bluuebunny/crossref_metadata_2025 huggingface dataset:
Petroselinum crispum, a commonly consumed food, affects sirolimus level in a renal transplant recipient: a case report
Authors: Kurtaran Melek , Koc Neriman Sila , Aksun Melek Seren , Yildirim Tolga , Yilmaz Şeref Rahmi , Erdem Yunus
Published: April 2021

Sirolimus is an immunosuppressive drug used to prevent graft rejection. Therapeutic drug monitoring is required as with other immunosuppressive drugs. Previous studies have shown the interactions between sirolimus and drugs that affect the activity of cytochrome P450 3A4 and P-glycoprotein. There is an increasing tendency for the use of herbal remedies in many countries. Medicinal herbs are rich sources of natural bioactive compounds that could interact with drugs. Parsley, Petroselinum crispum, is a food, spice, and also a medicinal herb. We report a case of a renal transplant recipient who had a supratherapeutic blood level of sirolimus due to consuming excessive parsley to highlight a possible herb–drug interaction. This is the first case report describing sirolimus–parsley interaction. Herb–drug interactions are especially important for drugs with a narrow therapeutic window. For this reason, healthcare professionals should question all patients, especially transplant patients, about the use of herbs or herbal products and report interactions.

Plain Language Summary

Parsley, a commonly consumed food, affects the level of an important drug in a renal transplant recipient: A case report Sirolimus is a drug that suppresses the immune response used to prevent organ rejection in people who have had kidney transplants. In order to reach the optimum balance between therapeutic efficacy and adverse effects, sirolimus blood levels should be closely monitored. Previous studies have shown the interactions between sirolimus and drugs that affect the activities of metabolizing enzymes and transporter proteins. Parsley is a food, spice, and also a medicinal herb. Medicinal herbs are rich sources of natural bioactive compounds that could interact with a prescription drug. We report a case of a renal transplant recipient who had a rise in the blood level of sirolimus due to the ingestion of an excessive amount of parsley to highlight possible herb–drug interaction.
An Empirical Study of Hospital’s Outpatient Loyalty From a Medical Center in Taiwan
Authors: Chao Shu-Hui , Chen Mu-Kuan , Wu Hsin-Hung
Published: April 2021

In a highly competitive medical industry, hospitals can continue to create medical values and competitive advantages using data mining technologies to identify patients’ needs and provide the medical services needed by various patients. This research focuses on the outpatients in a medical center in Taiwan and adopts recency, frequency, and monetary (RFM) model, self-organizing maps, and K-means method to construct a set of data exploration procedures so that the hospital can use the reference to deal with the related patient management issues, where R, F, and M measure the RFM spent for each outpatient in Year 2016. The results show that 321,908 outpatients can be classified into 12 groups and further categorized into loyal outpatients, new outpatients, and lost outpatients. The similarities and differences among groups can be further analyzed to allow hospital management to provide differentiation strategies to its patients. That is, with the model illustrated in this study, the hospital can establish a better and long-term relationship with its patients by increasing patient loyalty.
Pharmaceutical Product Liability, Litigation Regimes, and the Propensity to Patent: An Empirical Firm-Level Investigation
Authors: Kovac Mitja , Datta Salvini , Spruk Rok
Published: April 2021

Do different pharmaceutical product liability regimes in different countries induce propensity to patent? We exploit the variation in pharmaceutical liability and litigation rules across firms in the pharmaceutical industry and countries to explain the firm-level propensity to patent. Drawing on a large dataset from European Patent Office (EPO) covering over 9,950 pharmaceutical patents from 63 countries over the period 1991–2015, we compute the conditional probabilities of individual pharmaceutical firms to acquire a valid-based patent on the validation outcomes and examine whether different liability regimes encourage or deter firm-level propensity to patent. Our empirical strategy addresses firm-level idiosyncrasies, country-level unobserved effects, and common technology shocks that potentially invoke omitted variable bias in the effects of liability regimes on the propensity to patent. Our investigation reveals that liability regimes combined with damage caps, broad statutory excuses, and reversed burden of proof have a strong positive effect on the firm-level patent stock and a negative effect upon EPO patent validation rate. The evidence suggests that not all liability rules and related litigation procedures are created equal. Firms are systematically more likely to hold (firm-level patent stock) valid patents at the EPO when the liability and litigation rules are not complex and when the damage cap, broad statutory excuses, and reversed burden of proof are introduced.
Experiences of Patient-Centered Care Among Japanese and Australian Cancer Outpatients: Results of a Cross-Sectional Study
Authors: Carey Mariko L , Uchida Megumi , Zucca Alison C , Okuyama Toru , Akechi Tatsuo , Sanson-Fisher Rob W
Published: April 2021

