bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative transcriptomics of a monocotyledonous geophyte reveals shared molecular mechanisms of underground storage organ formation
Authors: Tribble Carrie M. , Martínez‐Gómez Jesús , Alzate‐Guarín Fernando , Rothfels Carl J. , Specht Chelsea D.
Published: January 2021

Many species from across the vascular plant tree‐of‐life have modified standard plant tissues into tubers, bulbs, corms, and other underground storage organs (USOs), unique innovations which allow these plants to retreat underground. Our ability to understand the developmental and evolutionary forces that shape these morphologies is limited by a lack of studies on certain USOs and plant clades. We take a comparative transcriptomics approach to characterizing the molecular mechanisms of tuberous root formation in Bomarea multiflora (Alstroemeriaceae) and compare these mechanisms to those identified in other USOs across diverse plant lineages; B. multiflora fills a key gap in our understanding of USO molecular development as the first monocot with tuberous roots to be the focus of this kind of research. We sequenced transcriptomes from the growing tip of four tissue types (aerial shoot, rhizome, fibrous root, and root tuber) of three individuals of B. multiflora. We identified differentially expressed isoforms between tuberous and non‐tuberous roots and tested the expression of a priori candidate genes implicated in underground storage in other taxa. We identify 271 genes that are differentially expressed in root tubers versus non‐tuberous roots, including genes implicated in cell wall modification, defense response, and starch biosynthesis. We also identify a phosphatidylethanolamine‐binding protein, which has been implicated in tuberization signalling in other taxa and, through gene‐tree analysis, place this copy in a phylogenetic context. These findings suggest that some similar molecular processes underlie the formation of USOs across flowering plants despite the long evolutionary distances among taxa and non‐homologous morphologies (e.g., bulbs vs. tubers). (Plant development, tuberous roots, comparative transcriptomics, geophytes).
Spatially restricted inhibition of cholinergic interneurons in the dorsolateral striatum encourages behavioral exploration
Authors: Amaya Kenneth A. , Smith Kyle S.
Published: January 2021

When pursuing desirable outcomes, one must make the decision between exploring possible actions to obtain those outcomes and exploiting known strategies to maximize efficiency. The dorsolateral striatum (DLS) has been extensively studied with respect to how actions can develop into habits and has also been implicated as an area involved in governing exploitative behavior. Surprisingly, prior work has shown that DLS cholinergic interneurons (ChIs) are not involved in the canonical habit formation function ascribed to the DLS but are instead modulators of behavioral flexibility after initial learning. To further probe this, we evaluated the role of DLS ChIs in behavioral exploration during a brief instrumental training experiment. Through designer receptors exclusively activated by designer drugs (DREADDs) in ChAT‐Cre rats, ChIs in the DLS were inhibited during specific phases of the experiment: instrumental training, free‐reward delivery, at both times, or never. Without ChI activity during instrumental training, animals biased their responding toward an “optimal” strategy while continuing to work efficiently. This effect was observed again when contingencies were removed as animals with ChIs offline during that phase, regardless of ChI inhibition previously, decreased responding more than animals with ChIs intact. These findings build upon a growing body of literature implicating ChIs in the striatum as gate‐keepers of behavioral flexibility and exploration.
Antibody Prevalence in Epilepsy before Surgery (APES) in drug‐resistant focal epilepsy
Authors: Li Yi , Tymchuk Sarah , Barry John , Muppidi Srikanth , Le Scheherazade
Published: January 2021

Objective

There is a growing recognition of immune‐mediated causes in patients with focal drug‐resistant epilepsy (DRE); however, they are not systematically assessed in the pre‐surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune‐mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies.

Methods

We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score.

Results`

A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub‐cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)–specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80.

Significance

Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune‐mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre‐surgical evaluation for focal refractory epilepsy with unknown cause.
“I feel like God doesn't like me”: Faith and Ambiguous Loss Among Transgender Youth
Authors: Okrey Anderson Sloan , McGuire Jenifer K.
Published: January 2021

Objective

The present study expands the use of ambiguous loss theory into the realm of religion and religious rejection for sexual‐ and gender‐minority people, an area that has previously been addressed primarily as an issue of minority stress.

Background

Research has demonstrated that religion‐based, nonaffirming messaging from family and faith communities is correlated with decreased health and well‐being of sexual‐ and gender‐minority persons, who are, like most Americans, likely to have been raised in religious (predominately Christian) homes. Existing research has begun to explain why nonaffirming faith affiliation seems to negatively impact sexual gender minority people, but it does not explain the mechanisms of long‐term distress.

Methods

This study is a qualitative thematic analysis of religion and family data from semistructured interviews with 63 transgender youth from the United States, Canada, and Ireland who reported being raised in religious Christian homes.

Results

Analysis revealed that the narratives of participants who had been members of a psychological family of faith included all of the core elements of ambiguous loss, suggesting that individuals can experience ambiguous loss in relationship to a faith community and to God.

Discussion

This study presents a new application of Boss's ambiguous loss theory and offers a framework for understanding why sexual‐ and gender‐minority people from Christian backgrounds might experience long‐term distress in relation to faith and spirituality whether they stay in their faith communities of origin or move on to something else.

