bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin‐1β‐dependent inflammation
Authors: Xia Yaoyao , Zhang Qingzhuo , Ye Yuyi , Wu Xiaoyan , He Fang , Peng Yuanyi , Yin Yulong , Ren Wenkai
Published: February 2022

Background

Immunotransmitters (e.g., neurotransmitters and neuromodulators) could orchestrate diverse immune responses; however, the elaborated mechanism by which melatonergic activation governs inflammation remains less defined.

Methods

Primary macrophages, various cell lines, and Pasteurella multocida (PmCQ2)‐infected mice were respectively used to illustrate the influence of melatonergic signalling on inflammation in vitro and in vivo. A series of methods (e.g., RNA‐seq, metabolomics, and genetic manipulation) were conducted to reveal the mechanism whereby melatonergic signalling reduces macrophage inflammation.

Results

Here, we demonstrate that melatonergic activation substantially lessens interleukin (IL)‐1β‐dependent inflammation. Treatment of macrophages with melatonin rewires metabolic program, as well as remodels signalling pathways which depends on interferon regulatory factor (IRF) 7. Mechanistically, melatonin acts via membrane receptor (MT) 1 to increase heat shock factor (Hsf) 1 expression through lowering the inactive glycogen synthase kinase (GSK3) β, thereby transcriptionally inhibiting interferon (IFN)‐γ receptor (IFNGR) 2 and ultimately causing defective canonical signalling events [Janus kinase (JAK) 1/2‐signal transducer and activator of transcription (STAT) 1‐IRF7] and lower IL‐1β production in macrophages. Moreover, we find that melatonin amplifies host protective responses to PmCQ2 infection‐induced pneumonia.

Conclusions

Our conceptual framework provides potential therapeutic targets to prevent and/or treat inflammatory diseases associating with excessive IL‐1β production.
EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma
Authors: Deng Guangtong , Zeng Furong , He Yi , Meng Yu , Sun Huiyan , Su Juan , Zhao Shuang , Cheng Yan , Chen Xiang , Yin Mingzhu
Published: February 2022

Background

Despite the remarkable breakthroughs achieved in the management of metastatic melanoma using immunotherapy and targeted therapies, long‐term clinical efficacy is often compromised due to dose‐limiting toxicity and innate or acquired resistance. Therefore, it is of vital importance to further explore the molecular mechanisms underlying melanoma progression and identify new targeted therapeutic approaches.

Methods

The function of eukaryotic elongation factor‐2 kinase (EEF2K) in melanoma were investigated in vitro and in vivo. RNA‐seq and chromatin immunoprecipitation (ChIP) assay were undertaken to explore the mechanisms. The antitumor effect of bromodomain and extra terminal domain (BET) inhibitors combined with cytarabine were assessed in melanoma both in vitro and in vivo.

Results

EEF2K silencing markedly attenuated the malignant phenotypes of melanoma cells, including proliferation, migration, invasion and metastasis. In contrast, EEF2K overexpression promoted melanoma cell proliferation, migration and invasion. Mechanistically, we demonstrated that EEF2K upregulates the phosphorylation of STAT3 (p‐STAT3) at Tyr705, which binds to the promoter region of SPP1 and enhances its transcription, thus facilitating melanoma progression. Transfection‐induced re‐expression of SPP1 partly negated the inhibitory effect of EEF2K silencing on melanoma, whereas inhibition of SPP1 or STAT3 significantly abolished the efficacy of EEF2K on melanoma cells. Intriguingly, EEF2K silencing combined with BET inhibitor treatment further inhibited cell proliferation and promoted apoptosis in melanoma. We further screened the US FDA‐approved antitumour drug library and identified cytarabine as a potential clinically applicable EEF2K inhibitor that could synergise with BET inhibitors in melanoma treatment.

Conclusion

EEF2K/p‐STAT3/SPP1 may be a novel oncogenic pathway in melanoma progression, which could be a target for novel combination therapy for melanoma.
The central role of a two‐way positive feedback pathway in molecular targeted therapies‐mediated pyroptosis in anaplastic thyroid cancer
Authors: Zhao Qiwu , Feng Haoran , Yang Zheyu , Liang Juyong , Jin Zhijian , Chen Lingxie , Zhan Ling , Xuan Ming , Yan Jiqi , Kuang Jie , Cheng Xi , Zhao Ren , Qiu Weihua
Published: February 2022

Background

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive tumours. We previously confirmed that apatinib has potential therapeutic effects on ATC via regulated cell death (RCD). As a newly identified RCD, pyroptosis demonstrates direct antitumour activity different from apoptosis or autophagy. Therefore, the clinical significance, regulatory role and underlying mechanisms of pyroptosis in ATC were focused on in this study.

Methods

In a phase II trial, patients with anaplastic or poorly differentiated thyroid carcinoma received apatinib 500 mg once daily. Multiple assays were implemented to evaluate the antitumour efficacy of apatinib and/or melittin in vitro and in vivo. High‐throughput sequencing was applied to analyse differential mRNAs expression in ATC cells treated by apatinib with or without melittin. In situ Hoechst 33342/PI double‐staining, LDH release assay and enzyme‐linked immunosorbent assay (ELISA) were employed to determine pyroptosis. In mechanism exploration, quantitative RT‐PCR, Western blotting and si‐RNA knocking down were executed.