There have been few international comparisons of patient-centered cancer care delivery. This study aimed to compare the experiences of patient-centered care (PCC) of Japanese and Australian radiation oncology patients. Participants were adults with cancer attending a radiotherapy appointment at a Japanese or Australian clinic. Participants completed a survey asking about 10 indicators of PCC. Overall, 259 Japanese and 285 Australian patients participated. Compared with Japanese participants, Australian participants were significantly more likely to report receiving information about: what the treatment is, and the short-term and long-term side effects of treatment. A higher proportion of Australian participants reported being asked whether they wanted a friend or family member present at the consultation. There were no differences in the frequency with which Japanese and Australian participants were asked by their clinicians about whether they were experiencing physical side effects or emotional distress. International differences highlight the (1) need to exercise caution when generalizing from one country to another; and (2) the importance of context in understanding PCC delivery and the subsequent design of quality improvement interventions.
Ethiopian Qene (Traditional and Living Oral Poetry) as a Medium for Biblical Hermeneutics
Authors: Assefa Daniel , Belachew Tekletsadik
Published: April 2021

Ethiopian Qene (traditional and living oral poetry) intertwines biblical interpretation with the observation of nature and critique of current events. It is always delivered as improvisation. It is performed in traditional schools, as well as at liturgical and social events. It contains metaphors, rhymes, and rhythm. It includes important values and is useful for theological studies and biblical hermeneutics.
Missionaries and the Construction of Christian Homes: Examining the Formation of African Social Identities in Colonial Malawi
Authors: Tembo Dorothy
Published: April 2021

Christian missions were introduced in Africa to bring commerce and civilization. Nevertheless, the modernizing ambitions of missions and the colonial government had considerable social and moral consequences, which are observable in the construction of a Christian family. This article will show that missionaries created a social revolution by prohibiting polygamy, leading to wives being treated as widows. Besides, the article will show that the construction of femininity and masculinity in mission schools was based on European culture. Eventually, some roles that in traditional society were reserved for men were defined as feminine tasks.
A survey of pediatric hematologists/oncologists’ perspectives on single patient Expanded Access and Right to Try
Authors: Chapman Carolyn Riley , Belli Hayley M , Leach Danielle , Shah Lesha D , Bateman-House Alison
Published: April 2021

Introduction:

Physicians in the United States play an essential role guiding patients through single patient pre-approval access (PAA) to investigational medical products via either the Food and Drug Administration (FDA)’s Expanded Access (EA) or the federal Right To Try (RTT) pathways. In this study, we sought to better understand pediatric hematologist/oncologists’ attitudes about seeking PAA, on behalf of single patients, to investigational drugs outside of clinical trials.

Methods:

A cross-sectional survey was developed and sent to pediatric hematologist/oncologists via St. Baldrick’s Foundation’s email distribution list.

Results:

Of 73 respondents (10.1% of those who received the survey), 56 met eligibility criteria and are included in the analysis. Over 80% ( n = 46) had prior experience with single patient PAA. Respondents were most concerned about the unknown risks and benefits of investigational drugs and financial implications of PAA for patients. One hundred percent and 91.1% of respondents indicated a willingness to support patients through EA and RTT pathways, respectively. When asked about their most recent experience with PAA, 40 out of 46 indicated that they used the FDA’s EA pathway to seek PAA and 4 out of 46 indicated that they used the RTT pathway. Of 44 respondents who had used the EA or RTT pathway, 43 indicated that the biotechnology or pharmaceutical company they solicited granted access to the requested product.

Conclusion:

Survey results support other findings suggesting a need for additional physician support and education about PAA and that physicians may have unequal access to information about investigational drugs and concerns about financial implications of PAA for their patients.
Evaluating predictors of renal injury with sorafenib in hepatocellular carcinoma: A multi-ethnic cohort study
Authors: Natsuhara Kelsey H , Zhang Li , Carlos Christopher A , Borno Hala T
Published: April 2021

Background:

Kidney injury is a well-described adverse event of tyrosine kinase inhibitors (TKIs), thought to be mediated predominantly through glomerular damage. However, risk factors for kidney injury and the mechanism of injury are poorly defined in a wide range of cancers.

Methods:

This is a secondary analysis of 539 patients in the control arm of an international randomized clinical trial of patients with hepatocellular carcinoma treated with sorafenib, a vascular endothelial growth-factor receptor (VEGFR) TKI. Risk factors for developing acute kidney injury (AKI) while being treated with sorafenib were evaluated by multivariable logistic regression. We performed subgroup analyses of AKI stratified into proteinuric and non-proteinuric AKI.

