bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of imposing gauge invariance in time-dependent density functional theory calculations with meta-generalized gradient approximations
Authors: Grotjahn Robin , Furche Filipp , Kaupp Martin
Published: September 2022

It has been known for more than a decade that the gauge variance of the kinetic energy density τ leads to additional terms in the magnetic orbital rotation Hessian used in linear-response time-dependent density functional theory (TDDFT), affecting excitation energies obtained with τ-dependent exchange–correlation functionals. While previous investigations found that a correction scheme based on the paramagnetic current density has a small effect on benchmark results, we report more pronounced effects here, in particular, for the popular M06-2X functional and for some other meta-generalized gradient approximations (mGGAs). In the first part of this communication, this is shown by a reassessment of a set of five Ni(II) complexes for which a previous benchmark study that did not impose gauge invariance has found surprisingly large errors for excitation energies obtained with M06-2X. These errors are more than halved by restoring gauge invariance. The variable importance of imposing gauge invariance for different mGGA-based functionals can be rationalized by the derivative of the mGGA exchange energy integrand with respect to τ. In the second part, a large set of valence excitations in small main-group molecules is analyzed. For M06-2X, several selected n → π* and π→π⊥* excitations are heavily gauge-dependent with average changes of −0.17 and −0.28 eV, respectively, while π→π‖* excitations are marginally affected (−0.04 eV). Similar patterns, but of the opposite signs, are found for SCAN0. The results suggest that reevaluation of previous gauge variant TDDFT results based on M06-2X and other mGGA functionals is warranted.
Study of ecological water-demand security in the Linghekou Reserve of north-eastern China, based on landscape pattern
Authors: Cheng Qian
Published: September 2022

Context The socio-economic development and the expansion of urbanisation boundaries are constantly eroding the ecological resources of wetlands, making them deteriorate, weakening their ecological functions and making the phenomenon of water shortage within them obvious. Aim Through the study of water-demand model and water distribution process in coastal wetlands, we cannot only improve the current situation of water shortage within wetlands and optimise water allocation, but also improve the research content of ecological water demand in wetlands. Methods In this study, Remote Sensing and Geographic Information System technology were used to study the landscape distribution characteristics and ecological water demand of the Linghekou Reserve, on the basis of the landscape pattern index and ecological water-demand model. Key results The ecological water demand decreases year by year, with obvious spatial and temporal variability, and the areas with higher ecological water demand are located mainly in the central and southern parts of the reserve. Among the total ecological water demand, the biological habitat has the largest proportion of water demand, and plays an important role in ensuring the water-demand security of the reserve. Conclusion The ecological environment quality of the reserve not only affects the landscape distribution characteristics, but also influences the total ecological water demand. Implications This study provides a research reference for water-shortage problems caused by ecological imbalance, and provides a scientific basis for other wetland-related problems in north-eastern China.
Phylogeny, classification and biogeography of
Authors: Batty Erin L. , Holmes Gareth D. , Murphy Daniel J. , Forster Paul I. , Neal Will C. , Bayly Michael J.
Published: September 2022

Philotheca sect. Erionema includes 14 species from eastern Australia and one from south-western Australia. We conducted a phylogenetic analysis of the section, including samples of all species, using sequences of the ITS and ETS regions of nuclear ribosomal DNA. Results were broadly congruent with a previous analysis based on morphological and flavonoid data. The analysis is consistent with the monophyly of the section and supports the monophyly of six species represented by multiple samples. Philotheca verrucosa (A. Rich.) Paul G. Wilson was resolved as paraphyletic with respect to P. freyciana Rozefelds but with poor support. Philotheca glasshousiensis, P. myoporoides and P. myoporoides subsp. myoporoides were clearly polyphyletic, including separate geographic clades and the classification of each of these taxa requires revision. In particular, disjunct northern populations of P. glasshousiensis probably represent a distinct species, the five subspecies of P. myoporoides could be treated as separate species and at least two other distinct groups that are currently included under the circumscription of subsp. myoporoides could be treated as species. The phylogeny revealed deeply divergent, geographically overlapping clades in eastern Australia and substantial distances (up to 900 km) between sister taxa. We infer that biogeography of the group has been shaped largely by vicariant differentiation of taxa.
Mockery and poetic satire
Authors: Chaves Thomas David F.
Published: September 2022

In a multilingual state, there is virtually no “linguistic” need to self-translate since both writers and their readers are bi- or trilingual. However, poetic self-translation has had a long and established history in the Philippines, brought about initially during the Spanish conquest in the 16th century, whose early writers were called “ladinos” (bilingual), following mainland Spanish tradition. Originally devotional in nature, self-translated poetry gradually acquired new and more secular configurations across time, especially during the American period (1898–1942) and the Philippines’ subsequent independence after WW II. While various language pairs have been utilized, today’s self-translated poetry revolves around English and a local regional language, notably Tagalog (Filipino) and Cebuano, in either direction. The main motivation for self-translation is sociological, that is, to establish one’s professional capital (in the Bourdieu sense), since many of these poets are well-established and have loyal readership, and to mark them off from those poets who write in one preferred language, and who form the majority.

