bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcomes of molecular targeted therapy following nivolumab in metastatic renal cell carcinoma
Authors: Bando Yukari , Furukawa Junya , Terakawa Tomoaki , Harada Kenichi , Hinata Nobuyuki , Nakano Yuzo , Fujisawa Masato 
Published: May 2021

Abstract

Objective
The purpose of this study was to assess the therapeutic efficacy of molecular targeted therapies following nivolumab in metastatic renal cell carcinoma and to examine the relationship between therapeutic efficacy and the specific molecular targeted therapy used.

Methods
We retrospectively reviewed the medical records of 115 metastatic renal cell carcinoma patients who were treated with nivolumab at our institution and five affiliated hospitals. Among them, 52 patients who received subsequent molecular targeted therapy following nivolumab were selected to survey treatment outcomes. Progression-free survival and overall survival were estimated with Kaplan-Meier curves, and differences were analyzed by the log-rank test.

Results
Among the 52 eligible patients, 40 (76.9%) were treated with tyrosine kinase inhibitors and 12 (23.1%) were treated with mammalian target of rapamycin inhibitor. The median time to treatment failure and progression-free survival of subsequent molecular targeted therapy were 5.6 and 8.0 months, respectively. The median overall survival from the initiation of first-line therapy was not reached. The disease control rate of subsequent molecular targeted therapy was 69.2% (partial response: 25.0%, stable disease: 44.2%). The median progression-free survival of subsequent tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor were 9.2 and 8.0 months, respectively (P = 0.37). The progression-free survival of patients whose best response to prior nivolumab was either progressive disease or stable disease/partial response were 6.3 and 11.3 months, respectively (P = 0.36).

Conclusions
Molecular targeted therapies following nivolumab had comparatively better therapeutic efficacy, which was confirmed regardless of the type of molecular targeted agent used.
Radical surgery for anal canal neuroendocrine carcinoma with pagetoid spread: a case report
Authors: Fukuhara Sotaro , Yoshimitsu Masanori , Yano Takuya , Oshita Ko , Bekku Kensuke , Okamoto Hitoshi , Toi Yoichiro , Ichimura Koichi , Okamoto Wataru , Okajima Masazumi 
Published: May 2021

Abstract
Anal canal neuroendocrine carcinoma (NEC) with pagetoid spread (PS) is a rare disease, and its treatment strategy remains unclear. The prognosis of anal canal NEC with PS is poor. Resection margin status is very important for anorectal carcinoma because it affects survival. When accompanied by PS, the defect of the resulting perineal wound following radical surgical intervention may be necessarily enlarged to ensure the appropriate margin status. This case report discusses the treatment of a patient with advanced anal canal NEC with PS, inguinal lymph node metastasis and sphincter infiltration in which total pelvic exenteration with plastic surgery was successfully performed. The plastic surgery incorporated a gracilis muscle flap that was useful for the reconstruction of the enlarged perineal defect.
Formation of light-harvesting complex II aggregates from LHCII–PSI–LHCI complexes in rice plants under high light
Authors: Wu Guangxi , Ma Lin , Yuan Cai , Dai Jiahao , Luo Lai , Poudyal Roshan Sharma , Sayre Richard T , Lee Choon-Hwan 
Published: May 2021

Abstract
During low light- (LL) induced state transitions in dark-adapted rice (Oryza sativa) leaves, light-harvesting complex (LHC) II become phosphorylated and associate with PSI complexes to form LHCII–PSI–LHCI supercomplexes. When the leaves are subsequently transferred to high light (HL) conditions, phosphorylated LHCII complexes are no longer phosphorylated. Under the HL-induced transition in LHC phosphorylation status, we observed a new green band in the stacking gel of native green–PAGE, which was determined to be LHCII aggregates by immunoblotting and 77K chlorophyll fluorescence analysis. Knockout mutants of protein phosphatase 1 (PPH1) which dephosphorylates LHCII failed to form these LHCII aggregates. In addition, the ability to develop non-photochemical quenching in the PPH1 mutant under HL was less than for wild-type plants. As determined by immunoblotting analysis, LHCII proteins present in LHCII–PSI–LHCI supercomplexes included the Lhcb1 and Lhcb2 proteins. In this study, we provide evidence suggesting that LHCII in the LHCII–PSI–LHCI supercomplexes are dephosphorylated and subsequently form aggregates to dissipate excess light energy under HL conditions. We propose that this LHCII aggregation, involving LHCII L-trimers, is a newly observed photoprotective light-quenching process operating in the early stage of acclimation to HL in rice plants.
Binary–binary close encounters in the Kuiper Belt
Authors: López María C , Brunini A 
Published: May 2021

