bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual effect of TAT functionalized DHAH lipid nanoparticles with neurotrophic factors in human BBB and microglia cultures
Authors: Hernando Sara , Nikolakopoulou Polyxeni , Voulgaris Dimitrios , Hernandez Rosa Maria , Igartua Manoli , Herland Anna 
Published: March 2022

Abstract
Background
Neurodegenerative diseases (NDs) are an accelerating global health problem. Nevertheless, the stronghold of the brain- the blood–brain barrier (BBB) prevents drug penetrance and dwindles effective treatments. Therefore, it is crucial to identify Trojan horse-like drug carriers that can effectively cross the blood–brain barrier and reach the brain tissue. We have previously developed polyunsaturated fatty acids (PUFA)-based nanostructured lipid carriers (NLC), namely DHAH-NLC. These carriers are modulated with BBB-permeating compounds such as chitosan (CS) and trans-activating transcriptional activator (TAT) from HIV-1 that can entrap neurotrophic factors (NTF) serving as nanocarriers for NDs treatment. Moreover, microglia are suggested as a key causative factor of the undergoing neuroinflammation of NDs. In this work, we used in vitro models to investigate whether DHAH-NLCs can enter the brain via the BBB and investigate the therapeutic effect of NTF-containing DHAH-NLC and DHAH-NLC itself on lipopolysaccharide-challenged microglia.

Methods
We employed human induced pluripotent stem cell-derived brain microvascular endothelial cells (BMECs) to capitalize on the in vivo-like TEER of this BBB model and quantitatively assessed the permeability of DHAH-NLCs. We also used the HMC3 microglia cell line to assess the therapeutic effect of NTF-containing DHAH-NLC upon LPS challenge.

Results
TAT-functionalized DHAH-NLCs successfully crossed the in vitro BBB model, which exhibited high transendothelial electrical resistance (TEER) values (≈3000 Ω*cm2). Specifically, the TAT-functionalized DHAH-NLCs showed a permeability of up to 0.4% of the dose. Furthermore, using human microglia (HMC3), we demonstrate that DHAH-NLCs successfully counteracted the inflammatory response in our cultures after LPS challenge. Moreover, the encapsulation of glial cell-derived neurotrophic factor (GNDF)-containing DHAH-NLCs (DHAH-NLC-GNDF) activated the Nrf2/HO-1 pathway, suggesting the triggering of the endogenous anti-oxidative system present in microglia.

Conclusions
Overall, this work shows that the TAT-functionalized DHAH-NLCs can cross the BBB, modulate immune responses, and serve as cargo carriers for growth factors; thus, constituting an attractive and promising novel drug delivery approach for the transport of therapeutics through the BBB into the brain.
The necessity of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy: a retrospective cohort study
Authors: Liao Yu-Tso , Huang John , Wu Chia-Tung , Chen Pei-Chen , Hsieh Tsung-Ting , Lai Feipei , Chen Tzu-Chun , Liang Jin-Tung 
Published: March 2022

Abstract
Background
This study aimed to evaluate the necessity of abdominal drainage after laparoscopic appendectomy in patients with complicated appendicitis.

Methods
Patients with acute appendicitis undergoing laparoscopic appendectomy at two hospitals between January 2014 and December 2018 were retrospectively included. Complicated appendicitis was defined as the American Association for the Surgery of Trauma (AAST) grade ≥ II. The patients were classified according to the AAST grade and the indwelling of abdominal drainage. The postoperative surgical outcomes and recovery were compared among patient groups to evaluate the impact of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy.

Results
A total of 1241 patients was retrospectively included. Among them, there were 820 patients with simple appendicitis (AAST grade I) and 421 patients with complicated appendicitis (AAST grade ≥ II). For complicated appendicitis, the drainage group (N = 192) tended to harbor more overall complications, intra-abdominal abscess formation, time to resume a soft diet, and the postoperative length of hospitalization (P = 0.0000 for all). Multivariate logistic regression confirmed that abdominal drainage increased the risk of overall complications [Odds ratio (OR) 2.439; 95% confidence interval (CI) 1.597–3.726; P ≤ 0.0001] and failed to decrease the risk of intra-abdominal abscess formation (OR 1.655; 95% CI 0.487–5.616; P = 0.4193). Multivariate linear regression analysis also showed that the drainage group harbored longer postoperative length of hospitalization (Coefficients: 20.697; 95% CI 15.251–26.143; P < 0.0001) and time to resume a soft diet (Coefficients: 45.899; 95% CI 34.502–57.297; P < 0.0001).

