bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurofilament light as a predictive biomarker of unresolved chemotherapy-induced peripheral neuropathy in subjects receiving paclitaxel and carboplatin
Authors: Burgess B. L. , Cho E. , Honigberg L. 
Published: September 2022

AbstractManagement of chemotherapy-induced peripheral neuropathy (CIPN) remains a significant challenge in the treatment of cancer. Risk mitigation for CIPN involves preemptive reduction of cumulative dose or reduction of dose intensity upon emergence of symptoms, despite the risk of reduced tumor efficacy. A predictive biomarker for dose-limiting CIPN could improve treatment outcomes by allowing providers to make informed decisions that balance both safety and efficacy. To identify a predictive biomarker of CIPN, markers of neurodegeneration neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), tau and ubiquitin c-terminal hydrolase L1 (UCHL1) were assessed in serum of up to 88 subjects drawn 21 days following the first of 6 treatments with chemotherapeutics paclitaxel and carboplatin. Serum NfL and GFAP were increased with chemotherapy. Further, NfL change predicted subsequent onset of grade 2–3 CIPN during the remainder of the trial (mean treatment duration = 200 days) and trended toward stronger prediction of CIPN that remained unresolved at the end of the study. These results confirm previous reports that serum NfL is increased in CIPN and provide the first evidence that NfL can be used to identify subjects susceptible to dose-limiting paclitaxel and carboplatin induced CIPN prior to onset of symptoms.
Insight into the heat transfer of third-grade micropolar fluid over an exponentially stretched surface
Authors: Guedri Kamel , Ameer Ahammad N. , Nadeem Sohail , Tag-ElDin ElSayed M. , Awan Aziz Ullah , Yassen Mansour F. 
Published: September 2022

AbstractDue to their unique microstructures, micropolar fluids have attracted enormous attention for their industrial applications, including convective heat and mass transfer polymer production and rigid and random cooling particles of metallic sheets. The thermodynamical demonstration is an integral asset for anticipating the ideal softening of heat transfer. This is because there is a decent connection between mathematical and scientific heat transfers through thermodynamic anticipated outcomes. A model is developed under the micropolar stream of a non-Newtonian (3rd grade) liquid in light of specific presumptions. Such a model is dealt with by summoning likeness answers for administering conditions. The acquired arrangement of nonlinear conditions is mathematically settled using the fourth-fifth order Runge-Kutta-Fehlberg strategy. The outcomes of recognized boundaries on liquid streams are investigated in subtleties through the sketched realistic images. Actual amounts like Nusselt number, Sherwood number, and skin-part coefficient are explored mathematically by tables. It is observed that the velocity distribution boosts for larger values of any of $$\alpha _1$$

α
1

, $$\beta$$
β
, and declines for larger $$\alpha _2$$

α
2

and Hartmann numbers. Furthermore, the temperature distribution $$\theta (\eta )$$

θ
(
η
)

shows direct behavior with the radiation parameter and Eckert number, while, opposite behavior with Pr, and K. Moreover, the concentration distribution shows diminishing behavior as we put the higher value of the Brownian motion number.
A machine learning COVID-19 mass screening based on symptoms and a simple olfactory test
Authors: Azeli Youcef , Fernández Alberto , Capriles Federico , Rojewski Wojciech , Lopez-Madrid Vanesa , Sabaté-Lissner David , Serrano Rosa Maria , Rey-Reñones Cristina , Civit Marta , Casellas Josefina , El Ouahabi-El Ouahabi Abdelghani , Foglia-Fernández Maria , Sarrá Salvador , Llobet Eduard 
Published: September 2022