Results

Seventeen patients were evaluable. Apatinib showed a promising therapeutic effect by a disease control rate (DCR) of 88.2%; however, treatment was terminated in 23.5% of patients due to intolerable toxicity. To reduce adverse events, a pyroptosis‐mediated synergistic antitumour effect of apatinib and melittin was identified in treatment of ATC in vitro and in vivo. The caspase‐1–gasdermin D (GSDMD) axis‐mediated pyroptosis was the key to extra antitumour effect of the combination of apatinib and melittin. Moreover, caspase‐3–gasdermin E (GSDME) pyroptosis pathway also functioned importantly in addition to caspase‐1–GSDMD pathway. Evidenced by in vitro and in vivo study, a two‐way positive feedback interaction was innovatively confirmed between caspase‐1–GSDMD and caspase‐3–GSDME axes.

Conclusions

Through pyroptosis mediated by caspase‐1–GSDMD and caspase‐3–GSDME axes synchronically, low‐dosage apatinib and melittin could synergistically achieve a comparable therapeutic potential with reduced AEs. More importantly, a two‐way positive feedback interaction is innovatively proposed between these two axes, which provide a new prospect of targeted therapy.
Context is key: Parasympathetic regulation in the classroom differentially predicts preschoolers’ socially competent behaviors
Authors: Darling Laura Nelson , Holochwost Steven J. , Coffman Jennifer , Propper Cathi B. , Wagner Nicholas J.
Published: February 2022

Research shows that children's early social competence predicts their later academic and interpersonal success. Accordingly, early childhood education programs increasingly aim to evaluate and support children's social skill development. Despite ample theoretical and empirical work demonstrating the role of the parasympathetic nervous system (PNS) in supporting neurophysiological processes that underlie social behaviors, no study has explicitly tested whether the assessment of PNS activity in childhood educational settings provides insight into children's social functioning. The current study addresses this gap by examining the influence of context‐specific PNS regulation, assessed via respiratory sinus arrhythmia (RSA), in predicting preschool children's socially competent behavior toward peers in the classroom. Results showed that: (1) RSA withdrawal (e.g., decreases relative to a baseline task) during unstructured classroom activities predicted children's socially competent behaviors during these unstructured activities but not during structured activities, whereas (2) withdrawal during structured classroom activities predicted children's socially competent behaviors during structured activities. These results indicate that PNS activity makes context‐specific contributions to children's social behaviors and highlight the importance of assessing neurophysiological regulation in context.
Light heterogeneity affects understory plant species richness in temperate forests supporting the heterogeneity–diversity hypothesis
Authors: Helbach Jan , Frey Julian , Messier Christian , Mörsdorf Martin , Scherer‐Lorenzen Michael
Published: February 2022

One of the most important drivers for the coexistence of plant species is the resource heterogeneity of a certain environment, and several studies in different ecosystems have supported this resource heterogeneity–diversity hypothesis. However, to date, only a few studies have measured heterogeneity of light and soil resources below forest canopies to investigate their influence on understory plant species richness. Here, we aim to determine (1) the influence of forest stand structural complexity on the heterogeneity of light and soil resources below the forest canopy and (2) whether heterogeneity of resources increases understory plant species richness. Measures of stand structural complexity were obtained through inventories and remote sensing techniques in 135 1‐ha study plots of temperate forests, established along a gradient of forest structural complexity. We measured light intensity and soil chemical properties on six 25 m² subplots on each of these 135 plots and surveyed understory vegetation. We calculated the coefficient of variation of light and soil parameters to obtain measures of resource heterogeneity and determined understory plant species richness at plot level. Spatial heterogeneity of light and of soil pH increased with higher stand structural complexity, although heterogeneity of soil pH did not increase in conditions of generally high levels of light availability. Increasing light heterogeneity was also associated with increasing understory plant species richness. However, light heterogeneity had no such effects in conditions where soil resource heterogeneity (variation in soil C:N ratios) was low. Our results support the resource heterogeneity–diversity hypothesis for temperate forest understory at the stand scale. Our results also highlight the importance of interaction effects between the heterogeneity of both light and soil resources in determining plant species richness.
Estimating the abundance of the critically endangered Baltic Proper harbour porpoise (Phocoena phocoena) population using passive acoustic monitoring
Authors: Amundin Mats , Carlström Julia , Thomas Len , Carlén Ida , Koblitz Jens , Teilmann Jonas , Tougaard Jakob , Tregenza Nick , Wennerberg Daniel , Loisa Olli , Brundiers Katharina , Kosecka Monika , Kyhn Line A. , Tiberi Ljungqvist Cinthia , Sveegaard Signe , Burt M. Louise , Pawliczka Iwona , Jussi Ivar , Koza Radomil , Arciszewski Bartlomiej , Galatius Anders , Jabbusch Martin , Laaksonlaita Jussi , Lyytinen Sami , Niemi Jussi , Šaškov Aleksej , MacAuley Jamie , Wright Andrew J. , Gallus Anja , Blankett Penina , Dähne Michael , Acevedo‐Gutiérrez Alejandro , Benke Harald
Published: February 2022

