bluuebunny/crossref_metadata_2025 huggingface dataset:
FDX1-dependent and independent mechanisms of elesclomol-mediated intracellular copper delivery
Authors: Zulkifli Mohammad , Spelbring Amy N. , Zhang Yuteng , Soma Shivatheja , Chen Si , Li Luxi , Le Trung , Shanbhag Vinit , Petris Michael J. , Chen Tai-Yen , Ralle Martina , Barondeau David P. , Gohil Vishal M.
Published: February 2023

Recent studies have uncovered the therapeutic potential of elesclomol (ES), a copper-ionophore, for copper deficiency disorders. However, we currently do not understand the mechanism by which copper brought into cells as ES–Cu(II) is released and delivered to cuproenzymes present in different subcellular compartments. Here, we have utilized a combination of genetic, biochemical, and cell-biological approaches to demonstrate that intracellular release of copper from ES occurs inside and outside of mitochondria. The mitochondrial matrix reductase, FDX1, catalyzes the reduction of ES–Cu(II) to Cu(I), releasing it into mitochondria where it is bioavailable for the metalation of mitochondrial cuproenzyme— cytochrome
c
oxidase. Consistently, ES fails to rescue cytochrome
c
oxidase abundance and activity in copper-deficient cells lacking FDX1. In the absence of FDX1, the ES-dependent increase in cellular copper is attenuated but not abolished. Thus, ES-mediated copper delivery to nonmitochondrial cuproproteins continues even in the absence of FDX1, suggesting alternate mechanism(s) of copper release. Importantly, we demonstrate that this mechanism of copper transport by ES is distinct from other clinically used copper-transporting drugs. Our study uncovers a unique mode of intracellular copper delivery by ES and may further aid in repurposing this anticancer drug for copper deficiency disorders.
Cross-species predictive modeling reveals conserved drought responses between maize and sorghum
Authors: Pardo Jeremy , Wai Ching Man , Harman Maxwell , Nguyen Annie , Kremling Karl A. , Romay Maria Cinta , Lepak Nicholas , Bauerle Taryn L. , Buckler Edward S. , Thompson Addie M. , VanBuren Robert
Published: February 2023

Drought tolerance is a highly complex trait controlled by numerous interconnected pathways with substantial variation within and across plant species. This complexity makes it difficult to distill individual genetic loci underlying tolerance, and to identify core or conserved drought-responsive pathways. Here, we collected drought physiology and gene expression datasets across diverse genotypes of the C4 cereals sorghum and maize and searched for signatures defining water-deficit responses. Differential gene expression identified few overlapping drought-associated genes across sorghum genotypes, but using a predictive modeling approach, we found a shared core drought response across development, genotype, and stress severity. Our model had similar robustness when applied to datasets in maize, reflecting a conserved drought response between sorghum and maize. The top predictors are enriched in functions associated with various abiotic stress-responsive pathways as well as core cellular functions. These conserved drought response genes were less likely to contain deleterious mutations than other gene sets, suggesting that core drought-responsive genes are under evolutionary and functional constraints. Our findings support a broad evolutionary conservation of drought responses in C4 grasses regardless of innate stress tolerance, which could have important implications for developing climate resilient cereals.
Study on magnetically blown arc characteristics and the resulting contact erosion mechanisms of high-power DC relays
Authors: Hou Guobin , Zhang Dandan , Li Zhenbiao , Pan Wenwu , Wan Zhiyu , Ye Xuebin , Huang Ziheng , You Yuwei
Published: February 2023

High-power DC relays are widely used in new energy power systems and DC distribution networks, and commonly use transverse magnetic fields to accelerate arc extinguishing. In this paper, the magnetically blown arc characteristics and the resulting contact erosion mechanisms of high-power DC relays are studied by experiments and simulations. The experiments are carried out to analyze the arc motion, contact erosion mass, and contact morphologies, and to verify the simulation model. Considering the energy transfer source term, the establishment of a more perfect magnetohydrodynamic arc model is accomplished, and an erosion model is further established. The results indicate that the magnetically blown arcing process has three stages while the arc shapes and motion characteristics are different, and the heat flux acting on the contact can be accurately obtained by the arc model. The greater external transverse magnetic field is more conducive to extinguishing the arc and reducing the arc erosion time. In contrast, the Archimedes force plays a very small positive role and the self-induced magnetic field of the arc has a negative effect. For contact erosion, the temperature distribution of the molten pool appears trailing effect. Moreover, the advanced mathematical model proposed for erosion mass has good accuracy. The calculation results of erosion rates show that Cr reduces erosion while the current increases erosion nonlinearly. Besides, the flow and deformation characteristics of the molten pool will lead to convex strip-shaped erosion traces and arcing position transfer, and the moving erosion will cause the lateral accretion effect. Furthermore, the analysis shows that the reason for edge droplet sputtering is the pressure difference caused by Plateau–Rayleigh instability, and optimization suggestions for reducing contact erosion are given.
Tetramethylammonium hexafluorophosphate interface modification for high-efficiency perovskite solar cells
Authors: Yuan Min , Han Liang , Hu Haihua , Wang Peng , Lin Ping , Xu Lingbo , Cui Can
Published: February 2023