AbstractThe early detection of symptoms and rapid testing are the basis of an efficient screening strategy to control COVID-19 transmission. The olfactory dysfunction is one of the most prevalent symptom and in many cases is the first symptom. This study aims to develop a machine learning COVID-19 predictive tool based on symptoms and a simple olfactory test, which consists of identifying the smell of an aromatized hydroalcoholic gel. A multi-centre population-based prospective study was carried out in the city of Reus (Catalonia, Spain). The study included consecutive patients undergoing a reverse transcriptase polymerase chain reaction test for presenting symptoms suggestive of COVID-19 or for being close contacts of a confirmed COVID-19 case. A total of 519 patients were included, 386 (74.4%) had at least one symptom and 133 (25.6%) were asymptomatic. A classification tree model including sex, age, relevant symptoms and the olfactory test results obtained a sensitivity of 0.97 (95% CI 0.91–0.99), a specificity of 0.39 (95% CI 0.34–0.44) and an AUC of 0.87 (95% CI 0.83–0.92). This shows that this machine learning predictive model is a promising mass screening for COVID-19.
Quantitative analysis of CRISPR/Cas9-mediated provirus deletion in blue egg layer chicken PGCs by digital PCR
Authors: Altgilbers Stefanie , Dierks Claudia , Klein Sabine , Weigend Steffen , Kues Wilfried A. 
Published: September 2022

AbstractPrimordial germ cells (PGCs), the precursors of sperm and oocytes, pass on the genetic material to the next generation. The previously established culture system of chicken PGCs holds many possibilities for functional genomics studies and the rapid introduction of desired traits. Here, we established a CRISPR/Cas9-mediated genome editing protocol for the genetic modification of PGCs derived from chickens with blue eggshell color. The sequence targeted in the present report is a provirus (EAV-HP) insertion in the 5’-flanking region of the SLCO1B3 gene on chromosome 1 in Araucana chickens, which is supposedly responsible for the blue eggshell color. We designed pairs of guide RNAs (gRNAs) targeting the entire 4.2 kb provirus region. Following transfection of PGCs with the gRNA, genomic DNA was isolated and analyzed by mismatch cleavage assay (T7EI). For absolute quantification of the targeting efficiencies in homozygous blue-allele bearing PGCs a digital PCR was established, which revealed deletion efficiencies of 29% when the wildtype Cas9 was used, and 69% when a high-fidelity Cas9 variant was employed. Subsequent single cell dilutions of edited PGCs yielded 14 cell clones with homozygous deletion of the provirus. A digital PCR assay proved the complete absence of this provirus in cell clones. Thus, we demonstrated the high efficiency of the CRISPR/Cas9 system in introducing a large provirus deletion in chicken PGCs. Our presented workflow is a cost-effective and rapid solution for screening the editing success in transfected PGCs.
Autoprocessing and oxyanion loop reorganization upon GC373 and nirmatrelvir binding of monomeric SARS-CoV-2 main protease catalytic domain
Authors: Nashed Nashaat T. , Kneller Daniel W. , Coates Leighton , Ghirlando Rodolfo , Aniana Annie , Kovalevsky Andrey , Louis John M. 
Published: September 2022

AbstractThe monomeric catalytic domain (residues 1–199) of SARS-CoV-2 main protease (MPro1-199) fused to 25 amino acids of its flanking nsp4 region mediates its autoprocessing at the nsp4-MPro1-199 junction. We report the catalytic activity and the dissociation constants of MPro1-199 and its analogs with the covalent inhibitors GC373 and nirmatrelvir (NMV), and the estimated monomer-dimer equilibrium constants of these complexes. Mass spectrometry indicates the presence of the accumulated adduct of NMV bound to MProWT and MPro1-199 and not of GC373. A room temperature crystal structure reveals a native-like fold of the catalytic domain with an unwound oxyanion loop (E state). In contrast, the structure of a covalent complex of the catalytic domain-GC373 or NMV shows an oxyanion loop conformation (E* state) resembling the full-length mature dimer. These results suggest that the E-E* equilibrium modulates autoprocessing of the main protease when converting from a monomeric polyprotein precursor to the mature dimer.
Mechanism of action of non-camptothecin inhibitor Genz-644282 in topoisomerase I inhibition
Authors: Nishida Masahiro , Terabayashi Takeshi , Matsuoka Shigeru , Okuma Tomoko , Adachi Sawako , Tomo Tadashi , Kawano Masanori , Tanaka Kazuhiro , Tsumura Hiroshi , Anai Hirofumi , Ishizaki Toshimasa , Nishida Yoshihiro , Hanada Katsuhiro 
Published: September 2022

