bluuebunny/crossref_metadata_2025 huggingface dataset:
Random effects models of lymph node metastases in breast cancer: quantifying the roles of covariates and screening using a continuous growth model
Authors: Isheden Gabriel , Czene Kamila , Humphreys Keith
Published: January 2021

We recently described a joint model of breast cancer tumor size and number of affected lymph nodes, which conditions on screening history, mammographic density, and mode of detection, and can be used to infer growth rates, time to symptomatic detection, screening sensitivity, and rates of lymph node spread. The model of lymph node spread can be estimated in isolation from measurements of tumor volume and number of affected lymph nodes, giving inference identical to the joint model. Here, we extend our model to include covariate effects. We also derive theoretical results in order to study the role of screening on lymph node metastases at diagnosis. We analyze the association between hormone replacement therapy (HRT) and breast cancer lymph node spread, using data from a case‐control study designed specifically to study the effects of HRT on breast cancer. Using our method, we estimate that women using HRT at time of diagnosis have a 36% lower rate of lymph node spread than nonusers (95% confidence interval [CI] =(8%,58%)). This can be contrasted with the effect of HRT on the tumor growth rate, estimated here to be 15% slower in HRT users (95% CI = (−34%,+7%)). For screen‐detected cancers, we illustrate how lead time can relate to lymph node spread; and using symptomatic cancers, we illustrate the potential consequences of false negative screens in terms of lymph node spread.
The influence of context stability on physical activity and sedentary behaviour habit and behaviour: An ecological momentary assessment study
Authors: Maher Jaclyn P. , Rebar Amanda L. , Dunton Genevieve F.
Published: January 2021

Objectives

This study used ecological momentary assessment (EMA) to empirically test the theoretical propositions that habit for and level of physical activity (PA) and sedentary behaviour (SB) should be associated with degree of context stability of those behaviours.

Design

Older adults (N = 104) completed a 10‐day EMA protocol and continuous accelerometer monitoring.

Methods

As part of the EMA protocol older adults answered 6 EMA prompts per day to assess current behaviour as well as social and physical contexts of behaviour. Temporal context was determined via time stamps of EMA questionnaires. Context stability was calculated as the reversed entropy scores of the contexts (physical, social, temporal, behavioural [i.e., type]) of PA and SB weighted for total frequency of context prompts. Habit for PA and SB (operationalized as self‐reported behavioural automaticity) was assessed via baseline questionnaire. An ActivPAL monitor was worn to assess average daily time spent in moderate‐vigorous PA (MVPA), light PA, and SB, and number of sit‐to‐stand transitions.

Results

More stable physical contexts for physical activity predicted more MVPA (β = 10.22) and more stable social contexts for sitting predicted more SB (β = 1.36). More variety of time people tended to report engaging in SB, the more SB engaged in (β = −13.76). No context stability scores predicted light PA, sit‐to‐stand transitions, or habit.

Conclusions

Although context stability was related to behaviour, this did not appear to be explained by habit, as habit did not differ by the degree of context stability surrounding bouts of PA or SB.
The inhibitory effect of human DEFA5 in growth of gastric cancer by targeting BMI1
Authors: Wu Zhongwei , Ding Zhaohui , Cheng Bo , Cui Zongchao
Published: January 2021

Defensins, a class of small cysteine‐rich cationic polypeptides across cellular life, are identified as antimicrobial compounds that display direct antimicrobial and immune signaling activities that are involved in the host defense. In addition to their roles in the innate immune system, accumulating studies have reported that some members of defensins are expressed and involved in some cancer cells, such as colon cancer, colorectal cancer, lung cancer and renal cell carcinomas. However, the roles of α‐Defensin 5 (DEFA5) in tumorigenesis and development remain unknown. In the present study, bioinformatics analysis and quantitative PCR results showed that the expression level of DEFA5 was dramatically downregulated in human gastric cancer. Overexpression of human DEFA5 in gastric cancer cell lines SGC7901 and BGC823 effectively diminished cell proliferation and reduced the colony forming ability. Moreover, DEFA5 overexpression induced cell cycle arrest by significantly increasing the number of G1‐phase cells. Consistently, in vivo tumor formation experiments in nude mice showed the suppression of the tumor growth by DEFA5 overexpression, suggesting an inhibitory effect of DEFA5 in gastric cancer. Mechanistically, DEFA5 directly binds to BMI1, which subsequently decreased its binding at the CDKN2a locus and upregulated the expression of 2 cyclin‐dependent kinase inhibitors, p16 and p19. Taken together, we concluded that DEFA5 showed an inhibitory effect in gastric cancer cell growth and may serve as a potential tumor suppressor in gastric cancer.
Role of crosstalk between endothelial cells and smooth muscle cells in vascular calcification in chronic kidney disease
Authors: Zhang Yu‐Xia , Tang Ri‐Ning , Wang Li‐Ting , Liu Bi‐Cheng
Published: January 2021