ABSTRACT
Trans-Neptunian binaries are among the objects carrying the most relevant information on the conditions that prevailed in the primitive outer Solar system. However, their present orbital architecture not necessarily reflects those conditions, because it is the result of complex evolutionary processes. There is evidence suggesting that binary systems dominated the primitive trans-Neptunian populations. Therefore, binary–binary interactions could be an important evolutionary path. In this paper, a series of numerical experiments of binary–binary close encounters were carried out, varying specific parameters related to their physical and orbital characteristics. The relative speeds with which the encounters occur play an important role in the relative variation of orbital elements, showing a good agreement with impulsive approximation models involving a binary and a single intruder. However, simulations varying the mass, semimajor axis, and closest approach distance between pairs of binaries, showed marked deviations from this model.
On the structure of the Enceladus plume
Authors: Fu Menghao , Gu Hao , Cui Jun , Xiao Zhiyong , He Fei , Wei Yong , Ren Zhipeng 
Published: May 2021

ABSTRACT
The detection of a water-rich plume erupting from ‘tiger stripes’ near the Enceladus south polar region is an important discovery of geologically active satellites within the Solar system. In this work, we apply an analytical approach to model the plume structure, using as a diagnostic the CO2 distribution extracted from the Cassini Ion and Neutral Mass Spectrometer measurements made during the E14, E17, and E18 flybys. Special focus is placed on the modelling of the spike-like structures by including only sources with substantial contributions to the plume densities. Such a procedure reduces greatly the model complexity and helps to better constrain the source parameters. Both the model source rate and Mach number are found to vary considerably among different sources during the same flyby and also among different flybys for the same source, revealing a complicated spatio-temporal variability in the plume structure. Our analysis suggests a total escape rate of (1.0–7.1) × 1026 s−1 for CO2 and (2.4–6.6) × 1028 s−1 for H2O, in broad agreement with previous estimates. Of particular interest is our identification of a tentative correlation between the Mach number and thermal brightness, of which the latter is a tracer of the geological activity of the emission source. Such a relation should be able to provide more insights into the nature of geyser emission along the ‘tiger stripes’.
Genetic and epigenetic features of promoters with ubiquitous chromatin accessibility support ubiquitous transcription of cell-essential genes
Authors: Fan Kaili , Moore Jill E , Zhang Xiao-ou , Weng Zhiping 
Published: May 2021

Abstract
Gene expression is controlled by regulatory elements within accessible chromatin. Although most regulatory elements are cell type-specific, a subset is accessible in nearly all the 517 human and 94 mouse cell and tissue types assayed by the ENCODE consortium. We systematically analyzed 9000 human and 8000 mouse ubiquitously-accessible candidate cis-regulatory elements (cCREs) with promoter-like signatures (PLSs) from ENCODE, which we denote ubi-PLSs. These are more CpG-rich than non-ubi-PLSs and correspond to genes with ubiquitously high transcription, including a majority of cell-essential genes. ubi-PLSs are enriched with motifs of ubiquitously-expressed transcription factors and preferentially bound by transcriptional cofactors regulating ubiquitously-expressed genes. They are highly conserved between human and mouse at the synteny level but exhibit frequent turnover of motif sites; accordingly, ubi-PLSs show increased variation at their centers compared with flanking regions among the ∼186 thousand human genomes sequenced by the TOPMed project. Finally, ubi-PLSs are enriched in genes implicated in Mendelian diseases, especially diseases broadly impacting most cell types, such as deficiencies in mitochondrial functions. Thus, a set of roughly 9000 mammalian promoters are actively maintained in an accessible state across cell types by a distinct set of transcription factors and cofactors to ensure the transcriptional programs of cell-essential genes.
RunBioSimulations: an extensible web application that simulates a wide range of computational modeling frameworks, algorithms, and formats
Authors: Shaikh Bilal , Marupilla Gnaneswara , Wilson Mike , Blinov Michael L , Moraru Ion I , Karr Jonathan R 
Published: May 2021

