bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of insulin resistance through a multiorgan microfluidic organ-on-chip
Authors: Tanataweethum Nida , Trang Allyson , Lee Chaeeun , Mehta Jhalak , Patel Neha , Cohen Ronald N , Bhushan Abhinav
Published: December 2021

The development of hepatic insulin resistance (IR) is a critical factor in developing type 2 diabetes (T2D), where insulin fails to inhibit hepatic glucose production but retains its capacity to promote hepatic de novo lipogenesis leading to hyperglycemia and hypertriglyceridemia. Improving insulin sensitivity can be effective in preventing and treating T2D. However, selective control of glucose and lipid synthesis has been difficult. It is known that excess white adipose tissue is detrimental to insulin sensitivity, whereas brown adipose tissue transplantation can restore it in diabetic mice. However, challenges remain in our understanding of liver-adipose communication because the confounding effects of hypothalamic regulation of metabolic function cannot be ruled out in previous studies. There is a lack of in vitro models that use primary cells to study cellular-crosstalk under insulin resistant conditions. Building upon our previous work on the microfluidic primary liver and adipose organ-on-chips, we report for the first time, the development of an integrated insulin resistant liver-adipose (white and brown) organ-on-chip. The design of the microfluidic device was carried out using computational fluid dynamics; the experimental studies were conducted by carrying out detailed biochemical analysis RNA-seq analysis on both cell types. Further, we tested the hypothesis that brown adipocytes (BAC) regulated both hepatic insulin sensitivity and de novo lipogenesis. Our results show that BAC effectively restored insulin sensitivity and supressed hepatic glucose production and de novo lipogenesis suggesting that the experimental platform could be useful for identifying potential therapeutics to treat IR and diabetes.
Assessing the role of compound drought and heatwave events on unprecedented 2020 wildfires in the Pantanal
Authors: Libonati Renata , Geirinhas João L , Silva Patrícia S , Russo Ana , Rodrigues Julia A , Belém Liz B C , Nogueira Joana , Roque Fabio O , DaCamara Carlos C , Nunes Ana M B , Marengo José A , Trigo Ricardo M
Published: December 2021

The year 2020 had the most catastrophic fire season over the last two decades in the Pantanal, which led to outstanding environmental impacts. Indeed, much of the Pantanal has been affected by severe dry conditions since 2019, with evidence of the 2020’s drought being the most extreme and widespread ever recorded in the last 70 years. Although it is unquestionable that this mega-drought contributed significantly to the increase of fire risk, so far, the 2020’s fire season has been analyzed at the univariate level of a single climate event, not considering the co-occurrence of extreme and persistent temperatures with soil dryness conditions. Here, we show that similarly to other areas of the globe, the influence of land-atmosphere feedbacks contributed decisively to the simultaneous occurrence of dry and hot spells (HPs), exacerbating fire risk. The ideal synoptic conditions for strong atmospheric heating and large evaporation rates were present, in particular during the HPs, when the maximum temperature was, on average, 6 °C above the normal. The short span of the period during those compound drought-heatwave (CDHW) events accounted for 55% of the burned area of 2020. The vulnerability in the northern forested areas was higher than in the other areas, revealing a synergistic effect between fuel availability and weather-hydrological conditions. Accordingly, where fuel is not a limiting factor, fire activity tends to be more modelled by CDHW events. Our work advances beyond an isolated event-level basis towards a compound and cascading natural hazards approach, simultaneously estimating the contribution of drought and heatwaves to fuelling extreme fire outbreaks in the Pantanal such as those in 2020. Thus, these findings are relevant within a broader context, as the driving mechanisms apply across other ecosystems, implying higher flammability conditions and further efforts for monitoring and predicting such extreme events.
Spring coherence in dissolved organic carbon export dominates total coherence in Boreal Shield forested catchments
Authors: Morison M Q , Higgins S N , Webster K L , Emilson E J S , Yao H , Casson N J
Published: December 2021

The wide range of forested landscapes in boreal environments store and cycle substantial amounts of carbon, although the capacity of these systems to act as either a carbon sink or source is uncertain under a changing climate. While there are clear reports of regional-scale increases in dissolved organic carbon (DOC) concentrations in streams and lakes, there remains substantial watershed-scale variability in these patterns. Coherence is a framework for examining if variables of interest within adjacent spatial units change synchronously or asynchronously through time and has been widely applied in the context of lentic hydrochemistry, and which can shed light on the relative importance of regional- vs. local-scale controls. The objective of this research was to quantify coherence in discharge, DOC concentrations, and DOC loads in forested boreal watersheds, and to what extent coherence varied by season. Coherence was assessed using data from three long-term ecological research sites spanning boreal forest environments (IISD-Experimental Lakes Area, Turkey Lakes Watershed Study, and Dorset Environmental Science Centre) that included 29 829 DOC measurements across 739 stream-years, examining correlation between stream-pairs within each site, but not between sites. Seasonal coherence in DOC export was consistent across the three sites; coherence was significantly greater in spring than all other seasons, and was strongly related to discharge coherence. Currently, the season with the greatest loads (spring) is also the most coherent season, suggesting that annual between-stream coherence may be reduced if spring becomes proportionally less important in hydrologic budgets under a changing climate. This research aids in determining which factors contribute to synchronous watershed behaviour, and which factors may contribute to the timing and extent of individual watershed-scale deviations from landscape-level patterns.
Strong regulation of daily variations in nighttime surface urban heat islands by meteorological variables across global cities
Authors: She Yihang , Liu Zihan , Zhan Wenfeng , Lai Jiameng , Huang Fan
Published: December 2021