Knowing the abundance of a population is a crucial component to assess its conservation status and develop effective conservation plans. For most cetaceans, abundance estimation is difficult given their cryptic and mobile nature, especially when the population is small and has a transnational distribution. In the Baltic Sea, the number of harbour porpoises (Phocoena phocoena) has collapsed since the mid‐20th century and the Baltic Proper harbour porpoise is listed as Critically Endangered by the IUCN and HELCOM; however, its abundance remains unknown. Here, one of the largest ever passive acoustic monitoring studies was carried out by eight Baltic Sea nations to estimate the abundance of the Baltic Proper harbour porpoise for the first time. By logging porpoise echolocation signals at 298 stations during May 2011–April 2013, calibrating the loggers’ spatial detection performance at sea, and measuring the click rate of tagged individuals, we estimated an abundance of 71–1105 individuals (95% CI, point estimate 491) during May–October within the population's proposed management border. The small abundance estimate strongly supports that the Baltic Proper harbour porpoise is facing an extremely high risk of extinction, and highlights the need for immediate and efficient conservation actions through international cooperation. It also provides a starting point in monitoring the trend of the population abundance to evaluate the effectiveness of management measures and determine its interactions with the larger neighboring Belt Sea population. Further, we offer evidence that design‐based passive acoustic monitoring can generate reliable estimates of the abundance of rare and cryptic animal populations across large spatial scales.
Sapling growth gradients interact with homogeneous disturbance regimes to explain savanna tree cover discontinuities
Authors: Holdo Ricardo M. , Donaldson Jason E. , Rugemalila Deusdedith M. , Anderson T. Michael
Published: February 2022

Savanna tree cover often exhibits sudden discontinuities across space. It has been proposed that local spatial processes imposed by variation in tree cover itself (as opposed to by external drivers such as edaphic variation) can reinforce such discontinuities. Despite this, we generally lack data on tree demography and the environmental drivers affecting the former as a function of tree neighborhoods in these systems. Given the importance of disturbance traps in savannas, spatial processes affecting the likelihood of escape from the seedling/sapling stage to the adult tree stage are likely to be critical. In a longitudinal survey of 800 saplings distributed along eight 1‐km transects spanning woodland–grassland transitions in Serengeti National Park, we found a positive association between tree cover and sapling growth and survival, but no relationship with sapling abundance, maximum tree height, disturbance, or topkill. Based on microclimate and soil moisture dynamics data, we found no evidence to suggest that tree cover itself drives variation in growth. Based on a prior analysis of soil properties along these transects, we hypothesized that underlying edaphic conditions may be responsible for variation in growth. Regardless of the underlying mechanism, we used simulations to show that subtle growth rate gradients interacted with intense disturbance regimes to produce sharp discontinuities in tree cover, with strong demographic bottlenecks where growth is slowest, explaining the observed patterns of tree cover along the transects. Our results indicated that disturbance and herbivory are equally intense in areas of high and low tree cover, and that although trees have the potential to successfully establish and reach adulthood in open, grassy sites, they grow too slowly to escape disturbance traps there. Importantly, we showed that although herbivory and fire are fundamental for explaining savanna structural patterns, their effects are not necessarily reinforced by tree cover itself.
Extremely Anisotropic Thermoelectric Properties of SnSe Under Pressure
Authors: Cao Wei , Wang Ziyu , Miao Ling , Shi Jing , Xiong Rui
Published: February 2022

SnSe has attracted extensive attention due to its ultralow thermal conductivity and excellent thermoelectric properties. In this work, pressure‐induced thermoelectric properties of Pnma SnSe are investigated via first‐principles calculations. We uncover distinct energy isosurfaces topology transition of conduction band by applying pressure. The newly created conduction band valley caused by pressure has a distinct anisotropic shape compared to the old one. Inducing pressure can greatly enhance the anisotropy of electronic transport properties of the n‐type Pnma SnSe. Furthermore, the lattice thermal conductivity also exhibits anisotropic behavior under pressure due to a special collaged phonon mode. The pressure‐induced lattice thermal conductivity along the a‐axis shows a slower growth trend than that along the b‐axis and c‐axis. The optimal ZT value of the n‐type Pnma SnSe along the a‐axis can reach 1.64 at room temperature. These results would be helpful for designing the Pnma SnSe‐based materials for the potential thermoelectric and valleytronic applications.
Living with endometriosis: Comorbid pain disorders, characteristics of pain and relevance for daily life
Authors: Leuenberger Janine , Kohl Schwartz Alexandra Sabrina , Geraedts Kirsten , Haeberlin Felix , Eberhard Markus , von Orellie Stefanie , Imesch Patrick , Leeners Brigitte
Published: February 2022

Background

Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross‐sectional case–control study analysed the association between endometriosis‐related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%).

Methods

Self‐administered questionnaires from the Brief Pain Inventory and the Pain Disability Index were used to investigate associations between pain characteristics (frequency, duration, intensity) and daily life. Also, associations between different endometriosis characteristics (rASRM stage, presence of adhesions, localisation of lesions) and pain were evaluated.

