bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the transcriptomic response of Ilyonectria robusta in relation to ginsenoside Rg1 treatment and the development of ginseng rusty root rot
Authors: Li Qiong , Zhan Yu , Xu Yonghua , Zhang Lianxue , Di Peng , Lu Baohui , Chen Changbao
Published: August 2022

Rusty root rot is a severe disease in ginseng (Panax ginseng C. A. Mey) production caused by Ilyonectria robusta. The severity of the disease may be related to the residual ginsenosides in soil. In order to elucidate the response mechanism between Rg1 treatment and the occurrence of ginseng rust, we performed growth, reproduction and transcriptome analysis on treated Rg1. The results showed that Rg1 significantly promoted the mycelial growth and sporulation compared with the control, and aggravated the disease symptoms of Panax ginseng. A total of 6708 transcripts out of 213 131 annotated genes identified from global transcriptomic analysis were differentially expressed in Ilyonectria robusta grown during the Rg1 treatment. These genes were found to be related to the carbon-nitrogen metabolism, transport and assimilation. Many of these genes were also associated with pathogenicity based on the Phi-base database. Several transcription factors were related to specific biological processes, such as nitrogen utilization. The current results revealed that Rg1 played a major role in the development of rusty root rot by promoting fungal cell growth and affected the expression of genes required for pathogenesis. Rg1 could aggravate the invasion of Ilyonectria robusta on ginseng root, which preliminarily revealed the reason for the aggravation of rusty root rot in ginseng soil-borne.
Cytological heterogeneity of heterochromatin among 10 sequenced Drosophila species
Authors: Marchetti Marcella , Piacentini Lucia , Berloco Maria Francesca , Casale Assunta Maria , Cappucci Ugo , Pimpinelli Sergio , Fanti Laura
Published: August 2022

In Drosophila chromosomal rearrangements can be maintained and are associated with karyotypic variability among populations from different geographic localities. The abundance of variability in gene arrangements among chromosomal arms is even greater when comparing more distantly related species and the study of these chromosomal changes has provided insights into the evolutionary history of species in the genus. In addition, the sequencing of genomes of several Drosophila species has offered the opportunity to establish the global pattern of genomic evolution, at both genetic and chromosomal level. The combined approaches of comparative analysis of syntenic blocks and direct physical maps on polytene chromosomes have elucidated changes in the orientation of genomic sequences and the difference between heterochromatic and euchromatic regions. Unfortunately, the centromeric heterochromatic regions cannot be studied using the cytological maps of polytene chromosomes because they are underreplicated and therefore reside in the chromocenter. In Drosophila melanogaster, a cytological map of the heterochromatin has been elaborated using mitotic chromosomes from larval neuroblasts. In the current work, we have expanded on that mapping by producing cytological maps of the mitotic heterochromatin in an additional 10 sequenced Drosophila species. These maps highlight 2 apparently different paths, for the evolution of the pericentric heterochromatin between the subgenera Sophophora and Drosophila. One path leads toward a progressive complexity of the pericentric heterochromatin (Sophophora) and the other toward a progressive simplification (Drosophila). These maps are also useful for a better understanding how karyotypes have been altered by chromosome arm reshuffling during evolution.
Adult Age Differences in Using Information From the Eyes and Mouth to Make Decisions About Others’ Emotions
Authors: Slessor Gillian , Insch Pauline , Donaldson Isla , Sciaponaite Vestina , Adamowicz Malgorzata , Phillips Louise H
Published: August 2022

Objectives

Older adults are often less accurate than younger counterparts at identifying emotions such as anger, sadness, and fear from faces. They also look less at the eyes and more at the mouth during emotion perception. The current studies advance understanding of the nature of these age effects on emotional processing.

Methods

Younger and older participants identified emotions from pictures of eyes or mouths (Experiment 1) and incongruent mouth–eyes emotion combinations (Experiment 2). In Experiment 3, participants categorized emotions from pictures in which face masks covered the mouth region.

Results

Older adults were worse than young at identifying anger and sadness from eyes, but better at identifying the same emotions from the mouth region (Experiment 1) and they were more likely than young to use information from the mouth to classify anger, fear, and disgust (Experiment 2). In Experiment 3, face masks impaired perception of anger, sadness, and fear more for older compared to younger adults.