One characteristic of this self-translated poetry is the cultivation of political satire, humorous and trenchant at the same time, especially protesting the abuses of two repressive regimes and commenting on persistent social ills such as economic injustice and gender inequality. Humor is ordinarily difficult to pull off in translation, especially when addressing “two” cultures simultaneously – yet Filipino self-translators seem to suffer no such challenges. This is made all the more laudable because many of these poets employ Venuti’s “domesticating” or Nida’s “faithful” strategies, and that because wordplay is the basis of much of this humor, something next-to-impossible for translation purposes. This paper therefore explores the specific modes or solutions applied in the unenviable task by four poets. These are Federico Licsi Espino, Jr. (Spanish-English), Jose Lacaba, Jr. (Tagalog-English), Eric Gamalinda (Tagalog-English) and Marjorie Evasco (Cebuano-English), all poets who write mainly in English as their base (a result of the continuing prestige of this colonial legacy), but who have successfully written political satire bilingually in a nation torn between elite-oriented democracy and repressive authoritarianism throughout much of its 75-year independent history.
Endosomal recycling defects link Huntington’s disease with McLeod syndrome
Authors: Marsan Elise , Huang Eric J.
Published: September 2022

Chhetri and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202112073) show that Rab11-mediated endosomal recycling regulates cell surface expression of McLeod syndrome protein XK. Mutant huntingtin interferes with the recycling of XK to the cell surface and significantly reduces manganese transport across cell membrane.
NCOA4: More than a receptor for ferritinophagy
Authors: Wang Zheng , Zhang Hong
Published: September 2022

Liquid–liquid phase separation (LLPS) triages protein cargoes for autophagic degradation. In this issue, Ohshima et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202203102) demonstrate that the autophagy receptor NCOA4 interacts with ferritin particles to form liquid-like condensates via LLPS. The NCOA4-ferritin condensates are delivered to lysosomes for degradation via either canonical macroautophagy or endosomal microautophagy to maintain intracellular iron homeostasis.
Mitochondria transfer mediates stress erythropoiesis by altering the bioenergetic profiles of early erythroblasts through CD47
Authors: Yang Chong , Yokomori Rui , Chua Lee Hui , Tan Shi Hao , Tan Darren Qiancheng , Miharada Kenichi , Sanda Takaomi , Suda Toshio
Published: September 2022

Intercellular mitochondria transfer is a biological phenomenon implicated in diverse biological processes. However, the physiological role of this phenomenon remains understudied between erythroblasts and their erythroblastic island (EBI) macrophage niche. To gain further insights into the mitochondria transfer functions, we infused EBI macrophages in vivo into mice subjected to different modes of anemic stresses. Interestingly, we observed the occurrence of mitochondria transfer events from the infused EBI macrophages to early stages of erythroblasts coupled with enhanced erythroid recovery. Single-cell RNA-sequencing analysis on erythroblasts receiving exogenous mitochondria revealed a subset of highly proliferative and metabolically active erythroid populations marked by high expression of CD47. Furthermore, CD47 or Sirpα blockade leads to a decline in both the occurrence of mitochondria transfer events and their mediated erythroid recovery. Hence, these data indicate a significant role of mitochondria transfer in the enhancement of erythroid recovery from stress through the alteration of the bioenergetic profiles via CD47–Sirpα interaction in the early stages of erythroblasts.
Acoustic wave amplification with thin film silicon bonded on lithium niobate
Authors: Ghosh Siddhartha
Published: September 2022

Signal processing with the use of acoustic waves is an important technology for various functions in radio frequency (RF) systems, including matched filtering in congested parts of the frequency spectrum. In order to generate long time delays on chip required for these applications, the acoustoelectric effect offers the ability to counter acoustic propagation losses while also generating inherent non-reciprocity. In this work, we demonstrate an approach to directly bond thin film silicon from 200 mm commercial silicon on insulator wafers on X-cut lithium niobate substrates with the use of plasma surface activation. The resulting delay line devices at 410 MHz demonstrate amplification of Rayleigh waves, with a peak non-reciprocal contrast between forward and reverse traveling waves of over 25 dB mm−1 under continuous direct current bias conditions. The demonstrated process can extend the functionality of traditionally passive piezoelectric RF microsystems.
Quantitative evaluation and removal of periodic error caused by ghost reflections in a double-path homodyne interferometer
Authors: Hori Yasuaki
Published: September 2022

This paper discusses periodic error caused by ghost reflections in a double-path homodyne interferometer, which is difficult to be removed by so-called Heydemann’s method due to its unique frequency. The mechanism of the periodic error is represented by a theoretical equation established focusing on the number of round trips of a measurement light path. Based on the theory, it was found that specific periodic errors are caused by the measurement light reflected on one surface of an optical element. To evaluate the presence and removal of the periodic error, the self-evaluation method, which was extended to include ghost reflections, was applied. Experimental evidence shows that a wedge provided on that surface prevents unwanted reflections and reduces the periodic error to approximately 2 pm.
Comparison of single-lead and multi-lead ECG for QT variability assessment using autoregressive modelling
Authors: El-Hamad Fatima , Baumert Mathias
Published: September 2022