Knowledge of the day-to-day dynamics of surface urban heat island (SUHI) as well as their underlying determinants is crucial to a better design of effective heat mitigation. However, there remains a lack of a globally comprehensive investigation of the responsiveness of SUHI variations to meteorological variables. Based on the MODIS land surface temperature and auxiliary data in 2017, here we investigated 10 000+ cities worldwide to reveal day-to-day SUHI intensity (SUHII) variations (termed as SUHIIdv) in response to meteorological variables using Google Earth Engine. We found that: (a) meteorological variables related to the thermal admittance, e.g. precipitation, specific humidity (SH) and soil moisture (SM) (represented by daily temperature range in rural area, DTRr), reveal a larger regulation on SUHIIdv than those related to the air conditions (e.g. wind speed and near-surface air temperature) over a global scale. (b) Meteorological regulations on SUHIIdv can differ greatly by background climates. The control of SH on SUHIIdv is significantly strengthened in arid zones, while that of wind speed is weakened prominently in equatorial zones. SUHIIdv is more sensitive to SM in cities with higher background temperatures. (c) All meteorological variables, except that related to SM (DTRr), show larger impact on SUHIIdv with antecedent precipitation over the global scale. Precipitation is observed to mitigate the SUHIIdv globally, and such effects are even more pronounced in equatorial and arid zones. We consider that our findings should be helpful in enriching the knowledge of SUHI dynamics on multiple timescales.
Attribution of the spatial heterogeneity of Arctic surface albedo feedback to the dynamics of vegetation, snow and soil properties and their interactions
Authors: Yu Linfei , Leng Guoyong , Python Andre
Published: December 2021

The Arctic warming rate is triple the global average, which is partially caused by surface albedo feedback (SAF). Understanding the varying pattern of SAF and the mechanisms is therefore critical for predicting future Arctic climate under anthropogenic warming. To date, however, how the spatial pattern of seasonal SAF is influenced by various land surface factors remains unclear. Here, we aim to quantify the strengths of seasonal SAF across the Arctic and to attribute its spatial heterogeneity to the dynamics of vegetation, snow and soil as well as their interactions. The results show a large positive SAF above −5% K−1 across Baffin Island in January and eastern Yakutia in June, while a large negative SAF beyond 5% K−1 is observed in Canada, Chukotka and low latitudes of Greenland in January and Nunavut, Baffin Island and Krasnoyarsk Krai in July. Overall, a great spatial heterogeneity of Arctic land warming induced by positive SAF is found with a coefficient of variation (CV) larger than 61.5%, and the largest spatial difference is detected in wintertime with a CV > 643.9%. Based on the optimal parameter-based geographic detector model, the impacts of snow cover fraction (SCF), land cover type (LC), normalized difference vegetation index (NDVI), soil water content (SW), soil substrate chemistry (SC) and soil type (ST) on the spatial pattern of positive SAF are quantified. The rank of determinant power is SCF > LC > NDVI > SW > SC > ST, which indicates that the spatial patterns of snow cover, land cover and vegetation coverage dominate the spatial heterogeneity of positive SAF in the Arctic. The interactions between SCF, LC and SW exert further influences on the spatial pattern of positive SAF in March, June and July. This work could provide a deeper understanding of how various land factors contribute to the spatial heterogeneity of Arctic land warming at the annual cycle.
The boundary integral equation for curved solid/liquid interfaces propagating into a binary liquid with convection
Authors: Titova E A , Alexandrov D V
Published: December 2021

The boundary integral method is developed for unsteady solid/liquid interfaces propagating into undercooled binary liquids with convection. A single integrodifferential equation for the interface function is derived using the Green function technique. In the limiting cases, the obtained unsteady convective boundary integral equation transforms into a previously developed theory. This integral is simplified for the steady-state growth in arbitrary curvilinear coordinates when the solid/liquid interface is isothermal (isoconcentration). Finally, we evaluate the boundary integral for a binary melt with a forced flow and analyze how the melt undercooling depends on Péclet and Reynolds numbers.
The two-step process of ovarian follicular growth and maturation in mammals can be compared to a fruit ripening where quality depends on the second step
Authors: Sirard Marc-André
Published: December 2021

In human in vitro fertilization, the main uncertainty factor impacting on success is oocyte quality, which largely depends on the follicular status at the time of collection. Decades of debate ensued to find the perfect stimulation protocol demonstrated the complexity of the ovarian response to exogenous gonadotropins and the dynamic nature of late folliculogenesis. Although several follicular markers, proteins, RNA from granulosa cells or microRNA, and follicular fluid metabolites have been associated with outcome, the possibility to influence them during stimulation remains elusive. The heterogeneity of the follicle’s maturity following control ovarian stimulation is also an important factor to explain average poor oocyte quality still observed today. In this review, the analogy between the apple ripening on the tree and follicular development is presented to focus the attention on a biphasic process: growth and differentiation. The molecular analysis of the progressive follicular differentiation indicates two competing phenomena: growth and differentiation, where a delicate balance must operate from one to the other to ensure proper maturity at ovulation. As long as follicle-stimulating hormone (FSH) stimulates growth, follicles remain green, and it is only when FSH is replaced by luteinizing hormone that the ripening process begins, and “apples” become red. Both fruits, follicles and apples, depend on a perfect timing of events to generate offspring.
Spatial dispositions in English instrumental consort music, c.1575–1650: a further examination
Authors: Rastall Richard
Published: December 2021

