bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture
Authors: Yuan Zixuan , Pavel Mahmud Arif , Wang Hao , Kwachukwu Jerome C. , Mediouni Sonia , Jablonski Joseph Anthony , Nettles Kendall W. , Reddy Chakravarthy B. , Valente Susana T. , Hansen Scott B. 
Published: September 2022

Abstract
Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ’s mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit the SARS-CoV-2 surface receptor angiotensin converting enzyme 2 (ACE2) to endocytic lipids, away from phosphatidylinositol 4,5 bisphosphate (PIP2) clusters. Here we employed super-resolution imaging of cultured mammalian cells (VeroE6, A549, H1793, and HEK293T) to show HCQ directly perturbs clustering of ACE2 receptor with both endocytic lipids and PIP2 clusters. In elevated (high) cholesterol, HCQ moves ACE2 nanoscopic distances away from endocytic lipids. In cells with resting (low) cholesterol, ACE2 primarily associates with PIP2 clusters, and HCQ moves ACE2 away from PIP2 clusters—erythromycin has a similar effect. We conclude HCQ inhibits viral entry through two distinct mechanisms in high and low tissue cholesterol and does so prior to inhibiting cathepsin-L. HCQ clinical trials and animal studies will need to account for tissue cholesterol levels when evaluating dosing and efficacy.
Magnetic resonance imaging analysis predicts nanoparticle concentration delivered to the brain parenchyma
Authors: Plaksin Michael , Bercovici Tiran , Sat Toltsis Gabriella Gabi , Grinfeld Javier , Shapira Boaz , Zur Yuval , de Picciotto Rafi , Zadicario Eyal , Siddeeq Mustaffa , Wohl Anton , Zibly Zion , Levy Yoav , Cohen Zvi R. 
Published: September 2022

AbstractUltrasound in combination with the introduction of microbubbles into the vasculature effectively opens the blood brain barrier (BBB) to allow the passage of therapeutic agents. Increased permeability of the BBB is typically demonstrated with small-molecule agents (e.g., 1-nm gadolinium salts). Permeability to small-molecule agents, however, cannot reliably predict the transfer of remarkably larger molecules (e.g., monoclonal antibodies) required by numerous therapies. To overcome this issue, we developed a magnetic resonance imaging analysis based on the ΔR2* physical parameter that can be measured intraoperatively for efficient real-time treatment management. We demonstrate successful correlations between ΔR2* values and parenchymal concentrations of 3 differently sized (18 nm–44 nm) populations of liposomes in a rat model. Reaching an appropriate ΔR2* value during treatment can reflect the effective delivery of large therapeutic agents. This prediction power enables the achievement of desirable parenchymal drug concentrations, which is paramount to obtaining effective therapeutic outcomes.
Maladaptive evolution or how a beneficial mutation may get lost due to nepotism
Authors: Aloni Irith , Ilany Amiyaal 
Published: September 2022

AbstractSpotted hyenas are an exception in the animal kingdom not only due to female dominance over males, but also because of the strict female linear hierarchy which determines priority of access to resources and produces considerable female reproductive skew. This special social system raises a question: what would become of a beneficial mutation if it occurred in a low-ranking female? We used several simulation models in order to address this question. Our modeling results indicate that such a social system may inhibit the establishment of a beneficial mutation. However, this negative effect may be counteracted by random choice of mates by females.
U-to-C RNA editing by synthetic PPR-DYW proteins in bacteria and human culture cells
Authors: Ichinose Mizuho , Kawabata Masuyo , Akaiwa Yumi , Shimajiri Yasuka , Nakamura Izumi , Tamai Takayuki , Nakamura Takahiro , Yagi Yusuke , Gutmann Bernard 
Published: September 2022

