bluuebunny/crossref_metadata_2025 huggingface dataset:
On the achievable rate of bandlimited continuous-time AWGN channels with 1-bit output quantization
Authors: Bender Sandra , Dörpinghaus Meik , Fettweis Gerhard P.
Published: March 2021

We consider a real continuous-time bandlimited additive white Gaussian noise channel with 1-bit output quantization. On such a channel the information is carried by the temporal distances of the zero-crossings of the transmit signal. We derive an approximate lower bound on the capacity by lower-bounding the mutual information rate for input signals with exponentially distributed zero-crossing distances, sine-shaped transition waveform, and an average power constraint. The focus is on the behavior in the mid-to-high signal-to-noise ratio (SNR) regime above 10 dB. For hard bandlimited channels, the lower bound on the mutual information rate saturates with the SNR growing to infinity. For a given SNR the loss with respect to the unquantized additive white Gaussian noise channel solely depends on the ratio of channel bandwidth and the rate parameter of the exponential distribution. We complement those findings with an approximate upper bound on the mutual information rate for the specific signaling scheme. We show that both bounds are close in the SNR domain of approximately 10–20 dB.
FGF gene expression in injured tendons as a prognostic biomarker of 1-year patient outcome after Achilles tendon repair
Authors: Chen Junyu , Svensson Joel , Sundberg Carl-Johan , Ahmed Aisha Siddiqah , Ackermann Paul W.
Published: March 2021

Purpose

Healing outcome after Achilles Tendon Rupture (ATR) is variable and unsatisfactory. Many ATR patients still exhibit pain, functional deficits and limitations in walking one-year post-surgery. The present study was designed to investigate the association between the expression of healing biomarkers and patient outcome after ATR.

Methods

Tendon biopsies were collected from 25 ATR patients during surgery. At 1-year post surgery, all patients completed questionnaires; Achilles tendon Total Rupture Score (ATRS) and Foot and Ankle Outcome Score (FAOS), and were tested for functional outcomes by heel-rise test. In biopsies, FGF, COL III, FN, COL I and MMP-9 mRNA levels were assessed by quantitative RT-PCR while protein expression was studied by immunohistochemistry (IHC).

Results

Our analysis confirmed the presence of FGF, COL III, FN, COL I and MMP-9 at mRNA and protein levels in tendon biopsies. FGF gene expression associated positively with improved total ATRS and better functional outcomes. Additionally, FGF mRNA levels were associated with less pain, less running limitations and less loss in physical activity. In addition, higher COL III mRNA expression was associated with more tendon strength.

Conclusion

Our findings indicate that FGF gene expression is associated with improved patient-reported outcome. FGF expression in surgical biopsies could potentially be used to assist the prognostic evaluation of patient outcome and may be used as a predictor for healing. However, further studies are needed to evaluate the role of FGF in Achilles tendon healing.

Level of evidence

II
Content validity and psychometric evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue scale in patients with chronic lymphocytic leukemia
Authors: Eek Daniel , Ivanescu Cristina , Corredoira Laura , Meyers Oren , Cella David
Published: March 2021

Purpose

Fatigue is a prominent symptom in individuals with chronic lymphocytic leukemia (CLL). This work evaluates the content validity and psychometric properties of the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-Fatigue) in patients with CLL to determine if it is fit for purpose in CLL research.

Methods

The FACIT-Fatigue yields a 13-item total score from a five-item symptom subscale and an eight-item impact subscale. To evaluate content validity, cognitive debriefing interviews were conducted with 40 patients with CLL in the first-line or relapsed or refractory setting. Psychometric properties, including structural validity, internal consistency, construct and known-groups validity, were investigated using data from a phase 3 trial in relapsed or refractory CLL (NCT02970318).

Results

Interviewed patients considered the FACIT-Fatigue items relevant to their CLL experience, understood the terminology and agreed with response options. Confirmatory factor analysis confirmed the presence of symptom and impact subscales, but also supported unidimensionality of the FACIT-Fatigue. The FACIT-Fatigue total, symptom and impact subscales demonstrated good internal consistency (Cronbach’s coefficient α > 0.85 and McDonald’s omega ω > 0.90), and strong correlations with relevant EORTC QLQ-C30 scales (all Spearman’s r ≥ 0.5). Known-groups validity was shown by significant differences between groups defined by baseline performance status, hemoglobin level and constitutional symptoms (all p < .0001). Cluster analysis supported FACIT-Fatigue score thresholds of 30 and 34 to define a severe fatigue population.