Musical sources in table format show the various dispositions of performers around the table prescribed by composers, scribes and printers. Examination of the instrumental printed sources and the textless manuscript sources shows that a majority conform to three principles that foster aural clarity and good ensemble. Previous work indicated that the music itself, whether transmitted in table format or in partbooks, was sometimes composed with such dispositions in mind. Seating arrangements that embody the three principles are therefore advantageous in private performance and rehearsal; and for performance before an audience, with performers ranged in an arc rather than in a circle, suitable modification can achieve similar results.
The homing problem for autoregressive processes
Authors: Lefebvre Mario
Published: December 2021

The problem of maximizing or minimizing the time spent by a stochastic process in an interval is considered for autoregressive processes. The control applied to the system is equal to 0, $b$ or $-b$. Particular cases are considered, and the appropriate integral equations are solved explicitly, either exactly or approximately.
A C1-virtual element method of high order for the Brinkman equations in stream function formulation with pressure recovery
Authors: Mora David , Reales Carlos , Silgado Alberth
Published: December 2021

In this paper, we propose and analyze a $C^1$-virtual element method of high order to solve the Brinkman problem formulated in terms of the stream function. The velocity is obtained as a simple post-process from stream function and a novel strategy is written to recover the fluid pressure. We establish optimal a priori error estimates for the stream function, velocity and pressure with constants independent of the viscosity. Finally, we report some numerical test illustrating the behavior of the virtual scheme and supporting our theoretical results on different families of polygonal meshes.
Clinical and microbiological outcomes, by causative pathogen, in the ASPECT-NP randomized, controlled, Phase 3 trial comparing ceftolozane/tazobactam and meropenem for treatment of hospital-acquired/ventilator-associated bacterial pneumonia
Authors: Martin-Loeches Ignacio , Timsit Jean-François , Kollef Marin H. , Wunderink Richard G. , Shime Nobuaki , Nováček Martin , Kivistik Ülo , Réa-Neto Álvaro , Bruno Christopher J. , Huntington Jennifer A. , Lin Gina , Jensen Erin H. , Motyl Mary , Yu Brian , Gates Davis , Butterton Joan R. , Rhee Elizabeth G.
Published: December 2021

Objectives

In the ASPECT-NP trial, ceftolozane/tazobactam was non-inferior to meropenem for treating nosocomial pneumonia; efficacy outcomes by causative pathogen were to be evaluated.

Methods

Mechanically ventilated participants with hospital-acquired/ventilator-associated bacterial pneumonia were randomized to 3 g ceftolozane/tazobactam (2 g ceftolozane/1 g tazobactam) q8h or 1 g meropenem q8h. Lower respiratory tract (LRT) cultures were obtained ≤36 h before first dose; pathogen identification and susceptibility were confirmed at a central laboratory. Prospective secondary per-pathogen endpoints included 28 day all-cause mortality (ACM), and clinical and microbiological response at test of cure (7–14 days after the end of therapy) in the microbiological ITT (mITT) population.

Results

The mITT population comprised 511 participants (264 ceftolozane/tazobactam, 247 meropenem). Baseline LRT pathogens included Klebsiella pneumoniae (34.6%), Pseudomonas aeruginosa (25.0%) and Escherichia coli (18.2%). Among baseline Enterobacterales isolates, 171/456 (37.5%) were ESBL positive. For Gram-negative baseline LRT pathogens, susceptibility rates were 87.0% for ceftolozane/tazobactam and 93.3% for meropenem. For Gram-negative pathogens, 28 day ACM [52/259 (20.1%) and 62/240 (25.8%)], clinical cure rates [157/259 (60.6%) and 137/240 (57.1%)] and microbiological eradication rates [189/259 (73.0%) and 163/240 (67.9%)] were comparable with ceftolozane/tazobactam and meropenem, respectively. Per-pathogen microbiological eradication for Enterobacterales [145/195 (74.4%) and 129/185 (69.7%); 95% CI: −4.37 to 13.58], ESBL-producing Enterobacterales [56/84 (66.7%) and 52/73 (71.2%); 95% CI: −18.56 to 9.93] and P. aeruginosa [47/63 (74.6%) and 41/65 (63.1%); 95% CI: −4.51 to 19.38], respectively, were also comparable.

Conclusions

In mechanically ventilated participants with nosocomial pneumonia owing to Gram-negative pathogens, ceftolozane/tazobactam was comparable with meropenem for per-pathogen 28 day ACM and clinical and microbiological response.
A web-based tool for automatically linking clinical trials to their publications
Authors: Smalheiser Neil R , Holt Arthur W
Published: December 2021

Objective

Evidence synthesis teams, physicians, policy makers, and patients and their families all have an interest in following the outcomes of clinical trials and would benefit from being able to evaluate both the results posted in trial registries and in the publications that arise from them. Manual searching for publications arising from a given trial is a laborious and uncertain process. We sought to create a statistical model to automatically identify PubMed articles likely to report clinical outcome results from each registered trial in ClinicalTrials.gov.

