bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid titration with oral sustained-release morphine plus subcutaneous morphine in a multi-center, randomized control study of cancer patients with moderate to severe cancer pain
Authors: Sun Yu , Wei Hao , Yu Min , Zheng Rujun , Li Junying , Fu Yan , Zheng Yuzhu , Zhang Xi , Shou Feng , Zhou Jin , Yao Wenxiu , Chen Ping , Liu Dingyi , Jia Yuming , Fu Yu , Wang Yan , Zhu Jiang 
Published: August 2022

Abstract

Background
Pain is one of the most common concomitant symptoms among cancer patients. Pharmacologic agents are regarded as a cornerstone of cancer pain management. ‘Dose titration’ with short-acting morphine is widely accepted. Such a titration method is very complicated. The analgesic background establishment is often delayed. Titration based on sustained-release opioids is also recommended, but the onset of analgesic effect requires hours, whereas the rescue analgesia is always needed. This study evaluated the optimized morphine titration scheme with a simultaneous combination of sustained-release morphine and subcutaneous morphine.

Methods
In a multicenter, 7-day, randomized controlled study, patients with moderate to severe cancer pain were assigned to receive either sustained-release morphine and subcutaneous morphine simultaneously (rapid titration) or only subcutaneous morphine to dose titration. The primary outcome was the safety and the number of times of rescue therapy as needed in the first 24 h.

Results
A total of 108 patients with moderate to severe cancer pain were included in the study. The number of times of rescue analgesics in the first 24 h significantly reduced in the rapid titration group (0.4 ± 0.48 vs. 2.3 ± 0.78, P = 0.000). No differences in the intensity of opioid-related symptoms were found between the two groups.

Conclusions
Rapid titration is safe and efficient, which could significantly decrease rescue analgesics in the first 24 h and achieve better analgesic efficacy for cancer pain patients.
Soybean GmHY2a encodes a phytochromobilin synthase that regulates internode length and flowering time
Authors: Zhang Zhirui , Yang Suxin , Wang Qiushi , Yu Hui , Zhao Beifang , Wu Tao , Tang Kuanqiang , Ma Jingjing , Yang Xinjing , Feng Xianzhong 
Published: August 2022

Abstract
Plant height and flowering time are important agronomic traits that directly affect soybean [Glycine max (L.) Merr.] adaptability and yield. Here, the Glycine max long internode 1 (Gmlin1) mutant was selected from an ethyl methyl sulfonate (EMS)-mutated Williams 82 population due to its long internodes and early flowering. Using bulked segregant analysis (BSA), the Gmlin1 locus was mapped to Glyma.02G304700, a homologue of the Arabidopsis HY2 gene, which encodes a phytochromobilin (PΦB) synthase involved in phytochrome chromophore synthesis. Mutation of GmHY2a results in failure of the de-etiolation response under both red and far-red light. The Gmlin1 mutant exhibits a constitutive shade avoidance response under normal light, and the mutations influence the auxin and gibberellin pathways to promote internode elongation. The Gmlin1 mutant also exhibits decreased photoperiod sensitivity. In addition, the soybean photoperiod repressor gene E1 is down-regulated in the Gmlin1 mutant, resulting in accelerated flowering. The nuclear import of phytochrome A (GmphyA) and GmphyB following light treatment is decreased in Gmlin1 protoplasts, indicating that the weak light response of the Gmlin1 mutant is caused by a decrease in functional phytochrome. Together, these results indicate that GmHY2a plays an important role in soybean phytochrome biosynthesis and provide insights into the adaptability of the soybean plant.
Spectroscopic study of five SB1 stars with CP components
Authors: Catanzaro G , Colombo C , Ferrara C , Giarrusso M 
Published: August 2022

ABSTRACT
In this paper, we present the results of a spectroscopic campaign devoted to ascertaining the actual nature of a sample of five objects reported as chemically peculiar stars in the Catalogue of Ap, HgMn and Am stars (2009, A&A, 498, 961). Spectroscopic observations were obtained with Catania Astrophysical Observatory Spectropolarimeter. For each of the objects, we derive the effective temperature, gravity, rotational and radial velocities, and chemical abundances using the spectral synthesis method. All the targets were found to be SB1 systems. Our abundance analysis led us to classify HD 40788 and HD 187959 as marginal Am stars and HD 202431 as an Am star, and to confirm HD 134793 as an SrEuCr Ap star and, finally, HD 189652 as a normal star. Finally, we confirm that Am stars can possibly be used as an accurate tool to date stellar populations in galaxies.
Phobos and Deimos surface composition: search for spectroscopic analogues
Authors: Poggiali Giovanni , Matsuoka M , Barucci M A , Brucato J R , Beck P , Fornasier S , Doressoundiram A , Merlin F , Alberini A 
Published: August 2022

