bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the autophagy pathway decreases dengue virus infection in Aedes aegypti cells
Authors: Chen Tse-Yu , Smartt Chelsea T. 
Published: October 2021

Abstract
Background
Mosquito-borne dengue virus (DENV) causes major disease worldwide, impacting 50–100 million people every year, and is spread by the major mosquito vector Aedes aegypti. Understanding mosquito physiology, including antiviral mechanisms, and developing new control strategies have become an important step towards the elimination of DENV disease. In the study reported here, we focused on autophagy, a pathway suggested as having a positive influence on virus replication in humans, as a potential antiviral target in the mosquito.

Methods
To understand the role played by autophagy in Ae. aegypti, we examined the activation of this pathway in Aag-2 cells, an Ae. aegypti-derived cell line, infected with DENV. Rapamycin and 3-methyladenine, two small molecules that have been shown to affect the function of the autophagy pathway, were used to activate or suppress, respectively, the autophagy pathway.

Results
At 1-day post-DENV infection in Aag-2 cells, transcript levels of both the microtubule-associated protein light chain 3-phosphatidylethanolamine conjugate (LC3-II) and autophagy-related protein 1 (ATG1) increased. Rapamycin treatment activated the autophagy pathway as early as 1-h post-treatment, and the virus titer had decreased in the Aag-2 cells at 2 days post-infection; in contrast, the 3-methyladenine treatment did not significantly affect the DENV titer. Treatment with these small molecules also impacted the ATG12 transcript levels in DENV-infected cells.

Conclusions
Our studies revealed that activation of the autophagy pathway through rapamycin treatment altered DENV infection in the mosquito cells, suggesting that this pathway could be a possible antiviral mechanism in the mosquito system. Here we provide fundamental information needed to proceed with future experiments and to improve our understanding of the mosquito’s immune response against DENV.

Graphical Abstract
Measuring athletic performance in post-metamorphic fire salamanders
Authors: de Rysky Erica , Roberta Bisconti , Andrea Chiocchio , Daniele Canestrelli 
Published: October 2021

Abstract
Objective
Athletic performances are dynamic movements that are physically challenging and often predict individual success in ecological contexts. They stem from a complex integration of multiple phenotypic traits—e.g., morphological, physiological and behavioural—that dictate animal survival and individual fitness. However, directly quantifying athletic performances can be particularly challenging in cryptic, slow-moving species or not very reactive in attitude. Here we present and describe a rapid, simple, and low-cost method to measure athletic performance in post-metamorphic individuals of the fire salamander Salamandra salamandra. While extremely reactive during the larval stage, adult salamanders are, in fact, cryptic and relatively slow-moving.

Results
Forcing terrestrial juveniles to swim under standard, albeit ecologically plausible, laboratory conditions, and using an automatic point-mass tracking tool, we were able to measure maximal and average performance indicators of post-metamorphic individuals. This method avoids inter-individual variation in motivation, as it forces individuals to perform at their best. Moreover, with this method, measures of athletic performance will be directly comparable between larval and terrestrial stages, allowing to study the contribution of carryover effects to the wide range of processes implicated in the eco-evo-devo of athletic performance in salamanders.
Aplastic anemia secondary to dual cancer immunotherapies a physician nightmare: case report and literature review
Authors: Younan Romy G. , Raad Roy A. , Sawan Bassem Y. , Said Rabih 
Published: October 2021

Abstract
Background
Treatment with immune checkpoint inhibitors has revolutionized cancer treatment over the past several years. Despite their clinical benefits, a wide range of immune-mediated toxicities can be observed including hematological toxicities. Although, the majority can easily be managed, immune-mediated adverse events rarely can be severe and difficult to approach. Herein, we are reporting a case of very severe aplastic anemia secondary to ipilimumab (I) and nivolumab (N) treatment that failed various treatment including intensive immune suppressive therapy.

