bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Function, An Adjunct to Brain Health Score for Phenotyping Cognitive Function Trajectories in Older Age: Findings From The Irish Longitudinal Study on Ageing (TILDA)
Authors: De Looze Céline , Williamson Wilby , Demnitz Naiara , O’Connor Deirdre , Hernández Belinda , Kenny Rose Anne
Published: January 2022

Background

Evidence is limited regarding the cumulative effect of risk factors on cognitive decline and the added value of physical function for cognitive function trajectory stratification. We operationalize 13 modifiable dementia risk factors in a scoring system and investigate the relationship between this brain health score, combined with simple measures of physical function, and risk of cognitive decline.

Methods

Population-based cohort study of persons aged 50 and older from the Irish Longitudinal Study on Ageing without a history of dementia at baseline who underwent repeated neuropsychological tests (8.08 ± 0.3-year follow-up) were included in the analyses. Exposures were the number of brain health metrics (defined by the Lancet Commission on Dementia Prevention, Intervention, and Care report) at recommended optimal levels. Physical function exposures included Timed Up and Go, dual-task walking speed, and grip strength. Each health metric and physical function measure at the recommended level was assigned a value of 1 and combined to generate brain health scores. Relationship with group-based trajectories of global cognitive function (multidomains composite score), estimated using K-means for longitudinal data, was assessed via ordinal logistic regressions.

Results

Among 2 327 participants (mean age, 61 years; 54% women), each additional optimal metric on the brain health score (odds 0.67 [0.62, 0.73]) was associated with reduced odds of cognitive decline. Adding Timed Up and Go (odds 0.71 [0.59, 0.84]) and dual-task walking speed (odds 0.74 [0.63, 0.89]) further improved model fit (ΔAIC = 14.8).

Conclusion

These findings support the promotion and maintenance of physical function in addition to brain health strategies to reduce the risk of cognitive decline.
Progress Over Time: Significant Changes in the Hungarian Patent Act and the Consequences Thereof
Authors: Cserny András , Geyer-Hirt Dora
Published: January 2022

The Hungarian Parliament recently adopted an amendment to the Hungarian Patent Act (HPA),1 introducing significant changes to the Hungarian patent system from 18 November 2021 and 1 January 2022. These changes affect the bifurcation system, the Bolar exemption and interim injunctions.
Dietary Patterns and Their Association With Symptoms Activity in Inflammatory Bowel Diseases
Authors: Limketkai Berkeley N , Hamideh Mohamed , Shah Rishabh , Sauk Jenny S , Jaffe Nancee
Published: January 2022

Background

Existing studies on diet and inflammatory bowel disease (IBD) have largely focused on evaluating the effects of single nutrients or whole predesigned diets but not on evaluating the effects of diverse dietary patterns. This study applied unsupervised methods to identify dietary patterns of individuals with IBD and evaluated their association with symptoms activity.

Methods

This retrospective study of adults with IBD collected current clinical data and typical diet recalled from the time when in clinical remission. Discrete dietary structures were defined by k-means clustering. Multivariable logistic regression evaluated the relationship between diet clusters and the presence of active symptoms, while adjusting for age, sex, disease duration, disease behavior, and medication use.

Results

Of 691 participants, 36% had Crohn’s disease (CD) and 64% had ulcerative colitis (UC) or IBD-unclassified. Five major dietary clusters were identified: 2 resembled a Western diet (WD) (WD1, WD2), 1 resembled a balanced diet, and 2 resembled a plant-based diet (PB) (PB1, PB2). Compared with WD1, PB2 was associated with lower odds of active symptoms for CD (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.83) and UC (OR, 0.31; 95% CI, 0.15-0.62). PB1 was associated with lower odds of active symptoms for participants with UC (OR, 0.45; 95% CI, 0.23-0.90) but not for participants with CD (OR, 0.95; 95% CI, 0.36-2.51).

Conclusions

Diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with CD.
Timing of maternal supplementation of dried distillers grains during late gestation influences postnatal growth, immunocompetence, and carcass characteristics ofBos indicus-influenced beef calves
Authors: Palmer Elizabeth A , Vedovatto Marcelo , Oliveira Rhaiza A , Ranches Juliana , Vendramini Joao M B , Poore Matthew H , Martins Thiago , Binelli Mario , Arthington John D , Moriel Philipe
Published: January 2022

