bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximate Likelihood Inference in Generalized Linear Models with Censored Covariates
Authors: Teimouri Mahdi , Sinha Sanjoy K
Published: March 2022

In many surveys and clinical trials, we obtain measurements on covariates or biomarkers that are left-censored due to the limit of detection. In such cases, it is necessary to correct for the left-censoring when studying covariate effects in regression models. The expectation-maximization (EM) algorithm is widely used for the likelihood inference in generalized linear models with censored covariates. The EM method, however, requires intensive computation involving high-dimensional integration with respect to the covariates when the dimension of the censored covariates is large. To reduce such computational difficulties, we propose and explore a Monte Carlo EM method based on the Metropolis algorithm. The finite-sample properties of the proposed estimators are studied using Monte Carlo simulations. An application is also provided using actual data obtained from a health and nutrition examination survey.
Journal of Statistical Research 2021, Vol. 55, No. 2, pp. 359-375
Penggunaan Corporate Social Responsibility Sebagai Intervening: Antara Komisaris Independen, Dewan Direksi, Komite Audit dan Kualitas Audit Terhadap Tax Avoidance
Authors: Yustin Agnestya Leonicha , Effendi Bahtiar
Published: March 2022

The purpose of this study is to determine the effect of corporate governance (independent commissioners, board of directors, audit committee and audit quality) on tax avoidance with mediating role of corporate social responsibility. The type of research used in this study is quantitative method. The population in this study are all manufacturer companies listed on Indonesia Stock Exchange in 2016-2019 as many as 182 companies with annual reports for 4 years, namely from 2016-2019. Sample selection with purposive sampling method and counted by slovin formula. The analytical method used to test hypotheses is the multiple regression test. The results show that independent commissioners have no effect on tax avoidance in manufacturing companies listed on the IDX in 2016-2019, the board of directors has no effect on tax avoidance in manufacturing companies listed on the IDX in 2016-2019, audit committees have no effect on tax avoidance in companies manufacturers listed on the IDX in 2016-2019, audit quality has an effect on tax avoidance in manufacturing companies listed on the IDX in 2016-2019, CSR affects tax avoidance in manufacturing companies listed on the IDX in 2016-2019 and CSR can mediate the influence of corporate Governance on Tax Avoidance.
ON VIOLATION OF THE RIGHT TO A FAIR TRIAL BY INSUFFICIENT REASONING OF THE DECISION
Authors: Molnár Peter
Published: March 2022

The author discusses a possible violation of the right to a fair trial due to deficiencies in the reasoning of the court decision. In the previous case law of the ordinary courts, the prevailing view was that deficient reasoning constituted so-called “other deficiency”. However, in the author's opinion, the recodification of civil procedure requires a reassessment of the case law from the time before the recodification, because despite different nominal grounds of cassation recourse (the so-called “other deficiency” is no longer a separate ground of cassation recourse) the scope of the right to a fair trial has not changed. The court decision is a part and culmination of the court’s conduct of proceedings, and in the reasoning of the decision, the court explains and defends the procedure it applied in establishing the factual and legal basis for its decision and the outcome of the proceedings itself. Therefore, the quality of the reasoning of a court decision must also be subject to effective examination in ordinary and extraordinary redress procedures. The Constitutional Court of the Slovak Republic has also been calling for a reassessment of older case law
The Effect of BI Rate and Exchange Rate on Inflation in Indonesia with the Money Supply as a Mediating Variable
Authors: Oktavia Vicky , Wahyudi Sugeng
Published: March 2022

Inflation can be interpreted as a tendency to increase the prices of goods and services in general and continuously which can be influenced by several factors such as reference interest rates, exchange rates, the money supply and so on. This study intends to analyze about the influence of the BI rate and the exchange rate on inflation in Indonesia with the money supply as an intervening variable. The population in this study is Inflation, BI Rate, Rupiah / USD Exchange Rate, and Money Supply. The sample used is this data in the 2010-2019 period which was analyzed using WarpPLS and Sobel Test. The results show that the BI rate, exchange rate and the money supply have a significant effect on inflation and the money supply can mediate the effect of the BI rate and the exchange rate on inflation which has been proven by the sobel test. Keywords:InflationBI RateExchange RateMoneySupply
Ecological and economic evaluation of technologies of growing of winter wheat selection material in regulated agroecosystems
Authors: Drebot O. , Dubovy V. , Adamovych І.
Published: March 2022

The influence of the main parameters of the external environment (lighting, its quality and quantity, temperature, sowing scheme and seasons) on early maturity, productivity of winter wheat plants in soil greenhouses and hothouses is shown. In 1978 at the price of 1 kopeck for 1 kW/h of electricity the cost of grown products was not relevant. Over time, when the price of electricity rose to UAH 1 gryvna 68 kopecks, the relevance of the cost of grown products, especially breeding material, is decisive. In this regard, we conducted a detailed economic analysis of electricity costs for growing 1 g of winter wheat grain and 1 m2 of usable area, depending on the types of lamps, sowing schemes, seasons, and proposed energy-saving growing technologies. The results of scientific research on the cultivation of winter wheat in the area with heated soil are presented. The study of the peculiarities of growth and development of winter wheat plants in this area and on this basis developed energy-saving technologies for its cultivation, which provided significant energy savings, contrasting it in the winter-spring period (January-March) soil greenhouse conditions. In the vacated greenhouse during this period the second generation of selection material of winter wheat was grown or vegetable crops were grown as an element of crop rotation. This area is a normal heating main, which is laid to the selection greenhouses ES-71 (k. GDR). In this area, represented by the usual arable layer of chernozem soil of our zone, which is 1.5 m wide and 50 m long.
Anxiety Status and Associated Factors of Health Personnel Working in a Tertiary Hospital in Turkey in the COVID-19 Pandemic
Authors: Kocakoglu Senay , Cadirci Dursun , Kivanc Terzi Nuray , Ayazoz Yesim
Published: March 2022

Aim: This research was conducted to evaluate the anxiety status and related factors of tertiary hospital personnel working in a densely populated area of ​​Turkey during the COVID-19 pandemic.