Results:

While on study, 16% of patients developed an AKI. A decrease in systolic blood pressure was positively associated with developing any AKI (OR 1.70, 95% CI 1.03–2.82). In the subgroup analyses, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI (OR 2.15, 95% CI 1.00–4.61), but there was no association with developing a non-proteinuric AKI.

Conclusions:

In patients with hepatocellular carcinoma taking sorafenib, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI. However, there was no association between a decrease in blood pressure and the development of a non-proteinuric AKI. Thus, the development of AKI among patients taking VEGFR-TKIs cannot be fully explained by a hemodynamic effect. Our study highlights the need to better understand the varying mechanisms of kidney injury in patients.
Tests for tuberculosis infection: landscape analysis
Authors: Hamada Yohhei , Cirillo Daniela Maria , Matteelli Alberto , Penn-Nicholson Adam , Rangaka Molebogeng X. , Ruhwald Morten
Published: April 2021

Background

Only the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube and T-SPOT.TB, are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than the TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed.

Methods

We reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally.

Results

We identified 20 tests for TB infection: 15in vitrotests and five skin tests. 13 of thein vitrotests are whole-blood IGRAs and 14 use early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. 10 of the tests are based on assays other than an ELISA, such as a fluorescent lateral flow assay that requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared with the existing IGRAs. Four of the five skin tests use ESAT-6 and CFP-10 proteins, while the remaining test uses a new antigen that is specific toMycobacterium tuberculosiscomplex.

Conclusions

New tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.
Experimental Investigation on Micro Deep Drawing of Stainless Steel Foils with Different Microstructural Characteristics
Authors: Zhao Jingwei , Wang Tao , Jia Fanghui , Li Zhou , Zhou Cunlong , Huang Qingxue , Jiang Zhengyi
Published: April 2021

In the present work, austenitic stainless steel (ASS) 304 foils with a thickness of 50 µm were first annealed at temperatures ranging from 700 to 1100 ℃ for 1 h to obtain different microstructural characteristics. Then the effects of microstructural characteristics on the formability of ASS 304 foils and the quality of drawn cups using micro deep drawing (MDD) were studied, and the mechanism involved was discussed. The results show that the as-received ASS 304 foil has a poor formability and cannot be used to form a cup using MDD. Serious wrinkling problem occurs on the drawn cup, and the height profile distribution on the mouth and the symmetry of the drawn cup is quite non-uniform when the annealing temperature is 700 ℃. At annealing temperatures of 900 and 950 ℃, the drawn cups are both characterized with very few wrinkles, and the distribution of height profile, symmetry and mouth thickness are uniform on the mouths of the drawn cups. The wrinkling becomes increasingly significant with a further increase of annealing temperature from 950 to 1100 ℃. The optimal annealing temperatures obtained in this study are 900 and 950 ℃ for reducing the generation of wrinkling, and therefore improving the quality of drawn cups. With non-optimized microstructure, the distribution of the compressive stress in the circumferential direction of the drawn foils becomes inhomogeneous, which is thought to be the cause of the occurrence of localized deformation till wrinkling during MDD.
Capturing cognitive and behavioral variability among individuals with Down syndrome: a latent profile analysis
Authors:   The Down Syndrome Cognition Project, Channell Marie Moore , Mattie Laura J. , Hamilton Debra R. , Capone George T. , Mahone E. Mark , Sherman Stephanie L. , Rosser Tracie C. , Reeves Roger H. , Kalb Luther G.
Published: April 2021

Background

There is a high degree of inter- and intra-individual variability observed within the phenotype of Down syndrome. The Down Syndrome Cognition Project was formed to capture this variability by developing a large nationwide database of cognitive, behavioral, health, and genetic information on individuals with Down syndrome, ages 6–25 years. The current study used the Down Syndrome Cognition Project database to characterize cognitive and behavioral variability among individuals with Down syndrome.

Methods

Latent profile analysis was used to identify classes across a sample of 314 participants based on their cognition (IQ and executive functioning), adaptive and maladaptive behavior, and autism spectrum disorder symptomatology. A multivariate multinomial regression model simultaneously examined demographic correlates of class.

Results

Results supported a 3-class model. Each class demonstrated a unique profile across the subdomains of cognition and behavior. The “normative” class was the largest (n = 153, 48%) and displayed a relatively consistent profile of cognition and adaptive behavior, with low rates of maladaptive behavior and autism symptomatology. The “cognitive” class (n = 109, 35%) displayed low cognitive scores and adaptive behavior and more autism symptomatology, but with low rates of maladaptive behavior. The “behavioral” class, the smallest group (n = 52, 17%), demonstrated higher rates of maladaptive behavior and autism symptomatology, but with cognition levels similar to the “normative” class; their adaptive behavior scores fell in between the other two classes. Household income and sex were the only demographic variables to differ among classes.