Implications

The experiences of transgender people examined through the framework of ambiguous loss and the concept of the psychological family of faith could be applied to research with people from any demographic in relation to loss of faith or faith community. This information may contribute to the study of family ruptures that occur as a result of family experiences of ideological or moral incompatibility (e.g., deconversion, political realignment, leaving a cult).
Precipitation alters the CO2 effect on water‐use efficiency of temperate forests
Authors: Belmecheri Soumaya , Maxwell R. Stockton , Taylor Alan H. , Davis Kenneth J. , Guerrieri Rossella , Moore David J. P. , Rayback Shelly A.
Published: January 2021

Increasing water‐use efficiency (WUE), the ratio of carbon gain to water loss, is a key mechanism that enhances carbon uptake by terrestrial vegetation under rising atmospheric CO2 (ca). Existing theory and empirical evidence suggest a proportional WUE increase in response to rising ca as plants maintain a relatively constant ratio between the leaf intercellular (ci) and ambient (ca) partial CO2 pressure (ci/ca). This has been hypothesized as the main driver of the strengthening of the terrestrial carbon sink over the recent decades. However, proportionality may not characterize CO2 effects on WUE on longer time‐scales and the role of climate in modulating these effects is uncertain. Here, we evaluate long‐term WUE responses to ca and climate from 1901 to 2012 CE by reconstructing intrinsic WUE (iWUE, the ratio of photosynthesis to stomatal conductance) using carbon isotopes in tree rings across temperate forests in the northeastern USA. We show that iWUE increased steadily from 1901 to 1975 CE but remained constant thereafter despite continuously rising ca. This finding is consistent with a passive physiological response to ca and coincides with a shift to significantly wetter conditions across the region. Tree physiology was driven by summer moisture at multi‐decadal time‐scales and did not maintain a constant ci/ca in response to rising ca indicating that a point was reached where rising CO2 had a diminishing effect on tree iWUE. Our results challenge the mechanism, magnitude, and persistence of CO2's effect on iWUE with significant implications for projections of terrestrial productivity under a changing climate.
Major and persistent shifts in below‐ground carbon dynamics and soil respiration following logging in tropical forests
Authors: Riutta Terhi , Kho Lip Khoon , Teh Yit Arn , Ewers Robert , Majalap Noreen , Malhi Yadvinder
Published: January 2021

Soil respiration is the largest carbon efflux from the terrestrial ecosystem to the atmosphere, and selective logging influences soil respiration via changes in abiotic (temperature, moisture) and biotic (biomass, productivity, quantity and quality of necromass inputs) drivers. Logged forests are a predominant feature of the tropical forest landscape, their area exceeding that of intact forest. We quantified both total and component (root, mycorrhiza, litter, and soil organic matter, SOM) soil respiration in logged (n = 5) and old‐growth (n = 6) forest plots in Malaysian Borneo, a region which is a global hotspot for emission from forest degradation. We constructed a detailed below‐ground carbon budget including organic carbon inputs into the system via litterfall and root turnover. Total soil respiration was significantly higher in logged forests than in old‐growth forests (14.3 ± 0.23 and 12.7 ± 0.60 Mg C ha−1 year−1, respectively, p = 0.037). This was mainly due to the higher SOM respiration in logged forests (55 ± 3.1% of the total respiration in logged forests vs. 50 ± 3.0% in old‐growth forests). In old‐growth forests, annual SOM respiration was equal to the organic carbon inputs into the soil (difference between SOM respiration and inputs 0.18 Mg C ha−1 year−1, with 90% confidence intervals of −0.41 and 0.74 Mg C ha−1 year−1), indicating that the system is in equilibrium, while in logged forests SOM respiration exceeded the inputs by 4.2 Mg C ha−1 year−1 (90% CI of 3.6 and 4.9 Mg C ha−1 year−1), indicating that the soil is losing carbon. These results contribute towards understanding the impact of logging on below‐ground carbon dynamics, which is one of the key uncertainties in estimating emissions from forest degradation. This study demonstrates how significant perturbation of the below‐ground carbon balance, and consequent net soil carbon emissions, can persist for decades after a logging event in tropical forests.
Olfactory‐cognitive index distinguishes involvement of frontal lobe shrinkage, as in sarcopenia from shrinkage of medial temporal areas, and global brain, as in Kihon Checklist frailty/dependence, in older adults with progression of normal cognition to Alzheimer's disease
Authors: Iritani Osamu , Okuno Tazuo , Miwa Takaki , Makizako Hyuma , Okutani Fumino , Kashibayashi Tetsuo , Suzuki Kumiko , Hara Hideo , Mori Eri , Omoto Shusaku , Suzuki Hirokazu , Shibata Minori , Adachi Hiroaki , Kondo Kenji , Umeda‐Kameyama Yumi , Kodera Kumie , Morimoto Shigeto
Published: January 2021

Aim

Olfactory impairment as a prodromal symptom, as well as sarcopenia, frailty and dependence as geriatric syndromes, is often associated with cognitive decline in older adults with progression of Alzheimer's disease. The present study aimed to evaluate the associations of olfactory and cognitive decline with these geriatric syndromes, and with structural changes of the brain in older adults.