Results

Chronic pain is negatively associated with almost all (12/14) aspects of daily life investigated, including standing, walking, sitting, defaecation, sleep, sports activities, family and domestic responsibilities, sexuality, social functioning, professional life, mood, and joy of life. Altogether, 33.7% of women with chronic pain reported moderate and 27.5% severe limitations. Comorbid pain disorders resulted in significantly more limitations. The length of pain episodes showed a particularly important influence, especially for family/domestic responsibilities (OR 22.94, p < 0.001), professional life (OR 16.56, p < 0.001) and social functioning (OR 41.03, p < 0.001).

Conclusions

Our data confirm that despite treatment, about 50% of women experience pain. Pain was associated with at least moderate negative effects on almost all areas of daily life; additional pain comorbidities increased limitations. Improving pain management is essential for improving quality of life in women with endometriosis.

Significance

The study provides an accurate overview of the impact of endometriosis‐associated pain on daily life. This is important because pain plays a central role in women living with endometriosis, and despite modern therapies, many women continue to suffer from chronic pain. The detailed analysis of its impact with a comprehensive survey of all aspects of daily life in a very large study population is unique. We expect an improved understanding of consequences of pain to significantly advance medical support in these patients.
Enzyme based field effect transistor: State‐of‐the‐art and future perspectives
Authors: Sarcina Lucia , Macchia Eleonora , Tricase Angelo , Scandurra Cecilia , Imbriano Anna , Torricelli Fabrizio , Cioffi Nicola , Torsi Luisa , Bollella Paolo
Published: February 2022

The review discloses the historical and technological evolution of enzyme‐based field‐effect transistors (EnFETs) underlying the importance of gate electrode modification toward the implementation of novel FETs configurations such as extended‐gate FET (EG‐FETs) or EG organic FETs (EG‐OFETs). The working principle of the EnFETs as postulated by Bergveld in 1970, who defined the EnFET as an ion‐selective FET (ISFET) modified with enzyme‐membrane, is also discussed considering the analytical equations related to the EnFET output response. For each category, namely EnFETs, EG‐FETs, and EG‐OFETs, we reviewed the key devices’ configurations that addressed the research in this field in the last 40 years with particular attention to the analytical figures of merit.
Shear‐controlling rocking‐isolation podium system for enhanced resilience of high‐rise buildings
Authors: Zhong Chiyun , Christopoulos Constantin
Published: February 2022

Rapid urban growth has been paired with a rapid increase in the demand for high‐rise buildings, and has accelerated the need for developing more resilient high‐rise buildings in earthquake‐prone regions. Current best practices for the seismic design of high‐rise buildings follow a performance‐based design approach that allows the designer to use innovative structural systems, select performance objectives, and verify seismic performances targeted at multiple levels of seismic intensity. As shortcomings in conventional code‐designed high‐rise buildings continue to be revealed by strong earthquakes, the importance of more resilient high‐rise systems is increasingly evident. Several high‐performance systems have been proposed to limit the excessive seismic demands attributed to higher‐mode effects in high‐rise buildings. However, these systems still face design challenges associated with distributed damage and residual deformations. This paper proposes a novel self‐centering base mechanism for high‐rise buildings that independently limits both shear forces and overturning moments at the base to mitigate higher‐mode effects, while eliminating residual deformations and controlling concentrated stresses within the structure that otherwise would need to be designed for. The schematic overview of the proposed system is first introduced, followed by the detailed design of a physical embodiment developed based on a reference 42‐story RC core wall building. Results of a numerical case‐study comparison confirm that an enhanced seismic performance is achieved through the proposed system with minimum damage and negligible residual deformations even following major seismic loading. The proposed system, with further investigations, also has the potential to be applied to a wider range of structural systems.
Genome‐wide meta‐analysis identifies susceptibility loci for autoimmune hepatitis type 1
Authors: Li You , Sun Ying , Liu Yanmin , Wang Bangmao , Li Jia , Wang Hanxiao , Zhang Haiping , Wang Xiaoyi , Han Xu , Lin Qiuxiang , Zhou Yang , Hu Lilin , Song Yuhu , Bao Jie , Gong Ling , Sun Mengying , Yuan Xiaoling , Zhang Xinhe , Lian Min , Xiao Xiao , Miao Qi , Wang Qixia , Li Ke‐Ke , Du Shiyu , Ma Anlin , Li Yiling , Xu Jie , Tang Shanhong , Shi Junping , Xu Yun , Yang Ling , Zhang Jiming , Huang Zuxiong , Zhou Lu , Cui Yong , Seldin Michael F. , Gershwin M. Eric , Yan Huiping , Zou Zhengsheng , Zuo Xianbo , Tang Ruqi , Ma Xiong ,   the Chinese AIH Consortium
Published: February 2022

Background and Aims

Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease.

Approach and Results

We conducted a case–control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta‐analysis was performed to ascertain variants associated with AIH type 1. A single‐nucleotide polymorphism within the human leukocyte antigen (HLA) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10−73). The meta‐analysis also identified two non‐HLA loci significantly associated with AIH: CD28/CTLA4/ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10−9) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10−9). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10−7), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10−7), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10−6), and LILRA4/LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10−6) had suggestive association signals with AIH.