Conclusions

Content validity and psychometric evaluation in patients with CLL demonstrated that the FACIT-Fatigue has good psychometric properties and is fit for purpose in CLL.
Robust singular value decomposition filtering for low signal-to-noise ratio seismic data
Authors: Wang Chao , Wang Yun
Published: March 2021

Reduced-rank filtering is a common method for attenuating noise in seismic data. Because conventional reduced-rank filtering distinguishes signals from noises only according to singular values, it performs poorly when the signal-to-noise ratio (S/N) is very low or when data contain high levels of isolate or coherent noise. Therefore, we have developed a novel and robust reduced-rank filtering method based on singular value decomposition in the time-space domain. In this method, noise is recognized and attenuated according to the characteristics of the singular values and the singular vectors. The left and right singular vectors corresponding to large singular values are selected first. Then, the right singular vectors are classified into different categories according to their curve characteristics, such as jump, pulse, and smooth. Each kind of right singular vector is related to a type of noise or seismic event, and it is corrected by using a different filtering technology, such as mean filtering, edge-preserving smoothing, or edge-preserving median filtering. The left singular vectors are also corrected by using the filtering methods based on frequency attributes such as main frequency and frequency bandwidth. To process seismic data containing a variety of events, local data are extracted along the local dip of the event. The optimal local dip is identified according to the singular values and singular vectors of the data matrices that are extracted along different trial directions. This new filtering method has been applied to synthetic and field seismic data, and its performance is compared with that of several conventional filtering methods. The results indicate that the new method is more robust for data with a low S/N, strong isolated noise, or coherent noise. The new method also overcomes the difficulties associated with selecting an optimal rank.
Cavity detection by SH-wave full-waveform inversion — A reflection-focused approach
Authors: Mecking Rebekka , Köhn Daniel , Meinecke Matthias , Rabbel Wolfgang
Published: March 2021

The detection of cavities with geophysical methods is a challenging task for which a general approach has not yet been found. We have found that viscoelastic SH full-waveform inversion (FWI), focusing primarily on reflection events, is able to accurately locate the position of cavities, areas of decompacted sediments, and, more generally, seismic low-velocity anomalies down to 30 m depth. The key for a successful FWI application is the enhancement of the reflected wavefield relative to the surface wavefield. For this purpose, we apply automatic gain control normalization in the objective function. By focusing the inversion on the reflected wavefield, we determine that one can differentiate between air-filled cavities with zero shear-wave (S-wave) velocity and low-velocity zones. Additionally, we test the FWI approach on a field data set, with a known collapsed tunnel system inside a 32 m high monumental antique grave mound. The results show that the location and extent, as well as the density and S-wave velocity of the collapsed tunnel system, can be determined with sufficient accuracy by applying a 2D FWI approach to intersecting profiles, despite the 3D nature of the problem.
Detection of subsurface lineaments using edge diffraction
Authors: Rochlin Itay , Landa Evgeny , Keydar Shemer
Published: March 2021

Detection and imaging of subwavelength features in the subsurface using diffracted waves are rapidly gaining momentum in the oil and gas industry as well as in the fields of engineering, archeology, and homeland security. Most of the methods include coherent summation of the recorded wavefield along diffraction traveltime surfaces from point scatterers. The summation focuses energy onto point-like diffractors that appear at the resulting images as prominent anomalies. However, in cases in which the target is an elongated object such as a fault plane, fracture, tunnel, or elongated cave, a more efficient imaging method can be constructed. We have developed an algorithm for detecting and characterizing linear subsurface elements using a linear-diffractor operator. Our algorithm is based on the coherent summation of the edge diffraction generated by the entire lineament and on the analysis of the calculated coherence measure (semblance). The advantages and limitations of our method are discussed, and the results are compared to conventional point-diffractor-based techniques. Synthetic and real data examples demonstrate that using a linear-diffractor-based algorithm can dramatically improve the detection of linear objects.
Numerical study of crosshole electromagnetic tunnel detection
Authors: Neese John W. , Jackson David R. , Zheng Yingcai , Thomsen Leon A.
Published: March 2021

Electromagnetic tunnel detection is studied numerically using a 3D analytic infinite lossy homogeneous space solution to magnetic dipole radiation and scattering from an infinite cylinder, in a crosshole context. At low frequencies, this serves as a model for a transmit coil radiating a time-varying magnetic field that is then detected from the open-circuit voltage induced on a receive coil. Numerical simulations illustrate how various parameters influence the signal strength and the ability to discern the scattered signal. Tunnel detection is achieved at relatively high frequencies (but below typical ground-penetrating radar frequencies) for fresh water-saturated sand and for weathered granite, which are lower loss media; for the coil and tunnel parameters used here, the optimum frequencies appear to be between 100 kHz and 1 MHz. Tunnel detection for fresh water-saturated clay, a much more lossy medium, can be achieved at a quite low frequency, with an optimum frequency between 1 and 10 kHz. These results suggest that, when a resonant coil system is used, tunnel detection may be possible in a wider range of earth media than previously reported, when the best-suited choice of frequency is used.
Extended Gassmann equation with dynamic volumetric strain: Modeling wave dispersion and attenuation of heterogeneous porous rocks
Authors: Zhao Luanxiao , Wang Yirong , Yao Qiuliang , Geng Jianhua , Li Hui , Yuan Hemin , Han De-hua
Published: March 2021