Conclusions

These findings highlight the importance of subtyping the cognitive and behavioral phenotype among individuals with Down syndrome to identify more homogeneous classes for future intervention and etiologic studies. Results also demonstrate the feasibility of using latent profile analysis to distinguish subtypes in this population. Limitations and future directions are discussed.
Associations between floods and bacillary dysentery cases in main urban areas of Chongqing, China, 2005–2016: a retrospective study
Authors: Ma Yang , Wen Tong , Xing Dianguo , Zhang Yan
Published: April 2021

Background

Understanding the association between floods and bacillary dysentery (BD) incidence is necessary for us to assess the health risk of extreme weather events. This study aims at exploring the association between floods and daily bacillary dysentery cases in main urban areas of Chongqing between 2005 and 2016 as well as evaluating the attributable risk from floods.

Methods

The association between floods and daily bacillary dysentery cases was evaluated by using distributed lag non-linear model, controlling for meteorological factors, long-term trend, seasonality, and day of week. The fraction and number of bacillary dysentery cases attributable to floods was calculated. Subgroup analyses were conducted to explore the association across age, gender, and occupation.

Results

After controlling the impact of temperature, precipitation, relative humidity, long-term trend, and seasonality, a significant lag effect of floods on bacillary dysentery cases was found at 0-day, 3-day, and 4-day lag, and the cumulative relative risk (CRR) over a 7-lag day period was 1.393 (95%CI 1.216–1.596). Male had higher risk than female. People under 5 years old and people aged 15–64 years old had significantly higher risk. Students, workers, and children had significantly higher risk. During the study period, based on 7-lag days, the attributable fraction of bacillary dysentery cases due to floods was 1.10% and the attributable number was 497 persons.

Conclusions

This study confirms that floods can increase the risk of bacillary dysentery incidence in main urban areas of Chongqing within an accurate time scale, the risk of bacillary dysentery caused by floods is still serious. The key population includes male, people under 5 years old, students, workers, and children. Considering the lag effect of floods on bacillary dysentery, the government and public health emergency departments should advance to the emergency health response in order to minimize the potential risk of floods on public.
Correction to: Automatic reconstruction of metabolic pathways from identified biosynthetic gene clusters
Authors: Sulheim Snorre , Fossheim Fredrik A. , Wentzel Alexander , Almaas Eivind
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Modeling transcriptional regulation using gene regulatory networks based on multi-omics data sources
Authors: Patel Neel , Bush William S.
Published: April 2021

Background

Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features.

Results

We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression.

Conclusions

Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.
Molecular characterization of cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene and frequency of blood types in stray cats of İzmir, Turkey
Authors: Can Hüseyin , Erkunt Alak Sedef , Köseoğlu Ahmet Efe , Şahar Umut , Bostanbaş Berna , Baydarlı Serdar , Döşkaya Mert , Ün Cemal
Published: April 2021

Background

Cytidine monophospho-n-acetylneuraminic acid hydroxylase(CMAH) gene associated with blood groups in cats encodes CMAH enzyme that converts Neu5Ac to Neu5Gc. Although variations inCMAHgene of pedigree cats have been revealed, the presence/lack of them in non-pedigree stray cats is unknown. Therefore, the present study aimed to investigate the variations inCMAHgene and the quantity of Neu5Ac and Neu5Gc on erythrocytes of non-pedigree stray cats (n:12) living in İzmir, Turkey. Also, the frequency of blood types was determined in 76 stray cats including 12 cats that were used forCMAHand Neu5A/Neu5Gc analysis.

Results

In total, 14 SNPs were detected in 5’UTR as well as in exon 2, 4, 9, 10, 11 and 12 ofCMAHgene. Among these SNPs, -495 C > T in 5’UTR was detected for the first time as heterozygous in type A and AB cats, and homozygous and heterozygous in type B cats. The remaining 13 that have been detected in previous studies were also found as homozygous or heterozygous. Both Neu5Gc and Neu5Ac were detected in type A and AB cats. In type B cats, only Neu5Ac was detected. Among two type AB cats, the level of Neu5Ac was found higher in cat carrying heterozygous form (T/C) of 1392T > C. The prevalence of type B cats (67.1 %) was higher than others.