Chronic kidney disease (CKD) is a severe health problem worldwide, and vascular calcification (VC) contributes substantially to the cardiovascular morbidity and high mortality of CKD. CKD is often accompanied by a variety of pathophysiological states, such as inflammation, oxidative stress, hyperglycaemia, hyperparathyroidism and haemodynamic derangement, that can cause injuries to smooth muscle cells (SMCs) and endothelial cells (ECs) to promote VC. Similar to SMCs, whose role has been widely explored in VC, ECs may contribute to VC via osteochondral transdifferentiation, apoptosis, etc. In addition, given their location in the innermost layer of the blood vessel lumen and preferential reception of various pro‐calcification stimuli, ECs can pass messages to vascular wall cells and communicate with them. Crosstalk between ECs and SMCs via cytokines through a paracrine mechanism, extracellular vesicles, miRNAs and myoendothelial gap junctions also plays a role in VC. In this review, we emphasize the role of intercellular crosstalk between ECs and SMCs in VC associated with CKD.
Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targetingCYP3A4*1Gallele function
Authors: Fohner Alison E. , Dalton Rachel , Skagen Kasse , Jackson Konner , Claw Katrina G. , Hopkins Scarlett E. , Robinson Renee , Khan Burhan A. , Prasad Bhagwat , Schuetz Erin G. , Nickerson Deborah A. , Thornton Timothy A. , Dillard Denise A. , Boyer Bert B. , Thummel Kenneth E. , Woodahl Erica L.
Published: January 2021

The frequencies of genetic variants in theCYP3A4andCYP3A5genes differ greatly across global populations, leading to profound differences in the metabolic activity of these enzymes and resulting drug metabolism rates, with important consequences for therapeutic safety and efficacy. Yet, the impact of genetic variants on enzyme activity are incompletely described, particularly in American Indian and Alaska Native (AIAN) populations. To characterize genetic variation inCYP3A4andCYP3A5and its effect on enzyme activity, we partnered with AIAN people living in two regions of Alaska: Yup’ik Alaska Native people living in the Yukon‐Kuskokwim Delta region of rural southwest Alaska and AIAN people receiving care at the Southcentral Foundation in Anchorage, Alaska. We identified low frequencies of novel and known variation inCYP3A4andCYP3A5, including low frequencies of theCYP3A4*1GandCYP3A5*1variants, and linkage disequilibrium patterns that differed from those we previously identified in an American Indian population in western Montana. We also identified increased activity of theCYP3A4*1Gallele in vitro and in vivo. We demonstrated that theCYP3A4*1Gallele confers increased protein content in human lymphoblastoid cells and both increased protein content and increased activity in human liver microsomes. We confirmed enhanced CYP3A4‐mediated 4β‐vitamin D hydroxylation activity in Yup’ik people with theCYP3A4*1Gallele. AIAN people in Alaska and Montana who carry theCYP3A4*1Gallele—coupled with low frequency of the functionalCYP3A5*1variant—may metabolize CYP3A substrates more rapidly than people with the referenceCYP3A4allele.
Adherence to triple‐component antihypertensive regimens is higher with single‐pill than equivalent two‐pill regimens: A randomized controlled trial
Authors: Sung Jidong , Ahn Kye Taek , Cho Byung‐Ryul , Lee Sung Yun , Kim Byung Jin , Kim Dae Kyeong , Park Joong‐il , Lee Wang‐Soo
Published: January 2021

Using a single‐pill combination (SPC) for hypertension (HTN) treatment resulted in better adherence and persistence than a free‐equivalent combination in previous observational studies. The aim of this study is to confirm superior adherence with a triple‐component SPC compared with an equivalent two‐pill regimen in a randomized controlled trial (RCT) using a medication event monitoring system (MEMS). This is a multicenter, open‐label, RCT. Subjects were persons with HTN whose clinic blood pressure was not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with a dual combination. Eligible patients were randomized to either the triple‐component SPC (olmesartan/amlodipine/hydrochlorothiazide 20/5/12.5 mg) group or the equivalent two‐pill (olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) group and maintained for 12 weeks. Primary outcomes were the difference in percentage of doses taken (PDT) and percentage of days with the prescribed dose taken correctly (PDTc) between the single‐ and two‐pill therapy groups, calculated from MEMS data. From 8 hospitals, 145 patients with HTN were randomized. The single‐pill group had significantly higher PDT and PDTc than the two‐pill group: median (25–75 percentile) PDT 95.1 (86.7–100.0) versus 92.1 (73.0–97.3); and PDTc 91.0 (79.4–96.5) versus 88.6 (69.2–96.3%), P = 0.04 for both by the Wilcoxon rank sum test. The single‐pill combination of the triple‐component antihypertensive regimen showed better adherence than the equivalent two‐pill therapy. Reducing pill burden by means of a single‐pill combination is an effective strategy for enhancing adherence to multiple‐agent antihypertensive therapy.

Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Previous studies suggested that the use of a single‐pill combination (SPC) in hypertension (HTN) treatment produced better adherence and persistence than a free‐equivalent combination. However, supportive data are confined to dual‐component SPC and came from observational studies using medication possession ratio as an outcome.

WHAT QUESTION DID THIS STUDY ADDRESS?

The objective of this study is to investigate whether a triple‐component SPC improved medication adherence over an equivalent two‐pill combination therapy in a randomized controlled trial using medication event monitoring systems.