Discussion

These studies indicate that older people are more able than young to interpret emotional information from the mouth, they are more biased to use information from the mouth, and suffer more difficulty in emotion perception when the mouth is covered with a face mask. This has implications for social communication in different age groups.
Evolution of complex genome architecture in gymnosperms
Authors: Wan Tao , Gong Yanbing , Liu Zhiming , Zhou YaDong , Dai Can , Wang Qingfeng
Published: August 2022

Gymnosperms represent an ancient lineage that diverged from early spermatophytes during the Devonian. The long fossil records and low diversity in living species prove their complex evolutionary history, which included ancient radiations and massive extinctions. Due to their ultra-large genome size, the whole-genome assembly of gymnosperms has only generated in the past 10 years and is now being further expanded into more taxonomic representations. Here, we provide an overview of the publicly available gymnosperm genome resources and discuss their assembly quality and recent findings in large genome architectures. In particular, we describe the genomic features most related to changes affecting the whole genome. We also highlight new realizations relative to repetitive sequence dynamics, paleopolyploidy, and long introns. Based on the results of relevant genomic studies of gymnosperms, we suggest additional efforts should be made toward exploring the genomes of medium-sized (5–15 gigabases) species. Lastly, more comparative analyses among high-quality assemblies are needed to understand the genomic shifts and the early species diversification of seed plants.
Metabolite Profiling, Stability Testing, Pharmacokinetics, and In Vivo Pattern Recognition Analysis of Arq-e-Keora: A Traditional Unani Formulation
Authors: Zahiruddin Sultan , Parveen Abida , Parveen Rabea , Khan Asim Ali , Ahmad Sayeed
Published: August 2022

Background

Arq-e-Keora is a liquid formulation of the Unani system of medicine and used since long for the management of weakness of heart, palpitations, etc.

Objective

The study was carried out to generate a scientific data for its metabolite profiling, stability testing, pharmacokinetics, and pattern recognition analysis of Arq-e-Keora.

Method

Arq-e-Keora has been prepared as water distillate of male wpadix of Pandanus odoratissimus L.f. TLC profiling of Arq-e-Keora was performed using hexane and acetone (7:3, v/v) as a solvent system. The metabolic profiling of volatile compounds was carried out using GC-MS. Pharmacokinetic analysis was performed through GC-MS to evaluate how quickly it absorbs and distributes in plasma. The pattern recognition analysis was performed in order to recognize the pattern and fate of metabolites in rat plasma up to 24 h after single oral administration of Arq-e-Keora.

Results

TLC and GC-MS analysis resulted in profiling of 11 and 21 metabolites, respectively. GC-MS analysis revealed that phenethyl alcohol, alpha-terpinolene, beta terpinene, alpha terpinene, beta fenchyl alcohol, hexadecanoic acid, and octadecanoic acid are the major metabolites found in Arq-e-Keora. The stability analysis showed that most of the compounds are stable at refrigerator temperature during their consumption. Pharmacokinetics data of phenethyl alcohol showed its absorption was rapid, with Tmax occurring within 1 h after oral administration of Arq-e-Keora. In vivo pattern recognition analysis suggests that some metabolite expression was altered after its oral administration.

Conclusions

As a result, our model could be used for quality, stability, and pharmacokinetic evaluation of various Unani formulations mentioned in Unani Pharmacopoeia of India.

Highlights

This is the first study of pharmacokinetic analysis and metabolite pattern of traditional Unani formulation after its oral administration in Wistar rats.
The Challenges of Implementing Special Sanctions (Sanciones Propias) in Colombia and Providing Retribution, Reparation, Participation and Reincorporation
Authors: Sandoval Clara , Martínez-Carrillo Hobeth , Cruz-Rodríguez Michael
Published: August 2022

The 2016 Final Peace Agreement between the Colombian State and the Revolutionary Armed Forces of Colombia-People’s Army (FARC) envisages an innovative approach to victims’ reparations from perpetrators including NSAG through special sanctions (sanciones propias). They are forms of lenient punishment consisting of effective restrictions of liberty to carry out works or activities, such as developing infrastructure, conditioned on the satisfaction of the rights of the victims, particularly reparation. This retributive and reparatory dimension of special sanctions is also linked to reincorporation of ex-combatants. While ambitious and creative, this approach is not immune from normative and practical implementation challenges that could jeopardize its effectiveness and potential. This article critically delves into eight challenges exploring key issues that are of theoretical and practical relevance for Colombia but also for the Transitional Justice field. It sheds light on potential solutions to these challenges but also notes how an incredibly complex system, like the Colombian one, faces major implementation challenges, something that other transitional justice experiences worldwide should learn as feasibility, without sacrificing victims’ rights, should be a key guiding principle of transitional justice efforts.
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