Case presentation
We described a case of a 45-year old white male, heavy smoker presented to the clinic complaining of left flank pain. He was found to have a metastatic renal cell carcinoma for which he was treated with dual immunotherapy and later complicated by severe immune related adverse events. The patient later died after failing intensive immune suppressive therapy.

Conclusion
Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with variant malignancies. Yet, lethal adverse events can occur in rare cases. It is our duty, as physicians, to remain alert and cautious.
De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures
Authors: Royer-Bertrand Beryl , Jequier Gygax Marine , Cisarova Katarina , Rosenfeld Jill A. , Bassetti Jennifer A. , Moldovan Oana , O’Heir Emily , Burrage Lindsay C. , Allen Jake , Emrick Lisa T. , Eastman Emma , Kumps Camille , Abbas Safdar , Van Winckel Geraldine ,   Undiagnosed Diseases Network, Chabane Nadia , Zackai Elaine H. , Lebon Sebastien , Keena Beth , Bhoj Elizabeth J. , Umair Muhammad , Li Dong , Donald Kirsten A. , Superti-Furga Andrea 
Published: October 2021

Abstract
Background
De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias.

Methods
Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database.

Results
We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype–phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator.

Limitations
The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time.

Conclusions
Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate.
Postpartum ovarian vein thrombosis manifesting as acute appendicitis: a case report
Authors: Tsitlakidis Christos , Al Ajmi Khalil Ibrahim Salim , Al Madhani Alya Yousuf , Ahmidat Adel Hassan 
Published: October 2021

AbstractBackgroundPostpartum ovarian thrombosis is an uncommon condition. It appears with the nonspecific, predominantly right-sided abdominal symptoms and must be differentiated from other acute visceral conditions. If left untreated, postpartum ovarian thrombosis can have severe consequences, including sepsis, pulmonary embolism, and even death. Momentarily, there are no specific guidelines for postpartum ovarian thrombosis management. We present a case of postpartum ovarian thrombosis admitted to our hospital with symptoms of acute appendicitis.Case presentation A 39-year-old Omani obese multiparous woman of Afro-Arab origin was admitted with acute symptoms, mainly abdominal pain, fever, and vomiting 1 week postpartum. Clinical picture and biochemical profile did not exhibit a recognizable pattern. Ultrasonography excluded retained products of conception. Computerized scan for abdomen and pelvis with oral and intravenous contrast reported a dilated tubular structure in the right adnexa extending up to the right renal hilum level with surrounding inflammation. Those findings were consistent with the thrombophlebitis of the right ovarian vein. Blood cultures and sensitivity showed group A β-hemolytic streptococci sensitive to penicillin G and clindamycin. The patient was treated successfully with antibiotics and therapeutic anticoagulants and discharged home 3 days later; follow-up was arranged.ConclusionThis pathology is an exceptional entity in Oman. Therefore, awareness of this unique condition is required so that clinicians will be vigilant, exploring similar cases with imaging and avoiding unnecessary surgical interventions.
QSPR modeling of selectivity at infinite dilution of ionic liquids
Authors: Klimenko Kyrylo , Carrera Gonçalo V. S. M. 
Published: October 2021

AbstractThe intelligent choice of extractants and entrainers can improve current mixture separation techniques allowing better efficiency and sustainability of chemical processes that are both used in industry and laboratory practice. The most promising approach is a straightforward comparison of selectivity at infinite dilution between potential candidates. However, selectivity at infinite dilution values are rarely available for most compounds so a theoretical estimation is highly desired. In this study, we suggest a Quantitative Structure–Property Relationship (QSPR) approach to the modelling of the selectivity at infinite dilution of ionic liquids. Additionally, auxiliary models were developed to overcome the potential bias from big activity coefficient at infinite dilution from the solute. Data from SelinfDB database was used as training and internal validation sets in QSPR model development. External validation was done with the data from literature. The selection of the best models was done using decision functions that aim to diminish bias in prediction of the data points associated with the underrepresented ionic liquids or extreme temperatures. The best models were used for the virtual screening for potential azeotrope breakers of aniline + n-dodecane mixture. The subject of screening was a combinatorial library of ionic liquids, created based on the previously unused combinations of cations and anions from SelinfDB and the test set extractants. Both selectivity at infinite dilution and auxiliary models show good performance in the validation. Our models’ predictions were compared to the ones of the COSMO-RS, where applicable, displaying smaller prediction error. The best ionic liquid to extract aniline fromn-dodecane was suggested.
Identification and solution of drug-related problems in the neurology unit of a tertiary hospital in China
Authors: Liu Pengpeng , Li Guangyao , Han Mei , Zhang Chao 
Published: October 2021