Conclusions

The presence of a new SNP as well as previous SNPs indicates that more variations can be found in stray cats with a more comprehensive study in the future. Also, the high prevalence of type B cats demonstrates the possible risk of neonatal isoerythrolysis among stray cats living in İzmir, Turkey.
Identification of the specific long-noncoding RNAs involved in night-break mediated flowering retardation in Chenopodium quinoa
Authors: Wu Qi , Luo Yiming , Wu Xiaoyong , Bai Xue , Ye Xueling , Liu Changying , Wan Yan , Xiang Dabing , Li Qiang , Zou Liang , Zhao Gang
Published: April 2021

Background

Night-break (NB) has been proven to repress flowering of short-day plants (SDPs). Long-noncoding RNAs (lncRNAs) play key roles in plant flowering. However, investigation of the relationship between lncRNAs and NB responses is still limited, especially in Chenopodium quinoa, an important short-day coarse cereal.

Results

In this study, we performed strand-specific RNA-seq of leaf samples collected from quinoa seedlings treated by SD and NB. A total of 4914 high-confidence lncRNAs were identified, out of which 91 lncRNAs showed specific responses to SD and NB. Based on the expression profiles, we identified 17 positive- and 7 negative-flowering lncRNAs. Co-expression network analysis indicated that 1653 mRNAs were the common targets of both types of flowering lncRNAs. By mapping these targets to the known flowering pathways in model plants, we found some pivotal flowering homologs, including 2 florigen encoding genes (FT (FLOWERING LOCUS T) and TSF (TWIN SISTER of FT) homologs), 3 circadian clock related genes (EARLY FLOWERING 3 (ELF3), LATE ELONGATED HYPOCOTYL (LHY) and ELONGATED HYPOCOTYL 5 (HY5) homologs), 2 photoreceptor genes (PHYTOCHROME A (PHYA) and CRYPTOCHROME1 (CRY1) homologs), 1 B-BOX type CONSTANS (CO) homolog and 1 RELATED TO ABI3/VP1 (RAV1) homolog, were specifically affected by NB and competed by the positive and negative-flowering lncRNAs. We speculated that these potential flowering lncRNAs may mediate quinoa NB responses by modifying the expression of the floral homologous genes.

Conclusions

Together, the findings in this study will deepen our understanding of the roles of lncRNAs in NB responses, and provide valuable information for functional characterization in future.
Bacterial community in saline farmland soil on the Tibetan plateau: responding to salinization while resisting extreme environments
Authors: Li Yi Qiang , Chai Ying Hui , Wang Xu Sheng , Huang Li Ying , Luo Xi Ming , Qiu Cheng , Liu Qing Hai , Guan Xiang Yu
Published: April 2021

Background

Salinization damages the health of soil systems and reduces crop yields. Responses of microbial communities to salinized soils and their functional maintenance under high salt stress are valuable scientific problems. Meanwhile, the microbial community of the salinized soil in the plateau environment is less understood. Here, we applied metagenomics technology to reveal the structure and function of microorganisms in salinized soil of the Tibetan Plateau.

Results

The diversity of composition and function of microbial community in saline soil have changed significantly. The abundances of chemoautotrophic and acidophilic bacteria comprising Rhodanobacter, Acidobacterium, Candidatus Nitrosotalea, and Candidatus Koribacter were significantly higher in saline soil. The potential degradation of organic carbon in the saline soil, as well as the production of NO and N2O via denitrification, and the production of sulfate by sulfur oxidation were significantly higher than the non-saline soil. Both types of soils were rich in genes encoding resistance to environmental stresses (i.e., cold, ultraviolet light, and hypoxia in Tibetan Plateau). The resistance of the soil microbial communities to the saline environment is based on the absorption of K+ as the main mechanism, with cross-protection proteins and absorption buffer molecules as auxiliary mechanisms in our study area. Network analysis showed that functional group comprising chemoautotrophic and acidophilic bacteria had significant positive correlations with electrical conductivity and total sulfur, and significant negative correlations with the total organic carbon, pH, and available nitrogen. The soil moisture, pH, and electrical conductivity are likely to affect the bacterial carbon, nitrogen, and sulfur cycles.

Conclusions

These results indicate that the specific environment of the Tibetan Plateau and salinization jointly shape the structure and function of the soil bacterial community, and that the bacterial communities respond to complex and harsh living conditions. In addition, environmental feedback probably exacerbates greenhouse gas emissions and accelerates the reduction in the soil pH. This study will provide insights into the microbial responses to soil salinization and the potential ecological risks in the special plateau environment.
Adaptation of cucumber seedlings to low temperature stress by reducing nitrate to ammonium during it’s transportation
Authors: Liu Yumei , Bai Longqiang , Sun Mintao , Wang Jun , Li Shuzhen , Miao Li , Yan Yan , He Chaoxing , Yu Xianchang , Li Yansu
Published: April 2021

Background

Low temperature severely depresses the uptake, translocation from the root to the shoot, and metabolism of nitrate and ammonium in thermophilic plants such as cucumber (Cucumis sativus). Plant growth is inhibited accordingly. However, the availability of information on the effects of low temperature on nitrogen transport remains limited.