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

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

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

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

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

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

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

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

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

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

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 < 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 < 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

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 <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 <10%. Median duration of response was also similar in the CD30 ≥10% and <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

Programmed 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.
Specific enterotype of gut microbiota predicted clinical effect of methotrexate in patients with rheumatoid arthritis
Authors: Qiao Jun , Zhang Sheng-Xiao , Chang Min-Jing , Cheng Ting , Zhang Jia-Qian , Zhao Rong , Song Shan , Liu Guang-Ying , Chang Jia-Song , Li Xiao-Feng
Published: August 2022

Objective

The most used drug for the treatment of rheumatoid arthritis (RA) remains methotrexate (MTX). Unfortunately, up to 50% of patients do not achieve a clinically adequate outcome. Here we study whether the gut microbiota patterns can aid in the prediction of MTX efficacy for RA.

Method

To dissect gut microbiome profiles of RA patients (n = 145), 16S rRNA gene sequencing was performed. Dirichlet multinomial mixture (DMM) clustering was used to identify enterotypes at genus level. The relationships between enterotypes and clinical measures (such as lymphocyte subsets and cytokines detected by flow cytometry) were explored. Then, enterotype stability was evaluated by the stratification of the RA patient cohort (n = 66) in Shanghai, China, using the same method. Finally, the enterotype-based gut microbial human index classifier was applied to another independent RA patient cohort (n = 27) to identify the factors associated with MTX clinical response.

Results

Our analysis revealed that the RA patients always displayed two different dysbiotic microbiota patterns: RA E1 comprised predominantly Prevotella and RA E2 comprised predominantly Bacteroides. Among all of the lymphocyte subsets and cytokines, only the number of CD8+ T cells showed a significant difference between RA E1 and RA E2. These results were validated in the RA patient cohort in Shanghai, China. Significant associations of RA E1 with clinical response to subsequent MTX treatment were confirmed by another independent RA patient cohort.

Conclusion

Together, the enterotype-based gut microbial human index (EGMI) classifier was useful to precisely and effectively identify enterotypes of individual RA patients, which could effectively evaluate MTX clinical responses.
Liberalization, democratization and the remaking of the South African corporate network 1993–2020
Authors: Reddy Niall
Published: August 2022

Two broad, complementary approaches have defined the literature on interlocking directorates. Inter-organizational theories see them as an outgrowth of firms’ efforts to monitor and manage their commercial environment. Intra-class theories focus on their functionality in harmonizing and coordinating the political action of different segments of the capitalist elite. But comparative work on network formation has drawn almost exclusively on the first of these approaches—linking variation in typologies to the economic institutions that shape patterns of inter-firm engagement. Here I deploy a synthesis of inter-organizational and intra-class theories to understand the evolution of the South African corporate network over the post-Apartheid period. I trace out a broad trend of fragmentation as a hierarchical business system gave way to one modeled on Anglo-Saxon lines. But I also demonstrate the persistence of a cohesive core in the network, firstly centered around the historically dominant social bloc, and subsequently around the personal networks of politically connected black directors. The results show the potential of intra-class theories to enrich our understanding of how corporate networks form and change.
The Journalistic Field in the Platform Economy: The New York Times and the Inverted Pyramid
Authors: Leeds Tyler
Published: August 2022

Bourdieu’s field theory has become a key heuristic for studying the impact of the market on American journalism, but this approach has not been employed to analyze the consequences of a technology-driven decline in advertising revenue. To understand this change and update the commercial critique of journalism, I extend the emerging Bourdieusian historical research program to chart transformations in the market’s heteronomous effects on journalism. To do so, I highlight how the New York Times was exceptionally positioned to manage heteronomy as it emanated through the technology, political, and financial fields. This analysis throws the crisis of the wider field into relief, a field I characterize as an “inverted pyramid” to reflect how the Times’ success deepened hierarchy, while also giving it the freedom to reinvent orthodoxy in a wide space of possibility atop the field.
Scylla or Charybdis? The beneficiary’s dilemma between contempt of court orders and Swiss–Liechtenstein Anti-Espionage Law
Authors: Gasser Johannes , Graham Toby
Published: August 2022