Abstract
Background
The prevalence and characteristics of drug-related problems (DRPs) and factors associated with the occurrence of DRPs in the neurology unit in China remain unknown. This study aimed to determine the prevalence, characteristics and severity ratings of DRPs and identify factors associated with the occurrence of DRPs in the neurology unit of a tertiary care and academic teaching hospital in China.

Methods
A retrospective study of DRPs and pharmacists’ interventions for neurology patients was performed during a non-consecutive 24-month study period. Patient demographics and clinical characteristics, and pharmacist’s intervention records were collected. The characteristics and severity ratings of DRPs were categorized using the Pharmaceutical Care Network Europe (PCNE) DRP classification tool V9.00 and the National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP) classification respectively.

Results
A total of 242 DRPs were detected for 974 admitted patients, an average of 0.25 DRPs per patient. Treatment safety was the major type of DRPs (106;43.8%) followed by treatment effectiveness (78;32.2%). The primary causes of DRPs were drug selection (124;44.1%) and dose selection (92;32.7%). Clinical pharmacists provided 525 interventions, and most interventions occurred at the prescriber level (241;45.9%). A total of 91.4% of these interventions were accepted, contributing to solving 93.0% of the identified problems. The majority of DRPs (210;86.8%) were rated at severity categories B to D (causing no patient harm). Multiple logistic regression showed that creatinine clearance, number of medications used, nasogastric feeding, diabetes, and infectious diseases were associated with more frequent DRPs (p < 0.05).

Conclusions
DRPs are relatively common in the neurology unit in China, with primary causes of drug and dose selection, and clinical pharmacists can effectively reduce and prevent DRPs to optimize medication therapy.
Biomechanical effects of Skeletally anchored Class III elastics on the maxillofacial complex: a 3D finite element analysis
Authors: Rai Priyank , Garg Dhiraj , Tripathi Tulika , Kanase Anup , Ganesh Gayatri 
Published: October 2021

Abstract
Background
Although, the outcomes and changes in the maxillofacial complex after the application of intraoral bone anchored Class III elastics, have been reported by multiple clinical studies, there was no finite element study to assess and evaluate the stress pattern and displacement on maxillomandibular complex with bimaxillary anchorage. The present study aims to evaluate the biomechanical effects on maxillomandibular complex of Skeletally anchored Class III elastics with varying angulations using the 3D finite element analysis.

Methodology
Two 3-dimensional analytical models were developed using the Mimics 8.11 (Materialise: Leuven, Belgium) and ANSYS software Version 12.1 (ANSYS Inc, Canonsburg, PA, USA) from sequential computed tomography images taken from a Skeletal Class III subject. The models were meshed into 465,091 tetrahedral elements and 101,247 nodes. Intraoral mechanics for skeletally anchored maxillary protraction (I-SAMP) were applied on two models i.e. A and B (without and with maxillary expansion respectively) between miniplates on maxilla and mandible on both right and left sides with three different angulations of forces—10°, 20° and 30°).

Results
Although the craniomaxillary complex in both the models (A and B) displaced forward while demonstrating rotations in opposite directions, the displacements and rotations decreased gradually with the increase of the angle of load application from 10° to 30°. The mandible rotated clockwise in both the simulations, but the displacement of mandibular surface landmarks was higher in Simulation A. However, the antero-inferior displacement of the glenoid fossa was higher in Simulation B than in A.