Sedimentary rocks are often heterogeneous porous media inherently containing complex distributions of heterogeneities (e.g., fluid patches and cracks). Understanding and modeling their frequency-dependent elastic and adsorption behaviors is of great interest for subsurface rock characterization from multiscale geophysical measurements. The physical parameter of dynamic volumetric strain (DVS) associated with wave-induced fluid flow is proposed to understand the common physics and connections behind known poroelastic models for modeling dispersion behaviors of heterogeneous rocks. We have derived the theoretical formulations of DVS for patchy saturated rock at the mesoscopic scale and cracked porous rock at microscopic grain scales, essentially embodying the wave-induced fluid-pressure relaxation process. By incorporating DVS into the classic Gassmann equation, a simple but practical “dynamic equivalent” modeling approach, the extended Gassmann equation, is developed to characterize the dispersion and attenuation of complex heterogeneous rocks at nonzero frequencies. Using the extended Gassmann equation, the effect of microscopic or mesoscopic heterogeneities with complex distributions on the wave dispersion and attenuation signatures can be captured. Our theoretical framework provides a simple and straightforward analytical methodology to calculate wave dispersion and attenuation in porous rocks with multiple sets of heterogeneities exhibiting complex characteristics. We also demonstrate that, with the appropriate consideration of multiple crack sets and complex fluid patches distribution, the modeling results can better interpret the experimental data sets of dispersion and attenuation for heterogeneous porous rocks.
Elastic full-waveform inversion of steeply dipping structures with prismatic waves
Authors: Wu Zheng , Liu Yuzhu , Yang Jizhong
Published: March 2021

High-resolution reconstruction of steeply dipping structures is an important but challenging subject in seismic exploration. Prismatic reflections that contain information on these structures are helpful for reconstructing steeply dipping structures. Elastic full-waveform inversion (EFWI) is a powerful tool that can accurately estimate subsurface parameters from multicomponent seismic data, which can provide information useful for characterizing oil and gas reservoirs. We have constructed the relationship between the forward and inverse problems related to the prismatic reflections by considering the multiparameter exact Hessian in realistic elastic media. We numerically analyze the characteristics of the multiparameter exact Hessian and determine that, when prismatic reflections are apparent in multicomponent data, the multiparameter delta Hessian has a strong influence. We develop this in more detail through forward analysis and determine that the multiparameter delta Hessian considers not only the prismatic reflections but also compensates for the primary reflections in multicomponent data. To use the prismatic waves, we develop a migration/demigration approach-based truncated Newton (TN) method in frequency-domain EFWI, whose storage requirements and computational costs are the same as those of the truncated Gauss-Newton (TGN) method. Realistic 2D numerical examples demonstrate that, compared with the TGN method based on the first-order Born approximation, the TN method can converge faster and obtain higher accuracy in the reconstruction of steeply dipping structures.
Using diving waves for detecting shallow overburden gas layers
Authors: Landrø Martin , Foseide Bjarte , Liu Izzie Yi
Published: March 2021

We have used simple time-shift analysis of diving waves to analyze shallow gas layers in a sedimentary overburden. By using simple equations for how the traveltime will change if a thin sand layer is charged by gas in a localized and constrained region, we show that such variations can be used to map and quantify the thickness of the gas layer. We use conventional 3D seismic data acquired close to a well where an unintended underground gas flow occurred in 1989. Raw seismic data are used as input, and time shifts are estimated for constant offsets for events that are interpreted as being predominantly diving waves. By assuming that the very shallow subsurface has a constant velocity gradient of [Formula: see text], we find diving wave time shifts that fit an average thickness of the gas layer of approximately 3–4 m. This is the minimum gas thickness because it is assumed that the time-shift analysis captures the diving wave hitting the top and the base of the gas layer (sufficiently dense offset sampling is important to achieve this). The outline and circumference of the close-to-circular gas anomaly around the well obtained by the diving wave analysis are confirmed by 3D reflection mapping of the same anomaly.
Training deep networks with only synthetic data: Deep-learning-based near-offset reconstruction for (closed-loop) surface-related multiple estimation on shallow-water field data
Authors: Qu Shan , Verschuur Eric , Zhang Dong , Chen Yangkang
Published: March 2021

Accurate removal of surface-related multiples remains a challenge in shallow-water cases. One reason is that the success of surface-related multiple estimation (SRME)-related algorithms is sensitive to the quality of the near-offset reconstruction. When it comes to a larger missing gap and a shallower water bottom, the state-of-the-art near-offset gap construction method — the parabolic Radon transform — fails to provide reliable recovery of the shallow reflections due to the limited information from the data and highly curved events at near offsets with strong lateral amplitude variations. Therefore, we have developed a novel workflow that first deploys a deep-learning-based reconstruction of the shallow reflections and then uses the reconstructed data as the input for the subsequent surface multiple removal. In particular, we use a convolutional neural network architecture — U-net that was developed from convolutional autoencoders with extra direct skip connections between different levels of encoders and the corresponding decoders. Instead of using field data directly in network training, the training set is carefully synthesized based on the prior water-layer information of the field data; thus, a fully sampled field data set, which is difficult to obtain, is not needed for training in our workflow. An inversion-based approach — closed-loop SRME — is used for the surface multiple removal, in which the primaries are directly estimated via full-waveform inversion in a data-driven manner. Finally, the effectiveness of our workflow is determined based on 2D North Sea field data in a shallow-water scenario (92.5 m water depth) with a relatively large minimum offset (150 m).
Electromagnetic radiation interference signal recognition in coal rock mining based on recurrent neural networks
Authors: Di Yangyang , Wang Enyuan
Published: March 2021