Beneficiaries of foreign trusts and foundations are sometimes required by English and other courts to provide information and disclose documents pertaining to their beneficial interests and any related rights they may have to receive payment from the assets or income. This may be relevant in many circumstances, most importantly in family feuds and in divorce proceedings, where courts often ascertain whether such beneficial interests are to be considered beneficiaries’ property and thus whether they are to be shared with, or entirely awarded to, other litigant(s). Contempt of court orders ensure that the court’s directions to produce such evidence will be honoured and followed by the beneficiary, who will then, nolens volens, seek to obtain such information from the foreign trustee or foundation board. However, as the most recent Liechtenstein case law has revealed, this is not as easy and straight-forward as one would think. If the beneficiary is directed by the foreign court to disclose the trust or foundation documents, she or he may become liable for prosecution in Switzerland or Liechtenstein for the violation of somewhat strange, but serious, anti-espionage laws. Concurrently, the trustee or foundation board may not provide information to the beneficiary. Like shipwrecked Odysseus facing sea monsters Scylla and Charybdis, beneficiaries are then caught between two equally unpleasant options and need to venture into and navigate these uncharted waters.
‘If you take a horse to water it usually does drink’—mandatory mediation of trust disputes in New Zealand: Wright v Pitfield [2022] NZHC 385
Authors: Barber Simon
Published: August 2022

Under the Trusts Act 2019, New Zealand’s High Court can compel parties to attend mediation against their will. Some argue that this compulsion is anathema to the voluntary and consensual nature of mediation. Others argue that it is pragmatic—recognising the proven success of mediation and its myriad advantages over litigation. In Wright v Pitfield, a typical family trust dispute between former spouses, the High Court exercised this power for the first time—finding that it was the ‘type of case Parliament had in mind when providing jurisdiction for the Court to require parties to attend mediation’. The question is whether courts will take a similarly liberal approach in more exceptional cases.
Exploratory toxicology studies of 2,3-substituted imidazo[1,2-a]pyridines with antiparasitic and anti-inflammatory properties
Authors: Serrano-Contreras José Iván , Meléndez-Camargo María Estela , Márquez-Flores Yazmín Karina , Soria-Serrano Martha Patricia , Campos-Aldrete María Elena
Published: August 2022

Background

Trichomoniasis and amoebiasis are neglected diseases and still remain as a global health burden not only for developing countries, from where are endemic, but also for the developed world. Previously, we tested the antiparasitic activity of a number of imidazo[1,2-a]pyridine derivatives (IMPYs) on metronidazole-resistant strains of Entamoeba Hystolitica (HM1:IMSS), and Trichomonas Vaginalis (GT3). Their anti-inflammatory activity was also evaluated.

Objective

The present work is a part of a project whose aim is to find new alternatives to standard treatments for these maladies, and to address the current concern of emerging resistant parasite strains. Here we report a non-clinical study focused on exploratory toxicology assays of seven IMPYs that showed the best antiparasitic and/or anti-inflammatory properties.

Methods

Acute, and subacute toxicity tests were carried out. After 14-day oral treatment, liver and kidney functionality assays in combination with chemometric methods were implemented to detect hepatic and/or kidney damage.

Results

Some compounds produced off-target effects. Vehicle effects were also detected. However, no signs of hepatic or renal toxicity were observed for any IMPY.

Conclusion

These compounds can continue non-clinical evaluations, and if possible, clinical trials as new candidates to treat trichomoniasis and amoebiasis, and inflammatory diseases. Further studies are also needed to fully elucidate a proposed dual effect that may exert these molecules against trichomoniasis and amoebiasis, which may also signify a novel mechanism of action to treat these infections.
A Diagnostic Guide for Red Crown Rot of Soybean
Authors: Kleczewski Nathan M. , Bradley Carl A. , Hartman Glen , Kandel Yuba , Mueller Daren , Salamanca Lina Rodriguez
Published: August 2022

Calonectria ilicicola is a soilborne fungus that causes red crown rot on soybeans. This guide describes means for identifying the disease through host symptomology, molecular, and morphological techniques. Methods for isolating, storing, and working with the fungus are described.
Protective effect of inhibiting necroptosis on gentamicin‐induced nephrotoxicity
Authors: Hu Bing‐feng , Gong Qian , Chen Shi‐qing , Yue Lin , Ma Wen‐xian , Wang Fang , Feng Xiao‐wen , Wang Jia‐nan , Li Chao , Liu Ming‐ming , Wang Xue‐fu , Meng Xiao‐ming , Li Jun , Wen Jia‐gen
Published: August 2022