AbstractComprehensive, predictive computational models have significant potential for science, bioengineering, and medicine. One promising way to achieve more predictive models is to combine submodels of multiple subsystems. To capture the multiple scales of biology, these submodels will likely require multiple modeling frameworks and simulation algorithms. Several community resources are already available for working with many of these frameworks and algorithms. However, the variety and sheer number of these resources make it challenging to find and use appropriate tools for each model, especially for novice modelers and experimentalists. To make these resources easier to use, we developed RunBioSimulations (https://run.biosimulations.org), a single web application for executing a broad range of models. RunBioSimulations leverages community resources, including BioSimulators, a new open registry of simulation tools. These resources currently enable RunBioSimulations to execute nine frameworks and 44 algorithms, and they make RunBioSimulations extensible to additional frameworks and algorithms. RunBioSimulations also provides features for sharing simulations and interactively visualizing their results. We anticipate that RunBioSimulations will foster reproducibility, stimulate collaboration, and ultimately facilitate the creation of more predictive models.
The COVID-19 Data Portal: accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing
Authors: Harrison Peter W , Lopez Rodrigo , Rahman Nadim , Allen Stefan Gutnick , Aslam Raheela , Buso Nicola , Cummins Carla , Fathy Yasmin , Felix Eloy , Glont Mihai , Jayathilaka Suran , Kadam Sandeep , Kumar Manish , Lauer Katharina B , Malhotra Geetika , Mosaku Abayomi , Edbali Ossama , Park Young Mi , Parton Andrew , Pearce Matt , Estrada Pena Jose Francisco , Rossetto Joseph , Russell Craig , Selvakumar Sandeep , Sitjà Xènia Pérez , Sokolov Alexey , Thorne Ross , Ventouratou Marianna , Walter Peter , Yordanova Galabina , Zadissa Amonida , Cochrane Guy , Blomberg Niklas , Apweiler Rolf 
Published: May 2021

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic will be remembered as one of the defining events of the 21st century. The rapid global outbreak has had significant impacts on human society and is already responsible for millions of deaths. Understanding and tackling the impact of the virus has required a worldwide mobilisation and coordination of scientific research. The COVID-19 Data Portal (https://www.covid19dataportal.org/) was first released as part of the European COVID-19 Data Platform, on April 20th 2020 to facilitate rapid and open data sharing and analysis, to accelerate global SARS-CoV-2 and COVID-19 research. The COVID-19 Data Portal has fortnightly feature releases to continue to add new data types, search options, visualisations and improvements based on user feedback and research. The open datasets and intuitive suite of search, identification and download services, represent a truly FAIR (Findable, Accessible, Interoperable and Reusable) resource that enables researchers to easily identify and quickly obtain the key datasets needed for their COVID-19 research.
De Novo Pial Arteriovenous Fistula Associated With Cerebral Infarction and Venous Hypertension: Report of 2 Cases Suggesting a “Second Hit Theory”
Authors: Terada Tomoaki , Nakayama Sadayoshi , Wada Akira , Tanaka Yuko , Yabuzaki Hajime , Matsuda Yoshikazu , Tsumoto Tomoyuki 
Published: May 2021

ABSTRACT

BACKGROUND AND IMPORTANCE
The etiology of de novo pial arteriovenous fistula (AVF) is unknown. We found 2 cases of de novo pial AVF, which appeared after cerebral infarction and which was associated with venous hypertension secondary to venous sinus thrombosis with a dural AVF (dAVF). Additional angiogenic stimuli (second hit) were considered as one of the mechanisms of de novo pial AVF.

CLINICAL PRESENTATION
A 63-yr-old male was admitted to our hospital due to an intraventricular hemorrhage. He had a history of cerebral infarction 2 yr before. Angiography demonstrated multiple dAVFs with bilateral occlusion of the distal transverse sinus associated with prominent retrograde cortical venous drainage. A pial AVF was found at the border of his previous cerebral infarction. Both lesions were successfully treated using endovascular technique.
A second case involved a 47-yr-old female who was admitted to our hospital due to venous infarction also associated with sinus thrombosis. De novo pial AVF at the border of the venous infarction and dAVF at the transverse sigmoid junction were demonstrated on angiography 6 mo later.

