
Background
Previous studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, although the details of mechanism are largely unknown. Here, we aimed to further explore the potential mechanism involved in IPF-related high cough sensitivity to capsaicin challenge in a guinea pig model of pulmonary fibrosis induced by bleomycin.

Methods
Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to measure the expression of TRP channel subfamily A, member 1 (TRPA1) and TRP vanilloid 1 (TRPV1), which may be involved in the cough reflex pathway. Immunohistochemical analysis and RT-qPCR were used to detect the expression of neuropeptides substance P (SP), Neurokinin-1 receptor (NK1R), and calcitonin gene-related peptide (CGRP) in lung tissues. Concentrations of nerve growth factor (NGF), SP, neurokinin A (NKA), neurokinin B (NKB), and brain-derived neurotrophic factor (BDNF) in lung tissue homogenates were measured by ELISA.

Results
Cough sensitivity to capsaicin was significantly higher in the model group than that of the sham group. RT-qPCR and immunohistochemical analysis showed that the expression of TRPA1 and TRPV1 in the jugular ganglion and nodal ganglion, and SP, NK1R, and CGRP in lung tissue was significantly higher in the model group than the control group. In addition, expression of TRP and neurogenic factors was positively correlated with cough sensitivity of the experimental animals.

Conclusion
Up-regulated expression of TRPA1 and TRPV1 in the cough reflex pathway and neurogenic inflammation might contribute to the IPF-related high cough sensitivity in guinea pig model.
Sociodemographic differences in motives for food selection: results from the LoCard cross-sectional survey
Authors: Konttinen Hanna , Halmesvaara Otto , Fogelholm Mikael , Saarijärvi Hannu , Nevalainen Jaakko , Erkkola Maijaliisa 
Published: June 2021

Abstract
Background
Although sociodemographic differences in dietary intake have been widely studied, the up-to-date evidence on the corresponding variations in motives for food selection is limited. We investigated how sociodemographic characteristics and special diets in households are associated with the relative importance of various food motives.

Methods
Participants were members of the S Group loyalty card program across Finland who consented to release their grocery purchase data to be used for research purposes and responded to a web-based questionnaire in 2018 (LoCard study). Self-reported information on sociodemographic factors (age, gender, marital status, living situation, education, household income), special diets in household and food motives (Food Choice Questionnaire) were utilized in the present analyses (N = 10,795). Age- and gender-adjusted linear models were performed separately for each sociodemographic predictor and motive dimension (derived by factor analysis) outcome. The importance of each sociodemographic predictor was evaluated based on an increase in R2 value after adding the predictor to the age- and gender-adjusted model.

Results
Age emerged as a central determinant of food motives with the following strongest associations: young adults emphasized convenience (∆R2 = 0.09, P < 0.001) and mood control (∆R2 = 0.05, P < 0.001) motives more than middle-aged and older adults. The relative importance of cheapness decreased with increasing socioeconomic position (SEP) (∆R2 = 0.08, P < 0.001 for income and ∆R2 = 0.04, P < 0.001 for education). However, the price item (“is good value for money”) depicting the concept of worth did not distinguish between SEP categories. Considerations related to familiarity of food were more salient to men (∆R2 = 0.02, P < 0.001) and those with lower SEP (∆R2 = 0.03, P < 0.001 for education and ∆R2 = 0.01, P < 0.001 for income). Respondents living in households with a vegetarian, red-meat-free, gluten-free or other type of special diet rated ethical concern as relatively more important than households with no special diets (∆R2 = 0.02, P < 0.001).