Methods: A total of 555 participants were included in this cross-sectional, prospective study. A socio-demographic data form was created and the Beck Anxiety Scale was applied to participants for evaluating anxiety status.

Results: The rate of men 64.86% (n=360) and women 35.14% (n=195). The distribution of anxiety scores was in the range of 8.39±9.16. 58.2% of them (n=323) had low, 41.8% (n=232) had high anxiety scores. Factors like age, gender, marital status, working status in areas where treatment/care is provided to suspected/positive patients with COVID-19, and fear of carrying infection from work to home are found to be statistically significantly related to anxiety.

Conclusion: High anxiety scores were measured in almost half of the participants. Taking measures to improve risk factors can reduce the damaging effects of the challenging working conditions due to the ongoing COVID-19 pandemic on hospital personnel.

Keywords: anxiety, COVID-19, health, health personnel, pandemics
CPD-Structured Multivariate Polynomial Optimization
Authors: Ayvaz Muzaffer , De Lathauwer Lieven
Published: March 2022

We introduce the Tensor-Based Multivariate Optimization (TeMPO) framework for use in nonlinear optimization problems commonly encountered in signal processing, machine learning, and artificial intelligence. Within our framework, we model nonlinear relations by a multivariate polynomial that can be represented by low-rank symmetric tensors (multi-indexed arrays), making a compromise between model generality and efficiency of computation. Put the other way around, our approach both breaks the curse of dimensionality in the system parameters and captures the nonlinear relations with a good accuracy. Moreover, by taking advantage of the symmetric CPD format, we develop an efficient second-order Gauss–Newton algorithm for multivariate polynomial optimization. The presented algorithm has a quadratic per-iteration complexity in the number of optimization variables in the worst case scenario, and a linear per-iteration complexity in practice. We demonstrate the efficiency of our algorithm with some illustrative examples, apply it to the blind deconvolution of constant modulus signals, and the classification problem in supervised learning. We show that TeMPO achieves similar or better accuracy than multilayer perceptrons (MLPs), tensor networks with tensor trains (TT) and projected entangled pair states (PEPS) architectures for the classification of the MNIST and Fashion MNIST datasets while at the same time optimizing for fewer parameters and using less memory. Last but not least, our framework can be interpreted as an advancement of higher-order factorization machines: we introduce an efficient second-order algorithm for higher-order factorization machines.
Harmonic Distortion of Blood Pressure Waveform as a Measure of Arterial Stiffness
Authors: Milkovich Nicholas , Gkousioudi Anastasia , Seta Francesca , Suki Béla , Zhang Yanhang
Published: March 2022

Aging and disease alter the composition and elastic properties of the aortic wall resulting in shape changes in blood pressure waveform (BPW). Here, we propose a new index, harmonic distortion (HD), to characterize BPW and its relationship with other in vitro and in vivo measures. Using a Fourier transform of the BPW, HD is calculated as the ratio of energy above the fundamental frequency to that at the fundamental frequency. Male mice fed either a normal diet (ND) or a high fat, high sucrose (HFHS) diet for 2–10 months were used to study BPWs in diet-induced metabolic syndrome. BPWs were recorded for 20 s hourly for 24 h, using radiotelemetry. Pulse wave velocity (PWV), an in vivo measure of arterial stiffness, was measured in the abdominal aorta via ultrasound sonography. Common carotid arteries were excised from a subset of mice to determine the tangent modulus using biaxial tension-inflation test. Over a 24-h period, both HD and systolic blood pressure (SBP) show a large variability, however HD linearly decreases with increasing SBP. HD is also linearly related to tangent modulus and PWV with slopes significantly different between the two diet groups. Overall, our study suggests that HD is sensitive to changes in blood pressure and arterial stiffness and has a potential to be used as a noninvasive measure of arterial stiffness in aging and disease.
Multiscale Mechanobiology in Brain Physiology and Diseases
Authors: Procès Anthony , Luciano Marine , Kalukula Yohalie , Ris Laurence , Gabriele Sylvain
Published: March 2022