Objective. Beat-to-beat fluctuations in the QT interval—QT variability (QTV)—have been shown to vary amongst the different ECG leads. This study aims to compare the utility of single and multi-lead ECG to disentangle the mechanisms contributing to QTV. Approach. Twelve-lead ECG was analysed in 57 coronary artery disease patients before and after an elective percutaneous transluminal coronary angiography (PTCA) procedure. QT, RR and respiration time series were extracted. QTV was decomposed into contributions by heart rate, respiration and QTV independent of heart rate and respiration using parametric autoregressive modelling. Signal-to-noise ratio, model goodness-of-fit, mean QT, corrected QT, QT variability and RR variability were also computed. Results from two single leads (Lead II and V5) and three one-dimensional representations of 12-lead ECG (principal component analysis (PCA), vector magnitude (VM), and root mean square of the 8 independent leads of the standard 12 leads (RMS8)) were compared during resting conditions, before and after PTCA, and between patients with myocardial infarction and those without. Main results. At baseline, mean QT and corrected QT were significantly lower in VM and RMS8 compared to single leads. While overall QT variability was not different between the leads, QT independent of heart rate and respiration was significantly lower in VM and RMS8. Following PTCA, changes in these variables were similar in all leads. Differences between patients with MI and those without MI were consistent in all leads. Significance. Despite the differences in some QTV components amongst various leads, single-lead ECG could be sufficient for analyzing QTV in populations with pathological cardiovascular conditions compared to those without, or for quantification of intervention effects.
A junctionless dual-gate MOSFET-based programmable inverter for secured hardware applications using nitride charge trapping
Authors: Karmakar Ananya , Mukherjee Adrija , Dhar Swastik , Sen Dipanjan , Chanda Manash
Published: September 2022

In this paper we investigate a junction-less dual-gate metal–oxide–semiconductor field effect transistor (JL-DG-MOSFET)-based programmable inverter with an oxide–nitride–oxide (SiO2/Si3N4/SiO2) gate stack, which offers short-/long-term memory as well as logic functionalities depending on charge trapping in the nitride layer. It has been shown that the pulsing interval plays a pivotal role in deciding the short-term plasticity/long-term plasticity window based on the charges trapped/detrapped at/near the oxide–nitride interface. Moreover, we have demonstrated a JL-DG-MOSFET-based complementary metal–oxide–semiconducor inverter with a programmable switching threshold and propose a scheme for secure key generation for authentication. The intra-Hamming distance among the 21 keys generated by the programmable inverter is also depicted to demonstrate the efficacy of the proposed framework. This will eliminate the physical separation between the logic and memory and can offer attractive solutions for silicon-based low-power neuromorphic computing and hardware security.
Analytic investigation of the compatibility condition and the initial evolution of a smooth velocity field for the Navier–Stokes equation in a channel configuration
Authors: Nagy Péter Tamás , Kiss Márton , Paál György
Published: September 2022

A partial differential equation has usually a regular solution at the initial time if the initial condition is smooth in space, fulfills the governing equations and is compatible with the boundary condition. In the case of the Navier–Stokes equation, the initial velocity field must also be divergence–free. It is common belief that the initial condition is compatible with the boundary condition if the initial condition fulfills the boundary condition but this is not sufficient. Such a field does not necessarily fulfill the full compatibility condition of the Navier–Stokes equation. If the condition is violated, the solution is not regular at the initial time (

t
=

0
+

). This issue has been known for a while but not in the full breadth of the engineering fluid dynamics community. In this paper, a practical calculation method is presented for checking the compatibility condition. Furthermore, a smooth initial condition is presented in a periodic channel flow that violates the compatibility condition and has therefore no smooth solution at the initial instant. The calculations were performed in an analytical framework. The results for a channel configuration show that in the absence of wall–normal velocity the condition is always fulfilled and the problem has a regular solution. If the wall–normal velocity component is non-zero, the condition is usually not fulfilled but exceptional cases, fulfilling the compatibility condition can be generated with optimization methods. The generation procedure of such a field is useful to provide correct initial conditions for such time-dependent numerical flow simulations, where the very first instances are important from an engineering point of view. The presented methods can provide insight about the applicability of the chosen initial conditions.
Shift-curvature, SGD, and generalization
Authors: Bradley Arwen V , Gomez-Uribe Carlos A , Vuyyuru Manish Reddy
Published: September 2022