Conclusions
We observed sociodemographic differences in a range of food motives that might act as barriers or drivers for adopting diets that benefit human and planetary health. Interventions aiming to narrow SEP and gender disparities in dietary intake should employ strategies that take into account higher priority of familiarity and price in daily food selection in lower-SEP individuals and males.
Clinical validation of kinematic assessments of post-stroke upper limb movements with a multi-joint arm exoskeleton
Authors: Grimm Florian , Kraugmann Jelena , Naros Georgios , Gharabaghi Alireza 
Published: June 2021

AbstractBackgroundThe clinical evaluation of the upper limb of severely impaired stroke patient is challenging. Sensor-based assessments may allow for an objective evaluation of this patient population. This study investigated the validity of a device-assisted approach in comparison to the clinical outcome that it is supposed to reflect.MethodsIn nineteen severely impaired chronic stroke patients, we applied a gravity-compensating, multi-joint arm exoskeleton (Armeo Spring) and compared this sensor-based assessment with the clinical outcome measure Upper Extremity Fugl-Meyer Assessment (UE-FMA) scale. Specifically, we assessed separately and subsequently the range of motion in joint space for four single joints (i.e., wrist, elbow and shoulder flexion/extension (FE), and shoulder internal/external rotation (IER)), and the closing and opening of the hand with a pressure sensor placed in the handle.ResultsWithin the kinematic parameters, a strong correlation was observed between wrist and elbow FE (r > 0.7, p < 0.003; Bonferroni corrected). The UE-FMA was significantly predicted by a multiple regression model (F (5, 13) = 12.22, p < 0.0005, adj.R2 = 0.83). Both shoulder IER and grip pressure added significantly (p < 0.05) to the prediction with the standardized coefficients β of 0.55 and 0.38, respectively.ConclusionsBy applying an exoskeleton-based self-contained evaluation of single-joint movements, a clinically valid assessment of the upper limb range of motion in severely impaired stroke patients is feasible. Shoulder IER contributed most relevantly to the prediction of the clinical status. These findings need to be confirmed in a large, independent patient cohort.
SARS-CoV-2 in hospital indoor environments is predominantly non-infectious
Authors: Krambrich Janina , Akaberi Dario , Ling Jiaxin , Hoffman Tove , Svensson Lennart , Hagbom Marie , Lundkvist Åke 
Published: June 2021

Abstract
Background
The ongoing SARS-CoV-2 pandemic has spread rapidly worldwide and disease prevention is more important than ever. In the absence of a vaccine, knowledge of the transmission routes and risk areas of infection remain the most important existing tools to prevent further spread.

Methods
Here we investigated the presence of the SARS-CoV-2 virus in the hospital environment at the Uppsala University Hospital Infectious Disease ward by RT-qPCR and determined the infectivity of the detected virus in vitro on Vero E6 cells.

Results
SARS-CoV-2 RNA was detected in several areas, although attempts to infect Vero E6 cells with positive samples were unsuccessful. However, RNase A treatment of positive samples prior to RNA extraction did not degrade viral RNA, indicating the presence of SARS-CoV-2 nucleocapsids or complete virus particles protecting the RNA as opposed to free viral RNA.

Conclusion
Our results show that even in places where a moderate concentration (Ct values between 30 and 38) of SARS-CoV-2 RNA was found; no infectious virus could be detected. This suggests that the SARS-CoV-2 virus in the hospital environment subsides in two states; as infectious and as non-infectious. Future work should investigate the reasons for the non-infectivity of SARS-CoV-2 virions.
EUS-guided drainage using lumen apposing metal stent and percutaneous endoscopic necrosectomy as dual approach for the management of complex walled-off necrosis: a case report and a review of the literature
Authors: Binda Cecilia , Sbrancia Monica , La Marca Marina , Colussi Dora , Vizzuso Antonio , Tomasoni Matteo , Agnoletti Vanni , Giampalma Emanuela , Ansaloni Luca , Fabbri Carlo 
Published: June 2021

Abstract
Background
Endoscopic ultrasound-guided drainage is suggested as the first approach in the management of symptomatic and complex walled-off pancreatic necrosis. Dual approach with percutaneous drainage could be the best choice when the necrosis is deep extended till the pelvic paracolic gutter; however, the available catheter could not be large enough to drain solid necrosis neither to perform necrosectomy, entailing a higher need for surgery. Therefore, percutaneous endoscopic necrosectomy through a large bore percutaneous self-expandable metal stent has been proposed.