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Medication adherence in the SPC group was superior to that of two‐pill group, confirming previous findings from observational studies.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This finding strongly supports the current HTN treatment guideline to prefer SPC with a higher level of evidence.
Utility of ultrasound‐guided fine needle aspiration cytology in assessing malignancy in head and neck pathology
Authors: Petrone Gianluigi , Rossi Esther Diana , Gallus Roberto , Petrelli Livia , Marrone Sabino , Rizzo Davide , Piras Antonio , Garofalo Gabriella , Rindi Guido , Galli Jacopo , Paludetti Gaetano , Bussu Francesco
Published: January 2021

Objective

Fine needle aspiration cytology (FNAC) is a well‐established diagnostic procedure for head and neck masses not clearly originating from mucosal or cutaneous surfaces. We analysed head and neck masses evaluated over a 2‐year period, to assess the reliability of FNAC for the evaluation of malignancy.

Methods

We enrolled all patients undergoing FNAC, from April 2013 to July 2015, in a single service of a large Italian university hospital. Relevant clinical data and ultrasonographic parameters of the lesions were recorded. We performed both conventional and thin‐prep smears. Clinical presentation, ultrasonographic features and final cytology diagnoses were analysed and correlated with histology.

Results

The series included 301 lesions in 285 patients, with a single (94.4%) or two (5.6%) lesions. Only eight samples were considered non‐diagnostic/inadequate (2.6%). Among the cases, 139 FNAC (46.1%) underwent surgery. Cytological‐histological correspondence was found in 89% of the cases. Concerning malignancy, we documented less than 4% false positives and less than 2.5% false negatives, with 92.7% sensitivity and 94.6% specificity.

Conclusion

FNAC diagnosis can be highly specific. Most importantly, it is highly reliable in assessing malignancy, thus defining the priority and guiding the management procedures.
Modelling species distributions and environmental suitability highlights risk of plant invasions in western United States
Authors: McMahon Devin E. , Urza Alexandra K. , Brown Jessi L. , Phelan Conor , Chambers Jeanne C.
Published: January 2021

Aim

Non‐native invasive plants impact ecosystems globally, and the distributions of many species are expanding. The current and potential distributions of many invaders have not been characterized at the broad scales needed for effective management. We modelled the distributions of 15 non‐native invasive grass and forb species of concern in western North America to define their environmental niches and predict potential invasion risk.

Location

Arid and semi‐arid western United States.

Methods

We modelled species distribution using presence/absence data from > 148,000 vegetation survey plots to predict the probability of presence of each species based on associated climate, soil, topography and disturbance records. Boosted regression tree models were trained and tested within a buffer distance from presence observations of each species. Buffers were optimized by adding absence observations from increasingly large areas until prediction of presence was maximized, as defined by the area under the precision‐recall curve (AUPRC). We evaluated model AUPRC and other metrics by cross‐validation within training areas, then projected final models within focal EPA level III ecoregions.

Results

Focal species were present in 2.7% to 21% of plots within model training areas of 40 to 340 km radius. Models conservatively estimated potential species presence, with typically low false positive rates and moderate sensitivity. The most influential predictors of presence included minimum temperature (especially for grasses), climatic water deficit, precipitation seasonality and fire history. Cold desert ecoregions were impacted by the most species, with predicted range expansion into the prairie ecoregions and infilling for Warm Desert species.

Main conclusions

Invasive forb and grass species are likely to expand their ranges and continued increases in temperature, aridity and area burned will increase invasion risk. Monitoring species presence and absence and mapping known and potential ranges with a focus on presence detection, as in our methodology, will aid in identifying new invasions and prioritizing prevention and control.
6–month–olds are sensitive to English morphology
Authors: Kim Yun Jung , Sundara Megha
Published: January 2021

Each language has its unique way to mark grammatical information such as gender, number and tense. For example, English marks number and tense/aspect information with morphological suffixes (e.g., ‐sor ‐ed). These morphological suffixes are crucial for language acquisition as they are the basic building blocks of syntax, encode relationships, and convey meaning. Previous research shows that English‐learning infants recognize morphological suffixes attached to nonce words by the end of the first year, although even 8‐month‐olds recognize them when they are attached to known words. These results support an acquisition trajectory where discovery of meaning guides infants' acquisition of morphological suffixes. In this paper, we re‐evaluated English–learning infants' knowledge of morphological suffixes in the first year of life. We found that 6–month–olds successfully segmented nonce words suffixed with–s,–ing,–edand a pseudo‐morpheme ‐sh. Additionally, they related nonce words suffixed with–s, but not ‐ing, ‐edor a pseudo‐morpheme–shand stems. By 8–months, infants were also able to relate nonce words suffixed with–ingand stems. Our results show that infants demonstrate knowledge of morphological relatedness from the earliest stages of acquisition. They do so even in the absence of access to meaning. Based on these results, we argue for a developmental timeline where the acquisition of morphology is, at least, concurrent with the acquisition of phonology and meaning.
Forecasting community reassembly using climate‐linked spatio‐temporal ecosystem models
Authors: Thorson James T. , Arimitsu Mayumi L. , Barnett Lewis A. K. , Cheng Wei , Eisner Lisa B. , Haynie Alan C. , Hermann Albert J. , Holsman Kirstin , Kimmel David G. , Lomas Michael W. , Richar Jon , Siddon Elizabeth C.
Published: January 2021

