bluuebunny/crossref_metadata_2025 huggingface dataset:
Treating sarcoidosis-associated progressive multifocal leukoencephalopathy with infliximab
Authors: Rosenkranz Sina C. , Häußler Vivien , Kolster Manuela , Willing Anne , Matschke Jakob , Röcken Christoph , Stürner Klarissa , Leypoldt Frank , Tolosa Eva , Friese Manuel A.
Published: December 2021

Although most of the progressive multifocal leukoencephalopathy cases in sarcoidosis patients are explained by the treatment with immunosuppressive drugs, it is also reported in treatment-naive sarcoidosis patients, which implies a general predisposition of sarcoidosis patients for progressive multifocal leukoencephalopathy. Indeed, it was shown that active sarcoidosis patients have increased regulatory T cell frequencies which could lead to a subsequent systemic immunosuppression. However, if sarcoidosis with systemic changes of T cell subsets frequencies constitute a risk factor for the development of progressive multifocal leukoencephalopathy, which could then be counteracted by sarcoidosis treatment, is not known. In this cohort study, we included, characterized and followed-up six patients with bioptically confirmed definite progressive multifocal leukoencephalopathy and definite or probable sarcoidosis presenting between April 2013 and January 2019, four of them had no immunosuppressive therapy at the time of developing first progressive multifocal leukoencephalopathy symptoms. Analysis of immune cell subsets in these patients revealed significant imbalances of CD4+ T cell and regulatory T cell frequencies. Due to the progression of progressive multifocal leukoencephalopathy in four patients, we decided to treat sarcoidosis anticipating normalization of immune cell subset frequencies and thereby improving progressive multifocal leukoencephalopathy. Notably, by treatment with infliximab, an antibody directed against tumour necrosis factor-α, three patients continuously improved clinically, JC virus was no longer detectable in the cerebrospinal fluid and regulatory T cell frequencies decreased. One patient was initially misdiagnosed as neurosarcoidosis and died 9 weeks after treatment initiation due to aspiration pneumonia. Our study provides insight that sarcoidosis can lead to changes in T cell subset frequencies, which predisposes to progressive multifocal leukoencephalopathy. Although immunosuppressive drugs should be avoided in progressive multifocal leukoencephalopathy, paradoxically in patients with sarcoidosis treatment with the immunosuppressive infliximab might restore normal T cell distribution and thereby halt progressive multifocal leukoencephalopathy progression.
SITVITBovis—a publicly available database and mapping tool to get an improved overview of animal and human cases caused by Mycobacterium bovis
Authors: Couvin David , Cervera-Marzal Iñaki , David Audrey , Reynaud Yann , Rastogi Nalin
Published: December 2021

Limited data are available for bovine tuberculosis and the infections it can cause in humans and other mammals. We therefore constructed a publicly accessible SITVITBovis database that incorporates genotyping and epidemiological data on Mycobacterium bovis. It also includes limited data on Mycobacterium caprae (previously synonymous with the name M. bovis subsp. Caprae) that can infect both animals and humans. SITVITBovis incorporates data on 25,741 isolates corresponding to 60 countries of origin (75 countries of isolation). It reports a total of 1000 spoligotype patterns: 537 spoligotype international types (SITs, containing 25 278 clinical isolates) and 463 orphan patterns, allowing a wide overview of the geographic distribution of various phylogenetical sublineages (BOV_1, BOV_2, BOV_3 and BOV_4-CAPRAE). The SIT identifiers of the SITVITBovis were compared to the SB numbers of the Mbovis.org database to facilitate crosscheck among databases. Note that SITVITBovis also contains limited information on mycobacterial interspersed repetitive units-variable number of tandem repeats when available. Significant differences were observed when comparing age/gender of human isolates as well as various hosts. The database includes information on the regions where a strain was isolated as well as hosts involved, making it possible to see geographic trends. SITVITBovis is publicly accessible at: http://www.pasteur-guadeloupe.fr:8081/SITVIT_Bovis. Finally, a future second version is currently in progress to allow query of associated whole-genome sequencing data.