Methods

The participants were 135 older adults (47 men and 88 women, mean age 79.5 years), consisting of 64 with normal cognition, 23 with mild cognitive impairment and 48 with Alzheimer's disease. Olfactory function was evaluated by the Open Essence odor identification test. Shrinkage of the regional brain was determined by magnetic resonance imaging.

Results

Logistic regression analysis with Open Essence, Mini‐Mental State Examination, age and sex as covariates showed higher olfactory‐cognitive index (|coefficient for Open Essence (a) / coefficient for Mini‐Mental State Examination (b)|) in participants with sarcopenia (Asia Working Group for Sarcopenia), and lower values of (|a/b|) in participants with Barthel Index dependence, Kihon Checklist frailty, Lawton Index dependence and support/care‐need certification as objective variables. Logistic regression analysis adjusted by age and sex also showed significant shrinkage of the frontal lobe in participants with AWGS sarcopenia, especially in women, and shrinkage of the medial temporal areas and global brain in participants with Kihon Checklist frailty/dependence.

Conclusions

Olfactory‐cognitive index (|a/b|) might be a useful tool to distinguish involvement of frontal lobe shrinkage, as in sarcopenia from shrinkage of the medial temporal areas, and global brain, as in frailty/dependence, in older adults with progression of normal cognition to Alzheimer's disease. Geriatr Gerontol Int 2021; ••: ••–••.
A New Randomized Binary Prior Model for Hydraulic Tomography in Fractured Aquifers
Authors: Poduri Sarada , Kambhammettu BVNP , Gorugantula Saisrinivas
Published: January 2021

We present a novel pilot‐point‐based hydraulic tomography (HT) inversion procedure to delineate preferential flow paths and estimate hydraulic properties in a fractured aquifer. Our procedure considers a binary prior model developed using a randomized algorithm. The randomized algorithm involves discretizing the domain into grid cells, assigning a binary label to each cell, traversing the grid randomly, and choosing the optimal grid configuration cell‐by‐cell. This binary prior model is used to guide the placement of pilot points and to constrain aquifer parameters during pilot‐point‐based HT inversion. A two‐dimensional fractured granite rock block was considered to test our methodology under controlled laboratory conditions. Multiple pumping tests were conducted at selected ports and the pressure responses were monitored. The pumping datasets thus obtained were preprocessed using median filters to remove random noise, and then analyzed using the proposed procedure. The proposed binary prior algorithm was implemented in C++ by supplying the forward groundwater model, HydroGeoSphere (HGS). Pilot‐point‐assisted HT inversion was performed using the parameter‐estimation tool, coupled to HGS. The resulting parameter distributions were assessed by: (1) a visual comparison of the K‐ and Ss‐tomograms with the known topology of the fractures and (2) comparing model predictions with measurements made at two validation ports that were not used in calibration. The performance assessment revealed that HT with the proposed randomized binary prior could be used to recover fracture‐connectivity and to predict drawdowns in fractured aquifers with reasonable accuracy, when compared to a conventional pilot‐point inversion scheme.
Fiber Optic Measurements of Soil Moisture in a Waste Rock Pile
Authors: Wu Robert , Martin Vincent , McKenzie Jeffrey M. , Broda Stefan , Bussière Bruno , Selker John , Aubertin Michel
Published: January 2021

The design and construction of a waste rock pile influences water infiltration and may promote the production of contaminated mine drainage. The objective of this project is to evaluate the use of an active fiber optic distributed temperature sensing (aFO‐DTS) protocol to measure infiltration and soil moisture within a flow control layer capping an experimental waste rock pile. Five hundred meters of fiber optic cable were installed in a waste rock pile that is 70 m long, 10 m wide, and was covered with 0.60 m of fine compacted sand and 0.25 m of non‐reactive crushed waste rock. Volumetric water content was assessed by heating the fiber optic cable with 15‐min heat pulses at 15 W/m every 30 min. To test the aFO‐DTS system 14 mm of recharge was applied to the top surface of the waste rock pile over 4 h, simulating a major rain event. The average volumetric water content in the FCL increased from 0.10 to 0.24 over the duration of the test. The volumetric water content measured with aFO‐DTS in the FCL and waste rock was within ±0.06 and ±0.03, respectively, compared with values measured using 96 dielectric soil moisture probes over the same time period. Additional results illustrate how water can be confined within the FCL and monitored through an aFO‐DTS protocol serving as a practical means to measure soil moisture at an industrial capacity.
Migration of Injected Wastewater with High Levels of Ammonia in a Saline Aquifer in South Florida
Authors: Sepúlveda Nicasio , Lohmann Melinda
Published: January 2021