Ecosystems are increasingly impacted by human activities, altering linkages among physical and biological components. Spatial community reassembly occurs when these human impacts modify the spatial overlap between system components, and there is need for practical tools to forecast spatial community reassembly at landscape scales using monitoring data. To illustrate a new approach, we extend a generalization of empirical orthogonal function (EOF) analysis, which involves a spatio‐temporal ecosystem model that approximates coupled physical, biological and human dynamics. We then demonstrate its application to five trophic levels for the eastern Bering Sea by fitting to multiple, spatially unbalanced datasets measuring physical characteristics (temperature measurements and climate‐linked forecasts), primary producers (spring and fall size‐fractionated chlorophyll‐a), secondary producers (copepods), juveniles (age‐0 walleye pollock), adult consumers (five commercially important fishes), human activities (seasonal fishing effort) and mobile predators (seabirds). We identify the spatial niche for each ecosystem component, as well as dominant modes of variability that are highly correlated with a known bottom–up driver of dynamics. We then measure spatial overlap between interacting variables (using Schoener's‐D) and identify that age‐0 pollock have decreased spatial overlap with copepods and increased overlap with adult pollock during warm years, and also that adult pollock have increased overlap with arrowtooth flounder and decreased overlap with catcher–processor fishing effort during these warm years. Given the warming conditions that are projected for the coming decade, the model forecasts increased prey and competitor overlap involving adult pollock (between age‐0 pollock, adult pollock and arrowtooth flounder) and decreased overlap with the copepod forage base and with the catcher–processor fishery during future warming. We recommend that joint species distribution models be extended to incorporate ‘ecological teleconnections' (correlations between distant locations arising from known mechanisms) arising from behavioral adaptation by mobile animals as well as passive advection of nutrients and planktonic juvenile stages.
Ephedra as a gymnosperm evo‐devo model lineage
Authors: Di Stilio Verónica S. , Ickert‐Bond Stefanie M.
Published: January 2021

Established model systems in the flowering plants have greatly advanced our understanding of plant developmental biology, facilitating in turn its investigation across diverse land plants. The reliance on a limited number of model organisms, however, constitutes a barrier for future progress in evolutionary developmental biology (evo‐devo). In particular, a more thorough understanding of seed plant character evolution and of its genetic and developmental basis has been hampered in part by a lack of gymnosperm model systems, since most are trees with decades‐long generation times. Guided by the premise that future model organisms should be selected based on their character diversity, rather than simply phylogenetic “position,” we highlight biological questions of potential interest that can be addressed via comparative studies in Ephedra (Gnetales). In addition to having relatively small genomes and shorter generation times in comparison to most other gymnosperms, Ephedra are amenable to investigations on the evolution of the key reproductive seed plant innovations of pollination and seed dispersal, as well as on polyploidy, and adaptation to extreme environments.
Transforming growth factor‐β‐regulated fractalkine as a marker of erosive bone invasion in oral squamous cell carcinoma
Authors: Son Seung Hwa , Park Junhee , Jung Min Ju , Lee Sun Kyoung , Kim Hyungkeun , Kim Ki Rim , Park Kwang‐Kyun , Chung Won‐Yoon
Published: January 2021

Patients with oral squamous cell carcinoma (OSCC) bone invasion are surgically treated with bone resection, which results in severe physical and psychological damage. Here, we investigated the potential of fractalkine (CX3CL1), which is regulated by transforming growth factor (TGF‐β), as a novel biomarker for correct prediction and early detection of OSCC‐associated bone invasion. TGF‐β knockdown and treatment with a TGF‐β‐neutralizing antibody decreased the level of fractalkine in the culture media of HSC‐2 and YD10B OSCC cells. Treatment with a fractalkine‐neutralizing antibody reduced TGF‐β‐stimulated invasion by HSC‐2 and YD10B cells. Fractalkine treatment increased the viability, invasion, and uPA secretion of both OSCC cell lines. Furthermore, OSCC cell bone invasion was assessed following subcutaneous inoculation of wild‐type or TGF‐β knockdown OSCC cells in mouse calvaria. TGF‐β knockdown prevented erosive bone invasion, reduced the number of osteoclasts at the tumor‐bone interface, and downregulated fractalkine expression in mouse tumor tissues. Our results indicate that the production of fractalkine is stimulated by TGF‐β and mediates TGF‐β‐induced cell invasion in several OSCC cell lines showing an erosive pattern of bone invasion. Fractalkine may be a useful predictive marker and therapeutic target for OSCC‐induced bone destruction.
Women's entrepreneurship in Saudi Arabia: Feminist solidarity and political activism in disguise?
Authors: Alkhaled Sophie
Published: January 2021