Materials and Methods

A machine learning-based model was trained on pairs (publications known to be linked to specific registered trials). Multiple features were constructed based on the degree of matching between the PubMed article metadata and specific fields of the trial registry, as well as matching with the set of publications already known to be linked to that trial.

Results

Evaluation of the model using known linked articles as gold standard showed that they tend to be top ranked (median best rank = 1.0), and 91% of them are ranked in the top 10.

Discussion

Based on this model, we have created a free, public web-based tool that, given any registered trial in ClinicalTrials.gov, presents a ranked list of the PubMed articles in order of estimated probability that they report clinical outcome data from that trial. The tool should greatly facilitate studies of trial outcome results and their relation to the original trial designs.
Memes, Memes, Everywhere, nor Any Meme to Trust: Examining the Credibility and Persuasiveness of COVID-19-Related Memes
Authors: Wasike Ben
Published: December 2021

This study used an experimental design to examine the credibility and persuasiveness of COVID-19-related Internet memes. The study used a random sample of U.S. social media users (N = 1,200) with source credibility as the theoretical framework. Results indicate that memes with expert source attribution are more credible than those with nonexpert source attribution. The same applies to the persuasiveness of the memes. Memes with an objective message tone are also more credible and persuasive than those with a subjective message tone. Additionally, there is a positive correlation between the credibility of a meme and its persuasiveness. Age correlates inversely with persuasion and pro-mask/vaccine memes are more credible and persuasive than anti-mask/vaccines memes. These results have implications regarding COVID-19 messaging as well as on meme-based communication.
Unification types in Euclidean modal logics
Authors: Alizadeh Majid , Ardeshir Mohammad , Balbiani Philippe , Mojtahedi Mojtaba
Published: December 2021

We prove that $\textbf {K}5$ and some of its extensions that do not contain $\textbf {K}4$ are of unification type $1$.
Chinese High People’s Court ruling sheds light on the protection of non-conventional works
Authors: Quan Yanmin , Zhang Xiaohao
Published: December 2021

Case Number 1037 of the High People’s Court of Shaanxi Province, People’s Republic of China (2020/ Shaan Min Zhong 1037), 1 November 2021

In a high-profile case involving copyright protection of a non-conventional work of culinary presentation, the appellate court, the High People’s Court of Shaanxi Province, found a culinary presentation eligible for copyright protection. Although the disputed culinary presentation Feizixiao (fair mistress’s smile) failed to meet the threshold for copyright protection as a work of fine arts, the court agreed to grant protection against unfair competition.
Differential Expression of Three Dopamine Receptors in Varroa-Resistant Honey Bees
Authors: Bilodeau Lelania , Beaman Lorraine
Published: December 2021

Various stocks of honey bees (Apis mellifera L. (Hymenoptera: Apidae)) employ multiple mechanisms to control varroa mite (Varroa destructor Anderson & Trueman (Mesostigmata: Varroidae)) infestations. Identification of trait-associated genes and markers can improve efficiency of selective breeding. Dopamine receptors show promise in this regard in their association with numerous traits in honey bees, high plasticity, and indicated association with varroa resistance through QTL analysis. We assessed the relationship between exposure to mite-infested brood and gene expression of the honey bee dopamine receptors, Amdop1, Amdop2, and Amdop3, in bees and stocks with known levels of varroa resistance, in Spring 2016 (VSH vs Italian) and Summer 2019 (Pol-line vs Italian). Relative mRNA expression levels varied both by honey bee stock and before/after exposure to varroa-infested brood, in 7-, 10-, and 14-day-old bees. However, the trials revealed contrasting patterns in expression of the three dopamine receptors. In 2016, downregulation was evident in VSH bees, but varied by days post-emergence and by gene. The 2019 trial showed upregulation post-exposure in both stocks, and at all ages, for Amdop1, Amdop2, and Amdop3, with the exception of 14 d Italian bees for Amdop2 and Amdop3. Stock comparison in 2019 showed upregulation of all three dopamine-like receptors in post-exposure bees of all ages. Season and associated differences in mite loads may have contributed to the differences observed across trials. Differential expression of all three dopamine receptors suggests a role for the dopaminergic system in varroa resistance and suggests that further characterization of these receptors for breeding potential is warranted.
Medical Ethics as Taught and as Practiced: Principlism, Narrative Ethics, and the Case of Living Donor Liver Transplantation
Authors: O’Brien Daniel C
Published: December 2021

The dominant model for bioethical inquiry taught in medical schools is that of principlism. The heritage of this methodology can be traced to the Enlightenment project of generating a universalizable justification for normative morality arising from within the individual, rational agent. This project has been criticized by Alasdair MacIntyre who suggests that its failure has resulted in a fragmented and incoherent contemporary ethical framework characterized by fundamental intractability in moral debate. This incoherence implicates principlist conceptions of bioethics. Medical ethics as practiced, though, is partially in keeping with teleological alternatives to principlism. Nonetheless, the hegemony of principlism threatens to harm the practice of good medicine whenever it is used to provide justification for the sanction or prohibition of practices, despite not being equipped to grant moral authority to such justifications. An example of this failure and its resulting harm is expressed in the growing obsolescence of living donor liver transplantation.
Scopoletin stimulates the secretion of insulin via a KATP channel-dependent pathway in INS-1 pancreatic β cells
Authors: Park Jae Eun , Kim Seon Young , Han Ji Sook
Published: December 2021

Objectives

In this study, we investigated whether scopoletin stimulated the secretion of insulin in pancreatic β cells as well as the underlying mechanism involved in this process.