The electromagnetic radiation (EMR) method is a promising geophysical method used to monitor and provide early warnings of coal rock burst disasters. In the underground mining process, personnel activities and electromechanical equipment produce EMR interference signals that affect the accuracy of EMR monitoring. Existing methods for identifying EMR interference signals mainly use the time and amplitude characteristics of the signals. However, these methods need further improvement. The recent advancements in deep learning provide an opportunity to develop a new method for identifying and filtering EMR interference signals. We have developed a method for EMR interference signal recognition based on deep-learning algorithms. The method uses bidirectional long short-term memory recurrent neural networks and the Fourier transform to analyze numerous EMR interference signals along with other signals to intelligently identify and filter EMR signal sequences. The results indicate that our method can respond positively to EMR interferences and accurately eliminate EMR interference signals. The method can significantly improve the reliability of EMR monitoring data and effectively monitor rock burst disasters.
Circulating Galectin-3 Levels Are Not Associated With Nonalcoholic Fatty Liver Disease: A Mendelian Randomization Study
Authors: Tremblay Maxime , Perrot Nicolas , Ghodsian Nooshin , Gobeil Émilie , Couture Christian , Mitchell Patricia L , Thériault Sébastien , Arsenault Benoit J
Published: March 2021

Context

The impact of galectin-3 inhibitors on nonalcoholic fatty liver diseases (NAFLD)-related outcomes is currently under investigation in randomized clinical trials. Whether there is a causal association between plasma galectin-3 levels and NAFLD is unknown.

Objective

To evaluate the causal effect of circulating galectin-3 levels on NAFLD as well as >800 other human diseases.

Design

Inverse variance-weighted (IVW) Mendelian randomization (MR) and phenome-wide MR.

Setting

Summary statistics of genome-wide association studies.

Patients

Participants of the UK Biobank, Electronic Medical Records and Genomics (eMERGE), FinnGen, Prevention of Renal and Vascular End-Stage Disease (PREVEND), and IMPROVE cohorts.

Intervention

Identification of independent single-nucleotide polymorphisms (SNPs) associated with galectin-3 levels (P < 5 × 10-8) in the PREVEND (14 SNPs) and IMPROVE (3 SNPs) cohorts.

Main outcome measures

Presence of NAFLD in a meta-analysis of genome-wide association study of the eMERGE, UK Biobank, and FinnGen cohorts (3042 NAFLD cases and 504 853 controls), as well as >800 other human diseases in the UK Biobank and FinnGen.

Results

Using IVW-MR, we found no causal association between galectin-3 levels and NAFLD in the meta-analysis of the 3 cohorts or in each individual cohort. After correction for multiple testing, we found no causal association between galectin-3 levels and >800 human disease-related traits.

Conclusions

This MR study revealed no causal associations between circulating galectin-3 levels and NAFLD or any other disease traits, suggesting that plasma galectin-3 levels may not be directly implicated in the pathogenesis of NAFLD or other human diseases.
Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women
Authors: Gong Rui , Xiao Hong-Mei , Zhang Yin-Hua , Zhao Qi , Su Kuan-Jui , Lin Xu , Mo Cheng-Lin , Zhang Qiang , Du Ya-Ting , Lyu Feng-Ye , Chen Yuan-Cheng , Peng Cheng , Liu Hui-Min , Hu Shi-Di , Pan Dao-Yan , Chen Zhi , Li Zhang-Fang , Zhou Rou , Wang Xia-Fang , Lu Jun-Min , Ao Zeng-Xin , Song Yu-Qian , Weng Chan-Yan , Tian Qing , Schiller Martin R , Papasian Christopher J , Brotto Marco , Shen Hui , Shen Jie , Deng Hong-Wen
Published: March 2021

Context

Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown.

Objective

We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women.

Design and Methods

We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments.

Results

Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM).

Conclusions

This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.
Low-Density Lipoprotein Cholesterol Is Associated With Insulin Secretion
Authors: Dannecker Corinna , Wagner Robert , Peter Andreas , Hummel Julia , Vosseler Andreas , Häring Hans-Ulrich , Fritsche Andreas , Birkenfeld Andreas L , Stefan Norbert , Heni Martin
Published: March 2021

Context

Pharmacological lowering of low-density lipoprotein (LDL) cholesterol potently reduces cardiovascular risk while concurrently increasing type 2 diabetes risk.

Objective

The aim of this study was to investigate the relationship between LDL cholesterol concentrations and insulin secretion and glucagon levels.

Methods

A total of 3039 individuals without cholesterol-lowering therapy, but with increased risk for diabetes, underwent routine blood tests and a 5-point oral glucose tolerance test (OGTT). Glucagon concentrations, insulin secretion, and insulin clearance indices were derived from the OGTT.