This paper is a longitudinal study that uses insights from postcolonial feminism to explore women's entrepreneurship as a political form of feminist organizing for social change in Saudi Arabia. Postcolonial feminist approaches challenge Western feminism, which can obscure the diversity of women's lived experiences, agency, and activism. Through Bayat's (2013) theory of “quiet encroachment,” I identify the ways in which contemporary Western conceptualizations of feminist solidarity and social movements have dismissed “Other” women's “silent,” protracted and (dis)organized activism in parts of the Middle East. By exploring how Saudi women have utilized their entrepreneurial space as a legitimate platform for change, I aim to enrich understanding of women's activism through everyday solidarity practices, which allow them to quietly encroach onto the previously forbidden political space. The findings exemplify how their activism “quietly” developed over time through a three‐step process—from the entrepreneur aiming to empower women within their organization, to developing feminist consciousness within their entrepreneurial network, to becoming a “political activist” lobbying for policy changes for women. These solidarity practices exemplify the West's relationship with “the Other,” and reveal that feminist organizing for social change must be explored within its own context in order to fully appreciate its global political potential.
Clinicopathologic and MRI features of combined hepatocellular‐cholangiocarcinoma in patients with or without cirrhosis
Authors: Yoon Jongjin , Hwang Jeong A. , Lee Sunyoung , Lee Ji E. , Ha Sang Y. , Park Young N.
Published: January 2021

Background and Aims

Differences in combined hepatocellular‐cholangiocarcinomas (cHCC‐CCAs) arising in high‐risk patients with or without liver cirrhosis have not been elucidated. This study aimed to compare the clinicopathologic and imaging characteristics of cHCC‐CCAs in patients with or without cirrhosis and to determine the prognostic factors for recurrence‐free survival (RFS) after curative resections of single cHCC‐CCAs.

Methods

This retrospective study included 113 patients with surgically resected single cHCC‐CCAs who underwent preoperative magnetic resonance imaging from January 2008 to December 2019 at two tertiary referral centres. Clinical, pathologic and imaging features of tumours were compared in high‐risk patients with or without cirrhosis. Imaging features were assessed using the Liver Imaging Reporting and Data System (LI‐RADS) version 2018. RFS and associated factors were evaluated using Cox proportional hazards regression analysis, Kaplan‐Meier analysis and log‐rank test.

Results

cHCC‐CCAs arising from cirrhotic livers had a smaller mean tumour size (2.9 cm vs. 4.5 cm; P < .001) and were more frequently categorized as LR‐5 or 4 (41.2% vs. 20.0%; P = .024) than those arising from non‐cirrhotic livers. In multivariable analysis, a tumour size of > 3 cm (hazard ratio [HR], 2.081; 95% confidence interval [CI], 1.180‐3.668; P = .011) and the LR‐M category (HR, 2.302; 95% CI, 1.198‐4.424; P = .012) were independent predictors associated with worse RFS.

Conclusions

The tumour size and distribution of LI‐RADS categories of cHCC‐CCAs differed in high‐risk patients with or without cirrhosis. And LR‐M category was a worse prognosis predictor after curative resections than LR‐5 or 4 category.
Systematic investigations of high‐pressure polymorphs in shocked ordinary chondrites
Authors: Miyahara Masaaki , Yamaguchi Akira , Saitoh Masato , Fukimoto Kanta , Sakai Takeshi , Ohfuji Hiroaki , Tomioka Naotaka , Kodama Yu , Ohtani Eiji
Published: January 2021

Shock‐induced melting textures and high‐pressure polymorphs in 178 ordinary chondrites of all chemical groups and petrologic types were investigated. The shock‐induced melting modes were classified into three types, namely pocket, line, and network. The type of shock‐induced melting depends on the petrologic type. The width of the shock‐induced melt increased with increasing the petrologic type number. The approximate estimated shock‐pressure ranges recorded in and around the shock‐induced melts of the H‐group ordinary chondrites based on the identified high‐pressure polymorphs were as follows: H3, less than 2 GPa; H4–H6, 2–6 GPa. For ordinary chondrites of the L/LL group, the values were as follows: L/LL3, 2–6 GPa; L/LL4, 2–14 GPa; L5: 14–20 GPa; LL5, 2–14 GPa; L6, 17–23 GPa; and LL6, 14–18 GPa. After adopting the estimated shock pressures into the onion shell‐structured parent body model, the shock pressure on the surface was much lower than in the interior. One possibility is that the apparent lower shock pressure on the surface is due to spallation during the impact. Considering the features of the high‐pressure polymorphs, the major disruption history of the parent bodies is different in each chemical group, although the L/LL chondrite parent bodies may have a similar major disruption history.
Alternative splicing and gene expression play contrasting roles in the parallel phenotypic evolution of a salmonid fish
Authors: Jacobs Arne , Elmer Kathryn R.
Published: January 2021