A longstanding debate surrounds the related hypotheses that low-curvature minima generalize better, and that stochastic gradient descent (SGD) discourages curvature. We offer a more complete and nuanced view in support of both hypotheses. First, we show that curvature harms test performance through two new mechanisms, the shift-curvature and bias-curvature, in addition to a known parameter-covariance mechanism. The shift refers to the difference between train and test local minima, and the bias and covariance are those of the parameter distribution. These three curvature-mediated contributions to test performance are reparametrization-invariant even though curvature itself is not. Although the shift is unknown at training time, the shift-curvature as well as the other mechanisms can still be mitigated by minimizing overall curvature. Second, we derive a new, explicit SGD steady-state distribution showing that SGD optimizes an effective potential related to but different from train loss, and that SGD noise mediates a trade-off between low-loss versus low-curvature regions of this effective potential. Third, combining our test performance analysis with the SGD steady state shows that for small SGD noise, the shift-curvature is the dominant of the three mechanisms. Our experiments demonstrate the significant impact of shift-curvature on test loss, and further explore the relationship between SGD noise and curvature.
Orientation dependence of electronic properties of antimony selenide nanowires
Authors: Vadapoo Rajasekarakumar , Krishnan Sridevi , Yilmaz Hulusi , Marin Carlos
Published: September 2022

We present a comprehensive DFT study of size-dependent atomic and electronic properties of antimony selenide (Sb
2
Se
3) nanowires in three main crystallographic directions. Our calculations show a significant enhancement in the band gap of wires oriented in [100] and [010] directions due to confinement effects, however the band gap of [001] oriented wires is reduced with respect to bulk. We attribute this anomaly in band gap reduction to the surface reconstructions in these nanostructures. These surface reconstructions are similar to the polyhedral distortions observed in bulk Sb
2
Se
3 under high pressure leading to the insulator-metal transition related to the topological insulating states and then at lower temperature (8K) to superconductivity.
Simulating the efficacy of vaccines on the epidemiological dynamics of SARS-CoV-2 in a membrane computing model
Authors: Campos Marcelino , Sempere José M , Galán Juan C , Moya Andrés , Cantón Rafael , Llorens Carlos , Baquero Fernando
Published: September 2022

Membrane computing is a natural computing procedure inspired in the compartmental structure of living cells. This approach allows mimicking the complex structure of biological processes, and, when applied to transmissible diseases, can simulate a virtual ‘epidemic’ based on interactions between elements within the computational model according to established conditions. General and focused vaccination strategies for controlling SARS-Cov-2 epidemics have been simulated for 2.3 years from the emergence of the epidemic in a hypothetical town of 10320 inhabitants in a country with mean European demographics where COVID-19 is imported. The age and immunological-response groups of the hosts and their lifestyles were minutely examined. The duration of natural, acquired immunity influenced the results; the shorter the duration, the more endemic the process, resulting in higher mortality, particularly among elderly individuals. During epidemic valleys between waves, the proportion of infected patients belonging to symptomatic groups (mostly elderly) increased in the total population, a population that largely benefits from standard double vaccination, particularly with boosters. There was no clear difference when comparing booster shots provided at 4 or 6 months after standard double-dose vaccination. Vaccines even of moderate efficacy (short-term protection) were effective in decreasing the number of symptomatic cases. Generalized vaccination of the entire population (all ages) added little benefit to overall mortality rates, and this situation also applied for generalized lockdowns. Elderly-only vaccination and lockdowns, even without general interventions directed to reduce population transmission, is sufficient for dramatically reducing mortality.
Public and Private Information in International Crises: Diplomatic Correspondence and Conflict Anticipation
Authors: Boussalis Constantine , Chadefaux Thomas , Decadri Silvia , Salvi Andrea
Published: September 2022

Scholars of international conflicts have long emphasized the role of private information in the onset of interstate wars. Yet, the literature lacks direct and systematic evidence of its effect. This is largely due to challenges with accessing decision-makers’ private and often confidential information and opinions. We compile a large corpus of declassified French diplomatic cables that span the period 1871–1914. Using these texts, we estimate a dynamic topic model to generate diplomatic thematic variables, which are then used to forecast the onset of French Militarized Interstate Disputes (MIDs). The inclusion of information from diplomatic correspondence greatly improves estimates of MID timing, compared to models that rely solely on public information such as structural determinants and revealed risk perceptions derived from financial markets or the press. These results emphasize the importance of private information in decisions to go to war and the limitations of empirical work that relies solely on publicly available data.
Tolerance analysis of a compliant assembly using random Non-Uniform Rational B-Spline curves and isogeometric method
Authors: Aghabeigi Mostafa , Khodaygan Saeed , Movahhedy Mohammad Reza
Published: September 2022

Non-Uniform Rational B-Spline (NURBS) is one of the most versatile tools of computer-aided design. The concept of random NURBS curves is introduced for modeling the geometrical errors in mechanical parts and assemblies. The proposed idea is utilized to solve an example problem involving deformable components. For this purpose, profile tolerances of the parts are transformed into covariance matrices of NURBS control polygon parameters. Then, the control polygons are used as vector chains to calculate geometrical error propagation. Afterwards, isogeometric analysis (IGA) is invoked to express deformations of the parts during the assembly process as changes in the shape of the underlying control polygons. Finally, the result of the calculations is translated back into the tolerance zone of the assembly. Numerical examples are employed to examine the effect of NURBS structure (degree, knot vector, and control points) on convergence and stability of results. Outcomes of the theory are compared with direct measurements of actual assemblies and results of a Monte Carlo finite element simulation to illustrate the validity of the results. Furthermore, the developed model is used to obtain practical guidelines regarding the reduction of geometrical errors by the optimum design of the assembly.
A general methodology for reliability-based robust design optimization of computation-intensive engineering problems
Authors: Lai Xiongming , Huang Ju , Zhang Yong , Wang Cheng , Zhang Xiaodong
Published: September 2022