Increasing evidence suggests that mechanics play a critical role in regulating brain function at different scales. Downstream integration of mechanical inputs into biochemical signals and genomic pathways causes observable and measurable effects on brain cell fate and can also lead to important pathological consequences. Despite recent advances, the mechanical forces that influence neuronal processes remain largely unexplored, and how endogenous mechanical forces are detected and transduced by brain cells into biochemical and genetic programs have received less attention. In this review, we described the composition of brain tissues and their pronounced microstructural heterogeneity. We discuss the individual role of neuronal and glial cell mechanics in brain homeostasis and diseases. We highlight how changes in the composition and mechanical properties of the extracellular matrix can modulate brain cell functions and describe key mechanisms of the mechanosensing process. We then consider the contribution of mechanobiology in the emergence of brain diseases by providing a critical review on traumatic brain injury, neurodegenerative diseases, and neuroblastoma. We show that a better understanding of the mechanobiology of brain tissues will require to manipulate the physico-chemical parameters of the cell microenvironment, and to develop three-dimensional models that can recapitulate the complexity and spatial diversity of brain tissues in a reproducible and predictable manner. Collectively, these emerging insights shed new light on the importance of mechanobiology and its implication in brain and nerve diseases.
Juglone and KPT6566 Suppress the Tumorigenic Potential of CD44+CD133+ Tumor-Initiating Caco-2 Cells In Vitro and In Vivo
Authors: Kim Junghoon , Lee Seonock , Sun Ruijing , Kim Jungho
Published: March 2022

Pin1, a cis/trans isomerase of peptidyl-prolyl peptide bonds, plays a crucial role in the pathogenesis of many human cancers. Although chemical inhibitors of Pin1 show potent antitumor therapeutic properties against various cancers, their effect on colorectal cancer, especially colorectal tumor-initiating cells, remains unknown. Here, we investigated the effect of Juglone and KPT6566 on Caco-2 cells and tumor-initiating Caco-2 cells. Juglone and KPT6566 inhibited cell growth and colony formation, and induced apoptosis of Caco-2 cells. We also found that Juglone and KPT6566 downregulated expression of G1-phase-specific cyclins and cyclin-dependent kinases in a time-dependent manner, consistent with suppression of Caco-2 cell proliferation and colony formation. Although tumor-initiating cells are thought to be responsible for resistance to traditional chemotherapeutic drugs, our experiments demonstrate that Juglone or KPT6566 kill both tumor-initiating and non-tumor-initiating Caco-2 cells with equal or similar efficacy. Finally, when CD44+CD133+ tumor-initiating Caco-2 cells were injected into NSG mice, Juglone or KPT6566 led to a meaningful reduction in tumor volume and mass compared with tumors isolated from mice that received control treatment. Overall, these results indicate that chemical Pin1 inhibitors may be a valuable therapeutic option against colorectal tumor-initiating cancer cells.
Two Novel Phenylpropanoid Trimers From Ligusticum chuanxiong Hort With Inhibitory Activities on Alpha-Hemolysin Secreted by Staphylococcus aureus
Authors: Wan Shi-Jie , Ren Han-Gui , Jiang Jia-Ming , Xu Gang , Xu Yu , Chen Si-Min , Chen Gan , Zheng Dan , Yuan Man , Zhang Hong , Xu Hong-Xi
Published: March 2022

The emergence of antibiotic resistance in Staphylococcus aureus has necessitated the development of innovative anti-infective agents acting on novel targets. Alpha-hemolysin (Hla), a key virulence factor of S. aureus, is known to cause various cell damage and death. In this study, with bioassay-guided fractionation, a pair of unusual epimeric lignan trimers, ligustchuanes A and B (1 and 2), were isolated from the rhizomes of Ligusticum chuanxiong Hort, together with two known phthalides being identified by UPLC-QTOF-MS. To the best of our knowledge, trimers with rare C8-C9″-type neolignan and ferulic acid fragments have not been identified in any natural product. Both of them were isolated as racemic mixtures, and their absolute configurations were determined by comparing experimental and calculated ECD spectra after enantioseparation. Ligustchuane B exhibited an outstanding inhibitory effect on α-hemolysin expression in both MRSA USA300 LAC and MSSA Newman strains at concentrations of 3 and 6 μM, respectively. Notably, a mouse model of infection further demonstrated that ligustchuane B could attenuate MRSA virulence in vivo.
An Assessment of Geophysical Survey Techniques for Characterising the Subsurface Around Glacier Margins, and Recommendations for Future Applications
Authors: Watts Hannah , Booth Adam D. , Reinardy Benedict T. I. , Killingbeck Siobhan F. , Jansson Peter , Clark Roger A. , Chandler Benjamin M. P. , Nesje Atle
Published: March 2022

Geophysical surveys provide an efficient and non-invasive means of studying subsurface conditions in numerous sedimentary settings. In this study, we explore the application of three geophysical methods to a proglacial environment, namely ground penetrating radar (GPR), seismic refraction and multi-channel analysis of surface waves (MASW). We apply these geophysical methods to three glacial landforms with contrasting morphologies and sedimentary characteristics, and we use the various responses to assess the applicability and limitations of each method for these proglacial targets. Our analysis shows that GPR and seismic (refraction and MASW) techniques can provide spatially extensive information on the internal architecture and composition of moraines, but careful survey designs are required to optimise data quality in these geologically complex environments. Based on our findings, we define a number of recommendations and a potential workflow to guide future geophysical investigations in analogous settings. We recommend the initial use of GPR in future studies of proglacial environments to inform (a) seismic survey design and (b) the selection of seismic interpretation techniques. We show the benefits of using multiple GPR antenna frequencies (e.g., 25 and 100 MHz) to provide decimetre scale imaging in the near surface (e.g., < 15 m) while also enabling signal penetration to targets at up to ∼40 m depth (e.g., bedrock). This strategy helps to circumvent changes in radar signal penetration resulting from variations in substrate conductivity or abundant scatterers. Our study also demonstrates the importance of combining multiple geophysical methods together with ground-truthing through sedimentological observations to reduce ambiguity in interpretations. Implementing our recommendations will improve geophysical survey practice in the field of glacial geology and allow geophysical methods to play an increasing role in the interpretation of glacial landforms and sediments.
New Insight From the First Application of Ti-in-Quartz (TitaniQ) Thermometry Mapping in the Eastern Khondalite Belt, North China Craton
Authors: Zheng Yuanyuan , Qi Yang , Zhang Di , Jiao Shujuan , Huang Guangyu , Guo Jinghui
Published: March 2022