Understanding the contribution of different molecular processes to evolution and development is crucial for identifying the mechanisms of adaptation. Here, we used RNA‐sequencing data to test the importance of alternative splicing and differential gene expression in a case of parallel adaptive evolution, the replicated postglacial divergence of the salmonid fish Arctic charr (Salvelinus alpinus) into sympatric benthic and pelagic ecotypes across multiple independent lakes. We found that genes differentially spliced between ecotypes were mostly not differentially expressed (<6% overlap) and were involved in different biological processes. Differentially spliced genes were primarily enriched for muscle development and functioning, while differentially expressed genes were involved in metabolism, immunity and growth. Furthermore, alternative splicing and gene expression were mostly controlled by independentcis‐regulatory quantitative trait loci (<3.4% overlap).Cis‐regulatory regions were associated with the parallel divergence in splicing (16.5% of intron clusters) and expression (6.7%–10.1% of differentially expressed genes), indicating shared regulatory variation across ecotype pairs. Contrary to theoretical expectation, we found that differentially spliced genes tended to be highly central in regulatory networks (“hub genes”) and were annotated to significantly more gene ontology terms compared to nondifferentially spliced genes, consistent with a higher level of pleiotropy. Together, our results suggest that the concerted regulation of alternative splicing and differential gene expression through different regulatory regions leads to the divergence of complementary processes important for local adaptation. This provides novel insights into the importance of contrasting but putatively complementary molecular processes in rapid parallel adaptive evolution.
Rescuing national unity with imagination: The case of Tabarnia
Authors: Baldoli Roberto , Mocca Elisabetta
Published: January 2021

This article analyses the drivers and developments of the recent rise of a fictional region: Tabarnia in Spain. This platform proposes the creation of a new autonomous region to oppose the project of secession of the independentist Catalan movement. Given the dearth of academic research, our article documents and explores the case of Tabarnia. We draw on a multimethod approach, entailing a thematic analysis and process‐tracing, to reconstruct the trajectory of this platform and to uncover its drivers, goals and strategies. By building on this evidence base, this article construes Tabarnia as an instance of imaginary regionalism created ex nihilo in the noosphere. As such, Tabarnia represents an a‐topia substantiated through a digital region‐building process heavily relying on the use of humour.
Precipitation regime controls bryosphere carbon cycling similarly across contrasting ecosystems
Authors: Grau‐Andrés Roger , Wardle David A. , Nilsson Marie‐Charlotte , Kardol Paul
Published: January 2021

In arctic and boreal ecosystems, ground bryophytes play an important role in regulating carbon (C) exchange between vast belowground C stores and the atmosphere. Climate is changing particularly fast in these high‐latitude regions, but it is unclear how altered precipitation regimes will affect C dynamics in the bryosphere (i.e. the ground moss layer including senesced moss, litter and associated biota) and the closely associated upper humus layer, and how these effects will vary across contrasting environmental conditions. Here, we set up a greenhouse experiment in which mesocosms were assembled containing samples of the bryosphere, dominated by the feather moss Hylocomium splendens, and the upper humus layer, that were collected from across a boreal forest chronosequence in northern Sweden which varies strongly in nutrient availability, productivity and soil biota. We tested the effect of variation in precipitation volume and frequency on CO2 exchange and dissolved organic carbon (DOC) export, and on moss growth. As expected, reduced precipitation volume and frequency lowered net CO2 efflux, DOC export and moss growth. However, by regulating moisture, the lower bryosphere and humus layers often mediated how precipitation volume and frequency interacted to drive C dynamics. For example, less frequent precipitation reduced moss growth only when precipitation volume was low. When volume was high, high moisture content of the humus layer helped avoid moss desiccation. Variation in precipitation regime affected C cycling consistently in samples collected across the chronosequence, despite large environmental variation along the sequence. This suggests that the bryosphere exerts a strong buffering effect on environmental variation at the forest floor, which leads to similar responses of C cycling to external perturbations across highly contrasting ecosystems. As such, our study indicates that projected increases in droughts and ground evapotranspiration in high‐latitude regions resulting from climate change will consistently reduce C losses from moss‐dominated ecosystems.
Chronic urticaria in children – New insights from a large cohort
Authors: Lachover‐Roth Idit , Rabie Ahmad , Cohen‐Engler Anat , Rosman Yossi , Meir‐Shafrir Keren , Confino‐Cohen Ronit
Published: January 2021

Background

Chronic spontaneous urticaria is well‐described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria.

Methods

This retrospective study followed children up to 18 years old, diagnosed with chronic spontaneous urticaria, between the years 2002‐2018, and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments, and outcomes were extracted from electronic medical records.

Results

Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, and 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25 ± 15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty‐seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2%, and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease.

Conclusions and clinical relevance

Chronic spontaneous urticaria in children is a self‐limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population, increasing the possibility of a special subgroup of TH2‐related chronic urticaria in children.
Characterization of the development dynamics within the linear growth bamboo leaf
Authors: Gao Zhipeng , Guo Lin , Chen Ming , Yu Fen , Wei Qiang
Published: January 2021

The leaf is the main photosynthetic organ in plants, such as bamboo. Leaves from bamboo are used as a food additive. However, according to our investigation, to date there have been no reports concerning the leaf development of bamboo. By measuring over 7500 parenchymal cells, we discovered that the linear leaf growth of Pseudosasa japonica could be divided into three growth sections. The first one is a roughly 1‐cm long division zone (DZ), containing about 1580 cells, located at the bottom of the leaf; the second one is an about 3‐cm long elongation zone (EZ), with ~1905 cells, located above the DZ; and the last is a mature zone (MZ) in which cell elongation is completed. The cell production rate of the DZ was 25.33–35.81 cells per hour, with an average of 29.73; and the cell division rate was ~0.45 cells per cell every 24 h. PacBio and Illumina transcriptome sequencing found 21 933 unigenes expressed in these zones. Further analysis revealed a dynamic transcriptome, with transcripts for cell division in the DZ changing to transcripts for cell elongation, photosynthetic development, secondary metabolism, stress resistance, and nutrition transport toward the leaf distal. Those transcriptome transformations correlated well with the changes of relative water content, biomass accumulation, and cellulose crystal degree and were supported by quantitative polymerase chain reaction data. These results revealed a developmental gradient of the bamboo linear growth leaf, which offers a foundation to elucidate and engineer leaf development in bamboo, an economically valuable plant.
Royal jelly may improve sperm characteristics during preservation of rooster semen: Gene expression of antioxidant enzymes
Authors: Hadavand Mirzaei Atefeh , Deldar Hamid , Ansari Pirsaraei Zarbakht , Shohreh Bahram
Published: January 2021