AbstractProgrammable RNA editing offers significant therapeutic potential for a wide range of genetic diseases. Currently, several deaminase enzymes, including ADAR and APOBEC, can perform programmable adenosine-to-inosine or cytidine-to-uridine RNA correction. However, enzymes to perform guanosine-to-adenosine and uridine-to-cytidine (U-to-C) editing are still lacking to complete the set of transition reactions. It is believed that the DYW:KP proteins, specific to seedless plants, catalyze the U-to-C reactions in mitochondria and chloroplasts. In this study, we designed seven DYW:KP domains based on consensus sequences and fused them to a designer RNA-binding pentatricopeptide repeat (PPR) domain. We show that three of these PPR-DYW:KP proteins edit targeted uridine to cytidine in bacteria and human cells. In addition, we show that these proteins have a 5′ but not apparent 3′ preference for neighboring nucleotides. Our results establish the DYW:KP aminase domain as a potential candidate for the development of a U-to-C editing tool in human cells.
Genome assembly and chemogenomic profiling of National Flower of Singapore Papilionanthe Miss Joaquim ‘Agnes’ reveals metabolic pathways regulating floral traits
Authors: Lim Abner Herbert , Low Zhen Jie , Shingate Prashant Narendra , Hong Jing Han , Chong Shu Chen , Ng Cedric Chuan Young , Liu Wei , Vaser Robert , Šikić Mile , Sung Wing-Kin Ken , Nagarajan Niranjan , Tan Patrick , Teh Bin Tean 
Published: September 2022

AbstractSingapore’s National Flower,Papilionanthe(Ple.) Miss Joaquim ‘Agnes’ (PMJ) is highly prized as a horticultural flower from the Orchidaceae family. A combination of short-read sequencing, single-molecule long-read sequencing and chromatin contact mapping was used to assemble the PMJ genome, spanning 2.5 Gb and 19 pseudo-chromosomal scaffolds. Genomic resources and chemical profiling provided insights towards identifying, understanding and elucidating various classes of secondary metabolite compounds synthesized by the flower. For example, presence of the anthocyanin pigments detected by chemical profiling coincides with the expression ofANTHOCYANIN SYNTHASE (ANS), an enzyme responsible for the synthesis of the former. Similarly, the presence of vandaterosides (a unique class of glycosylated organic acids with the potential to slow skin aging) discovered using chemical profiling revealed the involvement of glycosyltransferase family enzymes candidates in vandateroside biosynthesis. Interestingly, despite the unnoticeable scent of the flower, genes involved in the biosynthesis of volatile compounds and chemical profiling revealed the combination of oxygenated hydrocarbons, including traces of linalool, beta-ionone and vanillin, forming the scent profile of PMJ. In summary, by combining genomics and biochemistry, the findings expands the known biodiversity repertoire of the Orchidaceae family and insights into the genome and secondary metabolite processes of PMJ.
Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway
Authors: Inoue Miki , Baba Takashi , Takahashi Fumiya , Terao Miho , Yanai Shogo , Shima Yuichi , Saito Daisuke , Sugihara Kei , Miura Takashi , Takada Shuji , Suyama Mikita , Ohkawa Yasuyuki , Morohashi Ken-ichirou 
Published: September 2022

AbstractLeydig cells in fetal testes play crucial roles in masculinizing fetuses through androgen production. Gene knockout studies have revealed that growth factors are implicated in fetal Leydig cell (FLC) differentiation, but little is known about the mechanisms regulating this process. We investigate this issue by characterizing FLC progenitor cells using single-cell RNA sequencing. The sequence datasets suggest thatthymosin β10(Tmsb10) is transiently upregulated in the progenitors. While studying the function ofTmsb10, we reveal that platelet-derived growth factor (PDGF) regulates ciliogenesis through the RAS/ERK and PI3K/AKT pathways, and thereby promotes desert hedgehog (DHH)-dependent FLC differentiation.Tmsb10expressed in the progenitor cells induces their differentiation into FLCs by suppressing the RAS/ERK pathway. Through characterizing the transiently expressedTmsb10in the FLC progenitors, this study unveils the molecular process of FLC differentiation and shows that it is cooperatively induced by DHH and PDGF.
All-optical control of pendular qubit states with nonresonant two-color laser pulses
Authors: Mun Je Hoi , Minemoto Shinichirou , Kim Dong Eon , Sakai Hirofumi 
Published: September 2022

AbstractPractical methodologies for qubit controls are established by two prerequisites, i.e., preparation of a well-defined initial quantum state and coherent control of that quantum state. Here we propose a quantum control method, realized by irradiating nonresonant nanosecond two-color (ω and 2ω) laser pulses to molecules in the pendular (field-dressed) ground state. The two-color field nonadiabatically splits the initial pendular ground state $$|\tilde{0},\tilde{0}\rangle $$
∣