Treated wastewater with high levels of ammonia has been injected, since March 1983 into the deep saline units of the Lower Floridan aquifer (LFA) from a treatment plant near the east coast of Miami‐Dade County in southeastern Florida. Monitoring wells in the plant recorded ammonia concentrations above ambient levels at hydrogeologic units located about 1000 ft (304.8 m) above injection depths between 2500 and 2800 ft (762 and 853 m) below sea level. A solute‐transport model was developed to assess the horizontal and vertical extent of the injected ammonia, with ammonia moving from the injected zone into the overlying units: the upper semiconfining unit, the uppermost permeable zone of the LFA, and the middle semiconfining units of the Avon Park Formation. Ammonia is assumed to be transported under the effects of local heterogeneity in a porous limestone aquifer with high‐salinity ambient groundwater and via upward migration through quasi‐vertical pathways. A flow model of the migration of the injected ammonia was calibrated with PEST using head, salinity, and ammonia concentration data measured from 1983 to 2013. Borehole geophysical data support the high permeability of the uppermost permeable zone in the LFA. Average simulated head, normalized salinity, and ammonia concentration residuals over all monitoring wells were −1.37 ft, 0.01, and −0.67 mg/L, respectively. Model results are consistent with undetectable ammonia concentrations in the Upper Floridan aquifer.
Barriers and challenges of returning patients back to community after renal transplantation in Central Australia
Authors: Karepalli Vijay K. , Brown Megan , Sajiv Cherian , Fernandes David , Thomas Sajan , George Pratish , Nayar Sajith , Pawar Basant
Published: January 2021

Background

The majority of patients living in remote communities of Central Australia must relocate to Alice Springs for their dialysis treatments. There is limited information available about the challenges and barriers that Aboriginal patients encounter in the process of returning back to their communities after renal transplantation.

Aim

To determine the length of stay of patients in Alice Springs and challenges faced subsequent to renal transplantation, before they could safely return to their remote communities.

Methods

All transplant recipients from 2012 who are aged 18 years were analysed retrospectively.

Results

Thirty‐six patients received renal transplantation from Central Australia. Of them, 25 were from very remote communities of whom 24 were Aboriginal. Average length of stay in Alice Springs post‐transplantation prior to returning to community was 17.2 weeks (121 days). The most common challenge faced prior to returning to community was the need for monitoring and titration of immunosuppressive medication (100%) followed by infections (90%) and admissions to hospital (85%). The other common barrier was optimising glycaemic control (80%). Less common barriers included proficiency with self‐monitoring of blood sugar levels (50%), social factors (40%), blood pressure control (25%), leukopenia (25%), safe housing (20%) and rejection episodes (15%).

Conclusions

Multiple challenges are faced during post‐transplantation period in Alice Springs that prolong the time before recipients from remote communities can return home. Some barriers such as titration of immunosuppression are inherent in the transplant journey. However, some factors might be modifiable prior to transplantation.
Demystifying machine learning: a primer for physicians
Authors: Scott Ian A.
Published: January 2021

Machine learning is a tool for analysing digitised data sets and formulating predictions that can optimise clinical decision‐making. It aims to identify complex patterns in large data sets and encode them into models that can then classify new unseen cases or make predictions on new data. Machine learning methods take several forms and individual models can be of many different types. More than 50 models have been approved for use in routine healthcare, and the numbers continue to grow exponentially. The reliability and robustness of any model depends on multiple factors, including the quality and quantity of the data used to develop the models, and the selection of features in the data considered most important to maximising accuracy. In ensuring models are safe, effective and reproducible in routine care, physicians need to have some understanding of how these models are developed and evaluated, and to collaborate with data and computer scientists in their design and validation. This narrative review introduces principles, methods and examples of machine learning in a way that does not require mastery of highly complex statistical and computational concepts.
Nanocellulose‐based wound dressing for conservative wound management in children with second‐degree burns
Authors: Resch Annika , Staud Clement , Radtke Christine
Published: January 2021

The initial care of burn wounds and choice of dressing are pivotal to optimally support the healing process. To ensure fast re‐epithelialisation within 10–14 days and prevent complications, an optimal healing environment is essential. An innovative dressing based on nanocellulose was used for the treatment of burns in children. Children (0–16 years) with clean, partial‐thickness burn wounds, 1 to 10% of the total body surface area were included. Complete re‐epithelialisation was achieved within 7–17 days, with 13 patients showing re‐epithelialised >95% by day 10. Satisfying results concerning time to re‐epithelialisation and material handling were obtained. The possibility to leave the dressing on the wounds for 7 days showed a positive effect in the treatment of children, for whom every hospital visit may cause massive stress reactions. The nanocellulose‐based dressing is a promising tool in conservative treatment of burns. Reducing the frequency of dressing changes supports a fast and undisturbed recovery; moreover, the dressing provides an optimal moist healing environment. The time to re‐epithelialisation is comparable to frequently used materials, and cost reduction effect can be achieved without loss of quality. Possible pain and distress levels are kept to a minimum; therefore, flexibility and compliance of the patients and their parents are enhanced.
A systematic meta‐thematic synthesis to examine the views and experiences of women following water immersion during labour and waterbirth
Authors: Feeley Claire , Cooper Megan , Burns Ethel
Published: January 2021

Aims

To gather, quality assess, synthesize and interpret the views, feeling, and experiences of women who used water immersion during labour and/or birth.