Interface modification has been proved to be an effective method to improve the performance of perovskite solar cells (PSCs). In this paper, tetramethylammonium hexafluorophosphate (TMAPF6) is employed to modify the interface of SnO2/perovskite. Fluorine (F) in PF6
− will fill the oxygen vacancy by interacting with Sn in SnO2. Meanwhile, TMA+ and PF6
− in TMAPF6 will effectively fill the MA+ and I− vacancy in the interface. TMAPF6 modification enhances the hydrophobicity of the SnO2 surface, promotes the growth of high-quality perovskite film with large grain size, and then significantly suppresses the non-radiative recombination of PSCs. Furthermore, the TMAPF6 modification introduces a better energy level alignment between SnO2 and perovskite layer, enabling a more efficient electron extraction. As a result, the TMAPF6-modified MAPbI3 PSC achieves a significantly increasing power conversion efficiency (PCE) from 18.62% to 20.92% and an improved stability with only 15% PCE drop after 600 h of storage in air. This work develops an efficient interface modification molecule to increase the efficiency of PSCs, which would be a promising strategy for the large-scale commercialization of the photovoltaic devices.
Evidence of linear and cubic Rashba effect in non-magnetic heterostructure
Authors: Bhattacharya Sanchari , Datta Sanjoy
Published: February 2023

The

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O

3

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a
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3

system serves as a prototype to study the electronic properties that emerge as a result of spin–orbit coupling (SOC). In this article, we have used first-principles calculations to systematically study two types of defect-free (0 0 1) interfaces, which are termed as Type-I and Type-II. While the Type-I heterostructure produces a two dimensional (2D) electron gas, the Type-II heterostructure hosts an oxygen-rich 2D hole gas at the interface. Furthermore, in the presence of intrinsic SOC, we have found evidence of both cubic and linear Rashba interactions in the conduction bands of the Type-I heterostructure. On the contrary, there is spin-splitting of both the valence and the conduction bands in the Type-II interface, which are found to be only linear Rashba type. Interestingly, the Type-II interface also harbors a potential photocurrent transition path, making it an excellent platform to study the circularly polarized photogalvanic effect.
The recent advance of precisely designed membranes for sieving
Authors: Xu Miaomiao , Zhu Xianhu , Zhu Jihong , Wei Siyuan , Cong Xuelong , Wang Zhangyu , Yan Qiang , Weng Lixing , Wang Lianhui
Published: February 2023

Developing new membranes with both high selectivity and permeability is critical in membrane science since conventional membranes are often limited by the trade-off between selectivity and permeability. In recent years, the emergence of advanced materials with accurate structures at atomic or molecular scale, such as metal organic framework, covalent organic framework, graphene, has accelerated the development of membranes, which benefits the precision of membrane structures. In this review, current state-of-the-art membranes are first reviewed and classified into three different types according to the structures of their building blocks, including laminar structured membranes, framework structured membranes and channel structured membranes, followed by the performance and applications for representative separations (liquid separation and gas separation) of these precisely designed membranes. Last, the challenges and opportunities of these advanced membranes are also discussed.
On the space-charge effects in the beam extraction process of ion thrusters: the roles of compensating electrons and changing beam radius
Authors: Li Haolin , Zhang Liwei , Zhang Siyuan , Yang Jinyuan , Sun Anbang
Published: February 2023

Space-charge effects limit the beam-extraction capability of the ion optics and thus hinder the miniaturization and other performance improvements of ion thrusters. This paper presents numerical studies of the space-charge effects in ion optics using hybrid and full particle-in-cell (PIC) simulations, and proposes a modified Child–Langmuir (CL) law. As the injected current increases, the parallel-plane electrode system which corresponds to the classical CL law will reach an unstable and oscillatory state, while the ion optics system remains stable because the electrons from the bulk plasma compensate for the space-charge effects. Furthermore, the radial expansion of the ion beam and the loss of ions on the grids can counteract the space-charge effects when the injected current increases. In general, the space-charge effects in ion optics are self-consistently adjusted by the compensating electrons and the variation of the beam radius. Accordingly, we identify a region in ion optics where, generally, no electrons exist to exclude the influence of electron compensation, and then we modify the CL law of this region by taking into account the effect of the change in the beam radius. We validate the modified CL law and demonstrate its effectiveness in predicting the operating points of the ion optics, such as the perveance-limit point.
Thermally stable multi-directional magnetoelectric based embedded magnetic sensor
Authors: Kumar Amritesh , Chelvane J Arout , Arockiarajan A
Published: February 2023