AbstractTopoisomerase I (TOP1) controls the topological state of DNA during DNA replication, and its dysfunction due to treatment with an inhibitor, such as camptothecin (CPT), causes replication arrest and cell death. Although CPT has excellent cytotoxicity, it has the disadvantage of instability under physiological conditions. Therefore, new types of TOP1 inhibitor have attracted particular attention. Here, we characterised the effect of a non-camptothecin inhibitor, Genz-644282 (Genz). First, we found that treatment with Genz showed cytotoxicity by introducing double-strand breaks (DSBs), which was suppressed by co-treatment with aphidicolin. Genz-induced DSB formation required the functions of TOP1. Next, we explored the advantages of Genz over CPT and found it was effective against CPT-resistant TOP1 carrying either N722S or N722A mutation. The effect of Genz was also confirmed at the cellular level using a CPT-resistant cell line carrying N722S mutation in theTOP1gene. Moreover, we found arginine residue 364 plays a crucial role for the binding of Genz. Because tyrosine residue 723 is the active centre for DNA cleavage and re-ligation by TOP1, asparagine residue 722 plays crucial roles in the accessibility of the drug. Here, we discuss the mechanism of action of Genz on TOP1 inhibition.
Differences between gridded population data impact measures of geographic access to healthcare in sub-Saharan Africa
Authors: Hierink Fleur , Boo Gianluca , Macharia Peter M. , Ouma Paul O. , Timoner Pablo , Levy Marc , Tschirhart Kevin , Leyk Stefan , Oliphant Nicholas , Tatem Andrew J. , Ray Nicolas 
Published: September 2022

Abstract
Background
Access to healthcare is imperative to health equity and well-being. Geographic access to healthcare can be modeled using spatial datasets on local context, together with the distribution of existing health facilities and populations. Several population datasets are currently available, but their impact on accessibility analyses is unknown. In this study, we model the geographic accessibility of public health facilities at 100-meter resolution in sub-Saharan Africa and evaluate six of the most popular gridded population datasets for their impact on coverage statistics at different administrative levels.

Methods
Travel time to nearest health facilities was calculated by overlaying health facility coordinates on top of a friction raster accounting for roads, landcover, and physical barriers. We then intersected six different gridded population datasets with our travel time estimates to determine accessibility coverages within various travel time thresholds (i.e., 30, 60, 90, 120, 150, and 180-min).

Results
Here we show that differences in accessibility coverage can exceed 70% at the sub-national level, based on a one-hour travel time threshold. The differences are most notable in large and sparsely populated administrative units and dramatically shape patterns of healthcare accessibility at national and sub-national levels.

Conclusions
The results of this study show how valuable and critical a comparative analysis between population datasets is for the derivation of coverage statistics that inform local policies and monitor global targets. Large differences exist between the datasets and the results underscore an essential source of uncertainty in accessibility analyses that should be systematically assessed.
Peimine ameliorates pulmonary fibrosis via the inhibition of M2-type macrophage polarization through the suppression of P38/Akt/STAT6 signals
Authors: Cai Ze-hui , Tian Yan-ge , Li Jun-zi , Zhao Peng , Li Jian-sheng , Mei Xue , Bai Yun-ping 
Published: September 2022

Abstract
Peimine, a bioactive substance isolated from Chinese medicine Fritillaria, can potentially suppress pulmonary fibrosis (PF); however, its therapeutic mechanism remains unclear. Recent evidence suggests the participation of M2-type macrophages in the pathogenesis of PF. The present study aimed to investigate the effect of peimine on a bleomycin (BLM)-induced PF rat model and the underlying mechanism of this effect. After BLM administration, peimine was administered to rats from day 29 to day 42, with pirfenidone (PFD) as a positive control. H&E and Masson’s trichrome stain were used to analyze histological changes. Q-PCR and western blotting were used to measure mRNA levels and protein levels, respectively. High-throughput RNA sequencing (RNA-seq) technology detected the differentially expressed genes (DEGs) regulated by peimine. Our results revealed that peimine treatment significantly ameliorated BLM-induced PF by suppressing histological changes and collagen deposition. In addition, peimine decreased the number of M2 macrophages and the expression of profibrotic factors. RNA-seq results showed that DEGs regulated by peimine in IL-4-induced macrophages were mainly associated with immune system processes, the PI3K/Akt pathway, and the MAPKs pathway. Then, immunofluorescence assay and western blot results demonstrated that peimine treatment suppressed the expression of p-p38 MAPK and p-Akt (s473) and also inhibited the nuclear translocation of p-STAT6. In conclusion, the present study demonstrated that peimine has a protective effect on PF through the suppression of M2 polarization of macrophages by inhibiting the STAT6, p38 MAPK, and Akt signals.
Redefining the catalytic HECT domain boundaries for the HECT E3 ubiquitin ligase family
Authors: Kane Emma I. , Beasley Steven A. , Schafer Johanna M. , Bohl Justine E. , Lee Young Sun , Rich Kayla J. , Bosia Elizabeth F. , Spratt Donald E. 
Published: September 2022