Methods

We incubated the INS-1 pancreatic β cells with various concentrations of glucose (1.1, 5.6 or 16.7 mM) in the presence or absence of scopoletin. We then analysed the secretion of insulin in the cells treated with insulin secretion inhibitors or secretagogues. The intracellular influx of calcium induced by scopoletin was also analysed using the Fluo-2 AM dye.

Key findings

We found that scopoletin (1–20 µM) markedly induced the secretion of insulin in a glucose concentration-dependent manner compared with the control. At depolarizing concentrations of potassium chloride (KCl), scopoletin markedly enhanced the insulin secretion compared with the cells which were treated only with KCl. Moreover, the treatment with diazoxide-opening K+ATP channel and verapamil blocking Ca2+ channel significantly decreased the scopoletin-induced increase in insulin secretion. After the pre-treatment of cells with a Ca2+ fluorescent dye, treatment with 20 µM scopoletin resulted in a significant increase in the influx of intracellular Ca2+, exhibiting fluorescence changes in various spectra.

Conclusions

Scopoletin stimulates the secretion of insulin via a K+ATP channel-dependent pathway in the INS-1 pancreatic β cells.
Flood syndrome following right-sided heart failure: a case report
Authors: Murruste Marko , Kase Karri , Kivilo Martin , Lepner Urmas
Published: December 2021

Flood syndrome is a rare condition, where a patient with ascites suffers sudden umbilical hernia rupture and a subsequent drainage of ascitic fluid from the abdominal cavity. The cause of ascites is usually liver cirrhosis. Complications associated with cirrhosis of the liver make Flood syndrome difficult to manage. In these cases, conservative management has been associated with high morbidity. We describe, to our knowledge, for the first time a patient with Flood syndrome caused by right-sided heart failure. We also show that conservative treatment gives great initial outcome and is a viable option for this type of Flood syndrome.
Perspectival Ontology: Between Situated Knowledge and Multiculturalism
Authors: Massimi Michela
Published: December 2021

In this paper I give an overview of a perspectival realist ontology. I discuss the role of situated knowledge and multiculturalism in perspectival ontology and offer a working definition of ‘phenomena’ as the minimal unit of such ontological commitment. I clarify how the view (and underlying notion of scientific perspective) differs from Kuhn’s view, and highlight some of its implications for how to think of scientific knowledge as a multicultural and cosmopolitan inquiry.
Predictive factors for achievement of treatment goals in patients with postmenopausal osteoporosis treated with denosumab
Authors: Hattori Kyosuke , Takahashi Nobunori , Kojima Toshihisa , Imagama Shiro
Published: December 2021

Objectives

To investigate efficacy of long-term treatment with denosumab and predictive factors for achievement of treatment goals in patients with postmenopausal osteoporosis (PMO).

Methods

We enrolled 111 PMO patients who had T-scores ≤−2.5 either at the lumbar spine (L-) or femoral neck (FN-), who had never been treated for osteoporosis, and who could be followed for at least 3 years. We first evaluated changes in bone mineral density (BMD) for up to 7 years. We next defined the treatment goal as the achievement of a T-score >−2.5 at month 36 and performed multivariate analysis to identify predictive factors for achievement of the goal.

Results

Lumbar spine- and femoral neck bone-mineral density increased yearly for 7 years. Among 87 patients with baseline L-T-scores ≤−2.5, better baseline L-T-scores predicted achievement of L-T-scores >−2.5 at month 36. The cut-off value for baseline L-T-score was −3.4. Among 76 patients with baseline FN-T-scores ≤−2.5, better baseline FN-T-scores predicted achievement of FN-T-scores >−2.5 at month 36. The cut-off value for baseline FN-T-scores was −2.8.

Conclusions

Long-term treatment with denosumab was effective in PMO patients. As better baseline T-score predicted achievement of T-scores >−2.5, early initiation of treatment will contribute to better outcome.
Catalytic activities, molecular connections, and biological functions of plant RNA exosome complexes
Authors: Lange Heike , Gagliardi Dominique
Published: December 2021

RNA exosome complexes provide the main 3′–5′-exoribonuclease activities in eukaryotic cells and contribute to the maturation and degradation of virtually all types of RNA. RNA exosomes consist of a conserved core complex that associates with exoribonucleases and with multimeric cofactors that recruit the enzyme to its RNA targets. Despite an overall high level of structural and functional conservation, the enzymatic activities and compositions of exosome complexes and their cofactor modules differ among eukaryotes. This review highlights unique features of plant exosome complexes, such as the phosphorolytic activity of the core complex, and discusses the exosome cofactors that operate in plants and are dedicated to the maturation of ribosomal RNA, the elimination of spurious, misprocessed, and superfluous transcripts, or the removal of mRNAs cleaved by the RNA-induced silencing complex and other mRNAs prone to undergo silencing.
Somatic DNA demethylation generates tissue-specific methylation states and impacts flowering time
Authors: Williams Ben P , Bechen Lindsey L , Pohlmann Deborah A , Gehring Mary
Published: December 2021