This 2-yr study investigated the timing of dried distillers grains (DDG) supplementation during the third trimester of gestation of Bos indicus-influenced beef cows and its impact on their offspring performance. On day 0 of each year (84 d before calving), Brangus cows (n = 84/yr; cow age = 8 ± 3 yr) were stratified by initial body weight (BW; 482 ± 75 kg) and body condition score (BCS; 5.3 ± 0.8) and assigned randomly to one of six bahiagrass (Paspalum notatum) pastures (experimental units; 14 cows/pasture). Treatments were assigned randomly to pasture (2 pastures/treatment/yr) and consisted of no prepartum supplementation (CON), 2 kg/d of DDG from day 0 to 42 (LATE42), or 1 kg/d of DDG from day 0 to 84 (LATE84). Following calving (day 84), cow–calf pairs remained in their respective pastures, and cows were offered sugarcane molasses + urea (1.82 kg of dry matter/cow/d) from day 85 until the end of the breeding season (day 224). On day 347, steer calves (n = 38/yr; 11 to 15 steers/treatment/yr) were weaned and transported to the feedlot (1,193 km). Steers were penned according to cow prepartum pasture and managed similarly until the time of harvest. BCS at calving was greater (P < 0.01) for LATE42 and LATE84 vs. CON cows but did not differ (P = 0.16) between LATE42 and LATE84 cows. Calving date, calving percentage, and birth BW of the first offspring did not differ (P ≥ 0.22) among treatments. However, LATE42 cows calved their second offspring 8 d earlier (P = 0.04) compared with CON and LATE84 cows. At weaning (first offspring), LATE84 calves were the heaviest (P ≤ 0.05), CON calves were the lightest, and LATE42 calves had intermediate BW (P ≤ 0.05). Steer plasma concentrations of cortisol and haptoglobin and serum bovine viral diarrhea virus type-1 titers did not differ (P ≥ 0.21) between treatments. Steer serum parainfluenza-3 titers were greater (P = 0.03) for LATE42 vs. CON steers, tended to be greater (P = 0.10) for LATE84 compared with CON steers, and did not differ (P = 0.38) between LATE42 and LATE84 steers. Steer feedlot BW, average daily gain, dry matter intake, and hot carcass weight did not differ (P ≥ 0.36) between treatments. Marbling and the percentage of steers grading choice were greater (P ≤ 0.04) for LATE42 vs. CON steers, whereas LATE84 steers were intermediate. In summary, different timing of DDG supplementation during the third trimester of gestation could be explored to optimize cow BCS and offspring preweaning growth and carcass quality.
Productivity and the Welfare of Nations
Authors: Basu Susanto , Pascali Luigi , Schiantarelli Fabio , Serven Luis
Published: January 2022

We show that the welfare of a country’s infinitely lived representative consumer is summarized, to a first order, by total factor productivity (TFP), appropriately defined, and by the capital stock per capita. The result holds for both closed and open economies, regardless of the type of production technology and the degree of product market competition. Welfare-relevant TFP needs to be constructed with prices and quantities as perceived by consumers, not firms. Thus, factor shares need to be calculated using after-tax wages and rental rates. We use these results to calculate welfare gaps and growth rates in a sample of developed countries with high-quality data on output, hours worked, and capital. We also present evidence for a broader sample that includes both developed and developing countries.
Entity alignment via summary and attribute embeddings
Authors: Munne Rumana Ferdous , Ichise Ryutaro
Published: January 2022

Entity alignment is the task of integrating heterogeneous knowledge among different knowledge graphs (KGs). KG is a popular way of storing facts about real-world entities. Unfortunately, a very limited number of the entities stored in different KGs are aligned. This paper presents an embedding-based entity alignment method that finds entity alignment by measuring the similarities between entity embeddings. Existing methods mainly focus on the relational structures and attributes information for the alignment process. Such methods fail while the entities have a fewer number of attributes or when the relational structure could not capture the meaningful representation of the entities. To address this problem, we propose EASAE, an entity alignment method using summary and attribute embeddings. We exploit the entity summary information available in KGs for entities’ summary embedding. To learn the semantics of the entity summary, we employ bidirectional encoder representations from transformers (BERT). Our model learns the representations of entities by using relational triples, attribute triples and summary as well. We perform experiments on real-world datasets, and the results indicate that the proposed approach outperformed the state-of-the-art models for entity alignment.
Current State of Funded National Cancer Institute Grants That Include Economic Analyses
Authors: Halpern Michael T , McCarthy Sharon , Tuovinen Priyanga
Published: January 2022

Background

Health economics research is an integral part of the transdisciplinary research supported by the National Cancer Institute (NCI). To better understand NCI activities in this area, we conducted a portfolio analysis of funded NCI grants including health economics research.

Methods

We examined all competitive grants funded by NCI from fiscal years 2015 to 2020 that included economic analyses or outcomes. Grant titles, abstracts, and specific aims were independently reviewed by 2 study team members; content of included grants was then coded for analysis.

Results

A total 212 grants were identified from searches; 146 of these included economic analyses and were included in the portfolio analysis. These 146 grants represent approximately 0.9% of all NCI competitively funded grants awarded 2015-2020. Of these grants, 100 were R01 awards, representing approximately 2.4% of all NCI R01 grants funded 2015-2020. The most common study type was interventional randomized controlled-trial, followed by simulation or model. Screening and prevention were the most frequent grant cancer continuum topic; survivorship was included in only 16 grants (11.0%). Cost-effectiveness analysis was the most frequently listed economic outcome (97 grants, 66.4%), whereas policy impact (20 grants, 13.7%) and financial hardship (15 grants, 10.3%) were less-frequently included economic outcomes. However, economic outcomes differed by cancer control continuum topic, with financial hardship being included in a greater proportion of treatment and survivorship grants.