Results

There was no association between LDL cholesterol and fasting glucagon (P = .7, β = –.01) or post–glucose load glucagon levels (P = .7, β = –.07), but we detected significant positive associations of LDL cholesterol and C-peptide–based indices of insulin secretion (area under the curve [AUC]C-Peptide(0-30min)/AUCGlucose(0-30min): P < .001, β = .06; AUCC-Peptide(0-120min) /AUCGlucose(0-120min): P < .001, β = –.08). In contrast, we found a negative association of insulin-based insulin secretion indices with LDL concentrations (insulinogenic index: P = .01, β = –.04; disposition index: P < .001, β = –.06). LDL cholesterol levels, however, were positively associated with insulin clearance assessed from C-peptide and insulin concentrations, both in the fasting state and post–glucose load (P < .001, β = .09 and P < .001, β = .06, respectively).

Conclusion

As C-peptide based indices reflect insulin secretion independent of hepatic clearance, our results indicate lower insulin secretion in case of lesser LDL cholesterol. This could explain deteriorating glycemic control in response to cholesterol-lowering drugs.
Characterizing a Common CERS2 Polymorphism in a Mouse Model of Metabolic Disease and in Subjects from the Utah CAD Study
Authors: Nicholson Rebekah J , Poss Annelise M , Maschek J Alan , Cox James E , Hopkins Paul N , Hunt Steven C , Playdon Mary C , Holland William L , Summers Scott A
Published: March 2021

Context

Genome-wide association studies have identified associations between a common single nucleotide polymorphism (SNP; rs267738) in CERS2, a gene that encodes a (dihydro)ceramide synthase that is involved in the biosynthesis of very-long-chain sphingolipids (eg, C20-C26) and indices of metabolic dysfunction (eg, impaired glucose homeostasis). However, the biological consequences of this mutation on enzyme activity and its causal roles in metabolic disease are unresolved.

Objective

The studies described herein aimed to characterize the effects of rs267738 on CERS2 enzyme activity, sphingolipid profiles, and metabolic outcomes.

Design

We performed in-depth lipidomic and metabolic characterization of a novel CRISPR knock-in mouse modeling the rs267738 variant. In parallel, we conducted mass spectrometry-based, targeted lipidomics on 567 serum samples collected through the Utah Coronary Artery Disease study, which included 185 patients harboring 1 (n = 163) or both (n = 22) rs267738 alleles.

Results

In-silico analysis of the amino acid substitution within CERS2 caused by the rs267738 mutation suggested that rs267738 is deleterious for enzyme function. Homozygous knock-in mice had reduced liver CERS2 activity and enhanced diet-induced glucose intolerance and hepatic steatosis. However, human serum sphingolipids and a ceramide-based cardiac event risk test 1 score of cardiovascular disease were not significantly affected by rs267738 allele count.

Conclusions

The rs267738 SNP leads to a partial loss-of-function of CERS2, which worsened metabolic parameters in knock-in mice. However, rs267738 was insufficient to effect changes in serum sphingolipid profiles in subjects from the Utah Coronary Artery Disease Study.
A Body Weight Sensor Regulates Prepubertal Growth via the Somatotropic Axis in Male Rats
Authors: Jansson John-Olov , Dalmau Gasull Adria , Schéle Erik , Dickson Suzanne L , Palsdottir Vilborg , Palmquist Anders , Gironès Ferran Font , Bellman Jakob , Anesten Fredrik , Hägg Daniel , Ohlsson Claes
Published: March 2021

In healthy conditions, prepubertal growth follows an individual specific growth channel. Growth hormone (GH) is undoubtedly the major regulator of growth. However, the homeostatic regulation to maintain the individual specific growth channel during growth is unclear. We recently hypothesized a body weight sensing homeostatic regulation of body weight during adulthood, the gravitostat. We now investigated if sensing of body weight also contributes to the strict homeostatic regulation to maintain the individual specific growth channel during prepubertal growth. To evaluate the effect of increased artificial loading on prepubertal growth, we implanted heavy (20% of body weight) or light (2% of the body weight) capsules into the abdomen of 26-day-old male rats. The body growth, as determined by change in biological body weight and growth of the long bones and the axial skeleton, was reduced in rats bearing a heavy load compared with light load. Removal of the increased load resulted in a catch-up growth and a normalization of body weight. Loading decreased hypothalamic growth hormone releasing hormone mRNA, liver insulin-like growth factor (IGF)-1 mRNA, and serum IGF-1, suggesting that the reduced body growth was caused by a negative feedback regulation on the somatotropic axis and this notion was supported by the fact that increased loading did not reduce body growth in GH-treated rats. Based on these data, we propose the gravitostat hypothesis for the regulation of prepubertal growth. This states that there is a homeostatic regulation to maintain the individual specific growth channel via body weight sensing, regulating the somatotropic axis and explaining catch-up growth.
Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome
Authors: De Bem Tiago H C , Tinning Haidee , Vasconcelos Elton J R , Wang Dapeng , Forde Niamh
Published: March 2021