Conclusions
Abdominal drainage did not prevent overall complications in patients with complicated appendicitis; paradoxically, it delayed the convalescence. Our results discourage the routine use of abdominal drainage and suggest that abdominal drainage should be performed sparingly.
Attitudes about use of preoperative risk assessment tools: a survey of surgeons and surgical residents in an academic health system
Authors: Pradhan Nisha , Dyas Adam R. , Bronsert Michael R. , Lambert-Kerzner Anne , Henderson William G. , Qiu Howe , Colborn Kathryn L. , Mason Nicholas J. , Meguid Robert A. 
Published: March 2022

Abstract
Background
Formal surgical risk assessment tools have been developed to predict risk of adverse postoperative patient outcomes. Such tools accurately predict common postoperative complications, inform patients and providers of likely perioperative outcomes, guide decision making, and improve patient care. However, these are underutilized. We studied the attitudes towards and techniques of how surgeons preoperatively assess risk.

Methods
Surgeons at a large academic tertiary referral hospital and affiliate community hospitals were emailed a 16-question survey via REDCap (Research Electronic Data Capture) between 8/2019-6/2020. Reminder emails were sent once weekly for three weeks. All completed surveys by surgical residents and attendings were included; incomplete surveys were excluded. Surveys were analyzed using descriptive statistics (frequency distributions and percentages for categorical variables, means, and standard deviations for continuous variables), and Fisher’s exact test and unpaired t-tests comparing responses by surgical attendings vs. residents.

Results
A total of 108 surgical faculty, 95 surgical residents, and 58 affiliate surgeons were emailed the survey. Overall response rates were 50.0% for faculty surgeons, 47.4% for residents, and 36.2% for affiliate surgeons. Only 20.8% of surgeons used risk calculators most or all of the time. Attending surgeons were more likely to use prior experience and current literature while residents used risk calculators more frequently. Risk assessment tools were more likely to be used when predicting major complications and death in older patients with significant risk factors. Greatest barriers for use of risk assessment tools included time, inaccessibility, and trust in accuracy.

Conclusions
A small percentage of surgeons use surgical risk calculators as part of their routine practice. Time, inaccessibility, and trust in accuracy were the most significant barriers to use.
Potential of using surface temperature data to benchmark Sentinel-2-based forest phenometrics in boreal Finland
Authors: Majasalmi Titta , Rautiainen Miina 
Published: March 2022

AbstractKey messageWe present a new approach to calibrate timings of phenological events from satellite data (e.g., Sentinel-2 MSI data) with readily available surface temperature data. The new approach improves the estimation of growing season length in boreal forests.ContextSatellite data is used to calibrate phenology models employed in land surface model components of climate models. However, realistic quantification of forest phenological transitions, such as the greenup and senescence, across large spatial scales remains challenging due to the lack of sufficient ground validation data representative of both forest tree canopy and forest understory species compositions.AimsThe aim of this study was to develop a new approach to benchmark boreal forest land surface phenology obtained from Sentinel-2 (S2) against surface temperature data.MethodsWe computed S2 phenological transition dates and compared them to ground reference data on temperature from a network of meteorological stations across Finland (60–70N°).ResultsOur results showed that applying standard phenometrics directly to S2 data to estimate the growing season length in boreal forests may lead to clear biases in all species groups.ConclusionOur approach to use temperature data to calibrate boreal forest phenometrics allows flexible application across spatial scales (i.e., point or grid) and different satellite sensors. It can be combined with any vegetation land cover product to provide a link between surface temperature data and forest seasonal reflectance properties.
Longitudinal study of the mcr-1 gene prevalence in Spanish food-producing pigs from 1998 to 2021 and its relationship with the use of polymyxins
Authors: Miguela-Villoldo Pedro , Moreno Miguel A. , Rodríguez-Lázaro David , Gallardo Alejandro , Hernández Marta , Serrano Tania , Sáez José L. , de Frutos Cristina , Agüero Montserrat , Quesada Alberto , Domínguez Lucas , Ugarte-Ruiz María 
Published: March 2022