Sustainable production and the increasing number of embryonated hatching eggs are critical aspects of the poultry production industry. The present paper aims to appraise the effectiveness of royal jelly (RJ) on the semen characteristics of Native Mazandaran roosters in both liquid and frozen storage conditions. Semen collected from 10 sexually mature roosters and following dilution was supplemented with RJ at 0.0 (control), 5 (RJ5), 10 (RJ10), 20 (RJ20) and 40 (RJ 40) mg/ml. After cooling and freezing‐thawing, the percentage of forward progressive motility, viability, abnormality, hypo‐osmotic swelling test (HOST) and the mRNA abundance of antioxidant enzymes of spermatozoa were measured. Our results revealed that the addition of 5 mg/ml RJ to the semen extender significantly increased (p < .05) the percentages of forward progressive motility, viability and HOST during liquid and frozen storage. The abnormality of spermatozoa in the RJ5 group was significantly lower compared to the other groups. During liquid storage, a significant decrease in forward progressive motility was found after 48 hr in comparison with 24 hr at 4°C. High levels of RJ (from 10 to 40 mg/ml) were severely decreased the characteristics of rooster spermatozoa in comparison with RJ5 and the control group. The inclusion of RJ at 5 mg/ml to the semen extender enhanced the mRNA transcript of antioxidant enzymes of spermatozoa during liquid preservation. The mRNA abundance of antioxidant enzymes did not influence by cryostorage. Overall, these data suggest that supplementation of RJ at 5 mg/ml to the extender improved semen characteristics and redox status of rooster spermatozoa.
Spatio-Temporal Mixed Membership Models for Criminal Activity
Authors: Virtanen Seppo , Girolami Mark
Published: January 2021

We suggest a probabilistic approach to study crime data in London and highlight the benefits of defining a statistical joint crime distribution model which provides insights into urban criminal activity. This is achieved by developing a hierarchical mixture model for observations, crime occurrences over a geographical study area, that are grouped according to multiple time stamps and crime categories. The mixture components correspond to spatial crime distributions over the study area and the goal is to infer, based on the observations, how and to what degree the latent distributions are shared across the groups.
Changes in the autonomic and respiratory patterns in mice submitted to short‐term sustained hypoxia
Authors: Rodrigues Karla L. , Souza Juliana R. , Bazilio Darlan S. , de Oliveira Mauro , Moraes Melina P. S. , Moraes Davi J. A. , Machado Benedito H.
Published: January 2021

New Findings

What is the central question of this study?

Do mice submitted to sustained hypoxia present autonomic and respiratory changes similarly to rats?

What is the main finding and its importance?

Arterial pressure in the normal range, reduced baseline heart rate and tachypnoea were observed in behaving sustained hypoxia mice. Recordings in the in situ preparation of mice submitted to sustained hypoxia show an increase in cervical vagus nerve activity and a simultaneous reduction in thoracic sympathetic nerve activity correlated with changes in the respiratory cycle. Therefore, mice are an important model for studies on the modulation of sympathetic activity to the cardiovascular system and the vagus innervation of the upper airways due to changes in the respiratory network induced by sustained hypoxia.

Short‐term sustained hypoxia (SH) in rats induces sympathetic overactivity and hypertension due to changes in sympathetic–respiratory coupling. However, there are no consistent data about the effect of SH on mice due to the different protocols of hypoxia and difficulties associated with the handling of these rodents under different experimental conditions. In situ recordings of autonomic and respiratory nerves in SH mice have not been performed yet. Herein, we evaluated the effects of SH ( = 0.1 for 24 h) on baseline mean arterial pressure (MAP), heart rate (HR), respiratory frequency (fR) and responses to chemoreflex activation in behaving SH mice. A characterization of changes in cervical vagus (cVN), thoracic sympathetic (tSN), phrenic (PN) and abdominal (AbN) nerves in SH mice using the in situ working heart–brainstem preparation was also performed. SH mice presented normal MAP, significant reduction in baseline HR, increase in baseline fR, as well as increase in the magnitude of bradycardic response to chemoreflex activation. In in situ preparations, SH mice presented a reduction in PN discharge frequency, and increases in the time of expiration and incidence of late‐expiratory bursts in AbN activity. Nerve recordings also indicated a significant increase in cVN activity and a significant reduction in tSN activity during expiration in SH mice. These findings make SH mice an important experimental model for better understanding how changes in the respiratory network may impact on the modulation of vagal control to the upper airways, as well as in the sympathetic activity to the cardiovascular system.
The effect of time‐of‐day and circadian phase on vulnerability to seizure‐induced death in two mouse models
Authors: Purnell Benton S. , Petrucci Alexandra N. , Li Rui , Buchanan Gordon F.
Published: January 2021

Key points

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature death in patients with refractory epilepsy.

