bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a novel airbag system of abdominal compression for reducing respiratory motion: preliminary results in healthy volunteers
Authors: Li Wenxin , Konishi Kenta , Ohira Keiichi , Hirata Masanori , Wakabayashi Kohei , Aramaki Shuhei , Sakamoto Masataka , Nakamura Katsumasa 
Published: April 2022

Abstract
This study used cine-magnetic resonance imaging (cine-MRI) to evaluate the safety and efficacy of a novel airbag system combined with a shell-type body fixation system in reducing respiratory motion in normal volunteers. The airbag system consists of a six-sided polygon inflatable airbag, a same shape plate, a stiff air supply tube, an air-supply pump and a digital pressure load cell monitor. Piezoelectric sensors were installed in the plate to detect compression pressure load changes; pressure load data were transferred to the digital pressure load cell monitor through Bluetooth. Five volunteers underwent cine-MRI with and without airbag compression to detect differences in the respiratory motion of the organs. The volunteers’ physiologic signs were stable during the experiment. The maximum inspiration pressure load was 4.48 ± 0.86 kgf (range, 4.00–6.00 kgf), while the minimum expiration pressure load was 3.69 ± 0.95 kgf (range, 2.8–5.3 kgf). Under airbag compression, the right diaphragm movement was reduced from 19.50 ± 6.43 mm to 9.60 ± 3.61 mm (P &lt; 0.05) in the coronal plane and 23.12 ± 6.30 mm to 11.00 ± 3.69 mm (P &lt; 0.05) in the sagittal plane. The left diaphragm, pancreas and liver in the coronal plane and the right kidney and liver in the sagittal plane also showed significant movement reduction. This novel airbag abdominal compression system was found to be safe during the experiment and successful in the reduction of internal organ respiratory motion and promises to be a convenient and efficient tool for clinical radiotherapy.
Clinical Pathways When Considering Antimicrobials for the Treatment of Mild-to-Moderate COVID-19
Authors: Krauth Daniel S 
Published: April 2022

ABSTRACT
Amidst a constrained supply of novel therapeutics for the outpatient treatment of mild-to-moderate COVID-19, clinicians face new challenges, especially among those practicing at overseas military treatment facilities. Although prescribers may be unfamiliar with these medications, appropriate use necessitates detailed query of patient symptomatology and familiarization with each drug’s side effect profile. Risk stratification also requires careful consideration to patient-specific comorbidities and immunization status for determining whom to treat and how. In recognition of these complexities, a stepwise guide is provided here to aid clinicians in their management of outpatients with mild-to-moderate COVID-19.
Cosmic evolution of low-excitation radio galaxies in the LOFAR two-metre sky survey deep fields
Authors: Kondapally Rohit , Best Philip N , Cochrane Rachel K , Sabater José , Duncan Kenneth J , Hardcastle Martin J , Haskell Paul , Mingo Beatriz , Röttgering Huub J A , Smith Daniel J B , Williams Wendy L , Bonato Matteo , Calistro Rivera Gabriela , Gao Fangyou , Hale Catherine L , Małek Katarzyna , Miley George K , Prandoni Isabella , Wang Lingyu 
Published: April 2022

ABSTRACT
Feedback from low-excitation radio galaxies (LERGs) plays a key role in the lifecycle of massive galaxies in the local Universe; their evolution, and the impact of these active galactic nuclei on early galaxy evolution, however, remain poorly understood. We use a sample of 10 481 LERGs from the first data release of the LOFAR two-metre Sky Survey Deep Fields, covering ∼25 deg2, to present the first measurement of the evolution of the radio luminosity function (LF) of LERGs out to z ∼ 2.5; this shows relatively mild evolution. We split the LERGs into those hosted by quiescent and star-forming galaxies, finding a new dominant population of LERGs hosted by star-forming galaxies at high redshifts. The incidence of LERGs in quiescent galaxies shows a steep dependence on stellar mass out to z ∼ 1.5, consistent with local Universe measurements of accretion occurring from cooling of hot gas haloes. The quiescent-LERGs dominate the LFs at z &lt; 1, showing a strong decline in space density with redshift, tracing that of the available host galaxies, while there is an increase in the characteristic luminosity. The star-forming LERG LF increases with redshift, such that this population dominates the space densities at most radio-luminosities by z ∼ 1. The incidence of LERGs in star-forming galaxies shows a much weaker stellar-mass dependence, and increases with redshift, suggesting a different fuelling mechanism compared to their quiescent counterparts, potentially associated with the cold gas supply present in the star-forming galaxies.
Compact star merger events with stars composed of interacting strange quark matter
Authors: Kumar Anil , Thapa Vivek Baruah , Sinha Monika 
Published: April 2022