The thermal regime of the lower crust is a critical factor that controls crustal anatexis, high-grade metamorphism, and granite formation, which finally results in crustal differentiation. However, the large-scale thermal regime in the Precambrian continental crust is generally not well established. In this study, we first applied Ti-in-quartz (TitaniQ) thermometer to map the temperature variation in the lower crust within an area of ∼10,000 km2 in the Paleoproterozoic eastern Khondalite Belt, North China Craton. The studied rocks are aluminous gneisses/granulites, which contain abundant quartz that generally coexists with rutile. The results show that matrix-type quartz with substantial rutile exsolution generally contains the maximum Ti concentration, which is <300 ppm higher than that of inclusion-type quartz. This result suggests that two quartz types probably formed at the prograde and near-peak to early cooling metamorphic stages, respectively. Therefore, the temperature mapping result based on the maximum Ti concentrations of the matrix-type quartz can better represent the thermal regime than inclusion-type quartz. Our regime shows that the hottest Paleoproterozoic lower crust is underneath the Liangcheng-Heling’er-Zhuozi area, where ultrahigh-temperature (UHT) metamorphism is closely associated with abundant charnockite. The hottest region may represent the root of an ancient large hot orogeny. Our study provides a new insight into the formation of UHT metamorphism.
Electrical Energy Storage From First Principles
Authors: Jiang Zhijun , Xu Bin , Prosandeev Sergey , Íñiguez Jorge , Xiang Hongjun , Bellaiche L.
Published: March 2022

Dielectric capacitors are particularly suitable to store the electrical energy of a fast-changing nature. Here, we present a review of recent applications of first principles and first-principles-based effective Hamiltonian approaches to the study of energy storage in ferroelectrics, lead-free antiferroelectrics, relaxor ferroelectrics, and nitride semiconductors. Specifically, these approaches are used to investigate the energy density and efficiency in perovskite BaTiO3, PbTiO3, and KNbO3 ferroelectrics; Bi1−xRxFeO3 antiferroelectric solid solutions (where R is a rare-earth ion); Ba(Zr,Ti)O3 relaxor ferroelectrics; and epitaxial AlN/ScN superlattices. Ultrahigh energy densities and efficiencies are predicted in some of these compounds. In addition, phenomenological models are used to analyze and understand these energy storage results. Consequently, the numerical methods and simple models detailed here can be easily employed to design novel nonlinear dielectrics with further enhanced energy storage performance.
Clinical Experience of Use of Percutaneous Continuous Nervemonitoring in Robotic Bilateral Axillo-Breast Thyroid Surgery
Authors: Zhang Daqi , Wang Cheng , Wang Tie , Du Rui , Li Kunlin , Yang Mingyu , Xue Gaofeng , Dionigi Gianlorenzo , Sun Hui
Published: March 2022

Introduction and Objective

There is a need for a simplified technique for C-IONM in robotic surgery. The primary aim of this study was to describe our clinical experience with the use of percutaneous C-IONM in robotic bilateral axillary thyroid surgery.

Methods

This study prospectively enrolled 304 consecutive patients who underwent robotic thyroidectomy via the bilateral axillo-breast approach and standardized C-IONM via percutaneous probe stimulation.

Results

323 RLNs were analyzed. C-IONM with percutaneous probes was feasible in all cases. During this study, we did not record any cases of probe displacement, and no additional robotic maneuvers were required. The average stimulation intensity was 2 mA. There were no adverse local or systemic C-IONM side effects. The mean time required for probe positioning was 3 minutes. The EMG amplitude signal of 48 RLNs decreased significantly, < 50% from the original V1 signal. In these cases, the surgical procedure was modified.

Conclusion

The proposed percutaneous C-IONM provides a simplification of the continuous monitoring procedure for robotics. The advantage of percutaneous C-IONM is that it does not require additional trocar space, repeated instrument changes, and unmodified cosmesis. To our knowledge, this is the first study on the application of percutaneous C-IONM in robotic thyroid surgery.
Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma
Authors: Mai Shijie , Liang Liping , Mai Genghui , Liu Xiguang , Diao Dingwei , Cai Ruijun , Liu Le
Published: March 2022

Background

Lung cancer has been a prominent research focus in recent years due to its role in cancer-related fatalities globally, with lung adenocarcinoma (LUAD) being the most prevalent histological form. Nonetheless, no signature of lactate metabolism-related long non-coding RNAs (LMR-lncRNAs) has been developed for patients with LUAD. Accordingly, we aimed to develop a unique LMR-lncRNA signature to determine the prognosis of patients with LUAD.