Owing to the multifunctional behavior possessed by magnetoelectric (ME) composites, they are sought-after materials for various magnetic field sensing applications. This article proposes a three-directional ME-based embedded magnetic sensor that has been fabricated using the press-fit technique. The employed fabrication method negates the use of epoxy in the ME sensor, thus enabling its use at elevated temperatures in excess of 100 ∘C. The fabricated sensor is tested using an experimental setup capable of producing ac and dc bias magnetic fields in three coordinate directions. Experiments are performed for various dc magnetic field conditions, including x, y, z directions, their simultaneous combinations, and magnetic field aligned at an angle with the sensor. Under all testing conditions, the embedded sensor shows a significantly high output voltage response. Additionally, the effect of the magnetic field generated by the double magnet system and single magnet system on the sensor performance has also been demonstrated, wherein the embedded sensor is observed to be marginally affected by magnetic field due to the presence of only one magnet. Finally, quasi-static ME measurements are performed at elevated temperatures up to 100 ∘C, and it is observed that the novel embedded sensor has reliable sensing capabilities in aggravated thermal environments even in excess of 100 ∘C. Thus, the proposed three-directional embedded magnetic sensor offers reliable response under all conditions of magnetic field and temperature and can thus be a reliable alternative for the traditionally used layered-based counterparts.
Alterations in BNST Intrinsic Functional Connectivity in Early Abstinence from Alcohol Use Disorder
Authors: Flook Elizabeth A , Feola Brandee , Benningfield Margaret M , Silveri Marisa M , Winder Danny G , Blackford Jennifer Urbano
Published: February 2023

Aims

Maintaining abstinence from alcohol use disorder (AUD) is extremely challenging, partially due to increased symptoms of anxiety and stress that trigger relapse. Rodent models of AUD have identified that the bed nucleus of the stria terminalis (BNST) contributes to symptoms of anxiety-like behavior and drug-seeking during abstinence. In humans, however, the BNST’s role in abstinence remains poorly understood. The aims of this study were to assess BNST network intrinsic functional connectivity in individuals during abstinence from AUD compared to healthy controls and examine associations between BNST intrinsic functional connectivity, anxiety and alcohol use severity during abstinence.

Methods

The study included resting state fMRI scans from participants aged 21–40 years: 20 participants with AUD in abstinence and 20 healthy controls. Analyses were restricted to five pre-selected brain regions with known BNST structural connections. Linear mixed models were used to test for group differences, with sex as a fixed factor given previously shown sex differences.

Results

BNST-hypothalamus intrinsic connectivity was lower in the abstinent group relative to the control group. There were also pronounced sex differences in both the group and individual analyses; many of the findings were specific to men. Within the abstinent group, anxiety was positively associated with BNST-amygdala and BNST-hypothalamus connectivity, and men, not women, showed a negative relationship between alcohol use severity and BNST-hypothalamus connectivity.

Conclusions

Understanding differences in connectivity during abstinence may help explain the clinically observed anxiety and depression symptoms during abstinence and may inform the development of individualized treatments.
Uncovering genetic control of primary root length variation inBrassica napususing QTL-seq. A commentary on: ‘Rapid identification of a major locusqPRL-C06affecting primary root length inBrassica napusby QTL-seq’
Authors: Lale Aneesh , Swarup Ranjan , Bhosale Rahul
Published: February 2023

This article comments on:

Wei Wang, Haijiang Liu, Yiwen Xie, Graham John King, Philip John White, Jun Zou, Fangsen Xu, and Lei Shi. Rapid identification of a major locus qPRL-C06 affecting primary root length in Brassica napus by QTL-seq, Annals of Botany, Volume 131, Issue 4, 14 March 2023, Pages 569–583, https://doi.org/10.1093/aob/mcac123
Finding shortcuts through collective tunnel excavations in a subterranean termite
Authors: Michael Zion , Chouvenc Thomas , Su Nan-Yao , Lee Sang-Bin
Published: February 2023

Facilitating efficient resource transfer requires building an optimized transportation network which balances cost minimization with benefit maximization. For animals which forage for food located remotely, optimizing their transportation networks is critically related to survival. This process often involves finding and using the shortest route to save time and energy. Subterranean termites forage for wood resources by excavating underground foraging networks for search and transport. Because termites have no prior knowledge of food location during the food searching phase, establishment of a short tunnel between the nest and feeding site is difficult at the beginning of foraging. Thus, finding a short route should logically follow initial food discovery. However, it remains elusive as to how subterranean termites find the shortest route for food transportation. We simulated different scenarios using Coptotermes formosanus by providing different shapes and distances of pre-formed tunnels (straight, detour, and detour + twisting arenas) to food, where food items were located at a fixed distance from the arena entrance. Termites in the straight arena continuously used the pre-formed tunnel, showing negligible branching efforts. However, termites in the detour and detour + twisting arenas followed the pre-formed tunnel only for the initial few hours before excavating many branching tunnels. This branching activity ultimately resulted in termites finding shorter commuting routes than the pre-formed tunnels. In addition, the shortest established routes were widened over time. This study demonstrated that C. formosanus could actively alter tunnel networks to minimize the cost in food transportation by using short and wide tunnels.
Familial isolated acanthosis nigricans as a result of a recurrent FGFR3 truncating mutation
Authors: Pesqué David , March-Rodriguez Álvaro , Abreu-Rodríguez Irene , Pérez-Jurado Luis A , Pujol Ramon M
Published: February 2023