CONCLUSION
We speculate that venous hypertension associated with additional angiogenic stimuli (second hit) due to brain ischemia and/or brain injury related to infarction caused de novo pial AVF in these 2 cases.
Pineal Region Hemangioblastoma Resection Through Paramedian Supracerebellar Approach: 2-Dimensional Operative Video
Authors: Essayed Walid I B N , Aboud Emad , Al-Mefty Ossama 
Published: May 2021

Abstract
Pineal region tumors remain challenging lesions to safely resect because of their central location.
1
Patients frequently present with symptoms associated with hydrocephalus and brainstem compression.
2
Local anatomy, primarily the tentorium angle and venous anatomy, plays a central role in the selection of the approach.
3
The paramedian supracerebellar approach pioneered by Yaşargil in 1984
4
allows to access the pineal region through a less steep angle while avoiding the central thickened arachnoid and midline cerebellar and vermian veins.
3

Although the author strongly prefers the advantageous three-quarter concord position, this early case was performed in a sitting position, which requires a bubble test to rule out the presence of a persistent foramen ovale. The preoperative pineal differential diagnosis should be exhaustive, including blood and cerebrospinal fluid (CSF) tumor markers in suitable cases. Hemangioblastomas are seldom found or expected in the pineal area, and the surgeon must be alarmed by their typical “cherry nodule” appearance.
2

,

5
Their recognition prior to resection is paramount in avoiding excessive blood loss from tumor entry. Similar to arteriovenous malformations, hemangioblastoma surgical tenets include en bloc resection and preservation of the main draining veins until the last steps of the resection. Von Hippel-Lindau (VHL) syndrome genetic workup is necessary is similar patients, as more than 25% of hemangioblastomas are associated with VHL tumor suppressor gene mutations in chromosome 3.
2
The patient consented to the surgery and use of her photography.
Image at 2:41 from Ueyama et al, Bridging veins on the tentorial surface of the cerebellum: a microsurgical anatomic study and operative considerations, Neurosurgery, 1998, 43(5),
3
used with permission from the Congress of Neurological Surgeons.
Prone Single-Position Lateral Lumbar Interbody Fusion With Posterior Decompression and Pedicle Screw Fixation for the Treatment of Grade II Spondylolisthesis: 2-Dimensional Operative Video
Authors: Naeem Komal , Farber S Harrison , Bhargava Malika , Porter Randall W 
Published: May 2021

Abstract
Lateral lumbar interbody fusion (LLIF) provides indirect decompression without disruption of the posterior elements. It involves a larger implant footprint than that of posterior approaches. LLIF is typically performed with the patient in the lateral decubitus position. When a posterior fixation is indicated, a second-stage procedure is performed with the patient in the prone position. Single-position surgery provides the potential advantage of decreased operative time because both procedures can be performed without patient repositioning. Single-position LLIF and posterior fixation in the prone position have not been well validated to date. Herein, techniques for LLIF, percutaneous pedicle screw fixation, and facetectomy in the prone position are shown.
A 76-yr-old woman with osteoporosis presented with severe back and bilateral leg pain refractory to conservative management and imaging findings of grade 2 dynamic anterolisthesis at L4-L5 with severe stenosis. She underwent LLIF with percutaneous pedicle screw fixation and facetectomy. She was placed on a Jackson table in the prone position for the entire procedure, which was performed in a single stage. Percutaneous pedicle screws were placed, followed by a left-sided minimally invasive facetectomy. A left-sided retroperitoneal transpsoas approach was used to perform the LLIF in standard fashion. Finally, the rods were locked into place.
Postoperatively, the patient was neurologically stable, and imaging confirmed good hardware placement. At the 6-wk follow-up, the patient was doing well. This case demonstrates the feasibility of performing LLIF and posterior fixation in a single stage in the prone position. The patient provided informed consent. Used with permission from Barrow Neurological Institute.
Loss of inner-envelope K+/H+ exchangers impairs plastid rRNA maturation and gene expression
Authors: DeTar Rachael Ann , Barahimipour Rouhollah , Manavski Nikolay , Schwenkert Serena , Höhner Ricarda , Bölter Bettina , Inaba Takehito , Meurer Jörg , Zoschke Reimo , Kunz Hans-Henning 
Published: May 2021