Conclusions

Although relatively small, the NCI portfolio of funded grants including economic analyses is diverse, covering a range of cancer types, methods, and economic outcomes, and increasing over time.
Civil Society Networks and Malaysian Government Reform: Considering Issue Homophily in Interorganizational Relationships
Authors: Sommerfeldt Erich J , Saffer Adam J , Luoma-aho Vilma
Published: January 2022

While communication research on interorganizational homophily has grown, little is known about how issue homophily—defined here as the propensity to form ties based on shared issue priorities—influences interorganizational relationships in civil society. Our theoretical framework brings together homophily research and issue niche theory to explore the potential influence issues have on interorganizational network tie formation. Our empirical case is the network of civil society organizations focused on government reform in Malaysia. Using data gathered from a survey with organizational leaders (n = 90), exponential random graph models with binary and valued data explored how two types of homophily are associated with tie formation and cooperation in interorganizational relationships. Key findings from the study include that more important issues appear to drive tie formation and levels of cooperation in the network, only specific issues lead to homophilous ties, and issue homophily does not lead to greater levels of cooperation among civil society organizations.
Three cases of retroperitoneal sarcoma in which bioabsorbable spacers (bioabsorbable polyglycolic acid spacers) were inserted prior to carbon ion radiotherapy
Authors: Serizawa Itsuko , Kusano Yohsuke , Kano Kio , Shima Satoshi , Tsuchida Keisuke , Takakusagi Yosuke , Mizoguchi Nobutaka , Kamada Tadashi , Yoshida Daisaku , Katoh Hiroyuki
Published: January 2022

From August 2019 to August 2020, we inserted polyglycolic acid (PGA) spacers and administered carbon ion radiotherapy (CIRT) to three cases of retroperitoneal sarcoma at our hospital. We aimed to investigate its utility and safety for retroperitoneal sarcoma. We analyzed changes in PGA spacer volume and corresponding computed tomography (CT) values in addition to the dose distribution using in-room CT images that were obtained during treatment. We assessed adverse events and investigated the suitability, safety and effectivity of PGA spacer insertion. During treatment, changes in PGA spacer volumes and CT values were confirmed. Volumes increased in patients with a folded PGA spacer, and it increased 1.6-fold by the end of irradiation compared with planning CT. The CT values decreased by 20–50 Hounsfield units at the end of irradiation compared to the planning CT. Dose distribution evaluation showed that the dose to the gastrointestinal tract adjacent to the tumor was maintained below the tolerable dose, and a sufficient dose was delivered to the target by PGA spacer insertion. One case of subileus caused during abdominal surgery for PGA spacer insertion occurred. No other adverse events, such as digestive disorders, were observed. CIRT with PGA spacer insertion for retroperitoneal sarcomas is safe and effective. For cases in which there is no option but to perform irradiation using a PGA spacer, precautionary measures such as verification of dose distributions using CT images are necessary.
Large-scale gas flows and streaming motions in simulated spiral galaxies
Authors: Ramón-Fox F G , Bonnell I A
Published: January 2022

From a galactic perspective, star formation occurs on the smallest scales within molecular clouds, but it is likely initiated from the large-scale flows driven by galactic dynamics. To understand the conditions for star formation, it is important to first discern the mechanisms that drive gas from large scales into dense structures on the smallest scales of a galaxy. We present high-resolution smoothed particle hydrodynamics simulations of two model spiral galaxies: one with a live stellar disc (N-body) and one with a spiral potential. We investigate the large-scale flows and streaming motions driven by the simulated spiral structure. We find that the strength of the motions in the radial direction tends to be higher than in the azimuthal component. In the N-body model, the amplitude of these motions decreases with galactocentric radius whereas for the spiral potential, it decreases to a minimum at the corotation radius, and increases again after this point. The results show that in both simulations, the arms induce local shocks, an increase in kinetic energy that can drive turbulence and a means of compressing and expanding the gas. These are all crucial elements in forming molecular clouds and driving the necessary conditions for star formation.
Formation of ultra-massive carbon–oxygen white dwarfs from the merger of carbon–oxygen and helium white dwarf pairs
Authors: Wu Chengyuan , Xiong Heran , Wang Xiaofeng
Published: January 2022