ABSTRACT
Phobos and Deimos, the two satellites of Mars, were largely studied in the past using ground-based telescope and spacecraft data, although most of the data were obtained by opportunity observations performed by Mars dedicated orbiters. Despite the data available so far, the main composition of the two moons is not yet fully understood. The possible presence of hydrated minerals along with mafic minerals olivine and pyroxene seems to be the most plausible interpretation, but more investigations are needed. MIRS spectrometer on-board the future JAXA MMX sample return mission will help to unveil the open question on the composition of Phobos and Deimos. In this work, we review past spectroscopic observations of the Martian moons, both from ground observatories and spacecraft data set, aiming at better understanding the constraints in interpreting the Mars satellites composition and at identifying the best spectroscopic analogues. We also present new laboratory measurements on mineral mixing and meteorites to match the satellites spectral behaviour. New measurements were acquired at INAF-Astrophysical Observatory of Arcetri and IPAG laboratories at room conditions exploring different geometries and the results obtained set new constraints for future laboratory measurements. Our preliminary results confirm that the surface of Phobos and Deimos can be associated with samples characterized by a higher presence of dark components (e.g. amorphous carbon) or minerals produced by space weathering (e.g. Fe0 and FeS-bearing materials). Presence of dark component could also be totally responsible for the reduced hydrated band observed on the moons without invoking dehydration or OH-implantation on anhydrous surface.
Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria
Authors: Chen Meng-Yun , Teng Wen-Kai , Zhao Liang , Han Bo-Ping , Song Li-Rong , Shu Wen-Sheng 
Published: August 2022

Abstract
Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth’s biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.
Evolutionary Changes in the Chromatin Landscape Contribute to Reorganization of a Developmental Gene Network During Rapid Life History Evolution in Sea Urchins
Authors: Davidson Phillip L , Byrne Maria , Wray Gregory A 
Published: August 2022

Abstract
Chromatin configuration is highly dynamic during embryonic development in animals, exerting an important point of control in transcriptional regulation. Yet there exists remarkably little information about the role of evolutionary changes in chromatin configuration to the evolution of gene expression and organismal traits. Genome-wide assays of chromatin configuration, coupled with whole-genome alignments, can help address this gap in knowledge in several ways. In this study we present a comparative analysis of regulatory element sequences and accessibility throughout embryogenesis in three sea urchin species with divergent life histories: a lecithotroph Heliocidaris erythrogramma, a closely related planktotroph H. tuberculata, and a distantly related planktotroph Lytechinus variegatus. We identified distinct epigenetic and mutational signatures of evolutionary modifications to the function of putative cis-regulatory elements in H. erythrogramma that have accumulated nonuniformly throughout the genome, suggesting selection, rather than drift, underlies many modifications associated with the derived life history. Specifically, regulatory elements composing the sea urchin developmental gene regulatory network are enriched for signatures of positive selection and accessibility changes which may function to alter binding affinity and access of developmental transcription factors to these sites. Furthermore, regulatory element changes often correlate with divergent expression patterns of genes involved in cell type specification, morphogenesis, and development of other derived traits, suggesting these evolutionary modifications have been consequential for phenotypic evolution in H. erythrogramma. Collectively, our results demonstrate that selective pressures imposed by changes in developmental life history rapidly reshape the cis-regulatory landscape of core developmental genes to generate novel traits and embryonic programs.
Structural basis of DNA packaging by a ring-type ATPase from an archetypal viral system
Authors: Fung Herman K H , Grimes Shelley , Huet Alexis , Duda Robert L , Chechik Maria , Gault Joseph , Robinson Carol V , Hendrix Roger W , Jardine Paul J , Conway James F , Baumann Christoph G , Antson Alfred A 
Published: August 2022

Abstract
Many essential cellular processes rely on substrate rotation or translocation by a multi-subunit, ring-type NTPase. A large number of double-stranded DNA viruses, including tailed bacteriophages and herpes viruses, use a homomeric ring ATPase to processively translocate viral genomic DNA into procapsids during assembly. Our current understanding of viral DNA packaging comes from three archetypal bacteriophage systems: cos, pac and phi29. Detailed mechanistic understanding exists for pac and phi29, but not for cos. Here, we reconstituted in vitro a cos packaging system based on bacteriophage HK97 and provided a detailed biochemical and structural description. We used a photobleaching-based, single-molecule assay to determine the stoichiometry of the DNA-translocating ATPase large terminase. Crystal structures of the large terminase and DNA-recruiting small terminase, a first for a biochemically defined cos system, reveal mechanistic similarities between cos and pac systems. At the same time, mutational and biochemical analyses indicate a new regulatory mechanism for ATPase multimerization and coordination in the HK97 system. This work therefore establishes a framework for studying the evolutionary relationships between ATP-dependent DNA translocation machineries in double-stranded DNA viruses.
The expression of aminoglycoside resistance genes in integron cassettes is not controlled by riboswitches
Authors: Hipólito Alberto , García-Pastor Lucía , Blanco Paula , Trigo da Roza Filipa , Kieffer Nicolas , Vergara Ester , Jové Thomas , Álvarez Julio , Escudero José Antonio 
Published: August 2022