Results

Using non-invasive micro-test technology, the net nitrate (NO3−) and ammonium (NH4+) fluxes in the root hair zone and vascular bundles of the primary root, stem, petiole, midrib, lateral vein, and shoot tip of cucumber seedlings under normal temperature (NT; 26 °C) and low temperature (LT; 8 °C) treatment were analyzed. Under LT treatment, the net NO3− flux rate in the root hair zone and vascular bundles of cucumber seedlings decreased, whereas the net NH4+ flux rate in vascular bundles of the midrib, lateral vein, and shoot tip increased. Accordingly, the relative expression of CsNRT1.4a in the petiole and midrib was down-regulated, whereas the expression of CsAMT1.2a–1.2c in the midrib was up-regulated. The results of 15N isotope tracing showed that NO3−-N and NH4+-N uptake of the seedlings under LT treatment decreased significantly compared with that under NT treatment, and the concentration and proportion of both NO3−-N and NH4+-N distributed in the shoot decreased. Under LT treatment, the actual nitrate reductase activity (NRAact) in the root did not change significantly, whereas NRAact in the stem and petiole increased by 113.2 and 96.2%, respectively.

Conclusions

The higher net NH4+ flux rate in leaves and young tissues may reflect the higher NRAact in the stem and petiole, which may result in a higher proportion of NO3− being reduced to NH4+ during the upward transportation of NO3−. The results contribute to an improved understanding of the mechanism of changes in nitrate transportation in plants in response to low-temperature stress.
Identification of consistent QTL for time to maturation in Virginia-type Peanut (Arachis hypogaea L.)
Authors: Kunta Srinivas , Agmon Sara , Chedvat Ilan , Levy Yael , Chu Ye , Ozias-Akins Peggy , Hovav Ran
Published: April 2021

Background

Time-to-maturation (TTM) is an important trait contributing to adaptability, yield and quality in peanut (Arachis hypogaeaL). Virginia market-type peanut belongs to the late-maturingA. hypogaeasubspecies with considerable variation in TTM within this market type. Consequently, planting and harvesting schedule of peanut cultivars, including Virginia market-type, need to be optimized to maximize yield and grade. Little is known regarding the genetic control of TTM in peanut due to the challenge of phenotyping and limited DNA polymorphism. Here, we investigated the genetic control of TTM within the Virginia market-type peanut using a SNP-based high-density genetic map. A recombinant inbred line (RIL) population, derived from a cross between two Virginia-type cultivars ‘Hanoch’ and ‘Harari’ with contrasting TTM (12–15 days on multi-years observations), was phenotyped in the field for 2 years following a randomized complete block design. TTM was estimated by maturity index (MI). Other agronomic traits like harvest index (HI), branching habit (BH) and shelling percentage (SP) were recorded as well.

Results

MI was highly segregated in the population, with 13.3–70.9% and 28.4–80.2% in years 2018 and 2019. The constructed genetic map included 1833 SNP markers distributed on 24 linkage groups, covering a total map distance of 1773.5 cM corresponding to 20 chromosomes on the tetraploid peanut genome with 1.6 cM mean distance between the adjacent markers. Thirty QTL were identified for all measured traits. Among the four QTL regions for MI, two consistent QTL regions (qMIA04a,bandqMIB03a,b) were identified on chromosomes A04 (118680323–125,599,371; 6.9Mbp) and B03 (2839591–4,674,238; 1.8Mbp), with LOD values of 5.33–6.45 and 5–5.35 which explained phenotypic variation of 9.9–11.9% and 9.3–9.9%, respectively. QTL for HI were found to share the same loci as MI on chromosomes B03,B05, and B06, demonstrating the possible pleiotropic effect of HI on TTM. Significant but smaller effects on MI were detected for BH, pod yield and SP.