Cytosine methylation is a reversible epigenetic modification of DNA. In plants, removal of cytosine methylation is accomplished by the four members of the DEMETER (DME) family of 5-methylcytosine DNA glycosylases, named DME, DEMETER-LIKE2 (DML2), DML3, and REPRESSOR OF SILENCING1 (ROS1) in Arabidopsis thaliana. Demethylation by DME is critical for seed development, preventing experiments to determine the function of the entire gene family in somatic tissues by mutant analysis. Here, we bypassed the reproductive defects of dme mutants to create somatic quadruple homozygous mutants of the entire DME family. dme; ros1; dml2; and dml3 (drdd) leaves exhibit hypermethylated regions compared with wild-type leaves and rdd triple mutants, indicating functional redundancy among all four demethylases. Targets of demethylation include regions co-targeted by RNA-directed DNA methylation and, surprisingly, CG gene body methylation, indicating dynamic methylation at these less-understood sites. Additionally, many tissue-specific methylation differences are absent in drdd, suggesting a role for active demethylation in generating divergent epigenetic states across wild-type tissues. Furthermore, drdd plants display an early flowering phenotype, which involves 5′-hypermethylation and transcriptional down-regulation of FLOWERING LOCUS C. Active DNA demethylation is therefore required for proper methylation across somatic tissues and defines the epigenetic landscape of intergenic and coding regions.
Seawalls and Stilts: A Quantitative Macro Study of Climate Adaptation
Authors: Fried Stephie
Published: December 2021

Can we reduce the damage from climate change by investing in seawalls, stilts, or other forms of adaptation? Focusing on the case of severe storms in the US, I develop a macro heterogeneous-agent model to quantify the interactions between adaptation, federal disaster policy, and climate change. The model departs from the standard climate damage function and incorporates the damage from storms as the realization of idiosyncratic shocks. Using the calibrated model, I infer that adaptation capital comprises approximately 1$\%$ of the US capital stock. I find that while the moral hazard effects from disaster aid reduce adaptation in the US economy, federal subsidies for investment in adaptation more than correct for the moral hazard. I introduce climate change into the model as a permanent increase in either or both the severity or probability of storms. Adaptation reduces the damage from this climate change by approximately one-third. Finally, I show that modelling the idiosyncratic risk component of climate damage has quantitatively important implications for adaptation and for the welfare cost of climate change.
Is Ambient Weather a Risk Factor for Acute Encephalopathy Outbreaks in Children in Muzaffarpur, Bihar, India? Insight from a 9-Year Analysis
Authors: Singh Arun K , Shahi Sunil Kumar , Kumar Bhartendu , Das Manoja Kumar
Published: December 2021

Objectives

Despite periodic outbreaks, the causes and risk factors of acute encephalitis syndrome (AES) in children of Muzaffarpur, Bihar, India, remain unknown. We explored the correlation between AES caseload and the climate parameters.

Methods

Data for 1318 hospitalized children with AES during 2012–20 were used. The correlation between AES cases and daily climate parameters (temperature, sunshine, rainfall, humidity and wind speed) for the previous 24, 48 and 72 h were examined using Pearson’s and Spearman’s rank-order correlation and Poisson regression or negative binomial regression analyses.

Results

Most (91.8%) of the AES cases occurred during the summer season (May–July months), especially June month. Pearson’s and Spearman’s rank-order correlation analyses revealed that AES caseload had positive correlations with maximum (r = 0.275, ρ = 0.293) and minimum (r = 0.306, ρ = 0.306) temperatures during past 24 h and heat index (r = 0.325, ρ = 0.325) and negative correlation with humidity (r = −0.222, ρ = −0.222) and rainfall (r = −0.183, ρ = −0.183) (all p < 0.05). The correlation was consistent for the climate parameters for the past 24, 48 and 72 h. Regression analysis also documented a significant association of AES cases with daily maximum (β: 0.32–0.36) and minimum (β: 0.53–0.62) temperatures and heat index (β: 0.92–1.03) over past 24, 48 and 72 h (all p < 0.01). The number of AES cases exponentially increased when the daily maximum and minimum temperatures crossed 40°C and 31°C, respectively.