Abstract
Regulation of gene expression is a key factor influencing the success of antimicrobial resistance determinants. A variety of determinants conferring resistance against aminoglycosides (Ag) are commonly found in clinically relevant bacteria, but whether their expression is regulated or not is controversial. The expression of several Ag resistance genes has been reported to be controlled by a riboswitch mechanism encoded in a conserved sequence. Yet this sequence corresponds to the integration site of an integron, a genetic platform that recruits genes of different functions, making the presence of such a riboswitch counterintuitive. We provide, for the first time, experimental evidence against the existence of such Ag-sensing riboswitch. We first tried to reproduce the induction of the well characterized aacA5 gene using its native genetic environment, but were unsuccessful. We then broadened our approach and analyzed the inducibility of all AgR genes encoded in integrons against a variety of antibiotics. We could not observe biologically relevant induction rates for any gene in the presence of several aminoglycosides. Instead, unrelated antibiotics produced mild but consistently higher increases in expression, that were the result of pleiotropic effects. Our findings rule out the riboswitch control of aminoglycoside resistance genes in integrons.
Widespread repression of anti-CRISPR production by anti-CRISPR-associated proteins
Authors: Shehreen Saadlee , Birkholz Nils , Fineran Peter C , Brown Chris M 
Published: August 2022

Abstract
Many bacteria use CRISPR-Cas systems to defend against invasive mobile genetic elements (MGEs). In response, MGEs have developed strategies to resist CRISPR-Cas, including the use of anti-CRISPR (Acr) proteins. Known acr genes may be followed in an operon by a putative regulatory Acr-associated gene (aca), suggesting the importance of regulation. Although ten families of helix-turn-helix (HTH) motif containing Aca proteins have been identified (Aca1-10), only three have been tested and shown to be transcriptional repressors of acr-aca expression. The AcrIIA1 protein (a Cas9 inhibitor) also contains a functionally similar HTH containing repressor domain. Here, we identified and analysed Aca and AcrIIA1 homologs across all bacterial genomes. Using HMM models we found aca-like genes are widely distributed in bacteria, both with and without known acr genes. The putative promoter regions of acr-aca operons were analysed and members of each family of bacterial Aca tested for regulatory function. For each Aca family, we predicted a conserved inverted repeat binding site within a core promoter. Promoters containing these sites directed reporter expression in E. coli and were repressed by the cognate Aca protein. These data demonstrate that acr repression by Aca proteins is widely conserved in nature.
Targeted nanotherapy for kidney diseases: a comprehensive review
Authors: Sabiu Gianmarco , Kasinath Vivek , Jung Sungwook , Li Xiaofei , Tsokos George C , Abdi Reza 
Published: August 2022

ABSTRACT
Kidney diseases represent a major public health problem, affecting millions of people worldwide. Moreover, the treatment of kidney diseases is burdened by the problematic effects of conventional drug delivery, such as systemic drug toxicity, rapid drug clearance, and the absence of precise targeting of the kidney. Although the use of nanotechnology in medicine is in its early stage and lacks robust translational studies, nanomedicines have already shown great promise as novel drug-delivery systems for the treatment of kidney disease. On the basis of our current knowledge of renal anatomy and physiology, pathophysiology of kidney diseases, and physicochemical characteristics of nanoparticles, an expansive repertoire and wide use of nanomedicines could be developed for kidney diseases in the near future. Some limitations have slowed the transition of these agents from preclinical studies to clinical trials, however. In this review, we summarize the current knowledge on renal drug-delivery systems and recent advances in renal cell targeting; we also demonstrate their important potential as future paradigm-shifting therapies for kidney diseases.
Risk of obesity during a gluten-free diet in pediatric and adult patients with celiac disease: a systematic review with meta-analysis
Authors: Barone Michele , Iannone Andrea , Cristofori Fernanda , Dargenio Vanessa Nadia , Indrio Flavia , Verduci Elvira , Di Leo Alfredo , Francavilla Ruggiero 
Published: August 2022

Abstract

Context
Obesity is a significant risk factor for many pathological conditions. Whether a gluten-free diet (GFD) is a risk factor for overweight or obesity remains controversial.

Objective
The primary aim of this study was to assess the prevalence of body mass index (BMI) categories at disease presentation and the variation in BMI category from underweight/normal to overweight/obese and vice versa during a GFD.