Design

A systematic meta‐thematic synthesis and GRADE‐CERQual.

Data sources

We searched MEDLINE, CINHAL, PsychINFO, AMED, EMBASE (MIDIRS only), LILACS, AJOL. Additional searches were carried out using Ethos (thesis database), cross‐referencing against Google Scholar and citation chasing. Searches were carried out in August 2019, updated February 2020.

Methods

Studies that met the selection criteria were appraised for quality. Data were extracted from the studies using meta‐thematic analytical techniques; coding, descriptive findings, and analytical findings. The descriptive findings were subjected to confidence assessments using GRADE‐CERQual.

Results

Seven studies met the inclusion criteria. Nine key statements of findings were generated – one had high confidence, three moderate, three low and one very low confidence in the findings. The analytical findings generated three main themes: Liberation and Self‐Emancipation, Synergy, transcendence and demarcation and Transformative birth and beyond. Overall, women experienced warm water immersion during labour and/or birth positively. Both the water and pool itself, facilitated women's physical and psychological needs during labour and/or birth, including offering effective analgesia. Our findings indicated that birthing pools are versatile tools that provide for a space that women can adapt and influence to best suit their individual needs.

Conclusion

Women who used warm water immersion for labour and/or birth describe liberating and transformative experiences of welcoming their babies into the world. They were empowered, liberated, and satisfied. We recommend maternity professionals and services offer water immersion as a standard method of pain relief during labour/birth.

Impact

Understanding women's experiences of labour and birth will inform future clinical practice. Midwives are optimally positioned to enhance women's access to water immersion. These findings have implications for education, guideline, and policy development as well as clinical practice.
miR‐34a in extracellular vesicles from bone marrow mesenchymal stem cells reduces rheumatoid arthritis inflammation via the cyclin I/ATM/ATR/p53 axis
Authors: Wu Huaiguo , Zhou Xike , Wang Xuedong , Cheng Wei , Hu Xinjia , Wang Yueping , Luo Bing , Huang Wenjun , Gu Juan
Published: January 2021

Extracellular vesicles (Evs) participate in the development of rheumatoid arthritis (RA), but the mechanisms remain unclear. This study aimed to determine the mechanism by which microRNA‐34a (miR‐34a) contained in bone marrow mesenchymal stem cell (BM‐MSC)‐derived Evs functions in RA fibroblast‐like synoviocytes (RA‐FLSs). BM‐MSC‐derived Evs and an Evs inhibitor were extracted. A rat model of RA was established. miR‐34a gain‐ and loss‐of‐function experiments were performed, and the inflammation in rat synovial fluid and tissues was detected. The role of miR‐34a in RA‐FLSs was also measured in vitro. The target gene of miR‐34a was predicted using the online software TargetScan and identified using a dual‐luciferase reporter gene assay, and the activation of the ATM/ATR/p53 signalling pathway was assessed. BM‐MSC‐derived Evs mainly elevated miR‐34a expression, which reduced RA inflammation in vivo and inhibited RA‐FLS proliferation and resistance to apoptosis in vitro, while inhibited miR‐34a expression enhanced RA development. In addition, miR‐34a could target cyclin I to activate the ATM/ATR/p53 signalling pathway, thus inhibiting abnormal RA‐FLS growth and RA inflammation. Our study showed that miR‐34a contained in BM‐MSC‐derived Evs could reduce RA inflammation by inhibiting the cyclin I/ATM/ATR/p53 signalling pathway.
The tyrosine kinase v‐Src modifies cytotoxicities of anticancer drugs targeting cell division
Authors: Yuki Ryuzaburo , Hagino Mari , Ueno Sachi , Kuga Takahisa , Saito Youhei , Fukumoto Yasunori , Yamaguchi Noritaka , Yamaguchi Naoto , Nakayama Yuji
Published: January 2021

v‐Src oncogene causes cell transformation through its strong tyrosine kinase activity. We have revealed that v‐Src‐mediated cell transformation occurs at a low frequency and it is attributed to mitotic abnormalities‐mediated chromosome instability. v‐Src directly phosphorylates Tyr‐15 of cyclin‐dependent kinase 1 (CDK1), thereby causing mitotic slippage and reduction in Eg5 inhibitor cytotoxicity. However, it is not clear whether v‐Src modifies cytotoxicities of the other anticancer drugs targeting cell division. In this study, we found that v‐Src restores cancer cell viability reduced by various microtubule‐targeting agents (MTAs), although v‐Src does not alter cytotoxicity of DNA‐damaging anticancer drugs. v‐Src causes mitotic slippage of MTAs‐treated cells, consequently generating proliferating tetraploid cells. We further demonstrate that v‐Src also restores cell viability reduced by a polo‐like kinase 1 (PLK1) inhibitor. Interestingly, treatment with Aurora kinase inhibitor strongly induces cell death when cells express v‐Src. These results suggest that the v‐Src modifies cytotoxicities of anticancer drugs targeting cell division. Highly activated Src‐induced resistance to MTAs through mitotic slippage might have a risk to enhance the malignancy of cancer cells through the increase in chromosome instability upon chemotherapy using MTAs.
The Latent Diffusion Network among National Parliaments in the Early Warning System of the European Union
Authors: Malang Thomas , Leifeld Philip
Published: January 2021