Database URLhttp://www.pasteur-guadeloupe.fr:8081/SITVIT_Bovis
Spinal cord infarction and peripheral extracorporeal membrane oxygenation: a case series
Authors: Gangahanumaiah Shivanand , Zhu Michael , Summerhayes Robyn , Marasco Silvana F
Published: December 2021

Background

Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is increasingly utilized in patients with cardiogenic shock due to improved technology and outcomes. Peripheral VA ECMO offers several advantages over central ECMO and is becoming increasingly popular. However, when configured via the femoral vessels, retrograde flow to the descending aorta and arch of aorta competes with antegrade ventricular output and can be associated with a watershed phenomenon and increased risk of neurologic and visceral injury.

Case summary

In this case series, we report three patients who were supported with peripheral VA ECMO for cardiogenic shock. All three were successfully weaned from peripheral VA ECMO; however, they had developed bilateral lower limb paralysis. Magnetic resonance imaging revealed spinal cord infarction in all three patients. All patients subsequently succumbed to multiorgan failure and did not survive to hospital discharge.

Discussion

The use of mechanical circulatory support, in particular, peripheral ECMO, has escalated with advances in technology, better understanding of cardiac physiology and improving outcomes. Spinal cord infarction is a rare but serious complication of peripheral VA ECMO support with only a few case reports published. Further studies are needed to identify the exact cause and prevention of this rare but often terminal complication. Through this series of three patients supported on peripheral VA ECMO complicated by spinal cord infarction, we review previously published reports, analyse possible mechanisms, and propose alternate management strategies to be considered in patients at risk.
Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants
Authors: Kitzman Samuel Cole , Duan Tingting , Pufall Miles A , Geyer Pamela K
Published: December 2021

The nuclear lamina (NL) lines the inner nuclear membrane. This extensive protein network organizes chromatin and contributes to the regulation of transcription, DNA replication, and repair. Lap2-emerin-MAN1 domain (LEM-D) proteins are key members of the NL, representing proteins that connect the NL to the genome through shared interactions with the chromatin-binding protein Barrier-to-Autointegration Factor (BAF). Functions of the LEM-D protein emerin and BAF are essential during Drosophila melanogaster oogenesis. Indeed, loss of either emerin or BAF blocks germ cell development and causes loss of germline stem cells, defects linked to the deformation of NL structure, and non-canonical activation of Checkpoint kinase 2 (Chk2). Here, we investigate the contributions of emerin and BAF to gene expression in the ovary. Profiling RNAs from emerin and baf mutant ovaries revealed that nearly all baf misregulated genes were shared with emerin mutants, defining a set of NL-regulated genes. Strikingly, loss of Chk2 restored the expression of most NL-regulated genes, identifying a large class of Chk2-dependent genes (CDGs). Nonetheless, some genes remained misexpressed upon Chk2 loss, identifying a smaller class of emerin-dependent genes (EDGs). Properties of EDGs suggest a shared role for emerin and BAF in the repression of developmental genes. Properties of CDGs demonstrate that Chk2 activation drives global misexpression of genes in the emerin and baf mutant backgrounds. Notably, CDGs were found upregulated in lamin-B mutant backgrounds. These observations predict that Chk2 activation might have a general role in gene expression changes found in NL-associated diseases, such as laminopathies.
Health Confidence Is Associated With Disease Outcomes and Health Care Utilization in Inflammatory Bowel Disease: A Nationwide Cross-sectional Study
Authors: Tse Chung Sang , Siegel Corey A , Weaver S Alandra , Oliver Brant J , Bresee Catherine , van Deen Welmoed K , Melmed Gil Y
Published: December 2021

Background

We aimed to examine the associations between health confidence (one’s belief on the degree of control on their health and disease), inflammatory bowel disease (IBD) outcomes, and health care utilization among adults with IBD.