Conclusion
Significant displacement of maxillofacial sutures and structures was witnessed with I-SAMP with maxillary expansion and Class III elastics for correction of Skeletal Class III with maxillary retrognathism. Thus, I-SAMP with maxillary expansion is a desired protocol for treatment of maxillary retrognathism. However, the prescribed angulation of the Class III elastics should be as low as possible to maximise the desired effects.
Local seismotectonic analysis of the July 2019 Molucca Sea earthquake sequence based on moment tensor solutions
Authors: Prasetio Aditya Dwi , Hasib Mohammad , Amran Andi , Syuhada  , Febriani Febty , Dewi Cinantya Nirmala , Anggono Titi 
Published: October 2021

AbstractWe investigate the local seismotectonic of the Molucca Sea area using moment tensor calculations for the earthquakes that occurred in July 2019 at a depth of 10–55 km. The mainshock of Mw 6.8 occurred on July 7, followed by aftershocks until July 18, with magnitudes ranging from Mw 4.6 to Mw 5.8. Moment tensor solutions are calculated by applying Isolated Asperities (ISOLA) software using the full waveform data recorded at regional seismic stations. The analyzed frequency bands used in this study are 0.01–0.03 Hz and 0.04–0.05 Hz for the event with Mw ≥ 5 and Mw < 5, respectively. We provide validations of new moment tensor solutions for Mw < 5 events in the Molucca Sea region for the period during the earthquake sequence. The results show that thrust and oblique faults are dominant during this event, which indicate a compressional stress of divergent double subduction (DDS) of the Sangihe and Halmahera arcs. Only one full moment tensor solution reveals the normal fault mechanism, which may indicate the manifestation of strain release of compressional stress in the surrounding area. Furthermore, these results also support the previous studies suggesting that the Talaud-Mayu Ridge located in the middle of the Molucca Sea has developed as a consequence of the transpressional tectonic activity.
Baccharis trimera aqueous extract modulates inflammation and nociception in mice
Authors: de Almeida Natiely Silveira , Ferraz Alexandre de Barros Falcão , Pedron Claudia , Correa Dione Silva , Vieira Luciene Bruno , Antunes Flavia Tasmim Techera , de Souza Alessandra Hubner 
Published: October 2021

AbstractBackgroundThe aerial parts ofBaccharis trimera(Less.) are frequently used as a tea to treat several diseases. Therefore, the aim of this study was to identify the constituents of an aqueous extract ofB. trimera, focusing on their antioxidant, anti-inflammation, and antinociception activities and properties. For that, the researchers performed in vivo assays using the formalin test and Freund’s Complete Adjuvant (FCA) to measure the acute and chronic inflammatory pain in mice. Moreover, the myeloperoxidase enzyme (MPO) was analyzed in the subcutaneous tissue after the FCA injection, together with the counting of lymphocytes in the peripheral blood of the mice.ResultsThe qualitative phytochemical analysis indicated the presence of flavonoids and saponins in theB. trimeraaqueous extract. The high-performance liquid chromatography (HPLC) analyses showed the presence of phenolic compounds, such as chlorogenic acid, ellagic acid, rosmarinic acid, as well as flavonoids, such as rutin, quercetin, and luteolin. The DPPH assay was used in order to measure the antioxidant activity of the aqueous extract ofB. trimeraand this showed an IC50of 118.18 ± 1.02 μg/mg. The data from the formalin test demonstrated that a single dose of the aqueous extract ofB. trimerawas not able to decrease the nociceptive behavior during the neurogenic phase, at any of the tested doses (20, 40, or 80 mg/kg p.o.). However, during the inflammatory phase of this test, the aqueous extract ofB. trimeraat 80 mg/kg (p.o.) significantly decreased the nociceptive behavior, showing more effectiveness when compared to the other tested doses (p < 0.05). Importantly, in the chronic inflammatory model on the 5th day of treatment, the aqueous extract ofB. trimera(80 mg/kg p.o.) significantly reduced mechanical allodynia (p < 0.01), heat thermal hyperalgesia (p < 0.001), and paw edema (p < 0.05). There were no changes in the MPO activity, but the data exhibited an equivalent decrease in the number of lymphocytes in the blood of the mice that were treated withB. trimera(80 mg.kg− 1p.o.) and diclofenac sodium.ConclusionTaken together, the present data reinforces the potential of theB. trimeraaqueous extract as an anti-inflammatory and analgesic compound.
Patient powered research: an approach to building capacity for a hardly reached patient population to engage in cancer research
Authors: Charlot Marjory , Carolan Kelsi , Gawuga Cyrena , Freeman Elmer , Sprague Martinez Linda 
Published: October 2021