Since the Treaty of Lisbon, national parliamentary chambers in the European Union can issue reasoned opinions on legislative proposals by the European Commission. These individual reasoned opinions lead to a review if at least one third of all chambers raise such concerns. Hence, coordination among parliaments is key. Using advances in inferential network analysis, this article infers the underlying diffusion pathways among national parliaments through which chambers are related to each other in their decisions to raise subsidiarity concerns. The emerging diffusion network is characterised by a compartmentalization into communities of European Union budget net contributor and net recipient countries. This descriptive finding has implications for the institutional effectiveness and aspired democratic legitimacy of the Early Warning System. A multivariate statistical network analysis confirms that diffusion occurs among net recipient countries and that weak institutions follow the lead of strong institutions in the Early Warning System.
Updated assessment of potential biopesticide options for managing fall armyworm (Spodoptera frugiperda) in Africa
Authors: Bateman Melanie L. , Day Roger K. , Rwomushana Ivan , Subramanian Sevgan , Wilson Kenneth , Babendreier Dirk , Luke Belinda , Edgington Steve
Published: January 2021

The fall armyworm (FAW, Spodoptera frugiperda) has recently spread to many countries in Africa, the Near East, Asia and the Pacific. In sub‐Saharan Africa (SSA), more than 300 million people depend on FAW’s preferred host plant, maize, as a staple crop. Hence, the spread of FAW in SSA has the potential to negatively affect livelihoods and food security. Many farmers have responded to FAW by increasing their use of synthetic pesticides, but these are not always used safely or effectively. More information on sustainable alternatives to high‐risk synthetic pesticides is needed to inform decisions by farmers and policy makers. In a previous paper, the authors responded to this information need by identifying fifty biopesticides which had been registered for FAW management in one or more of 30 countries in FAWs native region and Africa. For each biopesticide identified, detailed profiles with information on their efficacy against FAW; associated human health and environmental hazards; their agronomic sustainability; and whether or not they are practical for use by smallholder farmers were developed Research for development (R4D) efforts is ongoing in Africa and Asia for development and use of biopesticides for FAW management. Hence, in this study the authors assessed the current state of knowledge and documented how information gaps have been filled (or not) since the previous paper was published. The authors found that for many biopesticides there is a growing body of information on their efficacy in the field in Africa and increased availability of commercialized products. They also note remaining information gaps, particularly the compatibility of the biopesticides with other recommended management practices, and cost‐benefit analyses, important for developing and implementing sustainable IPM. An updated list of priority biopesticides for research, development and promotion is provided.
Incorporating Outcomes that Matter to Older Adults into Surgical Research
Authors: Cheung Carling , Meissner Matthew A. , Garg Tullika
Published: January 2021

This editorial comments on the article by Thillainadesan et al. in this issue.
Clinical manifestations of placental mesenchymal dysplasia in Japan: A multicenter case series
Authors: Kodera Chisato , Aoki Saori , Ohba Takashi , Higashimoto Ken , Mikami Yoshiki , Fukunaga Masaharu , Soejima Hidenobu , Katabuchi Hidetaka
Published: January 2021

Aim

This study aimed to evaluate the clinical features and pregnancy outcomes of placental mesenchymal dysplasia (PMD) in Japan.

Methods

We requested detailed clinical information and placental tissue of PMD cases in 2000–2018 from Japanese facilities with departments of obstetrics and gynecology and analyzed the pregnancy course and neonatal outcomes.

Results

We collected 49 cases of PMD. Of 18 patients with measured maternal serum alpha‐fetoprotein (MSAFP) levels, 15 (83.3%) had elevated levels. Maternal serum human chorionic gonadotropin (MShCG) levels were transiently elevated in five (17.8%) of 28 patients. Forty‐seven patients continued their pregnancies. All pregnancies were singleton and 40 (85.1%) were associated with adverse events including fetal growth restriction (FGR), threatened premature delivery, fetal demise, and hypertensive disorder of pregnancy in 34 (72.3%), 14 (29.8%), eight (17.0%), and six (12.8%) patients, respectively. Of 47 infants, there were eight stillbirths. There were 40 (85.1%) female infants, and eight (17.0%) had Beckwith–Wiedemann syndrome. Of 39 live births, 23 (59.0%) were associated with premature induction of labor or cesarean section for obstetric indications related to FGR. Eighteen (46.2%) neonates had complications. PMD‐affected placentas were pathologically heterogeneous in both grossly PMD‐affected and non‐affected areas.