Ultra-massive white dwarfs (UMWDs) with masses larger than 1.05M⊙ are basically believed to harbour oxygen–neon (ONe) cores. Recently, Gaia data have revealed an enhancement of UMWDs on the Hertzsprung–Russell diagram (HRD), which indicates that an extra cooling delay mechanism such as crystallization and elemental sedimentation may exist in UMWDs. Further studies have suggested that some UMWDs should have experienced fairly long cooling delays, implying that they are carbon–oxygen (CO) WDs. However, the formation mechanism of these UMCOWDs is still under debate. In this work, we investigate whether the mergers of massive CO WDs with helium WDs (He WDs) can evolve to UMCOWDs. By employing the stellar evolution code mesa, we construct double WD merger remnants to investigate their final fates. We found that the post-merger evolution of the remnants is similar to R CrB stars. The helium burning of the He shell leads to mass growth of the CO core at a rate of 2.0 × 10−6–$5.0\times {10}^{-6}\, {\rm M}_\odot \, \rm {yr}^{-1}$. The final CO WD mass is influenced by the wind mass-loss rate during the post-merger evolution, and cannot exceed about 1.2M⊙. Remnants with core masses larger than $1.2\, {\rm M}_\odot$ will experience surface carbon ignition, which may finally end their lives as ONe WDs. The current results imply that at least some UMWDs that experience extra-long cooling delays may stem from the merging of CO WDs and He WDs.
Trailed source extraction with template matching
Authors: Du Junju , Hu Shaoming , Chen Xu , Cao Hai
Published: January 2022

In optical observations of moving targets, field stars can be trailed when the telescope tracks at the speed of the targets. When these trailed sources are relatively long, faint, or distorted, the popular source extraction techniques, such as thresholding and profile fitting, tend to fail. We present a new source extraction strategy based on the template-matching method. We described the pipeline of template matching in detail and tested its performance compared with thresholding on 9 × 4320 synthetic images and 349 real images. The indicators, including recall, position extraction error, and flux extraction error, are analysed and given. The results show that template matching can obtain higher recalls and smaller position and flux extraction errors for trailed sources.
Evolution of Amino Acid Propensities under Stability-Mediated Epistasis
Authors: Youssef Noor , Susko Edward , Roger Andrew J , Bielawski Joseph P
Published: January 2022

Site-specific amino acid preferences are influenced by the genetic background of the protein. The preferences for resident amino acids are expected to, on average, increase over time because of replacements at other sites—a nonadaptive phenomenon referred to as the “evolutionary Stokes shift.” Alternatively, decreases in resident amino acid propensity have recently been viewed as evidence of adaptations to external environmental changes. Using population genetics theory and thermodynamic stability constraints, we show that nonadaptive evolution can lead to both positive and negative shifts in propensities following the fixation of an amino acid, emphasizing that the detection of negative shifts is not conclusive evidence of adaptation. By examining propensity shifts from when an amino acid is first accepted at a site until it is subsequently replaced, we find that ≈50% of sites show a decrease in the propensity for the newly resident amino acid while the remaining sites show an increase. Furthermore, the distributions of the magnitudes of positive and negative shifts were comparable. Preferences were often conserved via a significant negative autocorrelation in propensity changes—increases in propensities often followed by decreases, and vice versa. Lastly, we explore the underlying mechanisms that lead propensities to fluctuate. We observe that stabilizing replacements increase the mutational tolerance at a site and in doing so decrease the propensity for the resident amino acid. In contrast, destabilizing substitutions result in more rugged fitness landscapes that tend to favor the resident amino acid. In summary, our results characterize propensity trajectories under nonadaptive stability-constrained evolution against which evidence of adaptations should be calibrated.
Transcriptomic analysis identifies candidate genes for shell colour formation in the Venus clamCyclina sinensis
Authors: Wei Min , Zhang Mingyue , Wu Yuchen , Wang Yiwo , Qiu Pan , Zhang Jiawen , Wu Lei , Song Jie , Sun Yuxuan , Tan Leilei , Yu Xue , Liu Yu , Dong Zhiguo
Published: January 2022

Some bivalves are important in fisheries and aquaculture, and provide significant economic benefits to humans. The diversity in shell colour among bivalves has received attention due to its potential in breeding and its relevance to the study of speciation and adaptation. In this study, the relationship between whole-genome-scale gene expression and shell coloration in the clam Cyclina sinensis was analysed using high-throughput Illumina sequencing technology. A total of 15,367 annotated genes and 4,425 novel genes were detected based on transcript assembly. The results of the transcriptome analysis show that 49 genes were differentially expressed in the outer mantle fold tissue of purple- vs white-shelled specimens. These genes include three lipoprotein receptor genes, low-density lipoprotein receptor gene (ldlr), low-density lipoprotein receptor-related protein 4 (lrp4) and scavenger receptor cysteine-rich protein gene (srcr). These genes may be involved in the transport of carotenoid pigments. Moreover, as shown by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, several receptor activity terms and a glycosphingolipid biosynthesis pathway were detected, and these might be involved in shell coloration. Together with the analyses of differentially expressed genes, our results suggest a possible molecular mechanism governing the selective transport of carotenoids in the mantle of purple-shelled clams and shell colour formation. The results of this study may help to elucidate the colour formation mechanism in clam shells.
spatzie: an R package for identifying significant transcription factor motif co-enrichment from enhancer–promoter interactions
Authors: Hammelman Jennifer , Krismer Konstantin , Gifford David K
Published: January 2022