Conclusions

The climate parameters, especially temperature appears to be a risk factor for AES in children. The definite aetiological role of heat for AES in children needs further exploration.
High Serum Total IgE at Admission Is Associated with Coronary Artery Lesions in Children with Kawasaki Disease
Authors: Wang Zhi , Liu Xiaohui , Duan Zhao , Peng Yu
Published: December 2021

Kawasaki disease (KD) is associated with allergy. As immunoglobulin E (IgE), a key element of allergic reactions, is related with coronary heart disease, we evaluated the serum total IgE levels, and investigated its clinical relevance in 339 children with KD. These patients were classified as high IgE group and normal IgE group according to the reference value of IgE. Serum IgE levels in the high group (279.76 ± 202.54 IU/mL) significantly increased compared with the normal group (5.51 ± 15.79 IU/mL) (p < 0.001). There were also no significant differences in the frequency of major clinical manifestation between the two groups. The number of patients who developed coronary artery lesions (CALs) was significantly higher in the high group (p = 0.004), and the serum levels of IgE were also markedly higher in the KD patients with CALs than in patients without CALs (p = 0.002). High total serum IgE was an independent prognostic for CALs in the multivariate analysis. In conclusion, serum IgE levels may be associated with CALs in children with KD.
Colonization of Mutualistic Mycorrhizal and Parasitic Blast Fungi Requires OsRAM2-Regulated Fatty Acid Biosynthesis in Rice
Authors: Dai Huiling , Zhang Xiaowei , Zhao Boyu , Shi Jincai , Zhang Chi , Wang Gang , Yu Nan , Wang Ertao
Published: December 2021

Arbuscular mycorrhizal (AM) fungi form a mutual association with the majority of land plants, including most angiosperms of the dicotyledon and monocotyledon lineages. The symbiosis is based upon bidirectional nutrient exchange between the host and symbiont that occurs between inner cortical cells of the root and branched AM hyphae called arbuscules that develop within these cells. Lipid transport and its regulation during the symbiosis have been intensively investigated in dicotyledon plants, especially legumes. Here, we characterize OsRAM2 and OsRAM2L, homologs of Medicago truncatula RAM2, and found that plants defective in OsRAM2 were unable to be colonized by AM fungi and showed impaired colonization by Magnaporthe oryzae. The induction of OsRAM2 and OsRAM2L is dependent on OsRAM1 and the common symbiosis signaling pathway pathway genes CCaMK and CYCLOPS, while overexpression of OsRAM1 results in increased expression of OsRAM2 and OsRAM2L. Collectively, our data show that the function and regulation of OsRAM2 is conserved in monocot and dicot plants and reveals that, similar to mutualistic fungi, pathogenic fungi have recruited RAM2-mediated fatty acid biosynthesis to facilitate invasion.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Population Diversity of ‘Candidatus Liberibacter asiaticus’ and Diaphorina citri in Sichuan: A Case Study for Huanglongbing Monitoring and Interception
Authors: Cui Xuejin , Liu Kehong , Huang Jie , Fu Shimin , Chen Qingdong , Liu Xu , Zhou Changyong , Wang Xuefeng
Published: December 2021

Citrus huanglongbing (HLB) is present in 10 provinces in China and is associated with ‘Candidatus Liberibacter asiaticus’ (CLas), which is transmitted by the Asian citrus psyllid (Diaphorina citri, ACP). To date, HLB and ACP have expanded to Yibin city of Sichuan Province, posing an imminent threat to the citrus belt of the upper and middle reaches of the Yangtze River, an important late-maturing citrus-producing area in China. To understand the epidemiological route of CLas and ACP in newly invaded regions of Sichuan and thereby better establish an HLB interception zone ranging from Leibo to Yibin, we evaluated the molecular variability of 19 CLas draft genomes from citrus or dodder (Cuscuta campestris). They include three type-specific prophage loci, three variable number tandem repeat loci, a miniature inverted-repeat transposable element, and population diversity of 44 ACP mitochondrial genomes. The results indicated that CLas isolates in the newly invaded area (Pingshan) were more diverse than those in the HLB endemic areas (Leibo and Ningnan). Phylogenetic analysis based on mitochondrial genomes demonstrated that ACPs in Leibo, Pingshan, and Xuzhou (rural areas) represent a new mitochondrial group (MG4), distinguished by the three unique single-nucleotide polymorphisms in cox1, nad4, and cytb. However, the ACPs sampled from the urban areas of Cuiping and Xuzhou belonged to the southeastern China group (MG2-1). Altogether, our study revealed multiple sources of ACP and CLas in the HLB interception zone and proposed their transmission route. This study contributes to the formulation of precise HLB prevention and control strategies in the HLB interception zone in Sichuan and could be useful for HLB management efforts in other regions.
The Top News Stories of 2021: The Hidden Toll of COVID-19
Authors: Sofer Dalia
Published: December 2021

Workplace violence, domestic abuse, and firearm-related deaths are on the rise.
B cells in systemic lupus erythematosus
Authors: Szelinski Franziska , Lino Andreia C. , Dörner Thomas
Published: December 2021

Purpose of review

New insight into altered B cell distribution including newly identified subsets and abnormalities in systemic lupus erythematosus (SLE) as well as their role in immune protection are summarized in this review.

Recent findings

SLE carries characteristic B cell abnormalities, which offer new insights into B cell differentiation and their disturbances including discoveries of pathogenic B cell subsets and intrinsic B cell abnormalities. A recent study in SLE found that antigen-experienced B cell subsets lacking expression of CD27 and IgD defined by their lack of CXCR5 and CD19low expression are expanded in SLE and represent plasmablasts likely escaping proper selection. In terms of therapeutic targeting with broader coverage than rituximab, second-generation anti-CD20, anti-CD38 and CD19-CART treatment experiences have advanced our understanding recently. However, the key role of qualitative and quantitative B cell requirements in connection with T cells became apparent during SARS-Cov2 infection and vaccination, especially in patients with gradual B cell impairments by rituximab, mycophenolate mofetil and cyclophosphamide.