ABSTRACT
We investigate the properties of stars participating in double compact star merger events considering interacting model of stable strange quark matter. We model the matter making it compatible with the recent astrophysical observations of compact star mass–radius and gravitational wave events. In this context, we consider modified MIT bag model and vector bag model with and without self-interaction. We find new upper bound on tidal deformability of $1.4\, {\rm M}_\odot$ strange star corresponding to the upper bound of effective tidal deformability inferred from gravitational wave event. Range of compactness of $1.4\, {\rm M}_\odot$ strange star is obtained as 0.175 ≤ C1.4 ≤ 0.199. Radius range of $1.5\, {\rm M}_\odot$ primary star is deduced to be 10.57 km ≤ R1.5 ≤ 12.04 km, following stringent GW170817 constraints. GW190425 constraints provide with upper limit on radius of 1.7 solar mass strange star that it should be less than $13.41\, \text{km}$.
Probing the rest-frame of the Universe with the near-IR cosmic infrared background
Authors: Kashlinsky A , Atrio-Barandela F 
Published: April 2022

ABSTRACT
While the cosmic microwave background (CMB) dipole is largely assumed to be entirely kinematic, there is evidence that part of it is primordial. Such a possibility arises in models implying a tilt, interpreted as a dark flow, across the observable Universe. The kinematic nature of the entire CMB dipole can be probed using the dipole of cosmic backgrounds from galaxies after the last scattering. The near-infrared (near-IR) cosmic infrared background (CIB) spectral energy distribution leads to an amplified dipole compared with the CMB. The CIB dipole is affected by galaxy clustering, decreasing with fainter, more distant galaxies, and by Solar System emissions and Galactic dust, which dominate the net CIB cosmological dipole in the optical/near-IR. We propose a technique that enables an accurate measurement of the kinematic near-IR CIB dipole. The CIB, effectively the integrated galaxy light (IGL), would be reconstructed from resolved galaxies in forthcoming space-borne wide surveys covering four bands, 0.9–2.5 μm. The galaxies will be subselected from the identified magnitude range where the dipole component from galaxy clustering is below the expected kinematic dipole. Using this technique, the dipole can be measured in each of the bands at the statistical signal-to-noise ratio S/N ≳50–100 with the forthcoming Euclid and Roman surveys, isolating the CMB dipole’s kinematic nature.
Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors: modeling the function of an inactivating receptor mutation
Authors: Lundin K , Sepponen K , Väyrynen P , Liu X , Yohannes D A , Survila M , Ghimire B , Känsäkoski J , Katayama S , Partanen J , Vuoristo S , Paloviita P , Rahman N , Raivio T , Luiro K , Huhtaniemi I , Varjosalo M , Tuuri T , Tapanainen J S 
Published: April 2022

Abstract
Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein–protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.
Bi-allelic variants in SHOC1 cause non-obstructive azoospermia with meiosis arrest in humans and mice
Authors: Wang Weili , Meng Lanlan , He Jiaxin , Su Lilan , Li Yong , Tan Chen , Xu Xilin , Nie Hongchuan , Zhang Huan , Du Juan , Lu Guangxiu , Luo Mengcheng , Lin Ge , Tu Chaofeng , Tan Yue-Qiu 
Published: April 2022