Few cases of isolated (nonsyndromic, nonendocrinopathy) familial acanthosis nigricans (FAN) have been described, and most have not included genetic testing. We present a three-generation family with isolated FAN, whose genetic study revealed a heterozygous FGFR3 gene variant [NM_0001425: c.2302G>T; p.(Glu768Ter); E768X]. We propose genetic mechanisms that could explain the pro-mitogenic effect on the skin without bone involvement and the spectrum of clinical manifestations associated with germline FGFR3 mutations.
Development of brain state dynamics involved in working memory
Authors: He Ying , Liang Xinyuan , Chen Menglu , Tian Ting , Zeng Yimeng , Liu Jin , Hao Lei , Xu Jiahua , Chen Rui , Wang Yanpei , Gao Jia-Hong , Tan Shuping , Taghia Jalil , He Yong , Tao Sha , Dong Qi , Qin Shaozheng
Published: February 2023

Human functional brain networks are dynamically organized to enable cognitive and behavioral flexibility to meet ever-changing environmental demands. Frontal-parietal network (FPN) and default mode network (DMN) are recognized to play an essential role in executive functions such as working memory. However, little is known about the developmental differences in the brain-state dynamics of these two networks involved in working memory from childhood to adulthood. Here, we implemented Bayesian switching dynamical systems approach to identify brain states of the FPN and DMN during working memory in 69 school-age children and 51 adults. We identified five brain states with rapid transitions, which are characterized by dynamic configurations among FPN and DMN nodes with active and inactive engagement in different task demands. Compared with adults, children exhibited less frequent brain states with the highest activity in FPN nodes dominant to high demand, and its occupancy rate increased with age. Children preferred to attain inactive brain states with low activity in both FPN and DMN nodes. Moreover, children exhibited lower transition probability from low-to-high demand states and such a transition was positively correlated with working memory performance. Notably, higher transition probability from low-to-high demand states was associated with a stronger structural connectivity across FPN and DMN, but with weaker structure–function coupling of these two networks. These findings extend our understanding of how FPN and DMN nodes are dynamically organized into a set of transient brain states to support moment-to-moment information updating during working memory and suggest immature organization of these functional brain networks in childhood, which is constrained by the structural connectivity.
Expressing appreciation is linked to interpersonal closeness and inter-brain coherence, both in person and over Zoom
Authors: Balters Stephanie , Miller Jonas G , Reiss Allan L
Published: February 2023

Expressing appreciation is essential for establishing interpersonal closeness, but virtual interactions are increasingly common and create social distance. Little is known about the neural and inter-brain correlates of expressing appreciation and the potential effects of virtual videoconferencing on this kind of interaction. Here, we assess inter-brain coherence with functional near-infrared spectroscopy while dyads expressed appreciation to one another. We scanned 36 dyads (72 participants) who interacted in either an in-person or virtual (Zoom®) condition. Participants reported on their subjective experience of interpersonal closeness. As predicted, expressing appreciation increased interpersonal closeness between dyad partners. Relative to 3 other cooperation tasks (i.e. problem-solving task, creative-innovation task, socio-emotional task), we observed increased inter-brain coherence in socio-cognitive areas of the cortex (anterior frontopolar area, inferior frontal gyrus, premotor cortex, middle temporal gyrus, supramarginal gyrus, and visual association cortex) during the appreciation task. Increased inter-brain coherence in socio-cognitive areas during the appreciation task was associated with increased interpersonal closeness. These findings support the perspective that expressing appreciation, both in-person and virtually, increases subjective and neural metrics of interpersonal closeness.
The Travails of Urban Planning in India: An Examination of the Planning Law Regime of Bangalore
Authors: Idiculla Mathew
Published: February 2023

Though the legal framework of urban planning plays a significant role in determining the nature of urban development, there is limited scholarship on the planning law regimes of different jurisdictions, especially in Asia and the global South. For countries like India, where the rule of law is seen to be weak and implemented arbitrarily, much of academic scholarship has focused on informality in urban planning, and the formal planning process has been relatively ignored. This article attempts to elucidate the planning law regime that operates in India through a close examination of the legal and institutional framework of urban planning in the city of Bangalore. It traces the colonial roots of India’s urban planning system, examines the institutions and processes of planning that operate in Bangalore, highlights the debates around the contents of the master plan, and examines the difficulty of enforcing the plan. This article argues that the fundamental concern with India’s urban planning regime is the disjuncture between the authority to plan and local democratic accountability. Even after the passing of the 74th Constitutional Amendment in 1992, which sought to empower municipalities by vesting them with multiple powers including that of urban planning, the master plan for Bangalore is still not prepared by the elected municipal government but by an unelected parastatal agency controlled by the state government. The article also discusses the concerns regarding the top-down planning process which does not provide adequate avenues for public participation, the static land-use based master plans that do not integrate key sectors of urban development, and the government’s approach of addressing non-enforcement of plans by legalizing violations of planning norms.
Epicosm—a framework for linking online social media in epidemiological cohorts
Authors: Tanner Alastair R , Di Cara Nina H , Maggio Valerio , Thomas Richard , Boyd Andy , Sloan Luke , Al Baghal Tarek , Macleod John , Haworth Claire M A , Davis Oliver S P
Published: February 2023

Motivation

Social media represent an unrivalled opportunity for epidemiological cohorts to collect large amounts of high-resolution time course data on mental health. Equally, the high-quality data held by epidemiological cohorts could greatly benefit social media research as a source of ground truth for validating digital phenotyping algorithms. However, there is currently a lack of software for doing this in a secure and acceptable manner. We worked with cohort leaders and participants to co-design an open-source, robust and expandable software framework for gathering social media data in epidemiological cohorts.