Conclusions

This study identified consistent QTL regions conditioning TTM for Virginia market-type peanut. The information and materials generated here can be used to further develop molecular markers to select peanut idiotypes suitable for diverse growth environments.
Character changes and Transcriptomic analysis of a cassava sexual Tetraploid
Authors: Chen Xia , Lai Hanggui , Li Ruimei , Yao Yuan , Liu Jiao , Yuan Shuai , Fu Shaoping , Hu Xinwen , Guo Jianchun
Published: April 2021

Background

Cassava (Manihot esculenta Crantz) is an important food crop known for its high starch content. Polyploid breeding is effective in its genetic improvement, and use of 2n gametes in sexual polyploid breeding is one of the potential methods for cassava breeding and improvement. In our study, the cassava sexual tetraploid (ST), which carries numerous valuable traits, was successfully generated by hybridizing 2n female gametes SC5 (♀) and 2n male gametes SC10 (♂). However, the molecular mechanisms remain unclear. To understand these underlying molecular mechanisms behind the phenotypic alterations and heterosis in ST plants, we investigated the differences in gene expression between polyploids and diploids by determining the transcriptomes of the ST plant and its parents during the tuber root enlargement period. We also compared the characters and transcriptomes of the ST plant with its parents.

Results

The ST plant was superior in plant height, stem diameter, leaf area, petiole length, plant weight, and root weight than the parent plants, except the leaf number, which was lower. The number of starch granules was higher in the roots of ST plants than those in the parent plants after five months (tuber root enlargement period), which could be due to a higher leaf net photosynthetic rate leading to early filling of starch granules. Based on transcriptome analysis, we identified 2934 and 3171 differentially expressed genes (DEGs) in the ST plant as compared to its female and male parents, respectively. Pathway enrichment analyses revealed that flavonoid biosynthesis and glycolysis/gluconeogenesis were significantly enriched in the ST plants, which might contribute to the colors of petiole (purple-red), root epidermis (dark brown), and tuber starch accumulation, respectively.

Conclusions

After sexual polyploidization, the phenotype of ST has changed significantly in comparison to their diploid parents, mainly manifest as enlarged biomass, yield, early starch filling, deep colored petiole and root epidermis. The tetraploid plants were also mature early due to early starch grain filling. Owing to enriched flavonoid biosynthesis and glycolysis/gluconeogenesis, they are possibly resistant to adversity stresses and provide better yield, respectively.
The effect of preoperative aminophylline on the recovery profile after major pelvic-abdominal surgeries: a randomized controlled double-blinded study
Authors: Kasim Samaa A. , Bahr Mahmoud Hussein , Abdelkader Mohamed , Rashwan Doaa Abu Elkassim
Published: April 2021

Background

This study compared the effects of premedication with different doses of aminophylline on the recovery profile after general anaesthesia.

Methods

Forty-five patients scheduled for pelvic-abdominal surgeries were divided into 3 groups: Group C: the patients received 100 ml of IV normal saline, Group A1: the patients received 2 mg/kg IV aminophylline, and Group A2: the patients received 4 mg/kg IV aminophylline 30 min before induction of general anaesthesia. The following data were recorded: demographic data, ASA physical status, duration of anaesthesia and surgery, heart rate, mean arterial blood pressure, propofol dose, fentanyl dose, times to reach BIS (48 ± 2) after induction of anaesthesia and to reach a value of 80 after discontinuation of sevoflurane anaesthesia, time to recovery of consciousness and to tracheal extubation and to discharge from the post-anaesthesia care unit, and side effects of aminophylline.

Results

The time to reach a BIS of 48 ± 2 was significantly lower for the control group than group A2 (70.67 ± 22.50 and 106.67 ± 34.77 s for groups C and A2, respectively, p -value =0.01). The time to reach a BIS of 80 was significantly longer for the control group than group A1 andA2 (5.6 ± 1.40,3.5 ± 1.93and 2.53 ± 1.72 min for groups C,A1 and A2, respectively, p -value < 0.01). The time to ROC was significantly longer for the control group than groups A1 and A2 (8.93 ± 0.92, 5.6 ± 2.47 and 4.53 ± 3.33 min for groups C, A1 and A2, respectively; p -value < 0.01). The extubation time was significantly longer for the control group than groups A1 and A2 (12.4 ± 1.08, 7.87 ± 3.27 and 6.6 ± 2.47 min for groups C, A1 and A2, respectively; p -value < 0.01).

Conclusion

Premedication with aminophylline enhanced the recovery profile after pelvic-abdominal surgeries under general anaesthesia without cardiovascular complications.

Clinical trial registration

Name of the registry: Register@ClinicalTrials.gov

Trial registration number: ClinicalTrials.gov Identifier: NCT04151381.

Date of registration, November 5, 2019, ‘Retrospectively registered’.
Intention-to-treat analysis may be more conservative than per protocol analysis in antibiotic non-inferiority trials: a systematic review
Authors:   for the McMaster Infectious Diseases Fellow Research Group, Bai Anthony D. , Komorowski Adam S. , Lo Carson K. L. , Tandon Pranav , Li Xena X. , Mokashi Vaibhav , Cvetkovic Anna , Findlater Aidan , Liang Laurel , Tomlinson George , Loeb Mark , Mertz Dominik
Published: April 2021

Background

In non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative.