Abstract
Meiosis is pivotal to gametogenesis and fertility. Meiotic recombination is a mandatory process that ensures faithful chromosome segregation and generates genetic diversity in gametes. Non-obstructive azoospermia (NOA) caused by meiotic arrest is a common cause of male infertility and has many genetic origins, including chromosome abnormalities, Y chromosome microdeletion and monogenic mutations. However, the genetic causes of the majority of NOA cases remain to be elucidated. Here, we report our findings of three Shortage in chiasmata 1 (SHOC1) bi-allelic variants in three NOA patients, of which two are homozygous for the same loss-of-function variant (c.231_232del: p.L78Sfs*9), and one is heterozygous for two different missense variants (c.1978G&gt;A: p.A660T; c.4274G&gt;A: p.R1425H). Testicular biopsy of one patient revealed impairment of spermatocyte maturation. Both germ-cell-specific and general Shoc1-knockout mice exhibited similar male infertility phenotypes. Subsequent analysis revealed comprehensive defects in homologous pairing and synapsis along with abnormal expression of DMC1, RAD51 and RPA2 in Shoc1-defective spermatocyte spreads. These findings imply that SHOC1 may have a presynaptic function during meiotic recombination apart from its previously identified role in crossover formation. Overall, our results provide strong evidence for the clinical relevance of SHOC1 mutations in patients with NOA and contribute to a deeper mechanistic understanding of the role of SHOC1 during meiotic recombination.
Gadolinium retention in the tunica media of arterial walls—a complementary study using elemental bioimaging and immunogold staining
Authors: Fingerhut Stefanie , Buchholz Rebecca , Bücker Patrick , Clasen Wolfgang , Sperling Michael , Müller Klaus-Michael , Rehkämper Jan , Radbruch Alexander , Richter Henning , Jeibmann Astrid , Karst Uwe 
Published: April 2022

Abstract
Gadolinium (Gd) deposition has been found in both animal and human tissues after injections of Gd-based contrast agents (GBCAs). Without the knowledge of which tissues are most affected, it is difficult to determine whether Gd accumulation could lead to any pathological changes. The current study aims at investigating histological sections of three patients who were exposed to GBCAs during their lifetime, and identify areas of Gd accumulation. Tissue sections of three autopsy cases were investigated by laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) to assess the distribution of Gd, and the deposition within tissue sections was quantified. Additional application of laser ablation–inductively coupled plasma–optical emission spectroscopy (LA–ICP–OES) enabled a sensitive detection of calcium (Ca) in the vessel walls, which is usually impeded in LA–ICP–MS due to the isobaric interference with argon. Complementary LA–ICP–MS and LA–ICP–OES analysis revealed that Gd was co-localized with zinc and Ca, in the area where smooth muscle actin was present. Notably, high levels of Gd were found in the tunica media of arterial walls, which requires further research into potential Gd-related toxicity in this specific location.
Reovirus μ2 protein modulates host cell alternative splicing by reducing protein levels of U5 snRNP core components
Authors: Boudreault Simon , Durand Mathieu , Martineau Carole-Anne , Perreault Jean-Pierre , Lemay Guy , Bisaillon Martin 
Published: April 2022

Abstract
Mammalian orthoreovirus (MRV) is a double-stranded RNA virus from the Reoviridae family presenting a promising activity as an oncolytic virus. Recent studies have underlined MRV’s ability to alter cellular alternative splicing (AS) during infection, with a limited understanding of the mechanisms at play. In this study, we investigated how MRV modulates AS. Using a combination of cell biology and reverse genetics experiments, we demonstrated that the M1 gene segment, encoding the μ2 protein, is the primary determinant of MRV’s ability to alter AS, and that the amino acid at position 208 in μ2 is critical to induce these changes. Moreover, we showed that the expression of μ2 by itself is sufficient to trigger AS changes, and its ability to enter the nucleus is not required for all these changes. Moreover, we identified core components of the U5 snRNP (i.e. EFTUD2, PRPF8, and SNRNP200) as interactors of μ2 that are required for MRV modulation of AS. Finally, these U5 snRNP components are reduced at the protein level by both MRV infection and μ2 expression. Our findings identify the reduction of U5 snRNP components levels as a new mechanism by which viruses alter cellular AS.
ERMer: a serverless platform for navigating, analyzing, and visualizingEscherichia coliregulatory landscape through graph database
Authors: Mao Zhitao , Wang Ruoyu , Li Haoran , Huang Yixin , Zhang Qiang , Liao Xiaoping , Ma Hongwu 
Published: April 2022