Genomic interactions provide important context to our understanding of the state of the genome. One question is whether specific transcription factor interactions give rise to genome organization. We introduce spatzie, an R package and a website that implements statistical tests for significant transcription factor motif cooperativity between enhancer–promoter interactions. We conducted controlled experiments under realistic simulated data from ChIP-seq to confirm spatzie is capable of discovering co-enriched motif interactions even in noisy conditions. We then use spatzie to investigate cell type specific transcription factor cooperativity within recent human ChIA-PET enhancer–promoter interaction data. The method is available online at https://spatzie.mit.edu.
The low-resolution structural models of hepatitis C virus RNA subdomain 5BSL3.2 and its distal complex with domain 3′X point to conserved regulatory mechanisms within the Flaviviridae family
Authors: Castillo-Martínez Jesús , Fan Lixin , Szewczyk Mateusz P , Wang Yun-Xing , Gallego José
Published: January 2022

Subdomain 5BSL3.2 of hepatitis C virus RNA lies at the core of a network of distal RNA–RNA contacts that connect the 5′ and 3′ regions of the viral genome and regulate the translation and replication stages of the viral cycle. Using small-angle X-ray scattering and NMR spectroscopy experiments, we have determined at low resolution the structural models of this subdomain and its distal complex with domain 3′X, located at the 3′-terminus of the viral RNA chain. 5BSL3.2 adopts a characteristic ‘L’ shape in solution, whereas the 5BSL3.2–3′X distal complex forms a highly unusual ‘Y’-shaped kissing junction that blocks the dimer linkage sequence of domain 3′X and promotes translation. The structure of this complex may impede an effective association of the viral polymerase with 5BSL3.2 and 3′X to start negative-strand RNA synthesis, contributing to explain the likely mechanism used by these sequences to regulate viral replication and translation. In addition, sequence and shape features of 5BSL3.2 are present in functional RNA motifs of flaviviruses, suggesting conserved regulatory processes within the Flaviviridae family.
Brexit and Japanese foreign direct investment in the UK: a sectoral analysis
Authors: Cieślik Andrzej , Ryan Michael
Published: January 2022

Political and economic stability significantly affect the economic performance of a country and its ability to attract inward investment. This article investigates Brexit-associated uncertainty and Japanese foreign direct investment (FDI) inflows into the UK. In contrast to most previous studies that use pre-vote behaviour to model post-vote outcomes, we include both pre- and post-announcement and post-vote data on Japanese firm-level FDI activity into Europe. In a Knowledge-Capital framework, we examine the annual count of newly established Japanese foreign affiliates into 80 countries between the years 1995 and 2019. Results from a negative binomial model reveal a statistically significant relationship between the Brexit announcement and decreased FDI in the UK. Our results identify significant sectoral heterogeneity, indicating the difficulty in making broad claims as to Brexit’s effect on the British economy’s future.
Real-world Impact of Age at Diagnosis on Treatment Patterns and Survival Outcomes of Patients with Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Elias Rawad , Cockrum Paul , Surinach Andy , Wang Shu , Chul Chu Bong , Shahrokni Armin
Published: January 2022

Background

Sixty-eight percent of patients with pancreatic ductal adenocarcinoma (PDAC) are 65 years and older. Older adults are under-represented in clinical trials and their care is complicated with multiple age-related conditions. Research suggests that older patients can experience meaningful responses to treatment for PDAC. The objective of this study was to evaluate the characteristics, rate of treatment, and survival outcomes of patients with metastatic PDAC (mPDAC) based on age at diagnosis.

Materials and Methods

Data were extracted for patients diagnosed with mPDAC between January 1, 2015, and March 31, 2020, from the Flatiron Health database. Patients were stratified into 3 age groups: <70 years old, 70-79 years, and ≥80 years. The proportion of patients who received first-line therapy, the types of regimens received in the metastatic setting, overall survival (OS) from the start of treatment were evaluated.

Results

Of the 8382 patients included, 71.3% (n = 5973) received treatment. Among patients who received treatment 55.5% (n = 3313) were aged <70 years at diagnosis, 33.0% (n = 1972) were 70-79 years, and 11.5% (n = 688) were ≥80 years. Patients ≥80 years of age were more likely to receive gemcitabine monotherapy and less likely to receive FOLFIRINOX. Among first-line treated patients, median OS significantly decreased with age. However, when comparing patients treated with the same first-line regimen, no significant differences in median OS were observed by age.