The molecular interactions between the maternal environment and the developing embryo are key for early pregnancy success and are influenced by factors such as maternal metabolic status. Our understanding of the mechanism(s) through which these individual nutritional stressors alter endometrial function and the in utero environment for early pregnancy success is, however, limited. Here we report, for the first time, the use of an endometrium-on-a-chip microfluidics approach to produce a multicellular endometrium in vitro. Isolated endometrial cells (epithelial and stromal) from the uteri of nonpregnant cows in the early luteal phase (Days 4-7) were seeded in the upper chamber of the device (epithelial cells; 4-6 × 104 cells/mL) and stromal cells seeded in the lower chamber (1.5-2 × 104 cells/mL). Exposure of cells to different concentrations of glucose (0.5, 5.0, or 50 mM) or insulin (Vehicle, 1 or 10 ng/mL) was performed at a flow rate of 1 µL/minute for 72 hours. Quantitative differences in the cellular transcriptome and the secreted proteome of in vitro–derived uterine luminal fluid were determined by RNA-sequencing and tandem mass tagging mass spectrometry, respectively. High glucose concentrations altered 21 and 191 protein-coding genes in epithelial and stromal cells, respectively (P < .05), with a dose-dependent quantitative change in the protein secretome (1 and 23 proteins). Altering insulin concentrations resulted in limited transcriptional changes including transcripts for insulin-like binding proteins that were cell specific but altered the quantitative secretion of 196 proteins. These findings highlight 1 potential mechanism by which changes to maternal glucose and insulin alter uterine function.
The high energetic cost of rapid force development in muscle
Authors: van der Zee Tim J. , Kuo Arthur D.
Published: March 2021

Muscles consume metabolic energy for active movement, particularly when performing mechanical work or producing force. Less appreciated is the cost for activating muscle quickly, which adds considerably to the overall cost of cyclic force production. However, the cost magnitude relative to the cost of mechanical work, which features in many movements, is unknown. We therefore tested whether fast activation is costly compared with performing work or producing isometric force. We hypothesized that metabolic cost would increase with a proposed measure termed force rate (rate of increase in muscle force) in cyclic tasks, separate from mechanical work or average force level. We tested humans (N=9) producing cyclic knee extension torque against an isometric dynamometer (torque 22 N m, cyclic waveform frequencies 0.5–2.5 Hz), while also quantifying quadriceps muscle force and work against series elasticity (with ultrasonography), along with metabolic rate through respirometry. Net metabolic rate increased by more than four-fold (10.5 to 46.8 W) with waveform frequency. At high frequencies, the hypothesized force-rate cost accounted for nearly half (40%) of energy expenditure. This exceeded the cost for average force (17%) and was comparable to the cost for shortening work (43%). The force-rate cost is explained by additional active calcium transport necessary for producing forces at increasing waveform frequencies, owing to rate-limiting dynamics of force production. The force-rate cost could contribute substantially to the overall cost of movements that require cyclic muscle activation, such as locomotion.
Orexin-A inhibits fictive air breathing responses to respiratory stimuli in the bullfrog tadpole (Lithobates catesbeianus)
Authors: Fonseca Elisa M. , Janes Tara A. , Fournier Stéphanie , Gargaglioni Luciane H. , Kinkead Richard
Published: March 2021

In pre-metamorphic tadpoles, the neural network generating lung ventilation is present but actively inhibited; the mechanisms leading to the onset of air breathing are not well understood. Orexin (ORX) is a hypothalamic neuropeptide that regulates several homeostatic functions, including breathing. While ORX has limited effects on breathing at rest, it potentiates reflexive responses to respiratory stimuli mainly via ORX receptor 1 (OX1R). Here, we tested the hypothesis that OX1Rs facilitate the expression of the motor command associated with air breathing in pre-metamorphic bullfrog tadpoles (Lithobates catesbeianus). To do so, we used an isolated diencephalic brainstem preparation to determine the contributions of OX1Rs to respiratory motor output during baseline breathing, hypercapnia and hypoxia. A selective OX1R antagonist (SB-334867; 5–25 µmol l−1) or agonist (ORX-A; 200 nmol l−1 to 1 µmol l−1) was added to the superfusion media. Experiments were performed under basal conditions (media equilibrated with 98.2% O2 and 1.8% CO2), hypercapnia (5% CO2) or hypoxia (5–7% O2). Under resting conditions gill, but not lung, motor output was enhanced by the OX1R antagonist and ORX-A. Hypercapnia alone did not stimulate respiratory motor output, but its combination with SB-334867 increased lung burst frequency and amplitude, lung burst episodes, and the number of bursts per episode. Hypoxia alone increased lung burst frequency and its combination with SB-334867 enhanced this effect. Inactivation of OX1Rs during hypoxia also increased gill burst amplitude, but not frequency. In contrast with our initial hypothesis, we conclude that ORX neurons provide inhibitory modulation of the CO2 and O2 chemoreflexes in pre-metamorphic tadpoles.
Distinct neuron phenotypes may serve object feature sensing in the electrosensory lobe of Gymnotus omarorum
Authors: Nogueira Javier , Castelló María E. , Lescano Carolina , Caputi Ángel A.
Published: March 2021