Methods

In total, 17,205 surveys were analyzed from a cross-sectional sample of IBD patients at 23 gastroenterology (GI) practices participating in the Crohn’s and Colitis Foundations’ IBD Qorus Learning Health System. We used bivariate analyses and multivariable logistic regression to examine associations between health confidence and disease activity, opioid use, glucocorticoid use, well-being, and health care utilization. We used receiver operating curve analysis to determine a clinically relevant cutoff for health confidence (0-10 Likert scale).

Results

Health confidence was highly correlated with patients’ well-being, symptomatic disease activity, opioid use, and glucocorticoid use (all P < .0001). Health confidence scores <8 had 69% sensitivity for emergency department (ED) visits and 66% for hospitalizations. In patients with inactive disease, patients with low health confidence (<8) were 10 times more likely to call/message the GI office >4 times/month (adjusted odds ratio [aOR], 10.3; 95% CI, 6.1-17.3; P < .0001), 3-4 times more likely to have an IBD-related ED visit (aOR, 4.0; 95% CI, 2.9, 5.4. P < .0001), or hospitalization (aOR, 3.0, 95% CI, 2.1, 4.1, P < .0001) compared with patients with high health confidence (≥8).

Conclusions

In a large, national sample of adults with IBD, there were strong associations between patients’ health confidence and multiple disease outcome measures. Health confidence scores <8 on a 0-10 Likert scale may be clinically useful to screen for patients who are at risk for ED visits and hospitalizations.
L-system models for image-based phenomics: case studies of maize and canola
Authors: Cieslak Mikolaj , Khan Nazifa , Ferraro Pascal , Soolanayakanahally Raju , Robinson Stephen J , Parkin Isobel , McQuillan Ian , Prusinkiewicz Przemyslaw
Published: December 2021

Artificial neural networks that recognize and quantify relevant aspects of crop plants show great promise in image-based phenomics, but their training requires many annotated images. The acquisition of these images is comparatively simple, but their manual annotation is time-consuming. Realistic plant models, which can be annotated automatically, thus present an attractive alternative to real plant images for training purposes. Here we show how such models can be constructed and calibrated quickly, using maize and canola as case studies.
Contesting the “Corrupt Elites,” Creating the “Pure People,” and Renegotiating the Hierarchies of the International Order? Populism and Foreign Policy-Making in Turkey and Hungary
Authors: Hisarlıoğlu Fulya , Yanık Lerna K , Korkut Umut , Civelekoğlu İlke
Published: December 2021

This article explores the link between populism and hierarchies in international relations by examining the recent foreign policy-making in Turkey and Hungary—two countries run by populist leaders. We argue that when populists bring populism into foreign policy, they do so by contesting the “corrupt elites” of the international order and, simultaneously, attempt to create the “pure people” transnationally. The populists contest the “eliteness” and leadership status of these “elites” and the international order and its institutions, that is, the “establishment,” that these “elites” have come to represent by challenging them both in discourse and in action. The creation of the “pure people” happens by discursively demarcating the “underprivileged” of the international order as a subcategory based on religion and supplementing them with aid, thus mimicking the distributive strategies of populism, this time at the international level. We illustrate that when populist leaders, insert populism into foreign policies of their respective states, through contesting the “corrupt elites” and creating the “pure people,” the built-in vertical stratification mechanisms of populism that stems from the antagonistic binaries inherent to populism provide them with the necessary superiority and inferiority labels allowing them to renegotiate hierarchies in the international system in an attempt to modify the existing ones or to create new ones.
Development of a Unified National Database of Burn Centers With Colocated Emergency Departments, 2020
Authors: Lu Lily Y , Boggs Krislyn M , Espinola Janice A , Sullivan Ashley F , Cash Rebecca E , Camargo Carlos A
Published: December 2021