Conclusions

This study highlights that older adults with mPDAC can benefit substantially by receiving appropriate levels of treatment.
Shaping successful mega-project investments
Authors: Coyle Diane
Published: January 2022

Many countries are proposing major public infrastructure investment, addressing the net zero imperative and need to recover from the pandemic. Yet the investments will deliver on these policy goals only if appraisals take account of strategic complementarities in determining the future path of the economy, including technological choices. Cost–benefit analysis as currently applied is unable to do this, even when incorporating wider economic benefits. Furthermore, in purporting to be a technical tool, it fails to acknowledge the inevitable political judgements and distributional consequences involved in selecting projects. There is a need for an approach to appraisal that identifies when major projects have transformational potential, and an approach to policy that ensures complementary investments occur, by tackling coordination failures either among different policy actors or between private- and public-sector activities.
Rapid stomatal closure contributes to higher water use efficiency in major C4 compared to C3 Poaceae crops
Authors: Ozeki Kengo , Miyazawa Yoshiyuki , Sugiura Daisuke
Published: January 2022

Understanding water use characteristics of C3 and C4 crops is important for food security under climate change. Here, we aimed to clarify how stomatal dynamics and water use efficiency (WUE) differ in fluctuating environments in major C3 and C4 crops. Under high and low nitrogen conditions, we evaluated stomatal morphology and kinetics of stomatal conductance (gs) at leaf and whole-plant levels in controlled fluctuating light environments in four C3 and five C4 Poaceae species. We developed a dynamic photosynthesis model, which incorporates C3 and C4 photosynthesis models that consider stomatal dynamics, to evaluate the contribution of rapid stomatal opening and closing to photosynthesis and WUE. C4 crops showed more rapid stomatal opening and closure than C3 crops, which could be explained by smaller stomatal size and higher stomatal density in plants grown at high nitrogen conditions. Our model analysis indicated that accelerating the speed of stomatal closure in C3 crops to the level of C4 crops could enhance WUE up to 16% by reducing unnecessary water loss during low light periods, whereas accelerating stomatal opening only minimally enhanced photosynthesis. The present results suggest that accelerating the speed of stomatal closure in major C3 crops to the level of major C4 crops is a potential breeding target for the realization of water-saving agriculture.
Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study
Authors: Tanaka Yoshiya , Yamaguchi Ayako , Miyamoto Toshiaki , Tanimura Kazuhide , Iwai Hideyuki , Kaneko Yuko , Takeuchi Tsutomu , Amano Koichi , Iwamoto Naoki , Kawakami Atsushi , Murakami Miho , Nishimoto Norihiro , Atsumi Tatsuya , Sumida Takayuki , Ohmura Koichiro , Mimori Tsuneyo , Yamanaka Hisashi , Fujio Keishi , Fujino Yoshihisa , Saito Kazuyoshi , Nakano Kazuhisa , Hirata Shintaro , Nakayamada Shingo
Published: January 2022

Objective

To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission.

Methods

At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at <2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs. At end of year 1, patients who achieved DAS28(ESR) <3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR) <2.6 at year 1 and 2, respectively.

Results

Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) <2.6 (continuation, 85.2%; MTX dose reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD dose reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR) <2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARDs. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group.

Conclusions

After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.
Effect of drinker type on water disappearance of nursery pigs
Authors: Vande Pol Katherine D , Grohmann Nicholas S , Weber Thomas E , Ritter Matthew J , Ellis Michael
Published: January 2022

This study was conducted to evaluate the water disappearance of nursery pigs (from weaning to 6 wk post-weaning; 6.4 ± 1.07 to 22.0 ± 3.39 kg live body weight) using a randomized complete block design to compare two Drinker Type treatments: Nipple vs. Cup. A total of 336 pigs housed in 16 pens with 21 pigs per pen in 2 rooms (8 pens per room) were used. Pens had fully-slatted concrete floors; floor space was 0.32 m2/pig and there was one feeder and one drinker per pen. Pigs were fed corn-soybean–based diets formulated to meet or exceed nutrient requirements. Pigs and feeders were weighed at the start and end of the study. Water disappearance was measured using a water-flow meter fitted to the water pipeline supplying the drinker in each pen. For the overall study period, Drinker Type did not affect (P > 0.05) growth performance; however, average daily water disappearance was greater (P < 0.05) for Nipple than Cup drinkers (2.74 and 2.25 liters/d, respectively; SEM = 0.139). Water to feed disappearance ratio was greater (P < 0.05) for the Nipple than the Cup treatment (5.23 vs. 4.22 liters:kg, respectively; SEM = 0.263). These results suggest that water disappearance from nipple drinkers was greater than for cup drinkers. The lack of an effect of Drinker Type treatment on pig growth performance suggests that the treatment difference for water disappearance was most likely due to greater water wastage for the nipple drinkers rather than any effect on water intake per se.
Gut-Selective Design of Orally Administered Izencitinib (TD-1473) Limits Systemic Exposure and Effects of Janus Kinase Inhibition in Nonclinical Species
Authors: Hardwick Rhiannon N , Brassil Patrick , Badagnani Ilaria , Perkins Kimberly , Obedencio Glenmar P , Kim Andrea S , Conner Michael W , Bourdet David L , Harstad Eric B
Published: January 2022