Necroptosis is defined as a novel programmed cell necrosis that is mediated by receptor interacting serine–threonine protein kinase 1 (RIPK1) and other related signals. Necrosis, apoptosis and inflammation are commonly considered as the leading mechanism in acute kidney injury (AKI) induced by gentamicin (GEN), which is a useful antibiotic for treating the infection of Gram‐negative bacterial. However, the necroptosis in the pathogenesis of GEN‐induced AKI is unknown. In this study, to investigate the process and function of necroptosis in GEN‐induced AKI, NRK‐52E and HK‐2 cells and SD rats were used as the models. The necroptosis‐related proteins, including RIPK1, RIPK3, mixed lineage kinase domain‐like (MLKL) and phosphorylated MLKL (p‐MLKL), were all increasing time‐dependently when GEN was continuously given. By using the RIPK1 inhibitor necrostatin‐1 (NEC‐1) and RIPK3 inhibitor (CPD42), the GEN‐induced toxicity of tubular cells was alleviated. Moreover, it was validated that GEN‐induced cell apoptosis and inflammation were attenuated after treating with NEC‐1 or CPD42, both in vivo and in vitro. When MLKL was knocked down by siRNA, NEC‐1 and CPD42 can not further protect the damage of tubular cells by GEN. Although the using of pan‐caspase inhibitor Z‐VAD significantly decreased GEN‐induced apoptosis, it enhanced necroptosis and slightly promoted the decreased cell viability in GEN‐treated cells, with the protective effects weaker than NEC‐1 or CPD42. Finally, in vitro minimum inhibitory concentration (MIC) tests and bacteriostatic ring studies showed that NEC‐1 did not interfere with the antibiotic effects of GEN. Thus, suppressing necroptosis can serve as a promising strategy for the prevention of GEN‐induced nephrotoxicity.
Comparing Learners’ Psychomotor Skills and Anxiety During Standardized Patient Simulation Using Cooperative Versus Individual Practice: A Randomized Controlled Trial
Authors: İlaslan Nagihan , Demiray Ayşe
Published: August 2022

Simulation has become increasingly important in teaching clinical nursing skills. Cooperative simulation practices based on social interdependence theory support skill acquisition by reducing student anxiety through practice. The aim of this experimental study, conducted with 60 junior nursing students, was to compare the effects of cooperative versus individual practice on psychomotor skill performance and student anxiety during simulation with a standardized patient. The results demonstrated that students who performed practice cooperatively had higher psychomotor skills scores and lower anxiety scores.
Research Methodologies in Health Professions Education Publications: Breadth and Rigor
Authors: Han Heeyoung , Youm Julie , Tucker Constance , Teal Cayla R. , Rougas Steven , Park Yoon Soo , J. Mooney Christopher , L. Hanson Janice , Berry Andrea
Published: August 2022

Purpose

Research methodologies represent assumptions about knowledge and ways of knowing. Diverse research methodologies and methodological standards for rigor are essential in shaping the collective set of knowledge in health professions education (HPE). Given this relationship between methodologies and knowledge, it is important to understand the breadth of research methodologies and their rigor in HPE research publications. However, there are limited studies examining these questions. This study synthesized current trends in methodologies and rigor in HPE papers to inform how evidence is gathered and collectively shapes knowledge in HPE.

Method

This descriptive quantitative study used stepwise stratified cluster random sampling to analyze 90 papers from 15 HPE journals published in 2018 and 2019. Using a research design codebook, the authors conducted group coding processes for fidelity, response process validity, and rater agreement; an index quantifying methodological rigor was developed and applied for each paper.

Results

Over half of research methodologies were quantitative (51%), followed by qualitative (28%), and mixed methods (20%). No quantitative and mixed methods papers reported an epistemological approach. All qualitative papers that reported an epistemological approach (48%) used social constructivism. Most papers included participants from North America (49%) and Europe (20%). The majority of papers did not specify participant sampling strategies (56%) or a rationale for sample size (80%). Among those reported, most studies (81%) collected data within 1 year.

The average rigor score of the papers was 56% (SD = 17). Rigor scores varied by journal categories and research methodologies. Rigor scores differed between general HPE journals and discipline-specific journals. Qualitative papers had significantly higher rigor scores than quantitative and mixed methods papers.

Conclusions

This review of methodological breadth and rigor in HPE papers raises awareness in addressing methodological gaps and calls for future research on how the authors shape the nature of knowledge in HPE.