Early sensory relay circuits in the vertebrate medulla often adopt a cerebellum-like organization specialized for comparing primary afferent inputs with central expectations. These circuits usually have a dual output, carried by center ON and center OFF neurons responding in opposite ways to the same stimulus at the center of their receptive fields. Here, we show in the electrosensory lateral line lobe of Gymnotiform weakly electric fish that basilar pyramidal neurons, representing ‘ON’ cells, and non-basilar pyramidal neurons, representing ‘OFF’ cells, have different intrinsic electrophysiological properties. We used classical anatomical techniques and electrophysiological in vitro recordings to compare these neurons. Basilar neurons are silent at rest, have a high threshold to intracellular stimulation, delayed responses to steady-state depolarization and low pass responsiveness to membrane voltage variations. They respond to low-intensity depolarizing stimuli with large, isolated spikes. As stimulus intensity increases, the spikes are followed by a depolarizing after-potential from which phase-locked spikes often arise. Non-basilar neurons show a pacemaker-like spiking activity, smoothly modulated in frequency by slow variations of stimulus intensity. Spike-frequency adaptation provides a memory of their recent firing, facilitating non-basilar response to stimulus transients. Considering anatomical and functional dimensions, we conclude that basilar and non-basilar pyramidal neurons are clear-cut, different anatomo-functional phenotypes. We propose that, in addition to their role in contrast processing, basilar pyramidal neurons encode sustained global stimuli such as those elicited by large or distant objects while non-basilar pyramidal neurons respond to transient stimuli due to movement of objects with a textured surface.
Exploring Metastable Oxynitrides by Thin Film Growth Approach
Authors: Hirose Yasushi , Hasegawa Tetsuya
Published: March 2021

Metal oxynitrides are expected to show unique chemical and physical properties suitable for various applications. However, compared with oxides, the chemical space of oxynitrides has not been well explored mainly due to their thermal instability and high reaction temperature required in conventional bulk synthesis methods. Highly nonequilibrium thin film growth is a promising route for obtaining those unexplored oxynitrides. In this account, we will overview recent studies on thin film synthesis of oxynitrides, especially focusing on exploration of metastable phases, such as mid- and late-transition metal compounds, metastable polymorphs, geometrical isomers with respect to anion coordination, and amorphous phases.
Macaroni Fullerene Crystals-Derived Mesoporous Carbon Tubes as a High Rate Performance Supercapacitor Electrode Material
Authors: Maji Subrata , Shrestha Rekha Goswami , Lee Jaewoo , Han Sang A , Hill Jonathan P , Kim Jung Ho , Ariga Katsuhiko , Shrestha Lok Kumar
Published: March 2021

Self-assembled macaroni fullerene C60 crystals (MFCs) of uniform shape and narrow size distribution are produced using the dynamic liquid-liquid interfacial precipitation method under ambient conditions. High temperature heat treatment (900 °C) of MFCs yields mesoporous carbons tubes (MCTs) retaining the initial morphology. This novel mesoporous carbon material exhibits excellent electrochemical supercapacitive performance due to high surface areas (1544 m2 g−1), large pore volume (2.936 cm3 g−1) and interconnected porous structures. In a three-electrode aqueous electrolyte system, the electrode achieved high specific capacitance ca. 422 F g−1 at a current density of 1 A g−1 followed by excellent cycling stability (>95%) after 10,000 charging-discharging cycles at 20 A g−1. We believe that the novel mesoporous carbon material derived from a π-electron carbon source can be used as an alternative electrode material in advanced supercapacitor devices.
A dosimetric study to improve the quality of nodal radiotherapy in breast cancer
Authors: Welgemoed Camarie , Coughlan Simon , McNaught Patti , Gujral Dorothy , Riddle Pippa
Published: March 2021

Objectives:

Field-based planning for regional nodal breast radiotherapy (RT) used to be standard practice. This study evaluated a field-based posterior axillary boost (PAB) and two forward-planned intensity-modulated RT (IMRT) techniques, aiming to replace the first.

Methods:

Supraclavicular and axillary nodes, humeral head, brachial plexus, thyroid, and oesophagus were retrospectively delineated on 12 CT scans. Three plans, prescribed to 40.05 Gy, were produced for each patient. Breast plans consisted of field-in-field IMRT tangential fields in all three techniques. Nodal plans consisted of a field-based PAB (anterior and posterior boost beam), and 2 forward-planned techniques: simple IMRT 1 (anterior and posterior beam with limited segments), and a more advanced IMRT 2 technique (anterior and fully modulated posterior beam).

Results:

The nodal V90% was similar between IMRT 1: mean 99.5% (SD 1.0) and IMRT 2: 99.4% (SD 0.5). Both demonstrated significantly improved results (p = 0.0001 and 0.005, respectively) compared to the field-based PAB technique. IMRT 2 lung V12Gy and humeral head V10Gy were significantly lower (p = 0.002, 0.0001, respectively) than the field-based PAB technique. IMRT 1 exhibited significantly lower brachial plexus Dmax and humeral head V5, 10, and 15Gy doses (p = 0.007, 0.013, 0.007 and 0.007, respectively) compared to the field-based PAB technique. The oesophagus and thyroid dose difference between methods was insignificant.