AbstractCellular regulation is inherently complex, and one particular cellular function is often controlled by a cascade of different types of regulatory interactions. For example, the activity of a transcription factor (TF), which regulates the expression level of downstream genes through transcriptional regulation, can be regulated by small molecules through compound–protein interactions. To identify such complex regulatory cascades, traditional relational databases require ineffective additional operations and are computationally expensive. In contrast, graph databases are purposefully developed to execute such deep searches efficiently. Here, we present ERMer (E. coli Regulation Miner), the first cloud platform for mining the regulatory landscape of Escherichia coli based on graph databases. Combining the AWS Neptune graph database, AWS lambda function, and G6 graph visualization engine enables quick search and visualization of complex regulatory cascades/patterns. Users can also interactively navigate the E. coli regulatory landscape through ERMer. Furthermore, a Q&A module is included to showcase the power of graph databases in answering complex biological questions through simple queries. The backend graph model can be easily extended as new data become available. In addition, the framework implemented in ERMer can be easily migrated to other applications or organisms. ERMer is available at https://ermer.biodesign.ac.cn/.
FastViFi: Fast and accurate detection of (Hybrid) Viral DNA and RNA
Authors: Javadzadeh Sara , Rajkumar Utkrisht , Nguyen Nam , Sarmashghi Shahab , Luebeck Jens , Shang Jingbo , Bafna Vineet 
Published: April 2022

Abstract
DNA viruses are important infectious agents known to mediate a large number of human diseases, including cancer. Viral integration into the host genome and the formation of hybrid transcripts are also associated with increased pathogenicity. The high variability of viral genomes, however requires the use of sensitive ensemble hidden Markov models that add to the computational complexity, often requiring &gt; 40 CPU-hours per sample. Here, we describe FastViFi, a fast 2-stage filtering method that reduces the computational burden. On simulated and cancer genomic data, FastViFi improved the running time by 2 orders of magnitude with comparable accuracy on challenging data sets. Recently published methods have focused on identification of location of viral integration into the human host genome using local assembly, but do not extend to RNA. To identify human viral hybrid transcripts, we additionally developed ensemble Hidden Markov Models for the Epstein Barr virus (EBV) to add to the models for Hepatitis B (HBV), Hepatitis C (HCV) viruses and the Human Papillomavirus (HPV), and used FastViFi to query RNA-seq data from Gastric cancer (EBV) and liver cancer (HBV/HCV). FastViFi ran in &lt;10 minutes per sample and identified multiple hybrids that fuse viral and human genes suggesting new mechanisms for oncoviral pathogenicity. FastViFi is available at https://github.com/sara-javadzadeh/FastViFi.
Endocrine outcomes after limited surgery and conformal photon radiation therapy for pediatric craniopharyngioma: Long-term results from the RT1 protocol
Authors: Merchant Thomas E , Edmonston Drucilla Y , Wu Shengjie , Li Yimei , Boop Frederick A , Lustig Robert H 
Published: April 2022