Implementation

Epicosm is implemented as a Python framework that is straightforward to deploy and run inside a cohort’s data safe haven.

General features

The software regularly gathers Tweets from a list of accounts and stores them in a database for linking to existing cohort data.

Availability

This open-source software is freely available at [https://dynamicgenetics.github.io/Epicosm/].
No carryover effect of feeding spray dried plasma to weanling pigs in phase 1 on energy and nutrient digestibility in phase 2 were observed
Authors: Bailey Hannah M , Campbell Joy M , Fanelli Natalia S , Stein Hans H
Published: February 2023

Spray dried plasma (SDP) is commonly used in phase 1 diets for weanling pigs, but it is unknown if SDP affects energy or nutrient digestibility of the subsequent diet. Therefore, two experiments were conducted to test the null-hypothesis that inclusion of SDP in a phase 1 diet fed to weanling pigs will not affect energy or nutrient digestibility of a phase 2 diet without SDP. In experiment 1, 16 newly weaned barrows with an initial body weight (BW) of 4.47 ± 0.35 kg were randomly allotted to a phase 1 diet without SDP or a diet including 6% SDP for 14 d. Both diets were fed on an ad libitum basis. All pigs (BW: 6.92 ± 0.42 kg) had a T-cannula surgically inserted in the distal ileum, moved to individual pens, and fed the common phase 2 diet for 10 d with ileal digesta collection on days 9 and 10. In experiments 2, 24 newly weaned barrows (initial BW: 6.60 ± 0.22 kg) were randomly allotted to phase 1 diets without SDP or a diet containing 6% SDP for 20 d. Both diets were provided on an ad libitum basis. All pigs (BW: 9.37 ± 1.40 kg) were then moved to individual metabolism crates and fed the common phase 2 diet for 14 d with the initial 5 d being the adaptation period to the diet followed by 7 d of fecal and urine collection according to the marker-to-marker procedure. The apparent ileal digestibility (AID) of starch, crude protein (CP), amino acids (AA), and acid hydrolyzed ether extract (AEE), was determined in experiment 1, and the apparent total tract digestibility (ATTD) of gross energy (GE), insoluble-, soluble-, and total-dietary fiber, Ca, and P, and the retention and biological value of N were determined in experiment 2. The statistical model included diet as fixed effect and block and pig within block as random effects. Results of experiment 1 indicated that the AID of starch, CP, AEE, and AA in phase 2 were not affected by phase 1 treatment. Results of experiment 2 indicated that the ATTD of GE, insoluble-, soluble-, and total-dietary fiber, Ca, and P and N retention and biological value in phase 2 were also not affected by phase 1 treatment. In conclusion, feeding weanling pigs a diet with 6% SDP in phase 1 did not affect the AID or ATTD of energy and nutrients in a phase 2 diet without SDP.
LncRNA HAGLR promotes the proliferation, migration, and neurotrophic factor production of Schwann cells via miR-204/CDK5R1 after sciatic nerve injury
Authors: Xia Lei , Li Peng , Bi Wenchao , Yang Ruize , Zhang Yuelin
Published: February 2023

Peripheral nerve injury induces motor and sensory defects and has serious impacts on patients’ quality of life. Schwann cells (SCs) are the major glial cells in the peripheral nervous system and play important roles in the repair and regeneration of peripheral nerves. Long noncoding RNA HAGLR has been reported to be highly expressed in neurons and to promote neuronal differentiation but its expression decreases after nerve injury, suggesting that HAGLR may be involved in the process of nerve injury repair. This study aimed to investigate the role and mechanism of HAGLR in neural repair functions of SCs. We found that HAGLR promoted SC proliferation and migration and facilitated the secretion of neurotrophic factors. Furthermore, HAGLR functions as a competing endogenous RNA to regulate CDK5R1 expression via sponging miR-204. Overexpression of miR-204 or silencing of CDK5R1 partially abolished the promoting effect of HAGLR on SCs. Moreover, overexpression of HAGLR promoted the functional recovery of sciatic nerve crush (SNC) model rats. In summary, HAGLR promoted SC proliferation, migration, neurotrophic factor production, and facilitated functional recovery of SNC rats via miR-204/CDK5R1. Therefore, it may provide a potential therapeutic target for peripheral nerve repair and regeneration.
Estimating heterogeneous treatment effects with right-censored data via causal survival forests
Authors: Cui Yifan , Kosorok Michael R , Sverdrup Erik , Wager Stefan , Zhu Ruoqing
Published: February 2023