Identification and characterization relevant B cell subsets together with altered regulatory mechanisms in SLE facilitates new approaches in targeting pathogenic B cells but require consideration of preservation of protection.
Perioperative Hypothermia Is Associated With Increased 30-Day Mortality in Hip Fracture Patients in the United Kingdom: Α Systematic Review and Meta-analysis
Authors: Mroczek Thomas J. , Prodromidis Apostolos D. , Pearce Adrian , Malik Rayaz A. , Charalambous Charalambos P.
Published: December 2021

Objectives:

To undertake a systematic review and meta-analysis to determine the relationship between perioperative hypothermia and mortality after surgery for hip fracture.

Data Sources:

A systematic literature search of Medline, EMBASE, CINAHL, and Cochrane CENTRAL databases was performed using the Cochrane methodology for systematic reviews with no publication year limit. Only studies available in the English language were included.

Study selection:

Predetermined inclusion criteria were patients of any age with a hip fracture, exposure was their body temperature and outcome was mortality rate. Any comparative study design was eligible.

Data extraction:

The quality of selected studies was assessed according to each study design with the Methodological Index for Non-Randomised Studies (MINORS) used for all the retrospective comparative studies. The GRADE approach was used to assess the quality of evidence.

Data synthesis:

A meta-analysis was conducted using a random-effects model.

Results:

The literature search identified 1016 records. After removing duplicates and those not meeting inclusion criteria, 3 studies measuring 30-day mortality were included. All included studies were carried out in the United Kingdom. The mortality rate was higher in the hypothermic groups as compared with the normothermic group in all the studies, with the difference being significant in 2 of the studies (P < 0.0001). The meta-analysis showed that low body temperature was associated with an increased mortality risk (estimated odds ratio: 2.660; 95% confidence interval: 1.948–3.632; P < 0.001) in patients undergoing surgery for hip fracture.

Conclusions:

This study shows that low body temperature in hip fracture patients is associated with an increased 30-day mortality risk in the United Kingdom. Randomized control trials are required to determine whether the association between perioperative hypothermia in hip fracture patients and mortality is causal. Nevertheless, based on this analysis, we urge the maintenance of normal body temperature in the perioperative period to be included in national hip fracture guidelines.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Development of a Clinical Reasoning Learner Blueprint: A Guide for Teaching, Learning, and Assessment
Authors: Reilly Michelle , Furze Jennifer , Black Lisa , Knight Heather , Niski Jessica , Peterson Julie , Jensen Gail
Published: December 2021

Background and Purpose:

Clinical reasoning (CR) is a foundational component of effective and innovative physical therapist practice. When considering the development of the CR process over time, a blueprint to guide both educators and students along the learner continuum is valuable to the teaching and learning process. This study describes the development of a learner blueprint for CR to guide educators in effective and evidence-based teaching, learning, and assessment strategies.

Method/Model Description and Evaluation:

A 4-phased process was used to develop the blueprint. Phase I (Critical literature review and content analysis): A literature search to identify articles relevant to the teaching, learning, and assessment of CR across the health professions was performed. Phase II (Creation of draft blueprint): Investigators reviewed all relevant articles, assigned them to a learner level, identified common themes and key concepts, and developed an overall summary statement of facilitation and assessment strategies. Phase III (Expert Analysis/validation and initial modification): Focus groups of content experts reviewed the blueprint for content, breadth, depth, and accuracy. Feedback from focus groups was used to inform initial modifications to the blueprint. Phase IV (Vetting of the blueprint with key stakeholders and final modifications): Key stakeholders including academic faculty, physical therapist students, physical therapist residents, and clinical instructors were recruited to review the blueprint for utility and applicability. Feedback from focus group data was used to inform a second round of blueprint modifications.

Outcomes:

After revisions based on the analysis of the stakeholder focus groups, a final blueprint was generated that represents linking learning theory with clinical practice expectations in describing teaching and learning strategies designed to facilitate and assess CR across the continuum of physical therapy education.

Discussion and Conclusion:

The CR learner blueprint can serve as a guide for educators to facilitate and assess CR across the educational continuum in both didactic and clinical environments. Further analysis and validation of the tool is needed.
Protein S Erlangen: a novel PROS1 gene mutation associated with quantitative protein S deficiency
Authors: Schneider Sabine , Reißig Julian , Weisbach Volker , Achenbach Susanne , Strobel Julian , Hackstein Holger
Published: December 2021

The members of a Caucasian family were genetically analyzed on suspicion of hereditary protein S deficiency. A novel mutation, c.1904T>C, associated with severe quantitative protein S deficiency was found. The novel PROS1 mutation was identified by sequencing of the PROS1 gene coding sequence. The identified c.1904T>C point mutation results in p.Phe635Ser amino acid exchange, which is located in the Laminin G-like 2 domain of protein S. Computational analysis indicates that this amino acid exchange affects the correct folding of the protein S antigen. Furthermore, this mutation is located in a region of the Laminin G-like 2 domain where changes in the amino acid sequence often result in decreased secretion. We postulate that the novel p.Phe635Ser mutation might lead to an incorrect folding, and thus, to a strongly impaired secretion of this protein S variant. We named this novel variant protein