Conclusions

Our study included the largest number of PMD cases with detailed clinical information. PMD is a high‐risk condition for both the mother and the child. Elevated MSAFP levels with normal MShCG levels indicate PMD. Conventional perinatal management of FGR in Japan might be effective in reducing the fetal mortality rate.
Advanced MRI Findings in Medulloblastomas: Relationship to Genetic Subtypes, Histopathology, and Immunohistochemistry
Authors: Reis Jonas , Stahl Robert , Zimmermann Hanna , Ruf Viktoria , Thon Niklas , Kunz Mathias , Liebig Thomas , Forbrig Robert
Published: January 2021

BACKGROUND AND PURPOSE

For diagnosis of medulloblastoma, the updated World Health Organization classification now demands for genetic typing, defining more precisely the tumor biology, therapy, and prognosis. We investigated potential associations between magnetic resonance imaging (MRI) parameters including apparent diffusion coefficient (ADC) and neuropathologic features of medulloblastoma, focusing on genetic subtypes.

METHODS

This study was a retrospective single‐center analysis of 32 patients (eight females, median age = 9 years [range, 1‐57], mean 12.6 ± 11.3) from 2012 to 2019. Genetic subtypes (wingless [WNT]; sonic hedgehog [SHH]; non‐WNT/non‐SHH), histopathology, immunohistochemistry (p53, Ki67), and the following MRI parameters were correlated: tumor volume, location (midline, pontocerebellar, and cerebellar hemisphere), edema, hydrocephalus, metastatic disease (presence/absence and each), contrast‐enhancement (minor, moderate, and distinct), cysts (none, small, and large), hemorrhage (none, minor, and major), and ADCmean. The ADCmean was calculated using manually set regions of interest within the solid tumor. Statistics comprised univariate and multivariate testing.

RESULTS

Out of 32 tumors, three tumors were WNT activated (9.4%), 13 (40.6%) SHH activated, and 16 (50.0%) non‐WNT/non‐SHH. Hemispherical location (n = 7/8, P = .003) and presence of edema (8/8; P < .001, specificity 100%, positive predictive value 100%) were significantly associated with SHH activation. The combined parameter “no edema + no metastatic disease + cysts” significantly discriminated WNT‐activated from SHH‐activated medulloblastoma (P = .036). ADCmean (10–6 mm2/s) was 484 for WNT‐activated, 566 for SHH‐activated, and 624 for non‐WNT/non‐SHH subtypes (P = .080). A significant negative correlation was found between ADCmean and Ki67 (r = –.364, P = .040).

CONCLUSION

MRI analysis enabled noninvasive differentiation of SHH‐activated medulloblastoma. ADC alone was not reliable for genetic characterization, but associated with tumor proliferation rate.
Heart rate variability and obstructive sleep apnea: Current perspectives and novel technologies
Authors: Ucak Seren , Dissanayake Hasthi U. , Sutherland Kate , de Chazal Philip , Cistulli Peter A.
Published: January 2021

Obstructive sleep apnea (OSA) is a highly prevalent condition, resulting in recurrent hypoxic events, sleep arousal, and daytime sleepiness. Patients with OSA are at an increased risk of cardiovascular morbidity and mortality. The mechanisms underlying the development of cardiovascular disease in OSA are multifactorial and cause a cascade of events. The primary contributing factor is sympathetic overactivity. Heart rate variability (HRV) can be used to evaluate shifts in the autonomic nervous system, during sleep and in response to treatment in patients with OSA. Newer technologies are aimed at improving HRV analysis to accelerate processing time, improve the diagnosis of OSA, and detection of cardiovascular risk. The present review will present contemporary understandings and uses for HRV, specifically in the realms of physiology, technology, and clinical management.
Interventions using behavioural insights to influence children's diet‐related outcomes: A systematic review
Authors: Chambers Timothy , Segal Alexa , Sassi Franco
Published: January 2021

The global prevalence of children with overweight and obesity continues to rise. Obesity in childhood has dire long‐term consequences on health, social and economic outcomes. Promising interventions using behavioural insights to address obesity in childhood have emerged. This systematic review examines the effectiveness and health equity implications of interventions using behavioural insights to improve children's diet‐related outcomes. The search strategy included searches on six electronic databases, reference lists of previous systematic reviews and backward searching of all included studies. One‐hundred and eight papers describing 137 interventions were included. Interventions using behavioural insights were effective at modifying children's diet‐related outcomes in 74% of all included interventions. The most promising approaches involved using incentives, changing defaults and modifying the physical environment. Information provision alone was the least effective approach. Health equity implications were rarely analysed or discussed. There was limited evidence of the sustainability of interventions—both in relation to their overall effectiveness and cost‐effectiveness. The limited evidence on health equity, long‐term effectiveness and the cost‐effectiveness of these interventions limit what can be inferred for policymakers. This review synthesises the use of behavioural insights to improve children's diet‐related outcomes, which can be used to inform future interventions.
Arabidopsis sirtuins and poly(ADP‐ribose) polymerases regulate gene expression in the day but do not affect circadian rhythms
Authors: Kim Jun Hyeok , Bell Laura J. , Wang Xiao , Wimalasekera Rinuckshi , Bastos Hugo P. , Kelly Krystyna A. , Hannah Matthew A. , Webb Alex A. R.
Published: January 2021