SUDEP typically occurs during the night, although the reason for this is unclear.

We found that, in normally entrained mice, time‐of‐day alters vulnerability to seizure‐induced death.

We found that, in free‐running mice, circadian phase alters the vulnerability to seizure‐induced death.

These findings suggest that circadian rhythmicity may be responsible for the increased night‐time prevalence of SUDEP

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy‐related death. SUDEP typically occurs during the night following a seizure. Many aspects of mammalian physiology are regulated by circadian rhythms in ways that might make seizures occuring during the night more dangerous. Using two mouse models of seizure‐induced death, we demonstrate that time‐of‐day and circadian rhythms alter vulnerability to seizure‐induced death. We exposed normally entrained DBA/1 mice to a potentially seizure‐inducing acoustic stimulus at different times of day and compared the characteristics and outcomes of the seizures. Time‐of‐day did not alter the probability of a seizure but it did alter the probability of seizure‐induced death. To determine whether circadian rhythms alter vulnerability to seizure‐induced death, we induced maximal electroshock seizures in free‐running C57BL/6J mice at different circadian time points at the same time as measuring breathing via whole body plethysmography. Circadian phase did not affect seizure severity but it did alter postictal respiratory outcomes and the probability of seizure‐induced death. By contrast to our expectations, in entrained and free‐running mice, vulnerability to seizure‐induced death was greatest during the night and subjective night, respectively. These findings suggest that circadian rhythmicity may be responsible for the increased night‐time prevalence of SUDEP and that the underlying mechanism is phase conserved between nocturnal and diurnal mammals. All of the seizures in the present study were induced during wakefulness, indicating that the effect of time point on vulnerability to seizure‐induced death was not the result of sleep. Understanding why SUDEP occurs more frequently during the night may inform future preventative countermeasures.
Physiology of physical inactivity, sedentary behaviours and non‐exercise activity: insights from the space bedrest model
Authors: Le Roux Elisa , De Jong Nathan P. , Blanc Stéphane , Simon Chantal , Bessesen Daniel H. , Bergouignan Audrey
Published: January 2021

Physical inactivity, i.e. not reaching the recommended level of physical activity (PA), and sedentary behaviours (SB), i.e. sitting time, have been associated with increased risk for common metabolic diseases. Recent epidemiological data suggest that high volumes of SB are detrimental to metabolic health, even in the presence of regular exercise, i.e. moderate/vigorous PA. This suggests that the health effects of SB are independent from those of exercise. However, experimentally testing this hypothesis is complicated because of the difficulty in disassociating SB from PA. Bedrest studies, a traditional space science model, can offer new insights. In some bedrest studies, an exercise training protocol has been used to counteract the harmful effects of inactivity. While bedrest induces an inactive and sedentary state, exercise with bedrest represents a unique model of sedentary yet physically active people. Here, we review bedrest studies with and without exercise training. Although exercise training prevents the loss of muscle mass and function, even large volumes of exercise are not sufficient to fully counteract the negative metabolic adaptations triggered by inactivity. This observation supports the existence of independent adverse health effects of SB, but also the potential benefits of non‐exercise activity, i.e. daily living light PA. We gathered available data to examine the complex relationships between exercise, non‐exercise activity, SB and health outcomes. Given the large amount of SB in modern societies, the sole promotion of exercise, i.e. moderate/vigorous PA may be insufficient, and promotion of light PA may be a complimentary approach to improve health.

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Transformar la asistencia de necesidad básica en un momento de cuidado
Authors: Pérez Giraldo Beatriz , Arroyo Marlés Ligia Patricia , Nonsoque Cholo Mónica Andrea , Sánchez Herrera Beatriz , Guevara Lozano Maryory
Published: January 2021

Introducción. Conocer y atender debidamente las necesidades de un ser humano en medio de su vulnerabilidad continúa siendo un reto vigente. Objetivo. Describir la transformación de la “Atención a las necesidades básicas” en un momento de cuidado de enfermería para favorecer la adaptación del paciente y su cuidador familiar durante la hospitalización, en la Clínica Universidad de La Sabana, para el periodo 2018-2019. Método. Esta es una investigación metodológica en enfermería, realizada bajo lineamientos del Modelo de Enfermería Universidad de La Sabana, que incluyó cuatro fases. Resultados. Es preciso que la atención a las necesidades básicas sea respaldada en la mejor evidencia disponible, y con un trato humanizado. Hacer visible este proceso permitió medirlo y mejorarlo. Conclusiones. Para brindar un cuidado humano y seguro, no basta la buena intención, es necesario garantizar dos condiciones; por un lado, el compromiso requerido para soportarlo con la mejor evidencia disponible, aumentando la calidad del cuidado y la calidez o tono humano; y, por otro, el respeto y reconocimiento de la dignidad de las personas, favoreciendo el vínculo con ellas y su autonomía, lo que a su vez repercute positivamente en el desarrollo de la enfermería.