The care of severely burned patients comes with unique requirements for specialized burn centers. The American Burn Association sets guidelines for burn centers and provides a voluntary program to verify their quality of care. However, not all burn centers are verified, and it is unclear which nonverified centers have met requirements set by their state health departments. To compile a complete database of all U.S. emergency departments in facilities with confirmed burn centers, we investigated state requirements to supplement data from the American Burn Association verification process. In 2020, only 13 states set requirements for burn centers; 3 states explicitly required American Burn Association verification, 4 used modified American Burn Association criteria, and 6 used alternate criteria. Only two states had separate requirements for pediatric burn centers. Based on adherence to state and American Burn Association criteria, we identified 90 confirmed burn centers in 2020, 85 of which had emergency departments. Of these 85, 45 (53%) were only verified, 17 (20%) were only state-confirmed, and 23 (27%) were both. Emergency departments in a confirmed burn center were more likely—than those without—to have higher adult and pediatric visit volumes, be academic, be a stroke or trauma (adult or pediatric) center, have a dedicated pediatric area, and have a pediatric emergency care coordinator. We compiled the first unified burn center database that incorporates state and American Burn Association lists. This database can be utilized in future health services research and is available to the public through a smartphone application.
Hepatic Functional Pathophysiology and Morphological Damage Following Severe Burns: A Systematic Review and Meta-analysis
Authors: Tapking Christian , Kilian Katja , Hundeshagen Gabriel , Haug Valentin , Teufel Andreas , Houschyar Khosrow S , Kneser Ulrich , Hirche Christoph
Published: December 2021

Severe burns are devastating injuries affecting multiple organ systems. Little is known about the influence on the hepatic system and its physiology. This systematic review aimed to assess the current state of research on morphologic liver damage following severe burns. A search was conducted in PubMed, Web of Science, and Cochrane databases using PRISMA guidelines. Outcomes included serum levels of transaminases, fatty infiltration, and necrosis. Weighted individual study estimates were used to calculate pooled transaminase levels and necrosis/fatty infiltration rates using a random-effects approach. Risk ratios or odds ratios and 95% confidence intervals (CIs) were used to describe pooled estimates for risk factors. The literature search retrieved 2548 hits, of which 59 studies were included in qualitative synthesis, and finally 10 studies were included in the meta-analysis. Studies were divided into those reporting autopsies and those reporting changes of serum transaminase levels. The majority of liver autopsies showed fatty infiltration, 82% (95% CI 39–97%) or necrosis of the liver, 18% (95% CI 13–24%). Heterogeneity in studies on hepatic functional damage following severe burns was high. Only a few were well-designed and published in recent years. Many studies could not be included because of insufficient numerical data. There is a high number of patients dying from burns that present with fatty infiltration or necrosis of hepatic tissue. Transaminases were elevated during the initial days postburn. Further research on how severe burns affect the hepatic function and outcome, especially long-term, is necessary. Systematic review registration: PROSPERO:CRD42020206061.
Semi-analytical model of multiple fractured horizontal well across a discontinuity in a linear composite reservoir
Authors: Ren Junjie , Liu Xiaoxue , Wu Qingxing , Wu Shuai
Published: December 2021

Many geologic settings can be treated as linear composite (LC) reservoirs, where linear discontinuities divide the formation into multiple zones with different properties. Although there have been many studies on pressure behavior of production wells in an LC reservoir, most of the studies focus on vertical wells. The modeling of multiple fractured horizontal (MFH) wells in an LC reservoir remains limited. The goal of the present work is to propose a general semi-analytical model of an MFH well situated anywhere in a two-zone LC reservoir. This model can take into account the situation where the horizontal well intersects with the discontinuity and hydraulic fractures are distributed in both the two zones. According to the point-source function method, the semi-analytical solution for an MFH well in LC reservoirs is derived by using superposition principle, fracture discrete scheme and numerical inversion algorithm of Laplace transformation. Type curves of MFH wells far away from a discontinuity and across a discontinuity in an LC reservoir are drawn and analysed, respectively. Furthermore, the effects of some parameters on pressure behavior and rate response of an MFH well across a discontinuity are studied. This research finds that the pressure behavior and rate response of an MFH well across a discontinuity are significantly affected by the well location, properties of hydraulic fractures and formation properties.
Evaluating strategies for estimation of local kinematic parameters in noisy land data: quality versus performance trade-offs
Authors: Bakulin Andrey , Silvestrov Ilya , Protasov Maxim
Published: December 2021