Method

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to derive the lncRNA expression patterns. Identification of LMR-lncRNAs was accomplished by analyzing the co-expression patterns between lncRNAs and LMR genes. Subsequently, the association between lncRNA levels and survival outcomes was determined to develop an effective signature. In the TCGA cohort, Cox regression was enlisted to build an innovative signature consisting of three LMR-lncRNAs, which was validated in the GEO validation cohort. GSEA and immune infiltration analysis were conducted to investigate the functional annotation of the signature and the function of each type of immune cell.

Results

Fourteen differentially expressed LMR-lncRNAs were strongly correlated with the prognosis of patients with LUAD and collectively formed a new LMR-lncRNA signature. The patients could be categorized into two cohorts based on their LMR-lncRNA signatures: a low-risk and high-risk group. The overall survival of patients with LUAD in the high-risk group was considerably lower than those in the low-risk group. Using Cox regression, this signature was shown to have substantial potential as an independent prognostic factor, which was further confirmed in the GEO cohort. Moreover, the signature could anticipate survival across different groups based on stage, age, and gender, among other variables. This signature also correlated with immune cell infiltration (including B cells, neutrophils, CD4+ T cells, CD8+ T cells, etc.) as well as the immune checkpoint blockade target CTLA-4.

Conclusion

We developed and verified a new LMR-lncRNA signature useful for anticipating the survival of patients with LUAD. This signature could give potentially critical insight for immunotherapy interventions in patients with LUAD.
The Effects of 12-Weeks Whey Protein Supplements on Markers of Bone Turnover in Adults With Abdominal Obesity – A Post Hoc Analysis
Authors: Fuglsang-Nielsen Rasmus , Rakvaag Elin , Vestergaard Peter , Hermansen Kjeld , Gregersen Søren , Starup-Linde Jakob
Published: March 2022

Background

While osteoporosis is characterized by skeletal fragility due to increased bone turnover and low bone mineral density (BMD), subjects with abdominal obesity and type-2 diabetes have increased risk of bone fractures despite low bone turnover and increased BMD. Diets with increased protein content are reported to increase bone turnover in healthy adults and may be a point of interest in preserving bone strength in subjects with abdominal obesity and/or type-2 diabetes.

Methods

We examined the effect of 12-weeks dietary intervention on bone turnover in 64 adults with abdominal obesity using data from the MERITS trial. The trial was a randomized, controlled, double blinded study in which participants were allocated to receive either 60 g/d of whey protein hydrolysate or maltodextrin in combination with either high (30 g/d) or low dietary fiber intake (10 g/d). Primarily, we assessed changes in plasma markers of bone turnover Procollagen type 1 N-terminal propeptide (p1NP), C-terminal telopeptide type-1 collagen (CTX), and parathyroid hormone (PTH) within the four intervention groups. In addition, we measured u-calcium and u-carbamide excretion, 25(OH)D, and BMD by whole body DXA scans. Finally, we compared changes in insulin resistance (Homeostasis-model assessment of insulin resistance, HOMA-IR) with changes in bone turnover markers.

The trial was registered at www.clinicaltrials.gov as NCT02931630.

Results

Sixty-four subjects were included in the study. We did not find any effect of twelve weeks of high protein or high fiber intake on plasma levels of P1NP or CTX. There was a nonsignificant positive association between protein intake and PTH levels (p=0.06). U-calcium and u-carbamide increased in both protein groups.

There was a positive association between change in HOMA-IR and PTH (p=0.042), while changes in P1NP and CTX did not associate to changes in HOMA-IR.

Conclusion

Twelve weeks of increased whey protein intake in subjects with abdominal obesity did not affect markers of bone turnover significantly, although tended to increase PTH levels. Dietary fiber intake did not affect bone turnover. We report a positive association between change in HOMA-IR and PTH supporting a hypothesis of insulin resistance as a potential key factor in the expanding field of bone fragility in T2D subjects.
Current Insights Into the Role of Neuropeptide Y in Skin Physiology and Pathology
Authors: Anderson Zoya T. , Dawson Alex D. , Slominski Andrzej T. , Harris Melissa L.
Published: March 2022

Neuropeptide Y is widely distributed within the body and has long been implicated as a contributor to skin disease based on the correlative clinical data. However, until recently, there have been few empirical investigations to determine whether NPY has a pathophysiological role in the skin. Due to appearance-altering phenotypes of atopic dermatitis, psoriasis, and vitiligo, those suffering from these diseases often face multiple forms of negative social attention. This often results in psychological stress, which has been shown to exacerbate inflammatory skin diseases – creating a vicious cycle that perpetuates disease. This has been shown to drive severe depression, which has resulted in suicidal ideation being a comorbidity of these diseases. Herein, we review what is currently known about the associations of NPY with skin diseases and stress. We also review and provide educated guessing what the effects NPY can have in the skin. Inflammatory skin diseases can affect physical appearance to have significant, negative impacts on quality of life. No cure exists for these conditions, highlighting the need for identification of novel proteins/neuropetides, like NPY, that can be targeted therapeutically. This review sets the stage for future investigations into the role of NPY in skin biology and pathology to stimulate research on therapeutic targeting NPY signaling in order to combat inflammatory skin diseases.
Predictive Effect of Triglyceride Glucose−Related Parameters, Obesity Indices, and Lipid Ratios for Diabetes in a Chinese Population: A Prospective Cohort Study
Authors: Li Xiaotong , Sun Mengzi , Yang Yixue , Yao Nan , Yan Shoumeng , Wang Ling , Hu Wenyu , Guo Ruirui , Wang Yuxiang , Li Bo
Published: March 2022

Objective

The purpose of this study was to evaluate the association between triglyceride glucose (TyG) index and new-onset diabetes under different glycemic states and to compare the predictive value of TyG−related parameters, obesity indices, and lipid ratios for new-onset diabetes.