Conclusions

Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome‐wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro‐immune interaction in the pathogenesis of AIH.
The assessment of a growing mobile anesthesia practice from 2016 to 2019: A retrospective observational cohort study of 89,999 cases comparing ambulatory surgery (ASC) and office‐based surgery (OBS) centers using a high‐fidelity, anesthesia‐specific electronic medical record (EMR)
Authors: Shapiro Fred E. , Park Brian H. , Levy Tal S. , Osman Brian M.
Published: February 2022

Office‐based surgery (OBS) has emerged as a significant subspecialty of ambulatory surgery. There are few clinical trials and limited published data on patient characteristics, anesthesia, or outcomes distinguishing OBS from ambulatory surgery centers (ASCs). We examined retrospective data from a large mobile anesthesia practice for 89,999 procedures from 2016 to 2019. Data was abstracted from billing and an anesthesia‐specific electronic medical record, segregating procedures performed in ASCs versus OBS. The number and breadth of procedures increased substantially. Compared to ASCs, OBS patients were more likely male (52% vs. 48%), older (61 years vs. 55 years), and to have a higher American Society of Anesthesiologists (ASAs) status (33% vs. 20% ASA 3 or higher). The procedure mix varied substantially between the two settings. The major complication rate was 0.07% for the ASCs and 0.24% for OBS (p = 0.2, confidence interval [CI] −0.15 to 0.04). Minor complications were 11.2% in OBS versus 17.3% the ASCs (p < 0.0001, 95% CI 5.2–7). The practice demonstrates a low rate of complications, and despite the limitations of this study, the organization and structure of this large mobile anesthesia practice serves as a template for effective risk mitigation and patient safety.
Stochastic downscaling of gridded precipitation to spatially coherent subgrid precipitation fields using a transformed Gaussian model
Authors: Switanek Matthew , Maraun Douglas , Bevacqua Emanuele
Published: February 2022

Climate impact models often require unbiased point‐scale observations, but climate models typically provide biased simulations at the grid scale. While standard bias adjustment methods have shown to generally perform well at adjusting climate model biases, they cannot overcome the gap between grid‐box and point scale. To overcome this limitation, combined bias adjustment and stochastic downscaling methods have been developed. These methods, however, are single‐site methods and cannot represent spatial dependence. Here we propose a multisite stochastic downscaling method that can be applied to bias‐adjusted climate model output for generating spatially coherent time series of daily precipitation at multiple stations, conditional on the driving climate model. The method is based on a transformed truncated multivariate Gaussian model and can also be used to downscale to a full field at finer‐grid resolution. An evaluation for stations across selected catchments in Austria demonstrates the good performance of the stochastic model at representing marginal, temporal and spatial aspects of daily precipitation, including extreme events.
Undernutrition is associated with mortality, exacerbation, and poorer quality of life in patients with chronic obstructive pulmonary disease: A systematic review with meta‐analysis of observational studies
Authors: Gattermann Pereira Thainá , Lima Júlia , Silva Flávia Moraes
Published: February 2022

Impaired nutrition status is recognized as a risk factor for worse clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to investigate how undernutrition is diagnosed, its prevalence, and whether there is an association between this condition and clinical outcomes in patients with COPD. The search for this systematic review of observational studies (PROSPERO: CRD42020191888) was performed in the PubMed, Embase, and Scopus databases, with no date or language restrictions. The studies had to report data on the diagnosis of undernutrition and its association with mortality, exacerbation, length of hospital stay, or quality of life in adult patients with COPD. A meta‐analysis with a random‐effects model was performed to combine data. Forty‐nine studies were included (20 of them classified as having a low risk of bias), and the most common diagnostic method of undernutrition was body mass index (BMI) (n = 36). The pooled prevalence of undernutrition was equal to 20% (95% CI, 0.15–0.25; I² = 100%), and it was associated with mortality (risk ratio = 1.97; 95% CI, 1.55–2.50; I² = 98%), exacerbation (risk ratio = 1.73; 95% CI, 1.03–2.91; I² = 96%), and poorer quality of life (mean difference = 8.25; 95% CI, 5.40–11.10; I² = 79%). For all outcomes, the certainty of evidence was very low. In conclusion, undernutrition is prevalent and is associated with poorer outcomes in patients with COPD. However, undernutrition is mainly diagnosed by BMI, which underreports its prevalence, and the certainty of the evidence is very low.
Nutritional outcomes of patients with pediatric and congenital heart disease requiring ventricular assist devices
Authors: Horsley Megan , Pathak Sagar , Morales David , Lorts Angela , Mouzaki Marialena
Published: February 2022

Background

Ventricular assist devices (VADs) support children with heart failure. The objective is to report on the nutrition outcomes of children requiring VAD.

Methods

This was a retrospective study performed in a tertiary care center. All patients undergoing VAD placement from 2010 to 2018 were included. Exclusion criteria were VAD placement in outside hospitals, missing baseline anthropometrics, and death in the first 15 days post‐VAD. Clinical, demographic, and nutrition data were collected from baseline and at 2 months post‐VAD. Descriptive statistics were used.