Modern land seismic data are typically acquired using high spatial trace density with small source and receiver arrays or point sources and sensors. These datasets are challenging to process due to their massive size and relatively low signal-to-noise ratio caused by scattered near-surface noise. Therefore, prestack data enhancement becomes a critical step in the processing flow. Nonlinear beamforming had proved very powerful for 3D land data. However, it requires computationally intensive estimations of local coherency on dense spatial/temporal grids in 3D prestack data cubes. We present an analysis of various estimation methods focusing on a trade-off between computational efficiency and enhanced data quality. We demonstrate that the popular sequential «2 + 2 + 1» scheme is highly efficient but may lead to unreliable estimation and poor enhancement for data with a low signal-to-noise ratio. We propose an alternative algorithm called «dip + curvatures» that remains stable for such challenging data. We supplement the new strategy with an additional interpolation procedure in spatial and time dimensions to reduce the computational cost. We demonstrate that the «dip + curvatures» strategy coupled with an interpolation scheme approaches the «2 + 2 + 1» method's efficiency while it significantly outperforms it in enhanced data quality. We conclude that the new algorithm strikes a practical trade-off between the performance of the algorithm and the quality of the enhanced data. These conclusions are supported by synthetic and real 3D land seismic data from challenging desert environments with complex near surface.
A calculation methodology of fault relative displacement used to study the mechanical characteristic of fault slip
Authors: Wang Hongwei , Shi Ruiming , Deng Daixin , Cui Fan , Jiang Yaodong
Published: December 2021

Fault slip caused by mining disturbance is a crucial issue that can pose considerable threats to the mine safety. This paper proposes a point-by-point integration calculated methodology of fault relative slip and studies fault instability behavior induced by coal seam mining. A physical model with the existence of a fault and an extra-thick rock stratum is constructed to simulate the fault movement and calculate relative slip using the methodology. The results indicate that the fault relative slip can be regarded as a dynamic evolution process from local slip to global slip on the fault surface. The movement of surrounding rock masses near the fault experiences three stages, including along vertical downward, parallel to the fault and then approximately perpendicular to the fault. There will be an undamaged zone in the extra-thick rock strata when the mining face is near the fault structure. The collapse and instability of this undamaged zone could induce a violent fault relative slip. In addition, the influence of dip angles on the fault relative slip is also discussed. A formula for risk of fault relative slip is further proposed by fitting the relative displacement curves with different fault dip angles.
The preferential accumulation and the settling velocity of small heavy particles in Taylor–Couette flows
Authors: Yang Tzu-Sen , Shy Shenqyang (Steven)
Published: December 2021

In a gap between two concentric cylinders, we discover that the small heavy particle settling velocity (Vs) is greater than its associated terminal velocity (Vt) in featureless turbulence that is generated by counter-rotating inner and outer cylinders simultaneously. The peak enhancement of Vs occurs at St × (Vt/u′) ∼ 1, where u′ and St are, respectively, the r.m.s. turbulence fluctuation velocity and the Stokes number defined as the ratio between the particle response time to the Kolmogorov turbulence time. The present (Vs − Vt)/u′ data as a function of St measured by the high-speed particle imaging velocimetry are compared with previous experimental results obtained from different turbulent flow configurations in an attempt to gain further understandings of the complicated interactions between small heavy particles and featureless turbulence with negligible mean velocities. Moreover, it is found that small heavy particles are preferentially accumulated around the edges of an array of counter-rotating turbulent Taylor vortices with the inner cylinder rotation alone when a time ratio between particle response and Taylor vortices is near unity. These experimental results are interesting that may deserve to disseminate in our fluid mechanics community.
Genotypic variation of plant biomass under nitrogen deficiency is positively correlated with conservative economic traits in wheat
Authors: Huang Guanjun , Fang Qing , Peng Shaobing , Li Yong
Published: December 2021