Methods

In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit.

Results

The analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of − 7.5% vs. -6.9%,p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%,p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001).

Conclusions

Contrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials.

Trial registration

PROSPERO registration numberCRD42020165040.
A 10-year cross-sectional retrospective study on Kawasaki disease in Iranian children: incidence, clinical manifestations, complications, and treatment patterns
Authors: Sadeghi Payman , Izadi Anahita , Mojtahedi Sayed Yousef , Khedmat Leila , Jafari Mohsen , Afshin Azadeh , Yarahmadi Pourya , Hosseinali Beigi Effat
Published: April 2021

Background

Kawasaki disease (KD) as an acute, systemic vasculitis is the leading cause of acquired heart disease in children under the age of 5 years.

Methods

A 10-year cross-sectional retrospective study was designed to assess 190 Iranian children with KD during 2008–2018. Demographic data, clinical and laboratory manifestations from the onset of symptoms to diagnosis, clinical signs and symptoms, and subsequent treatments were evaluated to predict hospitalization stay, complications, and response to treatment.

Results

Children with KD had a male-to-female ratio of 1.18:1 and an average age of 36 months. There was an insignificantly more incidence of KD in cold seasons. The most frequent symptoms were fever (92.6%), oral mucus membrane changes (75.8%), bilateral bulbar conjunctival injection (73.7%), polymorphous skin rash (73.2%), peripheral extremity changes (63.7%), and cervical lymphadenopathy (60.0%). The rate of gastrointestinal, cardiac, joint, and hepatic complications was determined to be 38.4, 27.9, 6.8, and 4.2%, respectively. 89.5% of patients received intravenous immunoglobulin (IVIG) plus aspirin as the first line of treatment, while, 16.3% of them needed an extra second line of treatment. Significantly low serum sodium levels and high platelet counts were detected in KD patients with cardiac complications. Cardiac complications often were more encountered in patients who did not respond to the first line of treatment. Higher platelet count, lower serum sodium amount, and C-reactive protein (CRP) level were significantly associated with a need for an additive second line of treatment. A significant relationship between hospitalization stay and hemoglobin level was found.

Conclusion

As most of the clinical manifestations and complications were following other reports released over the past few years, such data can be confidently used to diagnose KD in Iran. Seasonal incidence and a positive history of recent infection in a notable number of patients may provide clues to understand possible etiologies of KD. Laboratory markers can successfully contribute to health practitioners with the clinical judgment of the need for additional treatments, possible complications, and hospitalization duration.
Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson’s disease
Authors: Liu Ming , Luo Ya-Jun , Gu Han-Ying , Wang Yi-Ming , Liu Man-Hua , Li Kai , Li Jiao , Zhuang Sheng , Shen Yun , Jin Hong , Chen Jing , Mao Cheng-Jie , Liu Chun-Feng
Published: April 2021

Background

The clinical characteristics of Parkinson’s disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression.

Objective

To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO).

Methods

Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality.

Results

Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep.

Conclusion

More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.
Induction of labour during the COVID-19 pandemic: a national survey of impact on practice in the UK
Authors:   On behalf of the CHOICE Study Consortia, Harkness M. , Yuill C. , Cheyne H. , Stock S. J. , McCourt C.
Published: April 2021

Background

Induction of labour (IOL) is one of the most commonly performed interventions in maternity care, with outpatient cervical ripening increasingly offered as an option for women undergoing IOL. The COVID-19 pandemic has changed the context of practice and the option of returning home for cervical ripening may now assume greater significance. This work aimed to examine whether and how the COVID-19 pandemic has changed practice around IOL in the UK.

Method

We used an online questionnaire to survey senior obstetricians and midwives at all 156 UK NHS Trusts and Boards that currently offer maternity services. Responses were analysed to produce descriptive statistics, with free text responses analysed using a conventional content analysis approach.

Findings

Responses were received from 92 of 156 UK Trusts and Boards, a 59% response rate. Many Trusts and Boards reported no change to their IOL practice, however 23% reported change in methods used for cervical ripening; 28% a change in criteria for home cervical ripening; 28% stated that more women were returning home during cervical ripening; and 24% noted changes to women’s response to recommendations for IOL. Much of the change was reported as happening in response to attempts to minimise hospital attendance and restrictions on birth partners accompanying women.

Conclusions

The pandemic has changed practice around induction of labour, although this varied significantly between NHS Trusts and Boards. There is a lack of formal evidence to support decision-making around outpatient cervical ripening: the basis on which changes were implemented and what evidence was used to inform decisions is not clear.