Methods

Data were collected from the China Health and Retirement Longitudinal Study (CHARLS), consisting of 6,258 participants aged ≥45 years. Participants were grouped according to their glycemic states. Cox proportional hazards models and restricted cubic spline regression were used to explore the association between TyG index and diabetes. Cox proportional hazard models were applied to confirm the predictive value of the optimal marker. Receiver operating characteristic (ROC) curves were used to compare the predictive value.

Results

TyG index was positively correlated with the risk of diabetes (hazard ratio (HR), 1.75; 95% confidence interval (CI), 1.56–1.97), and the linear association existed (p < 0.001). The highest correlation with diabetes was visceral adiposity index (VAI) (HR, 2.04; 95% CI, 1.44–2.90) in normal fasting glucose (NFG) group and TyG-body mass index (TyG-BMI) (HR, 2.53; 95% CI, 1.97–3.26) in impaired fasting glucose (IFG) group. The largest area under curve (AUC) was observed in TyG-waist-to-height ratio (TyG-WHtR) in the NFG group (AUC, 0.613; 95% CI, 0.527–0.700), and TyG-BMI had the highest AUC in the IFG group (AUC, 0.643; 95% CI, 0.601–0.685).

Conclusion

The association between TyG index and new-onset diabetes was positive and linear. TyG-WHtR was a clinically effective marker for identifying the risks of diabetes in the NFG group and TyG-BMI was an effective marker to predict diabetes in the IFG group.
Impact of Nutrient Management on Wheat/Vegetable Yields and the Fate of 15N-Labeled Fertilizer in the Yangtze River Basin
Authors: Wang Sen , Yang Lin Sheng , Liao Shi Peng , Sun Bo , Shi Xiao Jun , Lu Jian Wei , Guo Shi Wei , Shen Jian Bo , Zhang Fu Suo , Goulding Keith , Liu Xue Jun
Published: March 2022

The Yangtze River Basin (YRB) crosses three economic zones and major agricultural regions of eastern, central, and western China. Increasing non-point source pollution, caused by excessive nitrogen (N) inputs to farms, is one of the main causes of water contamination in the YRB. To improve N fertilizer use efficiency, we conducted a field experiment using 15N-labeled urea at three sites located in upstream, midstream, and downstream regions of the YRB to evaluate the impacts of improved fertilizer management on crop yield, fertilizer N recovery, and losses in three crop rotations: rice–wheat (RW), rice–vegetable (RV) [tuber mustard at Jiangjin (Chongqing), cabbage at Shayang (Hubei), and savoy cabbage at Rugao (Jiangsu)] and maize–wheat (MW). Applying only 50% of the traditional application of N and P fertilizer maintained the wheat yield at Jiangjin and Shayang and savoy cabbage yield at Rugao. However, it caused a 27% reduction of the wheat yield at Rugao. The 15N recovery showed that 27% of the fertilizer N was retained in the soil and that 25% less fertilizer N was lost to the environment compared to the traditional fertilizer application. Improved fertilizer management would reduce the environmental cost of farming in the YRB, but with some consequences to winter crop yields.
Measuring CH4 Fluxes From Lake and Reservoir Sediments: Methodologies and Needs
Authors: D’Ambrosio Sofia L. , Harrison John A.
Published: March 2022

Accurately quantifying the diffusive flux of CH4 between sediments and the overlying water column is crucial when constructing CH4 budgets in lakes and reservoirs. Although a variety of ex situ and in situ techniques exist for determining this flux, no reviews have provided a comprehensive, comparative overview of these approaches or discussed implications of measurement method on flux estimation. Here, we critically review methods applied in 163 peer-reviewed studies to estimate diffusive CH4 fluxes from lake sediments, including sediment incubations, benthic chambers, and modeling approaches applied in the sediment or water column. For each method, we summarize the approach, discuss limitations and advantages, and summarize published comparisons between different methods. In addition, we examine how method limitations have likely shaped knowledge gaps in current understanding of lake CH4 dynamics. Finally, we call for the development and application of new methods, along with additional testing and intercomparison of existing methods, in order to advance understanding of lake CH4 fluxes.
Disease-Induced Cooperation Mitigates Populations Against Decline: The Cascade Effect of Cooperation Evolution
Authors: Zhang Feng , Cao Menglan , Shi Lei , Wang Ruiwu
Published: March 2022