Plant functional traits, including leaf and root economic traits, are important for understanding the composition and function of ecosystems. However, plant functional traits of crop species and the relationships between them, and their responses to environmental variations are not fully understood. In the present study, the traits in the leaf and root economics spectrum (LES and RES) and plant biomass were investigated in 14 wheat genotypes grown with sufficient or limited nitrogen (N) supply. We found that N had significant impacts on the LES and RES traits and on the relationships among them. Our results generally supported the hypothesized LES, but did not support the RES or plant economics spectrum concept among wheat plants regardless of N treatment. More importantly, we found that more conservative leaf and root economic traits are beneficial for shoot biomass accumulation in wheat plants grown with limited N supply, and for the improvement in the tolerance of wheat to N stress. The data presented suggest that growth conditions should be accounted for when studying trait-to-trait relationships, and that more conservative resource use strategies could be used as promising targets for wheat breeding programs with limited N input.
The Sum is Greater Than the Parts: Aligning Graduate Allied and Medical Health Education at a Training Institution
Authors: Bonjour Timothy J , True Mark W , Mu Thornton , Faux Brian M , Valdez Michelle M , Umlauf Jon A , Morris Michael J , Button Christopher J , Matos Renée I
Published: December 2021

Analysis of military Graduate Medical Education (GME) remains in the discussion forefront as resources continue to face scrutiny along with military-specific obligation challenges. The Military Health System Quadruple Aim of Better Care, Better Health, Lower Cost, and Increased Readiness continues to drive debate of the right approach to both GME and Graduate Allied Health education. In this paper, we expand the discussion beyond traditional physician-focused GME and include the military’s highly trained allied health specialists. Graduate Allied Health medical providers provide quality and effective medical care to the military’s service members and dependents. These specialists also carry a significant deployment and operational medicine footprint complimenting core physician medical specialties delivering cost-efficient, optimal patient care and providing a ready force. This paper addresses GME and GAH interprofessionalism, institutional culture endorsement, patient safety, increasing demand, research productivity, and encouraging physician retention altogether benefiting the Military Health System. This institution’s support for the interprofessional GME model works well, expanding physician and GAH specialists’ professional application and knowledge while garnering mutual respect across all medical disciplines ultimately benefiting all.
Impact of social support on severity of depressive symptoms by remission status in patients with rheumatoid arthritis
Authors: Yasuoka Mikako , Kojima Toshihisa , Waguri-Nagaya Yuko , Saito Tami , Takahashi Nobunori , Asai Shuji , Sobue Yasumori , Nishiume Tsuyoshi , Suzuki Mochihito , Mitsui Hiroto , Kawaguchi Yohei , Kuroyanagi Gen , Kamiji Koto , Watanabe Miki , Suzuki Sadao , Kondo Katsunori , Ojima Toshiyuki , Kojima Masayo
Published: December 2021

Objectives

We aimed to examine the psychosocial characteristics of patients with rheumatoid arthritis (RA) by remission status and determine the impacts of social support on severity of depressive symptoms.

Methods

We enrolled RA patients aged 40–79 years who visited university hospitals’ outpatient clinics. Severity of depressive symptoms (Beck Depression Inventory-II), physical disability (Health Assessment Questionnaire), and support were evaluated. Furthermore, RA disease activity was evaluated by 28-point Disease Activity Score (DAS28) calculation. The independent impacts of instrumental and emotional social support on depressive symptoms by remission status defined as DAS28 score < 2.6 were estimated by multivariable regression analysis.