Data Sources
PubMed, Scopus, and Web of Science databases were searched through February 2021 for retrospective, cross-sectional, and prospective studies reporting BMI categories at disease diagnosis and during a GFD.

Data Extraction
Data were extracted by 2 reviewers independently. Disagreements were resolved by consensus; a third reviewer was consulted, if necessary. Risk of bias was assessed with the Cochrane ROBINS-I tool.

Data Analysis
Subgroup analysis based on age (pediatric/adult patients), study design (prospective, cross-sectional, retrospective), and duration of GFD was performed.. Forty-five studies were selected (7959 patients with celiac disease and 20 524 healthy controls). The mean BMI of celiac patients at presentation was significantly lower than that of controls (P &lt; 0.001). During a GFD, the mean BMI increased significantly (mean difference = 1.14 kg/m2 [95%CI, 0.68–1.60 kg/m2]; I2 = 82.8%; P &lt; 0.001), but only 9% of patients (95%CI, 7%–12%; I2 = 80.0%) changed from the underweight/normal BMI category to the overweight/obese category, while 20% (95%CI, 11%–29%; I2 = 85.8%) moved into a lower BMI category.

Conclusion
Most celiac patients had a normal BMI at presentation, although the mean BMI was significantly lower than that of controls. A GFD does not increase the risk of becoming overweight/obese, especially in children. The quality of several studies was suboptimal, with moderate or high overall risk of bias and heterogeneity.
Response to Brentuximab Vedotin by CD30 Expression in Non-Hodgkin Lymphoma
Authors: Jagadeesh Deepa , Horwitz Steve , Bartlett Nancy L , Kim Youn , Jacobsen Eric , Duvic Madeleine , Little Meredith , Trepicchio William , Fenton Keenan , Onsum Matthew , Lisano Julie , Advani Ranjana 
Published: August 2022

Abstract

Background
The safety and efficacy of brentuximab vedotin (BV), an antibody-drug conjugate directed to the CD30 antigen, has been assessed in several trials in patients with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell non-Hodgkin lymphoma (NHL). The objective of this research was to examine the relationship between CD30 expression level and clinical response to BV.

Patients and Methods
We analyzed response in patients treated with BV monotherapy in 5 prospective clinical studies in relapsed or refractory PTCL, CTCL, or B-cell NHL. CD30 expression was assessed by immunohistochemistry (IHC) using the Ber H2 antibody for 275 patients.

Results
Across all 5 studies, 140 (50.9%) patients had tumors with CD30 expression &lt;10%, including 60 (21.8%) with undetectable CD30 by IHC. No significant differences were observed for any study in overall response rates between patients with CD30 expression ≥10% or &lt;10%. Median duration of response was also similar in the CD30 ≥10% and &lt;10% groups for all studies.

Conclusions
In this analysis of studies across a range of CD30-expressing lymphomas, CD30 expression alone, as measured by standard IHC, does not predict clinical benefit from BV, making the determination of a threshold level of expression uncertain.
Ectopic expression ofBOTRYTIS SUSCEPTIBLE1reveals its function as a positive regulator of wound-induced cell death and plant susceptibility toBotrytis
Authors: Cui Fuqiang , Li Xiaoxiao , Wu Wenwu , Luo Wenbo , Wu Ying , Brosché Mikael , Overmyer Kirk 
Published: August 2022

AbstractProgrammed cell death (PCD) is integral to plant life and required for stress responses, immunity, and development. Our understanding of the regulation of PCD is incomplete, especially concerning regulators involved in multiple divergent processes. The botrytis-susceptible (bos1) mutant of Arabidopsis is highly susceptible to fungal infection by Botrytis cinerea (Botrytis). BOS1 (also known as MYB108) regulates cell death propagation during plant responses to wounding. The bos1-1 allele contains a T-DNA insertion in the 5′-untranslated region upstream of the start codon. This insertion results in elevated expression of BOS1/MYB108. We used clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease 9 (Cas9) system (CRISPR/Cas9) to create new bos1 alleles with disrupted exons, and found that these lines lacked the typical bos1-1 wounding and Botrytis phenotypes. They did exhibit reduced fertility, as was previously observed in other bos1 alleles. Resequencing of the bos1-1 genome confirmed the presence of a mannopine synthase (MAS) promoter at the T-DNA left border. Expression of the BOS1 gene under control of the MAS promoter in wild-type plants conferred the characteristic phenotypes of bos1-1: Botrytis sensitivity and response to wounding. Multiple overexpression lines demonstrated that BOS1 was involved in regulation of cell death propagation in a dosage-dependent manner. Our data indicate that bos1-1 is a gain-of-function mutant and that BOS1 function in regulation of fertility and Botrytis response can both be understood as misregulated cell death.