Results

Of the 52 patients who had undergone VAD placement, 49 (65% male, 80% with cardiomyopathy; median age at VAD, 8 years) met the study criteria. The median length of stay following VAD was 63 days. Eight patients (16%) had malnutrition at baseline (five mild, two moderate, and one severe). At 2 months post‐VAD, seven (of 49) patients had undergone heart transplantation and three (6%) were deceased. The proportion of patients with malnutrition was significantly different at 2 months post‐VAD (P = 0.009), with six patients showing evidence of malnutrition (three mild, two moderate, and one severe; body mass index z score at baseline vs 2 months: 0.11 (± 1.72) vs 0.43 (± 0.94), P = 0.049). The percent of required energy consumed increased from 77% at baseline to 90% at 2 months post‐VAD (P = 0.021). The proportion of patients fed solely enterally also increased (62% vs 84%, respectively; P = 0.042).

Conclusion

VADs are associated with improved nutrition outcomes. Future studies should investigate the impact of VADs on body composition and longer‐term outcomes.
Improving enteral nutrition delivery in the critically ill trauma and surgical population
Authors: McCartt Jason , Loszko Abigail , Backes Kehaulani , Cunningham Kyle , Evans Susan , Draughon Matthew , Sachdev Gaurav
Published: February 2022

Background

Critically ill trauma and surgical patients often fail to achieve adequate enteral nutrition (EN) support. We hypothesize that implementation of an evidence‐based, multidisciplinary nutrition enhancement protocol (EP) will improve delivery of EN in critically ill trauma and surgical patients and align our institution with nationally recommended guidelines.

Methods

The study compared patients prior to protocol (PP) with patients after implementation of the EP. The primary outcome was delivery of >80% of daily prescribed EN kilocalories in critically ill trauma and surgical patients during their intensive care unit stay. Data were prospectively captured from daily rounds and the electronic health record. Statistical analysis was conducted to compare data between groups using Student t test for continuous variables and chi‐square test for categorical variables.

Results

In total, 256 patients in the PP group (2663 EN days) were compared with 232 patients in the EP group (2059 EN days). The primary outcome of average percentage of nutrition delivered (based on 24‐h kilocalorie requirements) improved after the implementation of the EP (75.3% PP vs 85.5% EP; P < 0.01). This improvement was evident in surgical (69.9% PP vs 78.7% EP; P < 0.01) and trauma (78.2% PP vs 87.3% EP; P < 0.01) subpopulations. The secondary outcome of percentage of patients receiving >80% of nutrition goal also improved (52.7% PP vs 65.2% EP; P < 0.01).

Conclusion

Implementation of an EP significantly increased delivery of EN by 10.2% and achieved compliance with American Society for Parenteral and Enteral Nutrition and Society of Critical Care Medicine recommended guidelines for critically ill trauma and surgical patients.
A long‐term retrospective analysis of single tooth implants and endodontic therapies in a university setting
Authors: Lee Chun‐Teh , Alfred Preston , Tran Duong , James Jennifer , Makins Scott R. , Gajjar Devanshi , Weltman Robin
Published: February 2022

Background

This study aimed to compare survival of single tooth implants (SI) to teeth receiving initial endodontic treatment (IET), non‐surgical (NET), and surgical endodontic retreatments (SET). The secondary aim was to determine success rate and identify factors associated with the survival and success of implant and endodontic treatments.

Methods

A retrospective cohort study using electronic health records (January 1st, 1995 to April 30th, 2017) was conducted. Every case that qualified for the study in SI (n = 321), NET (n = 211), and SET (n = 79) was included and cases in IET (n = 642) were selected at random and with a 2 to 1 case ratio to SI for data extraction efficiency. Statistical analyses were conducted to compare survival rates and estimate success rates between the four groups adjusting for confounders.

Results

The 3 year survival rates for SI, IET, NET, and SET were 99.0%, 92.1%, 90.5%, and 89.5% while the 5 year survival rates for SI, IET, NET, and SET were 99.0%, 87.6%, 84.4%, and 81.1%, respectively. Generally, the SI group had the highest survival rate and the SET group had the lowest survival rate. Short implants (≤8 mm) were significantly associated with implant failure (P < 0.01). Teeth with composite restoration had lower survival rates in IET and NET than other restorations (P < 0.01 and < 0.01).