Case presentation
In this study, we present the case of a 61-year-old man admitted to our hospital with a history of sepsis and persistent multiorgan failure secondary to walled-off pancreatic necrosis due to acute necrotizing pancreatitis. Firstly, the patient underwent transgastric endoscopic ultrasound-guided drainage using a lumen-apposing metal stent and three sessions of direct endoscopic necrosectomy. Because of recurrence of multiorgan failure and the presence of the necrosis deeper to the pelvic paracolic gutter at computed tomography scan, we decided to perform percutaneous endoscopic necrosectomy using an esophageal self-expandable metal stent. After four sessions of necrosectomy, the collection was resolved without complications. Therefore, we perform a revision of the literature, in order to provide the state-of-art on this technique. The available data are, to date, derived by case reports and case series, which showed high rates both of technical and clinical success. However, a not negligible rate of adverse events has been reported, mainly represented by fistulas and abdominal pain.

Conclusion
Dual approach, using lumen apposing metal stent and percutaneous self-expandable metal stent, is a compelling option of treatment for patients affected by symptomatic, complex walled-off pancreatic necrosis, allowing to directly remove large amounts of necrosis avoiding surgery. Percutaneous endoscopic necrosectomy seems a promising technique that could be part of the step-up-approach, before emergency surgery. However, to date, it should be reserved in referral centers, where a multidisciplinary team is disposable.
The short-term effectiveness and safety of second-generation patellofemoral arthroplasty and total knee arthroplasty on isolated patellofemoral osteoarthritis: a systematic review and meta-analysis
Authors: Li Chengxin , Li Zhizhuo , Shi Lijun , Gao Fuqiang , Sun Wei 
Published: June 2021

Abstract
Background
We aimed to compare second-generation patellofemoral arthroplasty (2G PFA) with total knee arthroplasty (TKA) in treating isolated patellofemoral osteoarthritis (PFOA) by assessing the percentages of revisions, complications, and patient-reported outcome measures (PROMs).

Methods
Studies that compared the outcomes of 2G PFA and TKA in the treatment of isolated PFOA were searched in electronic databases, including MEDLINE, Embase, and Web of Science. Two researchers independently identified eligible studies, extracted the data, and evaluated the quality of the literature. Pooled risk ratios (RRs) or weighted mean differences with 95% confidence intervals were calculated using either fixed or random effects models. Descriptive analysis was used when data could not be pooled.

Results
A total of six studies were included in the review. For the revision percentage and complications, there were no significant differences between 2G PFA and TKA (RR = 2.29, 95% CI 0.69–7.58, P = 0.17; RR = 0.56, 95% CI 0.23–1.40, P = 0.22, respectively). Second, the results demonstrated that the differences in the Oxford Knee Score (OKS) and the University of California, Los Angeles (UCLA) activity score between 2G PFA and TKA were not significant (WMD −4.68, 95% CI −16.32 to 6.97, p = 0.43; WMD 0.16, 95% CI −1.21 to 1.53, P = 0.82). The Knee Injury and Osteoarthritis Outcome Score (KOOS), the American Knee Society Score (AKSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were presented in a narrative form due to methodological heterogeneity.

Conclusion
For isolated PFOA, 2G PFA demonstrated similar results to TKA with respect to the percentages of revisions, complications, and PROMs.
Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab
Authors: Marcacci Gianpaolo , Fiorentino Giuseppe , Volzone Francesco , Falcone Umberto , Parrella Roberto , Donnarumma Daniela , D’Ovidio Silvia , Annunziata Anna , Micallo Giovanni , Portella Giuseppe , De Chiara Annarosaria , De Filippi Rosaria , Crisci Stefania , Pinto Antonio 
Published: June 2021

AbstractPatients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.