Abstract
Background
Resistance to colistin was an uncommon phenomenon traditionally linked to chromosome point mutations, but since the first description of a plasmid-mediated colistin-resistance in late 2015, transmissible resistance to colistin has become a Public Health concern. Despite colistin is considered as a human last resort antibiotic, it has been commonly used in swine industry to treat post-weaning diarrhoea in piglets. However, the progressively increase of colistin resistance during the last decade led to the Spanish Medicines and Healthcare Products Agency (AEMPS) to launch a strategic and voluntary plan aimed to reduce colistin consumption in pig production. Our longitudinal study (1998–2021) aimed to evaluate the trend of colistin resistance mediated through the mcr-1 mobile gene in Spanish food-producing pig population and compare it with published polymyxin sales data in veterinary medicine to assess their possible relationships.

Results
The first mcr-1 positive sample was observed in 2004, as all samples from 1998 and 2002 were mcr-1 PCR-negative. We observed a progressive increase of positive samples from 2004 to 2015, when mcr-1 detection reached its maximum peak (33/50; 66%). From 2017 (27/50; 54%) to 2021 (14/81; 17%) the trend became downward, reaching percentages significantly lower than the 2015 peak (p < 0.001). The abundance of mcr-1 gene in PCR-positive samples showed a similar trend reaching the highest levels in 2015 (median: 6.6 × 104mcr-1 copies/mg of faeces), but decreased significantly from 2017 to 2019 (median 2.7 × 104, 1.2 × 103, 4.6 × 102mcr-1 copies/mg of faeces for 2017, 2018 and 2019, respectively), and stabilizing in 2021 (1.6 × 102mcr-1 copies/mg of faeces) with similar values than 2019.

Conclusions
Our study showed the decreasing trend of colistin resistance associated to mcr-1 gene, after a previous increase from among 2004–2015, since the European Medicines Agency and AEMPS strategies were applied in 2016 to reduce colistin use in animals, suggesting a connection between polymyxin use and colistin resistance. Thus, these plans could have been effective in mcr-1 reduction, reaching lower levels than those detected in samples collected 17 years ago, when resistance to colistin was not yet a major concern.
Adverse Cardiovascular Complications following prescription of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors: a propensity-score matched Cohort Study with competing risk analysis
Authors: Zhou Jiandong , Lee Sharen , Lakhani Ishan , Yang Lei , Liu Tong , Zhang Yuhui , Xia Yunlong , Wong Wing Tak , Bao Kelvin King Hei , Wong Ian Chi Kei , Tse Gary , Zhang Qingpeng 
Published: March 2022

Abstract
Background
Programmed death-1 (PD-1) and programmed death- ligand 1 (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.

Methods
Patients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at publicly funded hospitals of Hong Kong, China, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction, atrial fibrillation, or atrial flutter with the last follow-up date of 31st December 2020. Propensity score matching between PD-L1 inhibitor use and PD-1 inhibitor use with a 1:2 ratio for patient demographics, past comorbidities and non-PD-1/PD-L1 medications was performed with nearest neighbour search strategy (0.1 caliper). Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple propensity matching approaches were considered for sensitivity analysis.