Conclusion

Within the limitations of this study, single tooth implants and the endodontic treatments yielded predictable survival and success in the short term but the survival and success rates in endodontic treatments dropped more rapidly than single tooth implants during the longer follow‐up period.
Preparative isolation of diterpenoids from Salvia bowleyana Dunn roots by high‐speed countercurrent chromatography combined with high‐performance liquid chromatography
Authors: Jiang Xiaohua , Chen Yueyuan , Yang Xuerong , Yan Xiaojie , Lu Fenglai , Liu Zhangbin , Li Dianpeng
Published: February 2022

The root of Salvia bowleyana Dunn (Lamiaceae) is used as a traditional Chinese medicine that has multiple therapeutic effects. In this study, an efficient strategy was developed to separate diterpenoid compounds, which are the main active ingredients in Salvia bowleyana Dunn roots, from complex crude extracts by high‐speed countercurrent chromatography combined with preparative high‐performance liquid chromatography. A two‐phase solvent system comprising n‐hexane–ethyl acetate–methanol–water (7:3:7:3, v/v/v/v) was selected for high‐speed countercurrent chromatographic separation. Three major diterpenoids, 6α‐hydroxysugiol (7), sugiol (8), and 6, 12‐dihydroxyabieta‐5,8,11,13‐tetraen‐7‐one (9) were obtained at purities of 98.9, 95.4, and 96.2%, respectively, and minor diterpenoids were enriched via one‐step separation. The enriched minor diterpenoids were further purified by continuous preparative high‐performance liquid chromatography to yield two new norabietanoids (1, 6) and four known compounds (2–5). The structures of these new compounds were determined using NMR spectroscopy, high‐resolution electrospray ionization mass spectrometry, and electronic circular dichroism spectroscopy. The results suggest that high‐speed countercurrent chromatography combined with preparative high‐performance liquid chromatography efficiently isolates diterpenoids, including minor components, from complex natural products.
Assessing local perceptions of deforestation, forest restoration, and the role of agroecology for agroecosystem restoration in northern Malawi
Authors: Kpienbaareh Daniel , Luginaah Isaac , Bezner Kerr Rachel , Wang Jinfei , Poveda Katja , Steffan‐Dewenter Ingolf , Lupafya Esther , Dakishoni Laifolo
Published: February 2022

Deforestation drives climate change and reinforces food insecurity in forest‐dependent communities. What drives deforestation varies by location and is shaped by livelihood systems. But how locals perceive restoration is crucial for developing restoration policies. Evidence suggests that applying sustainable farming strategies can potentially restore forests and sustain livelihoods. Applying a broad‐based conceptualization of deforestation and restoration in policymaking, however, results in missed opportunities for addressing deforestation and restoration. Here, we explore the drivers of deforestation, the perceptions of restoration, and the challenges to restoration among smallholder farmers in northern Malawi and examine how agroecology can contribute to restoring degraded agroecosystems. Participants report agricultural land expansion, charcoal production, climate change, burnt brick production, and government subsidies as the major drivers of deforestation. We observed that although perceptions of forest restoration reflect farmers' traditional ecological knowledge (TEK) to include reclamation of degraded farmlands, reconstruction of native tree species, and replacement of felled trees on farmlands, there are challenges including splitting families to gain access to more subsidized fertilizers and food aid, embedded cultural practices, growing demand for charcoal in cities, and weak ecosystem governance structures that hinder the effectiveness of restoration efforts. We, however, do find that agroecological intensification can increase yield from smaller farmlands and allow for larger and longer‐lasting fallows of spare lands which regenerate forests. Key overarching implications of these findings include the need to integrate livelihoods more explicitly into restoration plans, accounting for TEK in restoration policies in forest‐dependent communities and encouraging the adoption of agroecology.
An extension of Jónsson‐Tarski representation and model existence in predicate non‐normal modal logics
Authors: Tanaka Yoshihito
Published: February 2022

We give an extension of the Jónsson‐Tarski representation theorem for both normal and non‐normal modal algebras so that it preserves countably many infinite meets and joins. In order to extend the Jónsson‐Tarski representation to non‐normal modal algebras we consider neighborhood frames instead of Kripke frames just as Došen's duality theorem for modal algebras, and to deal with infinite meets and joins, we make use of Q‐filters, which were introduced by Rasiowa and Sikorski, instead of prime filters. By means of the extended representation theorem, we show that every predicate modal logic, whether it is normal or non‐normal, has a model defined on a neighborhood frame with constant domains, and we give a completeness theorem for some predicate modal logics with respect to classes of neighborhood frames with constant domains. Similarly, we show a model existence theorem and a completeness theorem for infinitary modal logics which allow conjunctions of countably many formulas.
Bioavailability and Health Impact of Ingested Amyloid‐like Protein Fibrils and their Link with Inflammatory Status: A Need for More Research?
Authors: Luyckx Trui , Grootaert Charlotte , Monge‐Morera Margarita , Delcour Jan A. , Rousseau Frederic , Schymkowitz Joost , Van Camp John
Published: February 2022

The use of amyloid‐like protein fibrils (ALFs) in food formulations looks very promising in terms of improving techno‐functional properties, but raises some concerns in terms of food safety, because of their structural resemblance to disease‐related endogenous amyloids. This review focuses on the biological fate and potential health implications of ingested ALF structures in both healthy and predisposed individuals. A comprehensive overview of ALF gastrointestinal digestion, intestinal absorption, and systemic dissemination is provided, in addition to a thorough assessment of potential ALF cross‐seeding of endogenous precursor proteins linked to (non)neurodegenerative amyloidosis. In general, this study concludes that the health impact of ALF consumption remains widely understudied and merits additional research efforts to determine the exact extent to which ALF ingestion may influence the general health status.
Prebiotic Oligosaccharides Enhance Iron Absorption Via Modulation of Protein Expression and Gut Microbiota in a Dose‐Response Manner in Iron‐Deficient Growing Rats
Authors: Chen Jie‐Hua , Wang Yiyuan , Pan Jialiang , Lu Louise Weiwei , Yu Jianfeng , Liu Bin , Chen Feng , Deng Hong
Published: February 2022

Scope

Iron deficiency anemia (IDA) in children is one of the most common nutrition‐related health conditions worldwide. Prebiotic oligosaccharides, fructo‐oligosaccharide (FOS) and galacto‐oligosaccharides (GOS), have shown to affect iron absorption in anemic subjects, but the results in previous studies are inconsistent, thus the underlying mechanism and the effective dose of GOS in mitigating anemia remain unclear.