Izencitinib (TD-1473), an oral, gut-selective pan-Janus kinase (JAK) inhibitor under investigation for treatment of inflammatory bowel diseases, was designed for optimal efficacy in the gastrointestinal tract while minimizing systemic exposures and JAK-related safety findings. The nonclinical safety of izencitinib was evaluated in rat and dog repeat-dose and rat and rabbit reproductive and developmental toxicity studies. Systemic exposures were compared with JAK inhibitory potency to determine effects at or above pharmacologic plasma concentrations (≥1× plasma average plasma concentration [Cave]:JAK 50% inhibitory concentration [IC50] ratio). In rats and dogs, 1000 and 30 mg/kg/day izencitinib, respectively, produced minimal systemic findings (ie, red/white cell changes) and low systemic concentrations (approximately 1× plasma Cave:JAK IC50 ratio) with an 8× nonclinical:clinical systemic area under the curve (AUC) margin compared with exposures at the highest clinically tested dose (300 mg, quaque die, once daily, phase 1 study in healthy volunteers). In dogs, it was possible to attain sufficient systemic exposures to result in immunosuppression characteristic of systemic JAK inhibition, but at high AUC margins (43×) compared with systemic exposures observed at the highest tested dose in humans. No adverse findings were observed in the gastrointestinal tract or systemic tissues. Izencitinib did not affect male or female fertility. Izencitinib did not affect embryonic development in rats and rabbits as commonly reported with systemic JAK inhibition, consistent with low maternal systemic concentrations (2–6× plasma Cave:JAK IC50 ratio, 10–33× nonclinical:clinical AUC margin) and negligible fetal exposures. In conclusion, the izencitinib gut-selective approach resulted in minimal systemic findings in nonclinical species at pharmacologic, clinically relevant systemic exposures, highlighting the impact of organ-selectivity in reducing systemic safety findings.
Enablers and barriers towards ensuring routine immunization services during the COVID-19 pandemic: findings from a qualitative study across five different states in India
Authors: Patel Kripalini , Nayak Bhagyashree , Rana Salaj , Krishnan Parthiban , Tandale Babasaheb Vishwanath , Basak Surajit , Sinha Abhik , Kumar Muthusamy Santhosh , Borah Prasant , Singh Harpreet , Gupta Nivedita , Dutta Shanta , Mohan Aswini , Das Manuj K , Landge Yovhan , Ganguly Bappaditya , Devi Utpala , Pati Sanghamitra , Palo Subrata Kumar
Published: January 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has led to disruption in delivering routine healthcare services including routine immunization (RI) worldwide. Understanding the enablers and barriers for RI services during a pandemic is critically important to develop context-appropriate strategies to ensure uninterrupted routine services.

Methods

A community-based, cross-sectional descriptive study was conducted in five different states of India, nested within an ongoing multicentric study on RI. Telephone in-depth interviews among 56 health workers were carried out and the data were analyzed using a content analysis method.

Results

During the COVID-19 pandemic, healthcare providers encountered many challenges at the health system, community and individual level when rendering RI services. Challenges like the limited availability of personal protective equipment and vaccines, deployment for COVID-19 duty at system level, the difficulty in mobilizing people in the community, fear among people at community level, mobility restrictions and limited family support, as well as the stress and stigma at individual level, were barriers to providing RI services. By contrast, the issuing of identification cards to health staff, engaging community volunteers, the support given to health workers by their families and training on COVID-19, were factors that enabled health workers to maintain RI services during the pandemic.

Conclusions

When addressing the COVID-19–related public health emergency, we should not lose sight of the importance of services like RI.
Comparison of Ticagrelor With Clopidogrel in East Asian Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Ma Ying , Zhong Peng-Yu , Shang Yao-Sheng , Bai Nan , Niu Ying , Wang Zhi-Lu
Published: January 2022

The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33–1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15–2.12; P = 0.004), and dyspnea (RR 2.60; 1.68–4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19–0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64–1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79–7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60–0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65–1.23; P = 0.49), and stroke (RR 0.84; 0.47–1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).
Poorly Differentiated Chordoma of the Clivus With Loss of SMARCB1 Expression in a Pediatric Patient: A Case Report
Authors: Yasue Shiho , Ozeki Michio , Endo Saori , Kanayama Tomohiro , Suzui Natsuko , Nakamura Sayaka , Kishimoto Kenji , Kosaka Yoshiyuki , Miyazaki Tatsuhiko , Demizu Yusuke , Soejima Toshinori , Kawamura Atsufumi , Ohnishi Hidenori
Published: January 2022

Poorly differentiated chordoma (PDC) is a rare, aggressive subtype of chordoma. A two-year-old girl presented with cervical pain, limb paralysis and respiratory failure. Magnetic resonance imaging and positron emission tomography-computed tomography revealed a tumor compressing the pons at the clivus and osteoblastic metastatic lesions of the left upper arm and right iliac bone. Her tumors shrank substantially after treatment with chemotherapy and proton beam therapy. Our initial diagnosis was an atypical teratoma/rhabdoid tumor, but final diagnosis of PDC was made on the basis of the immunohistochemical expression of brachyury. In addition, the detection of SMARCB1/INI1 mutation confirmed the diagnosis of PDC.
Epstein-Barr Virus in Childhood and Adolescent Classic Hodgkin Lymphoma in a French Cohort of 301 Patients
Authors: Pereira Victor , Boudjemaa Sabah , Besson Caroline , Leblanc Thierry , Rigaud Charlotte , Leruste Amaury , Garnier Nathalie , Lambilliotte Anne , Simonin Matthieu , Curtillet Catherine , Bonneau-Lagacherie Jacinthe , Coulomb Aurore , Landman-Parker Judith
Published: January 2022

Objective:

The aim was to analyze the role of Epstein-Barr virus (EBV) in the bioclinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France.