As for complex engineering structures, their single deterministic solutions need to be calculated with the help of computation-intensive finite element software, and the corresponding computation time always lasts very long. When referring to robust design optimization of complex engineering structures, the above expensive job should be repeatedly carried out for a considerable amount of time during the full optimization process. Hence, such repetitive jobs may be difficult to complete for most engineering applications. Aiming at this problem, the paper proposes a general methodology for reliability-based robust design optimization (RBRDO). Firstly, the improved formulation of the RBRDO problem is proposed based on the conventional RBRDO form, and the original probabilistic constraint functions in the improved formulation are changed into the deterministic ones by means of employing the performance measure approach (PMA). Secondly, the above-mentioned improved RBRDO problem is approximately replaced by a new sequence of approximate suboptimizations. For each suboptimization, its original PMA functions are replaced by the approximate explicit form only concerning the deterministic design variables rather than random variables. In this way, each suboptimization is deterministic. Furthermore, the trust-region method is adopted to ensure that the new sequence of suboptimization converge to the original improved RBRDO problem. Lastly, a test problem and three applications are adopted to demonstrate the effectiveness and efficiency of the above-proposed methods.

PACS(optional, as per journal): 75.40.-s; 71.20.LP
X-ray absorption and reprocessing in the z ∼ 2.5 lensed quasar 2MASS J1042+1641
Authors: Walton D J , Reynolds M T , Stern D , Brightman M , Lemon C
Published: September 2022

We present new broad-band X-ray observations of the z ∼ 2.5 lensed quasar 2MASS J1042+1641, combining XMM–Newton, Chandra, and NuSTAR to provide coverage of the X-ray spectrum over the 0.3–40 keV bandpass in the observed frame, corresponding to the ∼1–140 keV band in the rest frame of 2MASS J1042+1641. The X-ray data show clear evidence for strong (but still Compton-thin) X-ray absorption, NH ∼ 3–4 × 1023 $\rm \, cm^{-2}$, in addition to significant reprocessing by Compton-thick material that must lie away from our line of sight to the central X-ray source. We test two different interpretations for the latter: first that the reprocessing occurs in a classic active galactic nucleus torus, as invoked in unification models, and second that the reprocessing occurs in the accretion disc. Both models can successfully reproduce the observed spectra, and both imply that the source is viewed at moderately low inclinations (i < 50°) despite the heavy line-of-sight absorption. Combining the X-ray data with infrared (IR) data from WISE, the results seen from 2MASS J1042+1641 further support the recent suggestion that large X-ray and IR surveys may together be able to identify good lensed quasar candidates in advance of detailed imaging studies.
Exploration of 3D wavelet scattering transform coefficients for line-intensity mapping measurements
Authors: Chung Dongwoo T
Published: September 2022

The wavelet scattering transform (WST) has recently gained attention in the context of large-scale structure studies, being a possible generator of summary statistics encapsulating non-Gaussianities beyond the reach of the conventional power spectrum. This work examines the three-dimensional solid harmonic WST in the context of a three-dimensional line-intensity mapping measurement to be undertaken by current and proposed phases of the CO Mapping Array Project (COMAP). The WST coefficients demonstrate interpretable behaviour in the context of noiseless CO line-intensity simulations. The contribution of the cosmological z ∼ 3 signal to these coefficients is also detectable in principle even in the Pathfinder phase of COMAP. Using the peak-patch method to generate large numbers of simulations and incorporating observational noise, we numerically estimate covariance matrices and show that careful choices of WST hyperparameters and rescaled or reduced coefficient sets are both necessary to keep covariances well-conditioned. Fisher forecasts show that even a reduced ‘shapeless’ set of ℓ-averaged WST coefficients show constraining power that can exceed that of the power spectrum alone even with similar detection significance. The full WST could improve parameter constraints even over the combination of the power spectrum and the voxel intensity distribution, showing that it uniquely encapsulates shape information about the line-intensity field. However, practical applications urgently require further understanding of the WST in key contexts like covariances and cross-correlations.
Pharmacokinetics of hydroxychloroquine in Japanese systemic lupus erythematosus patients with renal impairment
Authors: Shimizu Mikiko , Furudate Sumito , Nagai Yoshiki , Shimada Kota , Ohshima Miho , Setoguchi Keigo , Hashiguchi Masayuki , Yokogawa Naoto
Published: September 2022

Objectives

Reduction of the hydroxychloroquine (HCQ) dosage is recommended in systemic lupus erythematosus (SLE) patients with renal impairment, but a pharmacokinetics (PK) study of patients with renal impairment has not yet been performed.