Abstract
There are 28 unique human members of the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligase family. Each member of the HECT E3 ubiquitin ligases contains a conserved bilobal HECT domain of approximately 350 residues found near their C-termini that is responsible for their respective ubiquitylation activities. Recent studies have begun to elucidate specific roles that each HECT E3 ubiquitin ligase has in various cancers, age-induced neurodegeneration, and neurological disorders. New structural models have been recently released for some of the HECT E3 ubiquitin ligases, but many HECT domain structures have yet to be examined due to chronic insolubility and/or protein folding issues. Building on these recently published structural studies coupled with our in-house experiments discussed in the present study, we suggest that the addition of ∼50 conserved residues preceding the N-terminal to the current UniProt defined boundaries of the HECT domain are required for isolating soluble, stable, and active HECT domains. We show using in silico bioinformatic analyses coupled with secondary structural prediction software that this predicted N-terminal α-helix found in all 28 human HECT E3 ubiquitin ligases forms an obligate amphipathic α-helix that binds to a hydrophobic pocket found within the HECT N-terminal lobe. The present study brings forth the proposal to redefine the residue boundaries of the HECT domain to include this N-terminal extension that will likely be critical for future biochemical, structural, and therapeutic studies on the HECT E3 ubiquitin ligase family.
Context‐aware Siamese network for object tracking
Authors: Zhang Jianwei , Wang Jingchao , Zhang Huanlong , Miao Mengen , Wu Di 
Published: September 2022

AbstractAt present, temporal and spatial contexts are widely used to improve the adaptability of a tracker. However, most existing methods usually focus on one aspect of the temporal or spatial context and rarely exploit them simultaneously. In this paper, a context‐aware Siamese Network (CSNet) is proposed, which skilfully integrates the modelling of temporal and spatial context into the Siamese tracking framework. Specifically, CSNet consists of a context‐based channel attention module and a context‐based cross‐attention module. The former aggregates spatial context information from different channels and dynamically emphasizes target features, which makes it easier for the tracker to distinguish the target from the background. The latter propagates the temporal context from the previous frames to the current frame to establish the part‐level relationship between the search region and the historical target state, which enables the tracker better adapt to the target deformation. In addition, to further mine context information, the CSNet is equipped with a state‐aware strategy to control the contribution of different context information in tracking. Extensive experiments on OTB2015, UAV123, GOT‐10k, LaSOT, and TrackingNet show that the proposed tracking method achieves comparable performance to the advanced trackers.
Reshaping and ejection processes on rubble-pile asteroids from impacts
Authors: Raducan S. D. , Jutzi M. , Zhang Y. , Ormö J. , Michel P. 
Published: September 2022

Context. Most small asteroids (< 50 km in diameter) are the result of the breakup of a larger parent body and are often considered to be rubble-pile objects. Similar structures are expected for the secondaries of small asteroid binaries, including Dimorphos, the smaller component of the 65 803 Didymos binary system and the target of NASA’s Double Asteroid Redirection Test (DART) and ESA’s Hera mission. The DART impact will occur on September 26, 2022, and will alter the orbital period of Dimorphos around Didymos.
Aims. In this work we assume Dimorphos-like bodies with a rubble-pile structure and quantify the effects of boulder packing in its interior on the post-impact morphology, degree of shape change, and material ejection processes.
Methods. We used the Bern smoothed particle hydrodynamics shock physics code to numerically model hypervelocity impacts on small, 160 m in diameter, rubble-pile asteroids with a variety of boulder distributions.
Results. We find that the post-impact target morphology is most sensitive to the mass fraction of boulders comprising the target, while the asteroid deflection efficiency depends on both the mass fraction of boulders on the target and on the boulder size distribution close to the impact point. Our results may also have important implications for the structure of small asteroids.
Post COVID and Apheresis – Where are we
Standing?
Authors: Steenblock Charlotte , Walther Romy , Tselmin Sergey , Jarzebska Natalia , Voit-Bak Karin , Toepfner Nicole , Siepmann Timo , Passauer Jens , Hugo Christian , Wintermann Gloria , Julius Ulrich , Barbir Mahmoud , Khan Tina Z. , Puhan Milo A. , Straube Richard , Hohenstein Bernd , Bornstein Stefan R. , Rodionov Roman N. 
Published: September 2022