Results
A total of 1959 patients were included. Over a median follow-up of 247 days (interquartile range [IQR]: 72-506), 320 (incidence rate [IR]: 16.31%) patients met the primary outcome after PD-1/PD-L1 treatment: 244 (IR: 12.57%) with heart failure, 38 (IR: 1.93%) with acute myocardial infarction, 54 (IR: 2.75%) with atrial fibrillation, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with lower risks of the composite outcome both before (hazard ratio [HR]: 0.32, 95% CI: [0.18-0.59], P value=0.0002) and after matching (HR: 0.34, 95% CI: [0.18-0.65], P value=0.001), and lower all-cause mortality risks before matching (HR: 0.77, 95% CI: [0.64-0.93], P value=0.0078) and after matching (HR: 0.80, 95% CI: [0.65-1.00], P value=0.0463). Patients who developed cardiac complications had shorter average readmission intervals and a higher number of hospitalizations after treatment with PD-1/PD-L1 inhibitors in both the unmatched and matched cohorts (P value<0.0001). Multivariable Cox regression models, competing risk analysis with cause-specific and subdistribution hazard models, and multiple propensity approaches confirmed these observations.

Conclusions
Compared with PD-1 treatment, PD-L1 treatment was significantly associated with lower risk of new onset cardiac complications and all-cause mortality both before and after propensity score matching.
Massively parallel sequencing of Cannabis sativa chloroplast hotspots for forensic typing
Authors: Roman Madeline G. , Gutierrez Ryan , Houston Rachel 
Published: March 2022

Abstract
Background
Marijuana (Cannabis sativa) is the most commonly used illicit drug in the USA, and the use of DNA barcodes could assist drug trafficking investigations by indicating the biogeographical origin and crop type of a sample and providing a means for linking cases. Additionally, the legality of marijuana in the USA remains complicated with some states fully legalizing marijuana for recreational use while federally marijuana remains completely illegal. Massively parallel sequencing (MPS) offers distinct advantages over capillary electrophoresis (CE), including more comprehensive coverage of target loci, analysis of hundreds of markers simultaneously, and high throughput capabilities.

Methods
This study reports on the development of a MiSeq FGx® assay targeting seven “hotspot” regions in the Cannabis sativa chloroplast genome that are highly polymorphic and informative in attempts to determine biogeographical origin and distinguishing between marijuana and hemp. Sequencing results were compared to previous studies that used CE-based genotyping methods.

Results
A total of 49 polymorphisms were observed, 16 of which have not been previously reported. Additionally, sequence data revealed isoalleles at one locus, which were able to differentiate two samples that had the same haplotype using CE-based methods. This study reports preliminary results from sequencing 14 hemp and marijuana samples from different countries using the developed MPS assay.

Conclusion
Future studies should genotype a more comprehensive sample set from around the world to build a haplotype database, which could be used to provide investigative leads for law enforcement agencies investigating marijuana trafficking.
Methyltransferase-like 3 gene (METTL3) expression and prognostic impact in acute myeloid leukemia patients
Authors: Nagy Reham Mohamed , Mohamed Amal Abd El Hamid , El-Gamal Rasha Abd El-Rahman , Ibrahim Shereen Abdel Monem , Pessar Shaimaa Abdelmalik 
Published: March 2022

AbstractBackgroundDNA methylation is involved in pathogenesis of acute myeloid leukemia (AML). N6-methyladenosine (m6A) modification of mRNA, mediated by methyltransferase-like 3 (METTL3), is one of the well-identified mRNA modifiers associated with the pathogenesis of AML. High level ofMETTL3mRNA is detected in AML cells, thus can be a potential target therapy for AML. This is a preliminary study that aimed at measuringMETTL3mRNA expression level in de novo AML patients and correlating it with clinicopathological, laboratory and prognostic markers.METTL3expression was analyzed by quantitative reverse transcription polymerase chain reaction in 40 newly diagnosed AML adults and was re-measured in the 2nd month of chemotherapy. Patients were followed up for periods up to 6 months post-induction therapy.ResultsMETTL3expression was found to be significantly upregulated in AML patients compared to control subjects (p < 0.001).METTL3gene was significantly expressed among non-responders compared to responders (p < 0.001). A cutoff value was assigned for normalizedMETTL3values to categorize AML patients according to response to therapy. Statistically significant association was observed between high pretreatment normalizedMETTL3gene level and failure to attain complete remission at 2nd, 4th and 6th month following therapy (p = 0.01, 0.02 and 0.003, respectively).However, insignificant correlation was found between pretreatment normalizedMETTL3gene level and event free survival or clinicopathological prognostic factors.ConclusionMETTL3is overexpressed in AML patients and is associated with adverse prognostic effect and failure to attain hematological remission within 6 months post-induction therapy.
Correlation between chest CT severity scoring system with oxygen saturation and laboratory inflammatory markers in adult patients with COVID-19 infection
Authors: Abd El Megid Ahmed Gamil Ibrahim , El Shabrawy Mohamed , Abdalla Ahmed Abd El-Hamid Mohamed 
Published: March 2022