Forest-based methods have recently gained in popularity for non-parametric treatment effect estimation. Building on this line of work, we introduce causal survival forests, which can be used to estimate heterogeneous treatment effects in survival and observational setting where outcomes may be right-censored. Our approach relies on orthogonal estimating equations to robustly adjust for both censoring and selection effects under unconfoundedness. In our experiments, we find our approach to perform well relative to a number of baselines.
Predictors of flare in SLE patients fulfilling lupus low disease activity state: a cohort study of 292 patients with 36-month follow-up
Authors: Cunha Rita N , Saraiva Liliana , Jesus Diogo , Doria Andrea , da Silva José P , Inês Luís S
Published: February 2023

Objectives

The treatment target in SLE should be maintained stable by preventing flares. The objectives were to identify predictors of flare in patients attaining lupus low disease activity state (LLDAS), and to assess whether remission with no glucocorticoids is associated with lower risk of flares.

Methods

This was a cohort study of SLE patients followed in a referral centre over 3 years. Baseline was the first visit where each patient attained LLDAS. Flares up to 36 months’ follow-up were identified by three instruments: revised Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) Flare Index (r-SFI), SLEDAI-2000 (SLEDAI-2K) and SLE Disease Activity Score (SLE-DAS). Demographic, clinical and laboratory parameters at baseline were evaluated as predictors of flare, with distinct models for each flare instrument, using survival analysis with univariate followed by multivariate Cox regression. Hazard ratios (HR) were determined with 95% CI.

Results

A total of 292 patients fulfilling LLDAS were included. Over follow-up, 28.4%, 24.7% and 13.4% of the patients developed one or more flare, according to r-SFI, SLE-DAS and SLEDAI-2K definitions, respectively. After multivariate analysis, the predictors of SLE-DAS flares were presence of anti-U1-ribonucleoprotein (anti-U1RNP) (HR = 2.16, 95% CI 1.30, 3.59), SLE-DAS score at baseline (HR = 1.27, 95% CI 1.04, 1.54) and immunosuppressants (HR = 2.43, 95% CI 1.43, 4.09). These predictors were equally significant for r-SFI and SLEDAI-2K flares. Remitted patients with no glucocorticoids presented a lower risk of SLE-DAS flares (HR = 0.60, 95% CI 0.37, 0.98).

Conclusion

In patients with LLDAS, anti-U1RNP, disease activity scored by SLE-DAS and SLE requiring maintenance immunosuppressants predict higher risk of flare. Remission with no glucocorticoids is associated with lower risk of flares.
Induction failure in granulomatosis with polyangiitis: a nationwide case-control study of risk factors and outcomes
Authors: Sorin Boris , Iudici Michele , Guerry Mary-Jane , Samson Maxime , Bielefeld Philip , Maillet Thibault , Nouvier Mathilde , Karras Alexandre , Meyer Lara , Lavigne Christian , Régent Alexis , Durel Cécile-Audrey , Fabre Marc , Charles Pierre , Raimbourg Quentin , Lanteri Aurélia , Pugnet Grégory , Rivière Frédéric , Pineton de Chambrun Marc , Cacoub Patrice , Le Guenno Guillaume , Jourdain Pierre , Mekinian Arsène , Paule Romain , Dion Jérémie , Legendre Paul , Cohen Pascal , Guillevin Loïc , Puéchal Xavier , Terrier Benjamin
Published: February 2023

Objective

To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy.

Methods

We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment.

Results

We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone.

Conclusion

In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.
Communication and Decision-Making Processes: Group-level Determinants of State Performance
Authors: Vilaça Luiz
Published: February 2023

Dominant explanations for variation in performance between state organizations focus on macro-level factors, such as political support, and meso-level factors, such as civil service capacity. However, these factors cannot account for why different groups within the same state organization perform better than others. I leverage a comparative analysis of state officials working under particularly challenging circumstances—task forces of prosecutors investigating high-level corruption in Brazil—to develop a framework to explain how small-group communication and decision-making processes affect performance. Drawing on document analysis and 124 original interviews with federal investigators, I argue that, even when we account for macro- and meso-level factors, prosecutors performed better when they cultivated frequent communication and collective decision-making. This study shows the mechanisms through which these processes affect performance: while frequent communication enables group members to generate knowledge connections that help them make unforeseen discoveries, collective decision-making helps build defensive alignment, which allows members to protect the group from external pressures and manage internal tensions.
Synthesis and evaluation of novel thiazole moiety-containing compounds as antibreast cancer agents
Authors: Abdelhamid Moustafa Salaheldin , El-Farargy Ahmed Fouad , Abdelhai Esawi Omnia
Published: February 2023