Conclusions:

Both IMRT techniques achieved the dose coverage requirements and reduced normal tissue exposure, decreasing the risk of radiation side effects. Despite the increased cost of IMRT, compared to non-IMRT techniques 1, both IMRT techniques are suitable for supraclavicular and axillary nodal RT.

Advances in knowledge:

Forward-planned IMRT already resulted in significant dose reduction to organs at risk and improved planning target volume coverage. 1 This new, simplified forward-planned IMRT one technique has not been published in this context and is easy to implement in routine clinical practice.
Development and validation of a new formula for sex estimation based on multislice computed tomographic measurements of maxillary and frontal sinuses among Brazilian adults
Authors: de Mendonça Diego Santiago , Kurita Lúcio Mitsuo , Carvalho Francisco Samuel Rodrigues , Tuji Fabrício Mesquita , Silva Paulo Goberlânio de Barros , Bezerra Tácio Pinheiro , de Aguiar Andréa Silvia Walter , Gurgel Costa Fábio Wildson
Published: March 2021

Objectives:

To evaluate the accuracy of the measurements of the maxillary sinus (MS) and frontal sinus (FS) in sex estimation among Brazilian adults using multislice computed tomography (MCT) and to develop and cross-validate a new formula for sex estimation.

Methods:

The present cross-sectional research was conducted in two phases: (1) development of a formula on the basis of the measurements of both the sinuses (50 males and 50 females); and (2) validation study (20 males and 20 females). The linear measurements (height, width and diameter) were assessed using the RadiAnt DICOM software. A new formula for sex estimation was developed (multivariate statistical approach) and validated. Receiver operating characteristic curves, area under the curve, sensitivity, specificity, positive and negative predictive values, accuracy and likelihood ratio were estimated.

Results:

Males displayed higher mean values (width, height and diameter) of the FS and MS (p < 0.05). The MS was a better predictor in sex estimation (males vs females), compared to the FS (accuracy between 61–74% and 58–69%, respectively). The distance between the right and left MS displayed the highest accuracy (74%). The sensitivity, specificity and accuracy of the new formula were 80%, 95.5% and 87.5%, respectively. 63.1% reduction was observed in the number of predictive values for sex estimation (individuals older than 30 years).

Conclusions:

The present MCT measurements showed a higher accuracy in the estimation of sex in males. The highest accuracy was associated with the distance between the right and left MS. The new formula displayed high precision for sex estimation.
Comparing the performance of QuantiFERON-TB Gold Plus with QuantiFERON-TB Gold in-tube among highly TB exposed gold miners in South Africa
Authors: Ntshiqa Thobani , Chihota Violet , Mansukhani Raoul , Nhlangulela Lindiwe , Velen Kavindhran , Charalambous Salome , Maenetje Pholo , Hawn Thomas R. , Wallis Robert , Grant Alison D. , Fielding Katherine , Churchyard Gavin
Published: March 2021

Background: QuantiFERON-TB Gold in-tube (QFT-GIT) is an interferon-gamma release assay (IGRA) used to diagnose latent tuberculosis infection. Limited data exists on performance of QuantiFERON-TB Gold-Plus (QFT-Plus), a next generation of IGRA that includes an additional antigen tube 2 (TB2) while excluding TB7.7 from antigen tube 1 (TB1), to measure TB specific CD4+ and CD8+ T lymphocytes responses. We compared the performance of QFT-Plus with QFT-GIT among highly TB exposed goldminers in South Africa.

Methods: We enrolled HIV-negative goldminers in South Africa, ≥33 years with no prior history of TB disease or evidence of silicosis. Blood samples were collected for QFT-GIT and QFT-Plus. QFT-GIT was considered positive if TB1 tested positive; while QFT-Plus was positive if both or either TB1 or TB2 tested positive, as per manufacturer's recommendations. We compared the performance of QFT-Plus with QFT-GIT using Cohen’s Kappa. To assess the specific contribution of CD8+ T-cells, we used TB2−TB1 differential values as an indirect estimate. A cut-off value was set at 0.6. Logistic regression was used to identify factors associated with having TB2-TB1>0.6 difference on QFT-Plus.

Results: Of 349 enrolled participants, 304 had QFT-Plus and QFT-GIT results: 205 (68%) were positive on both assays; 83 (27%) were negative on both assays while 16 (5%) had discordant results. Overall, there was 94.7% (288/304) agreement between QFT-Plus and QFT-GIT (Kappa = 0.87). 214 had positive QFT-Plus result, of whom 202 [94.4%, median interquartile range (IQR): 3.06 (1.31, 7.00)] were positive on TB1 and 205 [95.8%, median (IQR): 3.25 (1.53, 8.02)] were positive on TB2. A TB2-TB1>0.6 difference was observed in 16.4% (35/214), with some evidence of a difference by BMI; 14.9% (7/47), 9.8% (9/92) and 25.3% (19/75) for BMI of 18.5-24.9, 18.5-25 and >30 kg/m2, respectively (P=0.03).

Conclusion: In a population of HIV-negative goldminers, QFT-Plus showed a similar performance to QFT-GIT.