Due to density-dependent selection, the ecological factors impacting population dynamics can play an important role in promoting cooperation, and accordingly, benefit a population from the eco-evolutionary feedback. This implies that cooperation between individuals could help resist the attack of infectious diseases. Yet, little is known about how cooperation evolves in response to infections. We here examined theoretically the impact of disease infections with various transmission types on cooperation evolution and its feedback to population dynamics. Results show that infected populations can evolve to be more cooperative, and the level of cooperation increases with the transmission rate, which can protect the population against decline due to infection and prevent population extinction driven by defection. A high transmission rate can stabilize population fluctuation, while a relatively low transmission rate could destabilize population dynamics. We argue that the mechanism underlying such stress-induced cooperation is analogous to the cascade effect of trophic interactions in food webs: reduction in selfishness from environmental stress indirectly relaxes the exploitation of cooperators by defectors. These findings emphasize the role of eco-evolutionary feedback in evolving cooperation and the ecological significance of cooperation evolution for populations withstanding disease infection.
Unraveling Anthropocene Paleoenvironmental Conditions Combining Sediment and Foraminiferal Data: Proof-of-Concept in the Sepetiba Bay (SE, Brazil)
Authors: Silva Layla Cristine da , Alves Martins Maria Virgínia , Figueira Rubens , Frontalini Fabrizio , Pereira Egberto , Senez-Mello Thaise M. , Castelo Wellen Fernanda Louzada , Saibro Murilo Barros , Francescangeli Fabio , Mello e Sousa Silvia Helena , Bergamaschi Sérgio , Antonioli Luzia , Bouchet Vincent M. P. , Terroso Denise , Rocha Fernando
Published: March 2022

The Sepetiba Bay (SB), located in the state of Rio de Janeiro (SE Brazil), is a transitional ecosystem highly anthropized. Because of its great environmental, economic, and social importance, the SB has been the target of several studies to investigate the sources of pollution and their environmental impact. However, studies on the response of foraminifera to pollution are rare. This study applies for the first time in the SB the Ecological Quality Ratio (EQR) based on the biotic index exp(H’bc), related to foraminiferal diversity, coupled with granulometric, mineralogical, and geochemical data and a robust age model (based on 210Pb and 137Cs activity). This study aims to evaluate the paleo-ecological quality status (PaleoEcoQS) along core SP5, collected in the inner central region of the SB. In the sedimentary record of the first half of the 20th century, no foraminifera were found, and the moderate enrichment in lithogenic elements was probably related not only to weathering and erosion of rocks but also to mining activities in the region. From the second half of the 20th century, the study area was under higher marine influence. Progressive siltation took place because of anthropogenic interventions in river courses, eutrophication, and metal pollution. Weak hydrodynamic conditions favored the accumulation of fine-grained sediments and organic matters. In the same period, low diversified benthic foraminiferal assemblages, including mainly opportunist species, were developed. Paleo-ecological conditions inferred by the biotic index exp(H’bc) were poor around 1970 and worsened after the metal spill released by Companhia Ingá Mercantil (a zinc ore processing plant). After that, progressively recovery has led to good ecological conditions in 2015. This study shows how benthic foraminiferal methods could represent a very useful tool to track changes in the evaluation of PaleoEcoQS.
General Feasibility of Physical Models of Tree Branches
Authors: Tan Danielle S. , Maiti Ritwik , Tan Yi Wei , Wong Brendan Zhi Jie , Liew Yuqiang , Tan Jia Hao , Lee Daryl Tsen-Tieng , Burcham Daniel C.
Published: March 2022

We tested both real and model branches of four local tree species in a wind tunnel, for wind speeds up to 20 m/s. The model branches were same-size replicas of the real branches obtained via photogrammetry and 3D-printed or CNC-machined. Real leaves were attached to the models in approximately similar configuration. After comparing the streamwise force, drag coefficient (based on initial frontal area) and streamwise deflection, we found that the models exhibited similar trends to that of the real branches. Although not identical in value, the measurements for the model branches were similar in magnitude to the real branches. In particular, the drag coefficients appeared to approach very similar plateaus. We believe the differences in streamwise force and deflection to be due to the plastic used for the models, as well as perhaps how the leaves were attached to the models. We thus consider these physical models to be generally feasible for studying tree branches.
Comparative Analysis of Differentially Mutated Genes in Non-Muscle and Muscle-Invasive Bladder Cancer in the Chinese Population by Whole Exome Sequencing
Authors: Wang Fangming , Dong Xiying , Yang Feiya , Xing Nianzeng
Published: March 2022

Objective: To characterize the spectra of mutations in non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) in the Chinese population to identify any mutational features and find potential therapeutic targets.

Materials and methods: We collected fresh bladder tumor samples from NMIBC (n = 9) and MIBC patients (n = 11) along with adjacent normal bladder tissue specimen and peripheral blood sample. Using whole exome sequencing (WES), we analyzed the mutation spectra of those NMIBC and MIBC bladder cancer (BCa) specimen.

Results: Our results demonstrated that 95% of BCa patients (19/20) had varying degrees of driver gene mutations, FGFR3 (45%), KMT2D (40%), PIK3CA (35%), ARID1A (20%), EP300 (20%), KDM6A (20%), KMT2C (20%), and STAG2 (20%) were the most frequently mutated genes in BCa patients. NMIBC and MIBC exhibited different genomic alterations. FGFR3 (67%), PIK3CA (56%), and RHOB (44%) were the most frequently mutated genes in NMIBC patients. Of note, RHOB mutation only occurred in NMIBC, whereas mutations of KMT2D (55%), TP53 (36%) and KMT2B (27%) were frequently detected in MIBC, and TP53 and KMT2B mutation only occurred in MIBC. The frequency of mutations in DNA-damage repair (DDR) gene was higher in MIBC than that in NMIBC (91 vs 78%, 6.2 vs 2.4 gene mutations per patient). Copy number alterations (CNAs) occurred at more diverse chromosomal locations in NMIBC, but the CNA burden was higher in MIBC [9.01 (2.07–31.51) vs 4.98 (0.99–9.73) mutations/Mb]., the trend of which was consistent with the tumor mutation burden (TMB) [8.26 (4.63–21.84) vs 5.58 (3.87–9.58) mutations/Mb]. Among the current set of single-base substitution (SBS) signatures including SBS 1, 2, 5, 13, and 40, we identified one differently expressed signature between NMIBC and MIBC patients: SBS13.