Methods

We investigated the PK of both single and multiple doses of HCQ and its metabolites in SLE patients with renal impairment who newly started HCQ at a daily dose of 300 mg based on an ideal body weight dosage of 6.5 mg/kg. Population PK analysis was performed using a non-linear mixed-effects model.

Results

In total, 219 samples from 21 patients were analysed. The PK of HCQ in blood after single and multiple oral administrations followed the two-compartment model. At steady state, the concentration ratio of HCQ to each metabolite was HCQ:desethylhydroxychloroquine:desethylchloroquine:bisdesethylchloroquine = 1:0.28:0.1:0.06. The HCQ concentration correlated positively with that of each metabolite. The estimated values (relative standard error) of the population PK parameters were the total clearance at 110 l/h (31%) and a central volume of distribution of 398 l (19%). Co-administration of prednisolone and age, but not renal impairment, were factors affecting the total clearance of HCQ.

Conclusions

From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.
The roles of mutated SPINK1 gene in prostate cancer cells
Authors: Pan Xiuyi , Tan Junya , Yin Xiaoxue , Liu Qianqi , Zheng Linmao , Su Zhengzheng , Zhou Qiao , Chen Ni
Published: September 2022

SPINK1-positive prostate cancer (PCa) has been identified as an aggressive PCa subtype. However, there is a lack of definite studies to elucidate the underlying mechanism of the loss of SPINK1 expression in most PCa cells except 22Rv1 cells, which are derived from a human prostatic carcinoma xenograft, CWR22R. The aim of this study was to investigate the mechanisms of SPINK1 protein positive/negative expression and its biological roles in PCa cell lines. SPINK1 mRNA was highly expressed in 22Rv1 cells compared with LNCaP, C4-2B, DU145, and PC-3 cells, and the protein was only detected in 22Rv1 cells. Among these cell lines, the wild-type SPINK1 coding sequence was only found in 22Rv1 cells, and two mutation sites, the c.194G>A missense mutation and the c.210T>C synonymous mutation, were found in other cell lines. Our further research showed that the mutations were associated with a reduction in SPINK1 mRNA and protein levels. Functional experiments indicated that SPINK1 promoted PC-3 cell proliferation, migration, and invasion, while knockdown of SPINK1 attenuated 22Rv1 cell proliferation, migration, and invasion. The wild-type SPINK1 gene can promote the malignant behaviors of cells more than the mutated ones. Cell cycle analysis by flow cytometry showed that SPINK1 decreased the percentage of cells in the G0/G1 phase and increased the percentage of S phase cells. We demonstrated that the c.194G>A and c.210T>C mutations in the SPINK1 gene decreased the mRNA and protein levels. The wild-type SPINK1 gene is related to aggressive biological behaviors of PCa cells and may be a potential therapeutic target for PCa.
‘Agere Contra’as a strategy for survival: a spiritual philosophical perspective to fight the COVID-19 crisis
Authors: Situmorang Dominikus David Biondi
Published: September 2022

‘Agere Contra’ is a term introduced by St. Ignatius. The term comes from the Latin, meaning ‘to act against’ or ‘to act otherwise.’ In more depth, what conventional traders do does not necessarily go against government regulations. But they do the opposite, because on the basis of a higher than all, namely life. They are willing to sacrifice for their families to ‘go against’ government regulations, so that all their family members can still eat and survive in the current crisis situation.
Profiling of serum oxylipins identifies distinct spectrums and potential biomarkers in young people with very early onset gout
Authors: Wang Can , Lu Jie , Sun Wenyan , Merriman Tony R , Dalbeth Nicola , Wang Zhongjun , Wang Xuefeng , Han Lin , Cui Lingling , Li Xinde , Ji Aichang , Li Hailong , Ji Xiaopeng , He Yuwei , Li Changgui , Liu Zhen
Published: September 2022

Objective

Oxylipins modulate inflammation via complex pathways. The oxylipin profile in gout remains unexplored. In this study, we systemically profiled oxylipins in young men and identified new oxylipin biomarkers for clinical use in differentiating gout from hyperuricaemia.

Material and methods

Oxylipin profiling was performed in 90 men (30 very early onset gout, 30 asymptomatic hyperuricaemia [HU] and 30 normouricaemia [NU], all aged <20 years) divided into discovery and validation sample sets. The dataset was analysed based on orthogonal projection to latent structure-discriminant analysis. Correlation network and pathway enrichment were conducted to reveal potential oxylipin-involved pathways of gout. Candidate oxylipins were further evaluated and optimized in the validation cohort, and differential oxylipin biomarkers combined with or without serum urate were applied to construct diagnostic models.

Results

In discovery stage, 21 differential oxylipins in the gout vs HU comparisons and 14 differential oxylipins in the gout vs NU comparisons were discovered. Correlation network analysis was performed and 14(S)-HDHA (14S-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid) was identified as a hub metabolite in both comparisons. Seven down-regulated oxylipins in the gout vs HU group and five down-regulated oxylipins in the gout vs NU group were validated. Diagnostic models were constructed with the above oxylipins, with 14(S)-HDHA alone having an area under the curve of 1 (95% CI, 1, 1) in both comparisons.