Abstract
The inner-envelope K+ EFFLUX ANTIPORTERS (KEA) 1 and 2 are critical for chloroplast development, ion homeostasis, and photosynthesis. However, the mechanisms by which changes in ion flux across the envelope affect organelle biogenesis remained elusive. Chloroplast development requires intricate coordination between the nuclear genome and the plastome. Many mutants compromised in plastid gene expression (PGE) display a virescent phenotype, that is delayed greening. The phenotypic appearance of Arabidopsis thaliana kea1 kea2 double mutants fulfills this criterion, yet a link to PGE has not been explored. Here, we show that a simultaneous loss of KEA1 and KEA2 results in maturation defects of the plastid ribosomal RNAs. This may be caused by secondary structure changes of rRNA transcripts and concomitant reduced binding of RNA-processing proteins, which we documented in the presence of skewed ion homeostasis in kea1 kea2. Consequently, protein synthesis and steady-state levels of plastome-encoded proteins remain low in mutants. Disturbance in PGE and other signs of plastid malfunction activate GENOMES UNCOUPLED 1-dependent retrograde signaling in kea1 kea2, resulting in a dramatic downregulation of GOLDEN2-LIKE transcription factors to halt expression of photosynthesis-associated nuclear-encoded genes (PhANGs). PhANG suppression delays the development of fully photosynthesizing kea1 kea2 chloroplasts, probably to avoid progressing photo-oxidative damage. Overall, our results reveal that KEA1/KEA2 function impacts plastid development via effects on RNA-metabolism and PGE.
Blue light-dependent interactions of CRY1 with GID1 and DELLA proteins regulate gibberellin signaling and photomorphogenesis in Arabidopsis
Authors: Xu Peng , Chen Huiru , Li Ting , Xu Feng , Mao Zhilei , Cao Xiaoli , Miao Langxi , Du Shasha , Hua Jie , Zhao Jiachen , Guo Tongtong , Kou Shuang , Wang Wenxiu , Yang Hong-Quan 
Published: May 2021

Abstract
Cryptochromes are blue light photoreceptors that mediate various light responses in plants and mammals. In Arabidopsis (Arabidopsis thaliana), cryptochrome 1 (CRY1) mediates blue light-induced photomorphogenesis, which is characterized by reduced hypocotyl elongation and enhanced anthocyanin production, whereas gibberellin (GA) signaling mediated by the GA receptor GA-INSENSITIVE DWARF1 (GID1) and DELLA proteins promotes hypocotyl elongation and inhibits anthocyanin accumulation. Whether CRY1 control of photomorphogenesis involves regulation of GA signaling is largely unknown. Here, we show that CRY1 signaling involves the inhibition of GA signaling through repression of GA-induced degradation of DELLA proteins. CRY1 physically interacts with DELLA proteins in a blue light-dependent manner, leading to their dissociation from SLEEPY1 (SLY1) and the inhibition of their ubiquitination. Moreover, CRY1 interacts directly with GID1 in a blue light-dependent but GA-independent manner, leading to the inhibition of the interaction between GID1 with DELLA proteins. These findings suggest that CRY1 controls photomorphogenesis through inhibition of GA-induced degradation of DELLA proteins and GA signaling, which is mediated by CRY1 inhibition of the interactions of DELLA proteins with GID1 and SCFSLY1, respectively.
PROBABILISTIC ANALYSES OF 131I THYROID ACTIVITY IN PERSONS WITH SURFACE CONTAMINATION IN DIRECT MEASUREMENT WITH A STANDING-TYPE WHOLE-BODY COUNTER AS AN EMERGENCY RESPONSE IN A RADIOLOGICAL INCIDENT
Authors: Tani Kotaro , Igarashi Yu , Kim Eunjoo , Kowatari Munehiko , Iimoto Takeshi , Kurihara Osamu 
Published: May 2021

Abstract
The authors’ previous study suggested that a simple standing-type whole-body counter called FASTSCAN (Canberra, Meriden, CT, USA), widely installed throughout Japan after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in March 2011, could be used for thyroid measurements in internal dose assessment after a future radiological incident accompanied by the release of 131I into the environment. The present study performed Monte-Carlo simulations using a computational human phantom with several patterns of body surface contamination and used the results to formulate a method for probabilistic analyses of 131I thyroid activity in persons with surface contamination. The major advantage of this method is that the upper limit of the thyroid activity can be determined from the relative frequency distribution without identifying where body surface contamination remains. Therefore, this method is especially effective for use in the early phase of a radiological incident when time and resources are limited, making it difficult to physically remove all body surface contamination for the purpose of gaining more accurate population-wide thyroid screening measurements. As a case study of the FDNPP accident, the proposed method was applied to the results of in vivo measurements for a male subject with body surface contamination. In comparing the probabilistic analyses before and after removal of the subject’s contaminated work clothes, the uncertainty of the relative frequency distribution of 131I thyroid activity was reduced by their removal. Therefore, in terms of accurate estimates and avoidance of radiation exposure from their contaminated clothes, efforts to remove body surface contamination still should be made as much as possible in the chaotic situation of the early phase of a radiological incident.