0

̃

,

0

̃

⟩
to a superposition state of $$|\tilde{0},\tilde{0}\rangle $$
∣

0

̃

,

0

̃

⟩
and $$|\tilde{1},\tilde{0}\rangle $$
∣

1

̃

,

0

̃

⟩
, whose relative probability amplitudes can be controlled by the peak intensity of one wavelength component (ω) while the peak intensity of the other component (2ω) is fixed. The splitting of the quantum paths is evidenced by observing degrees of orientation of ground-state-selected OCS molecules by the velocity map imaging technique. This quantum control method is highly advantageous because any polar molecule can be controlled regardless of the molecular energy structures.
Bloch oscillations and matter-wave localization of a dipolar quantum gas in a one-dimensional lattice
Authors: Natale Gabriele , Bland Thomas , Gschwendtner Simon , Lafforgue Louis , Grün Daniel S. , Patscheider Alexander , Mark Manfred J. , Ferlaino Francesca 
Published: September 2022

AbstractThree-dimensional quantum gases of strongly dipolar atoms can undergo a crossover from a dilute gas to a dense macrodroplet, stabilized by quantum fluctuations. Adding a one-dimensional optical lattice creates a platform where quantum fluctuations are still unexplored, and a rich variety of phases may be observable. We employ Bloch oscillations as an interferometric tool to assess the role quantum fluctuations play in an array of quasi-two-dimensional Bose-Einstein condensates. Long-lived oscillations are observed when the chemical potential is balanced between sites, in a region where a macrodroplet is extended over several lattice sites. Further, we observe a transition to a state that is localized to a single lattice plane–driven purely by interactions–marked by the disappearance of the interference pattern in the momentum distribution. To describe our observations, we develop a discrete one-dimensional extended Gross-Pitaevskii theory, including quantum fluctuations and a variational approach for the on-site wavefunction. This model is in quantitative agreement with the experiment, revealing the existence of single and multisite macrodroplets, and signatures of a two-dimensional bright soliton.
Reconceptualizing Recovery After Concussion: A Phenomenological Exploration of College Student Experiences
Authors: Kemp Amy M. , O'Brien Katy H. , Wallace Tracey 
Published: September 2022

Purpose:
Typical measures of recovery from concussion—such as symptom scales, neurocognitive testing, or exertion measures—may not capture individualized experiences of concussion. This report examines how college students with concussion interact with and consider their recovery.

Method:
Sixteen college students who sustained concussions while in college completed 40- to 75-min semistructured interviews. All were enrolling to become mentors in a peer mentoring program for students with concussion. Questions addressed experiences as a college student with concussion, life changes following concussion, and role of peers in recovery. Using phenomenological reduction, analysis focused on the phenomenon of recovery and motivation for participation in a mentoring program.

Results:

Two main themes were found: (a)
What Recovery Looks Like
and (b)
Gaining Perspective, Learning to Cope and Adapting to Change
. Thirteen participants denied the label of “recovered” even though all had been deemed recovered and discharged from medical care. Instead, two subthemes emerged within
What Recovery Looks Like
:
Ongoing Recovery
and
Reconceptualizing Recovery
. Perceptions of recovery were influenced by effort, capacity, and resilience. In the second theme, students described strategies, resources, and supports used to cope with their injuries; most commonly used was emotion-focused coping.

Conclusions:
College students with concussion consider recovery as an ongoing process rather than a dichotomized condition. Student experiences may not be reflected in commonly used symptom scales or objective assessments.

Supplemental Material:

https://doi.org/10.23641/asha.21084925
Accuracy improvement of relational expressions regarding effective length vector of a dipole and expansion to V‐shaped dipole
Authors: Iigusa Kyoichi , Yamamoto Shin‐ichi , Miura Amane , Tsuji Hiroyuki 
Published: September 2022