Methods and Results

The present study aims to investigate the mechanism of how GOS/FOS affect iron absorption in an iron‐deficient growing rat model from the perspectives of protein expression and gut microbiota, and determine the optimum dose of GOS. Iron‐deficient models are established by providing young rats diet without iron addition for 14 days. Later, iron‐deficient rats are provided with standard rat chows supplemented with 0%, 3%, 5%, 10% GOS, and 10% FOS for 21 days. The results show that ≥5% GOS supplementation in diet improves iron status and significantly impacts iron‐binding/transport protein expression. Furthermore, a dose‐dependent modulating effect of GOS on gut microbiota is determined.

Conclusion

For the first time, the present study provides evidence that GOS supplementation induces a dose‐response effect on iron absorption and gut microbiota in the established model, suggesting a positive role of GOS in ameliorating IDA in children.
Preventive Effects of Sesamol on Deep‐Frying Oil‐Induced Liver Metabolism Disorders by Altering Gut Microbiota and Protecting Gut Barrier Integrity
Authors: Wang Lei , Chen Weixuan , Tian Yujie , Duan Xiaorong , Yuan Yi , Wang Na , Xu Chao , Liu Xuebo , Liu Zhigang
Published: February 2022

Scope

The total polar components (TPC) in the edible oil are produced during the frying process, and excessive intake of TPC may lead to metabolic disorders. This study aims to investigate the preventive effects of sesamol, a functional component from sesame, on suppressing TPC production, and on the deep‐frying oil (DFO)‐induced liver lipid metabolism disorders and gut homeostasis disruption.

Methods and results

Sesamol addition (0.2 mg mL−1) improves the quality of the soybean oil by reducing the production of TPC during the deep‐frying process (180 °C for 40 h). The diet‐induced obesity model is established by feeding mice with a high‐fat diet for 8 weeks. Either sesamol pre‐treated DFO or sesamol supplementation (0.2%, w/w) in the diet reduces the liver lipid accumulation in the obese mice by increasing lipolysis‐related genes expression. Sesamol elevates the antioxidant enzyme activities, protectes the integrity of the jejunum and colon barrier, and enhances the relative abundance of Bifidobacterium and Akkermansia in obese mice.

Conclusion

Sesamol suppresses TPC production and prolongs the use time of deep‐frying oil. Meanwhile, sesamol can improve TPC‐induced liver lipid metabolism disorders and gut dysbiosis, thus reducing the health risks associated with deep‐fried food.
Gene Expression Profiling of 1α,25(OH)2D3 Treatment in 2D/3D Human Hepatocyte Models Reveals CYP3A4 Induction but Minor Changes in Other Xenobiotic‐Metabolizing Genes
Authors: Pavek Petr , Dusek Jan , Smutny Tomas , Lochman Lukas , Kucera Radim , Skoda Josef , Smutna Lucie , Kamaraj Rajamanikkam , Soucek Pavel , Vrzal Radim , Dvorak Zdenek
Published: February 2022

Scope

CYP3A4 is the most important drug‐metabolizing enzyme regulated via the vitamin D receptor (VDR) in the intestine. However, less is known about VDR in the regulation of CYP3A4 and other drug‐metabolizing enzymes in the liver.

Methods and Results

This study investigates whether 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) regulates major cytochrome P450 enzymes, selected phase I and II enzymes, and transporters involved in xenobiotic and steroidal endobiotic metabolism in 2D and 3D cultures of human hepatocytes. The authors found that 1α,25(OH)2D3 increases hepatic CYP3A4 expression and midazolam 1′‐hydroxylation activity in 2D hepatocytes. The results are confirmed in 3D spheroids, where 1α,25(OH)2D3 has comparable effect on CYP3A4 mRNA expression as 1α‐hydroxyvitamin D3, an active vitamin D metabolite. Other regulated genes such as CYP1A2, AKR1C4, SLC10A1, and SLCO4A1 display only mild changes in mRNA levels after 1α,25(OH)2D3 treatment in 2D hepatocytes. Expression of other cytochrome P450, phase I and phase II enzyme, or transporter genes are not significantly influenced by 1α,25(OH)2D3. Additionally, the effect of VDR activation on CYP3A4 mRNA expression is abolished by natural dietary compound sulforaphane, a common suppressor of pregnane X receptor (PXR) and constitutive androstane receptor (CAR).

Conclusion

This study proposes that VDR or vitamin D supplementation is unlikely to significantly influence liver detoxification enzymes apart from CYP3A4.