Conclusions: There were different gene mutational characteristics and signatures between NMIBC and MIBC in the Chinese population. Frequency of DDR, CNA burden and TMB were higher in MIBC. Our analysis revealed that several genes in NMIBC did not overlap with those reported in MIBC, suggesting that a fraction of NMIBC and MIBC likely developed secondary to different precursor lesions.
Multiple Myeloma Patient Tumors With High Levels of Cereblon Exon-10 Deletion Splice Variant Upregulate Clinically Targetable Pro-Inflammatory Cytokine Pathways
Authors: Karagoz Kubra , Stokes Matthew , Ortiz-Estévez María , Towfic Fadi , Flynt Erin , Gooding Sarah , Pierceall William , Thakurta Anjan
Published: March 2022

Immunomodulatory drugs (IMiDs), including lenalidomide and pomalidomide, are used in the routine treatment for multiple myeloma (MM) patients. Cereblon (CRBN) is the direct molecular target of IMiDs. While CRBN is not an essential gene for MM cell proliferation, the frequency of CRBN genetic aberrations, including mutation, copy number loss, and exon-10 (which includes a portion of the IMiD-binding domain) splicing, have been reported to incrementally increase in later-line patients. CRBN exon-10 splicing has also been shown to be associated with decreased progression-free survival in both newly diagnosed and relapsed refractory MM patients. Although we did not find significant general splicing defects among patients with CRBN exon-10 splice variant when compared to those expressing the full-length transcript, we identified upregulated TNFA signaling via NFKB, inflammatory response, and IL-10 signaling pathways in patients with exon-10 splice variant across various data sets—all potentially promoting tumor growth via chronic growth signals. We examined master regulators that mediate transcriptional programs in CRBN exon-10 splice variant patients and identified BATF, EZH2, and IKZF1 as the key candidates across the four data sets. Upregulated downstream targets of BATF, EZH2, and IKZF1 are components of TNFA signaling via NFKB, IL2/STAT5 signaling pathways, and IFNG response pathways. Previously, BATF-mediated transcriptional regulation was associated with venetoclax sensitivity in MM. Interestingly, we found that an EZH2 sensitivity gene expression signature also correlated with high BATF or venetoclax sensitivity scores in these tumors. Together, these data provide a rationale for investigating EZH2 inhibitors or venetoclax in combination with the next generation CRBN-targeting agents, such as CELMoDs, for patients overexpressing the CRBN exon-10 splice variant.
Whole-Genome Sequencing of Endangered Dengchuan Cattle Reveals Its Genomic Diversity and Selection Signatures
Authors: Jin Liangliang , Qu Kaixing , Hanif Quratulain , Zhang Jicai , Liu Jianyong , Chen Ningbo , Suolang Quji , Lei Chuzhao , Huang Bizhi
Published: March 2022

Dengchuan cattle are the only dairy yellow cattle and endangered cattle among Yunnan native cattle breeds. However, its genetic background remains unclear. Here, we performed whole-genome sequencing of ten Dengchuan cattle. Integrating our data with the publicly available data, Dengchuan cattle were observed to be highly interbred than other cattle in the dataset. Furthermore, the positive selective signals were mainly manifested in candidate genes and pathways related to milk production, disease resistance, growth and development, and heat tolerance. Notably, five genes (KRT39, PGR, KRT40, ESR2, and PRKACB) were significantly enriched in the estrogen signaling pathway. Moreover, the missense mutation in the PGR gene (c.190T > C, p.Ser64Pro) showed a homozygous mutation pattern with higher frequency (83.3%) in Dengchuan cattle. In addition, a large number of strong candidate regions matched genes and QTLs related to milk yield and composition. Our research provides a theoretical basis for analyzing the genetic mechanism underlying Dengchuan cattle with excellent lactation and adaptability, crude feed tolerance, good immune performance, and small body size and also laid a foundation for genetic breeding research of Dengchuan cattle in the future.
Small Non-Coding RNAs in the Human Placenta: Regulatory Roles and Clinical Utility
Authors: Telkar Nikita , Stewart Greg L. , Pewarchuk Michelle E. , Cohn David E. , Robinson Wendy P. , Lam Wan L.
Published: March 2022

The placenta is a vital organ formed during pregnancy, and being the interface between the mother and fetus, it is paramount that placental functioning is strictly controlled. Gene expression in the placenta is finely tuned—with aberrant expression causing placental pathologies and inducing stress on both mother and fetus. Gene regulation is brought upon by several mechanisms, and small non-coding RNAs (sncRNAs) have recently been appreciated for their contribution in gene repression. Their dysregulation has been implicated in a range of somatic and inherited disorders, highlighting their importance in maintaining healthy organ function. Their specific roles within the placenta, however, are not well understood, and require further exploration. To this end, we summarize the mechanisms of microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), and transfer RNAs (tRNAs), their known contributions to human placental health and disease, the relevance of sncRNAs as promising biomarkers throughout pregnancy, and the current challenges faced by placental sncRNA studies.