AbstractThe accuracy of formulas for calculating le
(0) and α is improved, which are parameters representing the effective length vector of a dipole, from the length L and the width W of the dipole. The input resistance R and the input reactance X of the dipole can be approximately related to each other by using le
(0) and α. The relational expression can be applied accurately when the dipole is about half a wavelength or shorter, but it can be modified to be accurate up to about a wavelength by expressing the influence of the change in beam width due to the dipole size using le
(0). The authors found that this approximate relational expression can be applied to a V‐shaped dipole if the dipole length is about half a wavelength or shorter. The applicable range is extended to about a wavelength by introducing the cross‐polarized component of le
(0). The formulas for calculating le
(0) and α from the size parameters L and W and the bending angle ψ are also presented.
A new GM (1,1) model suitable for short‐term prediction of satellite clock bias
Authors: Tan Xiaorong , Xu Jiangning , Li Fangneng , Wu Miao , Chen Ding , Liang Yifeng 
Published: September 2022

AbstractDue to the sensitivity of spaceborne atomic clock to many factors, the variation law of satellite clock bias (SCB) can be regarded as a grey system. The GM (1,1) model is a most classical and basic model of grey system, which has been successfully applied in SCB prediction. Moreover, many improved models have been proposed and widely used in various forecasts since GM (1,1) was generated. However, the prediction performance of these models is not obviously improved compared with the classical models in clock bias prediction. In view of this, a new GM (1,1) model has been come up with in this paper by optimising fitting model and initial condition. The new fitting model is obtained by differentiating time response function of winterisation, and the new initial condition is generated through one or more components of the original clock bias sequence. The authors employ GPS rapid and precise SCB provided by the International GNSS Service (IGS) for prediction experiments. The results show that the new GM (1,1) model is effective and feasible, and its prediction accuracy and stability are enormously better than that of the classical GM (1,1) model, especially for ultra‐short‐term prediction.
Effect of Notes' Access and Complexity on OpenNotes' Utility
Authors: Khasawneh Amro , Kratzke Ian , Adapa Karthik , Marks Lawrence , Mazur Lukasz 
Published: September 2022

Abstract
Background Health care providers are now required to provide their patients access to their consultation and progress notes. Early research of this concept, known as “OpenNotes,” showed promising results in terms of provider acceptability and patient adoption, yet objective evaluations relating to patients' interactions with the notes are limited.
Objectives To assess the effect of the complexity level of notes and number of accesses (initial read vs. continuous access) on the user's performance, perceived usability, cognitive workload, and satisfaction with the notes.
Methods We used a 2*2 mixed subjects experimental design with two independent variables: (1) note's complexity at two levels (simple vs. complex) and (2) number of accesses to notes at two levels (initial vs. continuous). Fifty-three participants were randomly assigned to receive a simple versus complex radiation oncology clinical note and were tested on their performance for understanding the note content after an initial read, and then with continuous access to the note. Performance was quantified by comparing each participant's answers to the ones developed by the research team and assigning a score of 0 to 100 based on participants' understanding of the notes. Usability, cognitive workload, and satisfaction scores of the notes were quantified using validated tools.
Results Performance for understanding was significantly better in simple versus complex notes with continuous access (p = 0.001). Continuous access to the notes was also positively associated with satisfaction scores (p = 0.03). The overall perceived usability, cognitive workload, and satisfaction scores were considered low for both simple and complex notes.
Conclusion Simplifying notes can improve understanding of notes for patients/families. However, perceived usability, cognitive workload, and satisfaction with even the simplified notes were still low. To make notes more useful for patients and their families, there is a need for dramatic improvements to the overall usability and content of the notes.
Stereoselective Copolymerization of Olefin with Polar Monomers to Access Stereoregular Functionalized Polyolefins
Authors: Mu Hongliang , Jian Zhongbao 
Published: September 2022

Introducing polar functionalities to polyolefins such as polyethylene and polypropylene is highly desirable for improving physical properties of the otherwise non-polar material. The synthesis of stereoregular functionalized polyolefins, however, has been a relatively underdeveloped area compared to that of functionalized polyethylene because of the lack of suitable catalysts that tolerate polar groups while possessing stereoselectivity. This review summarizes recent advances concerning the access to stereoregular functionalized polyolefins, including synthetic strategies such as post-functionalization, chain transfer and direct copolymerization methods. The focus of the review lies in the copolymerization approach, in which various polar comonomers and versatile stereoselective polymerization catalysts based on both early and late transition metals are involved. Polymer properties and potential applications for these materials are simply discussed.1. Introduction2. Reactive-Intermediate-Polymer Approach to Stereoregular Functionalized Polypropylene3. Preparation of Stereoregular Functionalized Polypropylene by Chain-End Functionalization4. Stereoselective Copolymerization of Propylene and Polar Monomers by Early Transition Metal Catalysts5. Stereoselective Copolymerization of Propylene with Polar Monomers by Late Transition Metal Catalysts6. Stereoselective Copolymerization of α-Olefins with Polar Monomers7. Stereoselective Homopolymerization of Polar Monomers8. Polymer Properties and Potential Applications9. Conclusion and Outlook
Assessment of Dysphagia after Hemiglossectomy and Radiotherapy: A Prospective Study
Authors: Dasgupta Sohini , Samuel Soumi 
Published: September 2022