Progesterone receptor (PR) agonists represent pivotal agents in trapping breast cancer cells through modulating the expression of estrogen receptor (ER). The present investigation aimed to test three novel thiadiazole-containing compounds as antibreast cancer agents. Test compounds were synthesized and abbreviated as 2-{(5-amino-1, 3, 4-thiazole-2-yl) amino}-4-(4-chloro-3-methylphenyl)-4-oxobutanoic acid (TAB), 4-(4-chloro-3-methylphenyl)-4-oxo 2-[(5-sulfanyl-1, 3, 4-thiadiazol-2-yl)] sulfanyl-butanoic acid (TSB) and 4-(4-chloro-3-methylphenyl)-4-oxo 2-[(5-sulfanyl-1, 3, 4-thiadiazol-2-yl)] sulphonyl-botanic acid (TSSB). Molecular docking of the test compounds with PR was simulated. The IC50 of the test compounds against both Michigan cancer foundation-7 (MCF-7) and HepG2 was determined. Ehrlich solid tumor (EST) was grown in the right thigh of the mouse as a model of breast cancer in vivo. Hepatic and renal functions, besides hematological indicators, were tested. The expression of ER and ER genes in EST was determined using real-time PCR. Immunohistochemistry was carried out for the determination of Ki-67 and cyclin-dependent kinase 1 (CDK-1) in EST. Our results revealed that TAB, TSB and TSSB reduced Ehrlich tumor size by 48, 64 and 52%, respectively, compared to the EST control group. The docking scores achieved by TAB, TSB and TSSB with PR were −9.29, −9.41 and −9.24 kcal/mol, respectively. The most potent compound against MCF-7 was TSB, with an IC50 of 3.9 g/ml. The administration of test compounds suppressed Ki-67 and CDK1, and the best effect was observed at TSB. Our findings suggest that test compounds are applicants to be antibreast cancer agents.
A durable response to savolitinib in a patient with lung adenocarcinoma harboring two novel MET exon 14 skipping sites
Authors: Gu Linping , Zhao Yi , Wen Fengcai , Zhang Ding , Cai Jinping , Chen Zhiwei
Published: February 2023

MET exon 14 (METex14) skipping variants are oncogenic drivers in non-small-cell lung cancer. Several METex14 skipping alterations have been identified, but different mesenchymal-epithelial transition (MET) exon splicing variants tend to present different clinical outcomes. Here, we reported that a patient with lung adenocarcinoma harbored two novel METex14 skipping mutations (c.2888-35_2888-16del and c.2888-4T>G) identified by the tissue-based next-generation sequencing (NGS) and received savolitinib treatment after chemotherapy failed with brain metastasis. The patient responded well to savolitinib until disease progression in brain lesions and achieved a progress-free survival (PFS) of over 19.7 months. Considering the durable response for extracranial lesions and the same METex14 skipping sites identified by circulating tumor DNA-based NGS, the patient was still given savolitinib combined with stereotactic body radiation therapy for brain lesions. An extracranial PFS of 28 months was achieved. This is the first report of a patient with lung adenocarcinoma harboring two novel METex14 skipping mutations that responded to the MET inhibitor savolitinib. Our case may provide evidence for the treatment of patients with two novel METex14 skipping variants and offer a therapy regimen for those with intracranial progression.
Patients with a history of atopy have fewer cutaneous melanomas than those without atopy: a cross-sectional study in 496 patients at risk of skin cancers
Authors: Komulainen Jenni , Siiskonen Hanna , Haimakainen Salla , Kanasuo Emilia , Harvima Rauno J. , Harvima Ilkka T.
Published: February 2023

The connection between atopy and skin cancers may be related to the stimulation of protective immune response, for example, through autoreactive immunoglobulin-E (IgE), or to the predisposition to carcinogenesis through chronic inflammation. The aim of this study was to investigate whether a past or present atopic disorder is associated with cutaneous photodamage, pigment cell nevi and skin cancers. For this, adult subjects at risk of any type of skin cancer (aged 21–79 years, 250 males, 246 females, 94 with immunosuppression) were examined for past or present malignancies in skin and extracutaneous site (ECS), photodamage, nevi, past or present atopic disorder in skin or mucus membranes, and possible other cancer-related factors. No association between atopy and photodamage, keratinocyte carcinomas or nevus count was found. Instead, there were fewer subjects with melanoma in 171 atopic (14.6%) than in 325 nonatopic subjects (22.2%) (P = 0.044), and the investigator-estimated risk class of skin cancers was lower in atopic than nonatopic subjects. In all subjects, the multivariate odds ratio (OR) for melanoma was 0.583 (P = 0.046; 95% confidence interval, 0.343–0.990) in atopic subjects, but in immunocompetent subjects, the reduced risk was confined to mucus membrane atopy (OR, 0.417; P = 0.020). Also, there were fewer subjects with malignancy in ECS in atopic (8.8%) than nonatopic subjects (15.7%) (P = 0.031). No association between serum total IgE and skin cancers, photodamage, nevi or malignancies in ECS was found. In conclusion, the atopy, especially mucus membrane atopy, is associated with lower percentages of subjects with a history of melanoma.
Direct Costs of Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation (The Assists Trial)
Authors: Ma Jack X. , Chuang Alice Z. , Feldman Robert M. , Mansberger Steve L. , Tanna Angelo P. , Blieden Lauren S. , Shoham Daniel , Bell Nicholas P. , Gross Ronald L. , Pasquale Louis R. , Greenfield David S. , Liebmann Jeffrey M. , Weinreb Robert N. ,   the ASSISTS Study Group
Published: February 2023

Précis:

The cost of cyclophotocoagulation is less than the cost of a second glaucoma drainage device.