Conclusions

Young men with very early onset gout have distinct oxylipin spectrums, especially those derived from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Differential oxylipins could serve as candidate serum biomarkers in differentiating gout from hyperuricaemia.
Obstetric outcomes in women with rheumatic disease and COVID-19 in the context of vaccination status
Authors: Maguire Sinead , Al-Emadi Samar , Alba Paula , Aguiar Mathia Cecilia , Al Lawati Talal , Alle Gelsomina , Bermas Bonnie , Bhana Suleman , Branimir Anic , Bulina Inita , Clowse Megan , Cogo Karina , Colunga Iris , Cook Claire , Cortez Karen J , Dao Kathryn , Gianfrancesco Milena , Gore-Massey Monique , Gossec Laure , Grainger Rebecca , Hausman Jonathon , Hsu Tiffany Y T , Hyrich Kimme , Isnardi Carolina , Kawano Yumeko , Kilding Rachael , Kusevich Daria A , Lawson-Tovey Saskia , Liew Jean , McCarthy Eoghan , Montgumery Anna , Moyano Sebastian , Nasir Noreen , Padjen Ivan , Papagoras Charalampos , Patel Naomi J , Pera Mariana , Pisoni Cecilia , Pons-Estel Guillermo , Quiambao Antonio L , Quintana Rosana , Ruderman Eric , Sattui Sebastian , Savio Veronica , Sciascia Savino , Sencarova Marieta , Morales Rosa Serrano , Siddique Faizah , Sirotich Emily , Sparks Jeffrey , Strangfeld Anja , Sufka Paul , Tanner Helen , Tissera Yohana , Wallace Zachary , Werner Marina L , Wise Leanna , Worthing Angus B , Zell JoAnn , Zepa Julija , Machado Pedro M , Yazdany Jinoos , Robinson Philip , Conway Richard
Published: September 2022

Objective

To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy.

Methods

Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020–25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fisher’s exact test.

Results

There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2).

Conclusions

In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.
Incidental Os Odontoideum in an Adolescent Athlete With Sports-Related Concussion
Authors: Howell Nathan , Walker Gregory , Hankinson Todd , Armento Aubrey
Published: September 2022

Sports-related concussion (SRC) is a frequent injury in the adolescent population with presentation including a wide array of signs and symptoms. There are no universally agreed upon guidelines for when to pursue advanced imaging, such as magnetic resonance imaging (MRI), in the workup of SRCs in the adolescent population. Our experience indicates that MRI rarely contributes to management. This case report highlights a rare finding of os odontoideum on MRI imaging in an adolescent female soccer player in the setting of treatment of an SRC that altered the course of her clinical management.
Changing the Buffer in Buffered Lidocaine
Authors: Plohal Ann , Dutchover Eric P. , Root Jennifer , Kurilla Brian , Balas Randy
Published: September 2022

Hospitalized patients require venous access for procedures, treatments, or therapies. The use of lidocaine for pain relief during central vascular access device (CVAD) insertion is a standard of practice. Lidocaine buffered with sodium bicarbonate has been shown to provide significantly more pain relief in the sensation of pain upon injection. Shortages of lidocaine with bicarbonate provided an opportunity to explore other options to provide pain relief during CVAD insertion. The PICO question for this project was: In adult patients requiring CVAD insertion, how does lidocaine buffered with bicarbonate compare with lidocaine buffered with saline in minimizing pain with lidocaine injection? This study assessed how lidocaine buffered with bicarbonate compares with lidocaine buffered with saline in minimizing pain with lidocaine injection. Sixty patients received the buffered lidocaine before having a peripherally inserted central catheter inserted. Thirty patients received lidocaine buffered with bicarbonate and 30 patients received lidocaine buffered with saline. Pain and vasoconstriction were the 2 outcomes monitored during the project. Although the trial was only 2 wk due to the urgency of the rollout, the pilot was able to offer clinicians the opportunity to compare the 2 products. The saline-buffered lidocaine provided comparable pain relief compared with the lidocaine buffered with bicarbonate. The clinicians also measured the amount of vasoconstriction caused by the 2 products with similar outcomes.
A Quality Collaborative Study of the Concordance of Electrodiagnostic Scores and Clinical Severity in Carpal Tunnel Syndrome
Authors: Billig Jessica I. , Kotsis Sandra V. , Ouyang Zhongzhe , Wang Lu , Chung Kevin C. ,   M-CHIQS Collaborators
Published: September 2022

Background:

Electrodiagnostic studies (EDS) are commonly used to diagnose CTS. However, these exams are prone to false positive and negative values, questioning their use as a reference standard. The study purpose was to evaluate the agreement of EDS severity, clinical assessment scores (CAS), and probability of carpal tunnel syndrome (CTS-6 scores) and to determine factors associated with EDS severity.