AbstractBackgroundTo estimate the incidence of endocrinopathy in children and adolescents with craniopharyngioma after treatment with photon-based conformal and intensity-modulated radiation therapy (CRT).MethodsOne hundred one pediatric patients were enrolled on a phase II single-institution protocol beginning in 1998 (n = 76) or followed a similar non-protocol treatment plan (n = 25). Surgery was individualized. CRT (54 Gy) was administered using a 1.0-cm or ≤0.5-cm clinical target volume margin. Patients underwent baseline and serial evaluation of the hypothalamic-pituitary axis.ResultsThe 10-year cumulative incidence (CI) of growth hormone deficiency (GHD) was 68.42% (±11.27) for black patients and 94.23% (±3.57) for white patients (P = .0286). The CI of thyroid-stimulating hormone deficiency (TSHD) was 70.94% (±8.44) at 10 years for non-shunted patients and 91.67% (±10.40) at 6 years for shunted patients (P = .0260). The CI of TSHD was 100% (±14.29) at 4 years for those with diabetes insipidus (DI) and 71.36% (±8.86) at 10 years for those without DI (P = .0008). The 10-year CI of adrenocortical hormone deficiency was 70.00% (±16.15) for those with DI and 48.39% (±9.19) for those without DI (P = .0080). The 10-year CI of LH/FSH deficiency was 43.33% (±9.32) age &lt;7 years, 61.29% (±9.11) aged 7-10 years, and 78.95% (±6.38) age ≥10 years (P &lt; .0001). BMI was significantly greater prior to CRT in white patients with DI (P = .0004) and preexisting GHD (P = .0275).ConclusionsHormone deficiencies are common in pediatric patients with craniopharyngioma and are associated with host, tumor, and treatment factors. Understanding the incidence and time to onset may facilitate intervention and patient selection for treatment.
The intrinsic and microenvironmental features of diffuse midline glioma: Implications for the development of effective immunotherapeutic treatment strategies
Authors: Persson Mika L , Douglas Alicia M , Alvaro Frank , Faridi Pouya , Larsen Martin R , Alonso Marta M , Vitanza Nicholas A , Dun Matthew D 
Published: April 2022

Abstract
Diffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors of the central nervous system (CNS). Recognized as the most lethal of all childhood cancers, palliative radiotherapy remains the only proven treatment option, however, even for those that respond, survival is only temporarily extended. DMG harbor an immunologically “cold” tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning the cold TME are not well understood. Low expression levels of immune checkpoint proteins, including PD-1, PD-L1, and CTLA-4, are recurring features of DMG and likely contribute to the lack of response to immune checkpoint inhibitors (ICIs). The unique epigenetic signatures (including stem cell-like methylation patterns), a low tumor mutational burden, and recurring somatic mutations (H3K27M, TP53, ACVR1, MYC, and PIK3CA), possibly play a role in the reduced efficacy of traditional immunotherapies. Therefore, to circumvent the lack of efficacy thus far seen for the use of ICIs, adoptive cell transfer (including chimeric antigen receptor T cells) and the use of oncolytic viruses, are currently being evaluated for the treatment of DMG. It remains an absolute imperative that we improve our understanding of DMG’s intrinsic and TME features if patients are to realize the potential benefits offered by these sophisticated treatments. Herein, we summarize the limitations of immunotherapeutic approaches, highlight the emerging safety and clinical efficacy shown for sophisticated cell-based therapies, as well as the evolving knowledge underpinning the DMG-immune axis, to guide the development of immunotherapies that we hope will improve outcomes.
A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide
Authors: Schmidt Keith T , Karzai Fatima , Bilusic Marijo , Cordes Lisa M , Chau Cindy H , Peer Cody J , Wroblewski Susan , Huitema Alwin D R , Schellens Jan H M , Gulley James L , Dahut William L , Figg William D , Madan Ravi A 
Published: April 2022

AbstractBackgroundDespite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide.MethodsThis was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide. A lead-in dose escalation evaluated the recommended phase 2 dose of NLG207 in combination with enzalutamide. Patients received NLG207 via IV infusion every 2 weeks and enzalutamide 160 mg orally once daily.ResultsBetween March 2019 and June 2021, four patients were accrued to the lead-in dose escalation. Two of the four patients were evaluable and both experienced DLTs at the NLG207 12 mg/m2 dose level; one DLT was related to a dose delay for noninfective cystitis and myelosuppression, the other a grade 3 noninfective cystitis. Further evaluation of NLG207 in combination with enzalutamide was halted and the study was ultimately terminated. PSA declines from baseline were observed in two patients.ConclusionNLG207 12 mg/m2 in combination with enzalutamide was not well tolerated in patients with mCRPC following several lines of the standard of care therapy.ClinicalTrials.gov IdentifierNCT03531827.