Purpose:

To compare the total direct costs of implantation of a second glaucoma drainage device (SGDD) with transscleral cyclophotocoagulation (CPC) for patients with inadequately controlled intraocular pressure (IOP) reduction, despite the presence of a preexisting glaucoma drainage device in the ASSISTS clinical trial.

Methods:

We compared the total direct cost per patient, including the initial study procedure, medications, additional procedures, and clinic visits during the study period. The relative costs for each procedure during the 90-day global period and the entire study period were compared. The cost of the procedure, including facility fees and anesthesia costs, were determined using the 2021 Medicare fee schedule. Average wholesale prices for self-administered medications were obtained from AmerisourceBergen.com. The Wilcoxon rank sum test was used to compare costs between procedures.

Results:

Forty-two eyes of 42 participants were randomized to SGDD (n=22) or CPC (n=20). One CPC eye was lost to follow-up after initial treatment and was excluded. The mean (±SD, median) duration of follow-up was 17.1 (±12.8, 11.7) months and 20.3 (±11.4, 15.1) months for SGDD and CPC, respectively (P=0.42, 2 sample t test). The mean total direct costs (±SD, median) per patient during the study period were $8790 (±$3421, $6805 for the SGDD group) and $4090 (±$1424, $3566) for the CPC group (P<0.001). Similarly, the global period cost was higher in the SGDD group than in the CPC group [$6173 (±$830, $5861) vs. $2569 (±$652, $2628); P<0.001]. The monthly cost after the 90-day global period was $215 (±$314, $100) for SGDD and $103 (±$74, $86) for CPC (P=0.31). The cost of IOP-lowering medications was not significantly different between groups during the global period (P=0.19) or after the global period (P=0.23).

Conclusion:

The total direct cost in the SGDD group was more than double that in the CPC group, driven largely by the cost of the study procedure. The costs of IOP-lowering medications were not significantly different between groups. When considering treatment options for patients with a failed primary GDD, clinicians should be aware of differences in costs between these treatment strategies.
Three-year multinational clinical study on an aspheric hydrophobic acrylic intraocular lens
Authors: Nuijts Rudy M.M.A. , Bhatt Uday , Nanavaty Mayank A. , Roberts Timothy V. , Peterson Rachael , Teus Miguel A.
Published: February 2023

Purpose:

To present the results of a study investigating the 3-year effectiveness and safety of the Clareon single-piece intraocular lens (IOL).

Setting:

19 multinational sites.

Design:

Prospective multicenter single-arm study.

Methods:

Patients were bilaterally implanted with Clareon IOLs. Assessments included uncorrected distance visual acuity, corrected distance visual acuity (CDVA), manifest refraction, tilt, decentration, applanation tonometry, and fundus examination, including glistenings and posterior capsule opacification (PCO) evaluation. The primary outcomes for effectiveness and safety were evaluated at 1 year and compared with ISO historical safety and performance endpoint (SPE) rates. Patients were followed for up to 3 years after implantation.

Results:

424 eyes of 215 patients were implanted (n = 215 first eye, n = 209 second eye), and 183 patients completed the trial at 3 years (with 364 binocular and 1 monocular patient). At 1 year, the cumulative and persistent adverse event rates were below SPE targets, and 99.5% of eyes achieved a monocular CDVA of ≤0.3 logMAR (vs the SPE target of 92.5%). At 3 years, the mean monocular CDVA was −0.032, with 93.4% (341/365) of eyes achieving a CDVA of 0.1 logMAR or better, 100% of eyes presented with grade 0 glistenings ≤25 MV/mm2, and 92.9% of eyes (394/424) had either no PCO or clinically nonsignificant PCO.

Conclusions:

This study supports the long-term safety and effectiveness of the Clareon IOL. The visual outcomes were excellent and stable over the 3-year study period, PCO rates were very low, and 100% of IOLs had grade 0 glistenings.
Primary Care Consultations Among UK Police Officers and Staff
Authors: Trompeter Nora , Fear Nicola T. , Greenberg Neil , Hotopf Matthew , Irizar Patricia , Wessely Simon , Stevelink Sharon A.M.
Published: February 2023

Objective

The current study examined links between adverse mental health, job strain, and likelihood and frequency of primary care consultations among police employees.

Methods

We conducted secondary data analysis on the Airwave Health Monitoring Study data (n = 33,730). Measures included self-report data on mental health, job strain, job support, and primary care consultations in the past 12 months. Data were analyzed using a zero-inflated Poisson regression framework.

Results

Findings showed that overall, help seeking was low based on mental health status and job strain. Adverse mental health was associated with more primary care consultations. Police employees with high, active, or passive job strain reported more primary care consultation compared with police employees with low strain.

Conclusions

Findings suggest that more work to reduce stigma of taking the initial step of help seeking would be beneficial.