Methods:

This is a retrospective cohort study of 609 patients with CTS (941 hands). Data were collected from 9 hand surgery practices in the Michigan Collaborative Hand Initiative for Quality in Surgery. Patients were categorized as having mild, moderate, or severe CTS based on CAS scores and low, medium, or high probability of CTS based on CTS-6 scores. Goodman and Kruskal’s gamma statistics measured the agreement between EDS and CAS and between EDS and CTS-6 scores. We performed cumulative logistic regression with mixed effects to evaluate the association among EDS severity, clinical assessments (CAS and CTS-6), and patient characteristics.

Results:

The concordance between EDS severity and CTS-6 scores was ɤ=0.31 (0.21-0.40) with an accuracy of 43%. The concordance between EDS severity and CAS was ɤ=0.66 (0.58-0.74) with an accuracy of 58%. Wide site-level variation in the gamma coefficient between EDS and CAS and between EDS and CTS-6 was seen. Male sex, increasing age, and increasing body mass index (BMI) were significantly associated with increased odds of EDS severity.

Conclusions:

Wide practice-level variation underscores the variability in diagnostic testing accuracy. Physicians should consider patient characteristics (sex, age, BMI) when assessing CTS severity.
Effectiveness of Botulinum Toxin Type A Injection on Scars: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Li Man-Yun , Chiu Wen-Kuan , Wang Hsian-Jenn , Chen I-Fan , Chen Jin-Hua , Chang Ta-Pang , Ko Yu , Chen Chiehfeng
Published: September 2022

Background:

Scars can cause pain as well as long-term physical dysfunction and psychological harm. Botulinum toxin type A (BoNT-A) is one of the treatment choices for scars. However, further evidence is needed to confirm its efficacy.

Methods:

This systematic review included randomized controlled trials (RCTs) that investigated the effectiveness of BoNT-A on scars. We extracted the mean and standard deviation for the Vancouver scar scale (VSS), Stony Brook Scar Evaluation Scale (SBSES), Visual Analog Scale (VAS) for appearance evaluation, VAS for scar pain evaluation and scar width. Subgroup analysis was performed to understand the effect of active control.

Results:

Overall, 21 RCTs met the inclusion criteria. VSS results revealed that the BoNT-A group had a lower score than the saline group [standardized mean difference (SMD): −0.82, 95% confidence interval (CI): −1.24 to −0.39, I
2 = 65%, P = 0.0002], whereas the BoNT-A group had a higher score than the steroid group (SMD: 0.85, 95% CI: 0.27 to 1.43, P = 0.004). Moreover, the BoNT-A group exhibited a higher grade than the saline group in SBSES (SMD: 1.42, 95% CI: 0.83 to 2.20, I
2 = 48%, P < 0.00001). VAS for appearance evaluation revealed significantly higher scores in the BoNT-A group than in the saline group (SMD: 1.25, 95% CI: 0.77 to 1.74, I
2 = 72%, P < 0.00001). Moreover, VAS for scar pain evaluation revealed that the BoNT-A group had a significantly lower score than the steroid group (SMD: −2.57, 95% CI: −4.40 to −0.74, I
2 = 95%, P = 0.006). Furthermore, the scar width was significantly shorter in the BoNT-A group than in the control group (SMD: −1.19, 95% CI: −1.49 to −0.89, I
2 = 0%, P < 0.00001)

Conclusion:

BoNT-A injection is more effective in treating scars than saline injection, although steroids may exhibit higher potency. Therefore, BoNT-A can be considered an alternative in patients not amenable to steroid treatment.
Adequate exposure of 50 mg dolutegravir in children weighing 20 to 40 kg outside of sub-Sahara Africa
Authors: Waalewijn Hylke , Stol Kim , van der Knaap Linda , Fraaij Pieter L.A. , Vermont Clementien , van Rossum Annemarie M.C. , Strik-Albers Riet , Burger David M. , Svensson Elin M. , Colbers Angela
Published: September 2022

Dolutegravir 50 mg is registered for use in children weighing 20–40 kg. This approval is based on data from an African paediatric cohort, and no pharmacokinetic data was available from children outside of Africa. This study provides further evidence of the effective use of dolutegravir 50 mg in children weighing 20 to 40 kg by showing that concentration data gathered in clinical practice shows adequate concentration levels in Dutch children without a safety signal.
Effects of early human immunodeficiency virus infection on cerebral white matter blood flow autoregulation
Authors: Sen Souvik , An Hongyu , Oakes Jonathan , Eron Joseph , Robertson Kevin , Powers William
Published: September 2022

Blood flow autoregulation in cerebral white matter was measured before and after acute nicardipine-induced changes in mean arterial pressure of 10–21% in 21 treatment naïve HIV-positive adults and 32 controls. The autoregulatory index (−% cerebral blood flow change/% mean arterial pressure change) was not different at baseline (P = 0.71) or after 1 year of treatment (n = 11, P = 0.17). We found no autoregulatory defect to explain the increased stroke risk or the development of cerebral white damage in people with HIV.