Abstract
Background Malignancy of the tongue is a common condition affecting patients and their day-to-day activities. The tongue plays an important role in deglutition. The combination treatment modality involving surgical resection with or without reconstruction and radiation is the most commonly used modality for such lesions. This in turn has a profound impact on the quality of life of the patients owing to the nature of the treatment.
Aim of the study This study aimed to assess swallowing in patients with carcinoma tongue following hemiglossectomy and radiotherapy (RT).
Methodology A prospective study carried out in 20 patients who underwent hemiglossectomy with primary closure for carcinoma of the tongue followed by RT. All patients were evaluated for swallowing using the Dysphagia Handicap Index before surgery; after surgery on the 10th and 30th days; during RT after 15 fractions of radiation; and after 1, 2, and 3 months postcompletion of RT.
Results The Dysphagia Handicap Index has significantly increased from the preoperative value following both surgery and RT on all follow-up visits (p < 0.001). The most severe self-reported dysphagia was noted during and after RT(p < 0.001).
Conclusion This study shows that hemiglossectomy followed by primary closure with adjuvant RT has a severe negative impact on swallowing, thereby affecting the quality of life.
The More Recent History of Hemophilia Treatment
Authors: Franchini Massimo , Mannucci Pier Mannuccio 
Published: September 2022

AbstractThe availability first in the 1970s of plasma-derived and then in the 1990s of recombinant clotting factor concentrates represented a milestone in hemophilia care, enabling not only treatment of episodic bleeding events but also implementation of prophylactic regimens. The treatment of hemophilia has recently reached new landmarks. The traditional clotting factor replacement therapy for hemophilia has been substituted over the last 10 years by novel treatments such as bioengineered factor VIII and IX molecules with extended half-life and non-factor treatments including the bispecific antibody emicizumab. This narrative review is dedicated to these newer therapies, which are contributing significantly to improving the long-term management of prophylaxis in hemophilia patients. Another section is focused on the current state of gene therapy, which is a promising definitive cure for severe hemophilia A and B.
Viscoelastic Testing in the Management of Adult Patients on Mechanical Circulatory Support Devices with Focus on Extracorporeal Membrane Oxygenation
Authors: Volod Oksana , Wegner Julie 
Published: September 2022

AbstractThromboembolic and hemorrhagic complications continue to remain frequent complications that significantly impact the morbidity and mortality of patients implanted with mechanical circulatory support devices (MCSDs). The severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) has resulted in a number of COVID-19 patients being supported by MCSDs, specifically extracorporeal membrane oxygenation (ECMO), which in turn has created a crucial need for rapid assessment of hemostatic status in these patients to avoid bleeding and thrombotic complications. Currently, conventional plasma-based coagulation assays such as prothrombin time and activated partial thromboplastin time (aPTT) are used to assess hemostasis, and the activated clotting time (ACT) and aPTT are the most common tests used to monitor heparin anticoagulation in patients on ECMO. Unfractionated heparin remains the mainstay anticoagulation therapy for patients on ECMO. Extracorporeal Life Support Organization (ELSO) offers little guidance on the subject but does state that each institution should create its internal anticoagulation protocols. Viscoelastic assays (VEAs) are increasingly recognized by ELSO and ECMO community for their potential to assess hemostatic derangements in patients implanted with MCSDs as well as guidance for appropriate hemostatic therapy. This review focuses on the evidence for the use of viscoelastic assays to assess overall hemostasis and to guide the treatment of adult patients connected to an ECMO circuit. Limitations of the use of conventional assays, ACT, and VEA are also discussed.