Abstract
Background
COVID-19 pneumonia is responsible for the latest pandemics. Chest computed tomography (CT) scan is known to be an essential tool for diagnosis of COVID-19. In this research, the relationship between on-admission chest CT severity score, capillary blood oxygen saturation level, and laboratory inflammatory markers results in patients with SARS-COV-2 pneumonia was investigated.

Methods
This prospective analytical study was conducted in COVID-19 isolation unit, Zagazig University Hospitals, from 1st to end of April 2021. Adult patients with COVID-19 infection were included. Chest CT scan was performed for all patients, and CT severity score was computed. The initial capillary oxygen saturation was also assessed at the time of admission. The information was gathered and analyzed.

Results
A total number of 305 COVID-19 patients were involved in the study with the following data: age, gender, presence of co morbidities, capillary blood oxygen saturation, laboratory tests including absolute lymphocytic count, CRP, D-dimer and ferritin levels, as well as chest CT severity score. Based on chest CT severity score, we found that 110 cases (36.1%) were mild, 163 cases (53.4%) were moderate, and 32 cases (10.5%) were severe, with significant male predominance among moderate and severe cases. The initial measurements of blood oxygen saturation values revealed that mean blood oxygen saturation was 95.6% among mild to moderate cases and 85.4% among severe cases. Furthermore, there was a high statistically significant negative correlation between chest CT severity score and absolute lymphocytic count of studied cases, while there was a statistically significant positive correlation with D-dimer, CRP and ferritin levels.

Conclusions
CT scans can help clinicians in developing a management strategy and serve as a predictor of illness severity and possible outcomes. In individuals with COVID-19 infection, the severity of a chest CT scan is positively correlated to inflammatory markers and oxygen demand.
Automated fault detection in the Arabian Basin
Authors: Alohali Ruaa , Alzubaidi Fatimah , van Kranendonk Martin , Clark Stuart 
Published: March 2022

In recent years, there has been a rapid development of the computer-aided interpretation of seismic data to reduce the otherwise intensive manual labor. A variety of seed detection algorithms for horizon and fault identification are integrated into popular seismic software packages. Recently, there has been an increasing focus on using neural networks for fully automatic fault detection without manually seeding each fault. These networks are usually trained with synthetic fault data sets. These data sets can be used across multiple seismic data sets; however, they are not as accurate as real seismic data, particularly in structurally complex regions associated with several generations of faults. The approach taken here is to combine the accuracy of manual fault identification in certain parts of the data set with a convolutional neural network that can then sweep through the entire data set to identify faults. We have implemented our method using 3D seismic data acquired from the Arabian Basin in Saudi Arabia covering an area of 1051 km2. The network is trained, validated, and tested with samples that included a seismic cube and fault images that are labeled manually corresponding to the seismic cube. The model successfully identifies faults with an accuracy of 96% and an error rate of 0.12 on the training data set. To achieve a robust model, we further enhance the prediction results using postprocessing by linking discontinued segments of the same fault line, thus reducing the number of detected faults. The postprocessing improves the prediction results from the test data set by 77.5%. In addition, we introduce an efficient framework to correlate the predictions and the ground truth by measuring their average distance value. Furthermore, tests using this approach also have been conducted on the F3 Netherlands survey with complex fault geometries and find promising results. As a result, fault detection and diagnosis are achieved efficiently with structures similar to the trained data set.