Nicotinamide‐adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP‐ribose) polymerases (PARPs) that add poly(ADP‐ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by‐product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA‐seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression.
An auxin‐mediated regulatory framework for wound‐induced adventitious root formation in tomato shoot explants
Authors: Alaguero‐Cordovilla Aurora , Sánchez‐García Ana Belén , Ibáñez Sergio , Albacete Alfonso , Cano Antonio , Acosta Manuel , Pérez‐Pérez José Manuel
Published: January 2021

Adventitious roots (ARs) are produced from non‐root tissues in response to different environmental signals, such as abiotic stresses, or after wounding, in a complex developmental process that requires hormonal crosstalk. Here, we characterized AR formation in young seedlings of Solanum lycopersicum cv. ‘Micro‐Tom’ after whole root excision by means of physiological, genetic and molecular approaches. We found that a regulated basipetal auxin transport from the shoot and local auxin biosynthesis triggered by wounding are both required for the re‐establishment of internal auxin gradients within the vasculature. This promotes cell proliferation at the distal cambium near the wound in well‐defined positions of the basal hypocotyl and during a narrow developmental window. In addition, a pre‐established pattern of differential auxin responses along the apical‐basal axis of the hypocotyl and an as of yet unknown cell‐autonomous inhibitory pathway contribute to the temporal and spatial patterning of the newly formed ARs on isolated hypocotyl explants. Our work provides an experimental outline for the dissection of wound‐induced AR formation in tomato, a species that is suitable for molecular identification of gene regulatory networks via forward and reverse genetics approaches.
Acetaminophen elevates unbound bilirubin levels by the glucose oxidase‐peroxidase method
Authors: Ichimura Shintaro , Kakita Hiroki , Asai Shimpei , Mori Mari , Takeshita Satoru , Ueda Hiroko , Kondo Tomoko , Ohashi Wataru , Okumura Akihisa , Yamada Yasumasa
Published: January 2021

Background

Acetaminophen is widely administered to neonates but its effect on unbound bilirubin (UB) levels remains unclear. The aim of this study was to clarify whether administration of acetaminophen is related to an elevation of UB levels.

Method

Infants with a birthweight of ˂1,500 g admitted to our neonatal intensive care unit between January 2017 and April 2020 were retrospectively reviewed. Seventy‐one infants were enrolled, five of whom had received acetaminophen. Clinical data were analyzed when the highest UB value (UB peak) in each infant was recorded. Demographic data and information on treatment within the 24 h before the UB peak were also collected. UB was determined by the glucose oxidase‐peroxidase (GOD‐POD) method. Infants were categorized according to the presence or absence of acetaminophen administration (acetaminophen and no acetaminophen groups) within 24 h of the UB peak. The relationship between UB values and various clinical variables was then compared.

Results

Both the peak UB value and the ratio of gastrointestinal disease were higher in the acetaminophen group than in the no acetaminophen group. Univariate analysis revealed that a total of seven variables were potentially correlated with UB peak values (P < 0.10). Multivariate analysis showed that acetaminophen and direct bilirubin were independently associated with UB peak values.

Conclusion

Our study suggests that administration of acetaminophen is related to higher UB levels by the GOD‐POD method. UB values measured by the GOD‐POD method should not be used in infants treated with acetaminophen for evaluation of bilirubin neurotoxicity avoidance.
Factors associated with bleeding after endoscopic variceal ligation in children
Authors: Yokoyama Shinya , Ishizu Yoji , Ishigami Masatoshi , Honda Takashi , Kuzuya Teiji , Ito Takanori , Hinoki Akinari , Sumida Wataru , Shirota Chiyoe , Tainaka Takahisa , Makita Satoshi , Yokota Kazuki , Uchida Hiroo , Fujishiro Mitsuhiro
Published: January 2021

Background

Endoscopic variceal ligation (EVL) is a widely accepted treatment for esophagogastric varices in patients with portal hypertension (PHT). It is used for urgent treatment and prophylactic treatment of esophagogastric varices in pediatric as well as adult patients. However, major life‐threatening adverse events such as early rebleeding can occur. Although early rebleeding after EVL among children and adolescents has been reported, the risk factors remain obscure. This study evaluated the risk factors for early rebleeding after EVL in children and adolescents.

Methods

The subjects were children and adolescents (<18 years) with PHT who underwent EVL for esophagogastric varices. Early rebleeding was defined as hematemesis, active bleeding, or blood retention in the stomach, confirmed by esophagogastroduodenoscopy from 2 h to 5 days after EVL.

Results

A total of 50 EVL sessions on 22 patients were eligible for this study. There were four episodes of early rebleeding. No other major adverse event has occurred. Multivariate analysis showed that EVL implemented at cardiac varices just below the esophagogastric junction (EGJ), within 5 mm from the EGJ, is the independent factor for a higher risk of early rebleeding: odds ratio 18.2 (95% confidence interval: 1.40–237.0), P = 0.02.

Conclusions

Children and adolescents who undergo EVL for cardiac varices just below the EGJ have a higher risk of early rebleeding than those who do not.