Abstract
Background
Participating in clinical trials is a metric of high-quality cancer care and improves survival. However, Black individuals with cancer are less likely to be enrolled in clinical trials and experience a disproportionate burden of cancer mortality compared to Whites. Patient-engaged research is one potential strategy to address racial inequities in clinical trials, but little is known about best practices for engaging Black individuals and communities impacted by cancer in research partnerships.

Methods
We used a community engaged research approach to establish a patient advisory council (PAC) representative of the patient population served by a safety net hospital cancer center. We outline the process of establishing the PAC and the lessons learned.

Results
The inaugural PAC included 7 members representative of the cancer center’s patient demographics. PAC members developed a patient centered vision, mission and action plan. PAC and community-academic research partners experienced the transformative power of centering the lived experiences of patients of color to promote health equity in cancer research.

Conclusion
Establishing a patient advisory council at a safety net hospital cancer care center provided a platform for engaging a hardly reached population in patient centered research.
Novel double-filtration plasmapheresis preserves fibrinogen while removing immunoglobulin-G antibodies before ABO blood type-incompatible kidney transplantation
Authors: Iwami Daiki , Matsumoto Takenao , Ono Kota , Hotta Kiyohiko , Ota Minoru , Chiba Yuki , Sasaki Hajime , Hirose Takayuki , Higuchi Haruka , Takada Yusuke , Iwahara Naoya , Murai Sachiyo , Shinohara Nobuo 
Published: October 2021

Abstract
Background
Removal of anti-blood group antibodies is important for successful ABO-incompatible kidney transplantation (ABOi-KTx). Double-filtration plasmapheresis (DFPP) using albumin solution removes antibodies effectively. However, fibrinogen is largely removed resulting in hemostatic failure. Herein, we designed an altered combination of plasma membranes in DFPP (novel DFPP, nDFPP) to retain more fibrinogen while removing IgG, and assessed its efficacy and safety compared with conventional DFPP (cDFPP).

Methods
Consecutive ABOi-KTx recipients (from 2015 to 2018) were enrolled. For the first membrane, we used Cascadeflo EC-50W in nDFPP and Plasmaflo OP-08W in cDFPP, and Cascadeflo EC-20W as the second membrane in both modalities. Removal rates (RR) of IgG, IgM and fibrinogen per DFPP session, and adverse events were compared with historical control patients who underwent cDFPP before ABOi-KTx, between 2006 and 2015.

Results
nDFPP and cDFPP groups included 12 and 23 cases, respectively. nDFPP was inferior to cDFPP in RR of IgG and IgM. nDFPP was also inferior to cDFPP in the decline in anti-blood group IgG and IgM antibody titers. However, fibrinogen was more preserved in nDFPP compared with cDFPP, indicating that nDFPP has more selective removal properties (median RR of IgG, IgM, and fibrinogen: 62.1%, 15.7% and 37.6%, respectively, in nDFPP; and 74.5%, 85.0% and 76.6%, respectively, in cDFPP). In the comparison of hemostatic function among the patients who had arteriovenous fistula for hemodialysis, prolonged hemostasis (> 20 min) at the cannulation site was significantly less frequently observed in nDFPP group (1 in 9 cases, 9.1%) than in cDFPP group (all 18 cases, 10%, p < 0.0001).

Conclusions
nDFPP preserves fibrinogen while removing anti-blood type IgG antibodies before ABOi-KTx.