Methods:

Biopathologic data of 301 patients treated for a cHL in/or according to the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed.

Results:

Median age at diagnosis was 14 (3 to 18) years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV positivity by in situ hybridization was observed for 68/301 (23%) patients, significantly associated with mixed cellularity subtype and male sex, particularly overrepresented in boys below 10 years: 15/23 (65%) versus 28/139 among other male patients (20%). EBV viral load was detectable in 22 of 108 (22%) tested cases and was overrepresented in EBV cHL (13/28) versus non-EBV cHL (9/80) patients. Detailed semiquantitative histologic analysis showed a high number of B-cell residual follicles in EBV cHL relative to EBV-negative HL.

Conclusion:

Distribution of EBV cHL in children and adolescents is associated with young age and male sex, suggesting a specific physiopathology and may require a differential therapeutic approach.
Gemtuzumab Ozogamicin Followed by Unrelated Cord Blood Transplantation With Reduced-intensity Conditioning for a Child With Refractory Acute Promyelocytic Leukemia
Authors: Yamada Yuji , Osumi Tomoo , Kato Motohiro , Shioda Yoko , Kiyotani Chikako , Terashima Keita , Hayakawa Akira , Iijima-Yamashita Yuka , Horibe Keizo , Matsumoto Kimikazu , Tomizawa Daisuke
Published: January 2022

There is no established treatment for patients with acute promyelocytic leukemia (APL) refractory to targeted therapies with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). We report here a case of an 8-month-old girl with APL who failed standard ATRA-combined chemotherapy. Although molecular remission was achieved after introducing ATRA/ATO combination therapy, molecular relapse occurred during the ATO consolidation courses. Subsequent molecular remission was rapidly achieved after administering 2 doses of gemtuzumab ozogamicin. She was successfully treated with unrelated cord blood transplantation using reduced-intensity conditioning. Gemtuzumab ozogamicin might be a preferable choice for patients with APL refractory to standard therapy.
Myeloablative Conditioning Regimen in Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide in Children With High-risk Hematologic Malignancies
Authors: Dufort y Alvarez Gustavo
Published: January 2022

Limited information is available on outcomes of haploidentical stem cell transplantation (haploSCT) with posttransplant cyclophosphamide using myeloablative conditioning regimens in children and adolescents. We report the results of a single-institution retrospective study of myeloablative haploSCT in 36 children and adolescents (median age, 8 y; range, 9 mo to 22 y) with high-risk hematologic malignancies. Donor engraftment occurred in 31 of 33 evaluable patients (94%). Recovery of neutrophils and platelets occurred at a median of 15 and 20 days. Cumulative incidence of acute graft-versus-host-disease (GVHD) grades II to IV and grades III to IV at 100 days was 36±8.7% and 10±5.4% and of chronic GVHD at 1 year was 55±9.2%, with 31±8.6% moderate to severe. Nonrelapse mortality was 16±6.1% and 22±6.9% at 100 days and 1 year. The cumulative incidence of relapse at 4 years was 32±8.8%. With a median follow-up of 57 months (range, 8 to 89 mo), the overall survival and event-free survival at 4 years was 55.6±8.7% and 44.8±8.5%. Myeloablative conditioning T-replete haploSCT with posttransplant cyclophosphamide is a viable alternative to matched unrelated transplantation for children and adolescents with high-risk hematologic malignancies. The high rates of nonrelapse mortality and chronic GVHD is a concern and deserves careful consideration.
Suspected Drug-induced Liver Injury Due to 6-Mercaptopurine With a Superimposed SARS-CoV-2 Infection in a Patient With B-ALL
Authors: Cablay Kory , Borowicz Violet M. , Fulton Ryan
Published: January 2022

6-mercaptopurine is a chemotherapeutic drug that exhibits hepatotoxic effects due to its toxic metabolites. This report describes a case of suspected drug-induced liver injury exacerbated by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 16-year-old male with very high risk B-cell acute lymphoblastic leukemia was admitted for hyperbilirubinemia 2 months after a 6-mercaptopurine dosage increase and found to have an active SARS-CoV-2 infection. Liver function improved throughout hospitalization and the patient was discharged on allopurinol. Following liver function after a dosage increase of hepatoxic chemotherapy and in a pediatric oncology patient with an active SARS-CoV-2 infection undergoing treatment is vital due to potential liver impact.