AbstractA continual increase in cases of Long/Post COVID constitutes a medical
and socioeconomic challenge to health systems around the globe. While the true
extent of this problem cannot yet be fully evaluated, recent data suggest that
up to 20% of people with confirmed SARS-CoV-2 suffer from clinically
relevant symptoms of Long/Post COVID several weeks to months after the
acute phase. The clinical presentation is highly variable with the main symptoms
being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis
has been suggested to alleviate symptoms of Post/COVID. Thus, numerous
patients are currently treated with apheresis. However, at present there is no
data from randomized controlled trials available to confirm the efficacy.
Therefore, physicians rely on the experience of practitioners and centers
performing this treatment. Here, we summarize clinical experience on
extracorporeal apheresis in patients with Post/COVID from centers across
Germany.
Advances in the Management of Coagulopathy in Trauma: The Role of Viscoelastic Hemostatic Assays across All Phases of Trauma Care
Authors: Meizoso Jonathan P. , Barrett Christopher D. , Moore Ernest E. , Moore Hunter B. 
Published: September 2022

AbstractUncontrolled bleeding is the leading cause of preventable death following injury. Trauma-induced coagulopathy can manifest as diverse phenotypes ranging from hypocoagulability to hypercoagulability, which can change quickly during the acute phase of trauma care. The major advances in understanding coagulation over the past 25 years have resulted from the cell-based concept, emphasizing the key role of platelets and their interaction with the damaged endothelium. Consequently, conventional plasma-based coagulation testing is not accurate in predicting bleeding and does not provide an assessment of which blood products are indicated. Viscoelastic hemostatic assays (VHA), conducted in whole blood, have emerged as a superior method to guide goal-directed transfusion. The major change in resuscitation has been the shift from unbridled crystalloid loading to judicious balanced blood product administration. Furthermore, the recognition of the rapid changes from hypocoagulability to hypercoagulability has underscored the importance of ongoing surveillance beyond emergent surgery. While the benefits of VHA testing are maximized when used as early as possible, current technology limits use in the pre-hospital setting and the time to results compromises its utility in the emergency department. Thus, most of the reported experience with VHA in trauma is in the operating room and intensive care unit, where there is compelling data to support its value. This overview will address the current and potential role of VHA in the seriously injured patient, throughout the continuum of trauma management.
Single versus Three Doses of Intraarticular Platelet-Rich Plasma Injection in Treatment of Early Osteoarthritis Knee Joint—A Prospective Comparative Study
Authors: Varma Hashmukh Shantilal , Lodhi Jeetendra Singh , Vidyarthi Ashok , Jayaprakasan Vishnu 
Published: September 2022

Background
Autologous platelet-rich plasma (PRP), which contains a pool of growth factors, appears to offer an easy solution for delivering multiple growth factors needed for tissue repair. The objective of the study is to compare between single versus three doses of intraarticular platelet-rich plasma injection in the treatment of early osteoarthritis knee joint.

Materials and Methods
A prospective comparative study was done on 100 patients with early osteoarthritis knee who were randomized into two groups in an alternating fashion—single-dose injection and triple-dose injection groups. PRP (5 mL) obtained by double-spin method was injected per knee and followed up at 1, 3, and 6 months and outcomes measured using WOMAC (Western Ontario and McMaster universities osteoarthritis index) and VAS (visual analog scale) scores.

Results
VAS scores showed a statistically significant difference in triple-dose group at all follow-ups. In WOMAC, such a difference was observed for stiffness subscore at all the follow-ups, but the pain subscore and total score showed an improvement only at the final follow-up with the functional assessment subscore showing no statistical difference at any follow-ups.

Conclusion
PRP injection appears to be effective in early symptomatic osteoarthritis with better clinical results using a triple-dose regimen.