Results

This study included 360 RA patients. In the remission group, emotional support showed a statistically significant negative impact on depressive symptoms, whereas instrumental support had an extremely limited contribution to severity of depressive symptoms. In the non-remission group, instrumental support showed a negative tendency of impact on severity of depressive symptoms, whereas emotional support had a wide range of influence.

Conclusions

Favourable association between emotional support and depressive symptoms is confirmed only among RA patients in remission status. The influence of emotional support in non-remission patients and that of instrumental support regardless of remission status are inconclusive.
Apremilast in a Japanese subgroup with Behçet’s syndrome: Results from a Phase 3, randomised, double-blind, placebo-controlled study
Authors: Takeno Mitsuhiro , Dobashi Hiroaki , Tanaka Yoshiya , Kono Hajime , Sugii Shouji , Kishimoto Mitsumasa , Cheng Sue , McCue Shannon , Paris Maria , Chen Mindy , Ishigatsubo Yoshiaki
Published: December 2021

Objectives

Apremilast efficacy and safety was assessed in a prespecified subgroup of Japanese patients with oral ulcers associated with Behçet’s syndrome from a Phase 3 randomized, placebo-controlled, double-blind study of apremilast (RELIEF).

Methods

The primary end point was area under the curve for number of oral ulcers during the 12-week placebo-controlled phase (AUCWk0–12). Key secondary end points were change from baseline in oral ulcer pain, complete oral ulcer resolution, and measures of disease activity and quality of life (QoL).

Results

Thirty-nine Japanese patients were randomised (apremilast 30 mg BID: n = 19; placebo: n = 20). Improvements at Week 12 were observed for apremilast vs. placebo in AUCWk0–12 for the number of oral ulcers (115.9 vs. 253.3; nominal P = 0.0168); 57.9% vs. 25.0% achieved complete oral ulcer resolution, 47.4% vs. 0.0% achieved oral ulcer resolution by Week 6 and maintained oral ulcer-free status for ≥6 additional weeks; mean change from baseline in BSAS was −10.5 vs. 0.5. Favourable effects were observed for apremilast vs. placebo in other secondary end points, including QoL. Clinical benefits were sustained over 28 weeks of continued apremilast treatment. Adverse events were consistent with apremilast’s known safety profile.

Conclusions

Apremilast reduced the number of oral ulcers and overall disease activity in this Japanese subgroup with Behçet’s syndrome.
Correction of rheumatoid swan-neck deformity of the finger using the modified Thompson–Littler method
Authors: Kakutani Rika , Ishikawa Hajime , Abe Asami , Funamura Kei , Sudo Masanori , Sakai Shunsuke , Otani Hiroshi , Ito Satoshi , Nakazono Kiyoshi , Murasawa Akira , Kondo Naoki , Kawashima Hiroyuki
Published: December 2021

Objectives

To investigate the outcomes of the modified Thompson–Littler (m-TL) method, a corrective surgical method utilising a dynamic tenodesis, in patients with rheumatoid swan-neck deformity.

Methods

Twenty-seven fingers in 10 patients with rheumatoid arthritis (RA) underwent surgical correction. The mean age at the time of surgery was 60.3 (45–77) years, the mean duration of RA was 19.3 (4–34) years, and the mean postoperative follow-up period was 2.4 (0.5–6) years.

Results

The deformity was corrected and the proximal interphalangeal (PIP) joint pain disappeared in all operated fingers. The mean pinch power between the thumb and the operated finger increased. The active extension decreased, the active flexion increased, and the total arc of motion decreased. Comparing the range of motion by Nalebuff’s type classification, the postoperative arc of motion decreased as the type advanced.

Conclusions

The m-TL method provided a favourable outcome in cases of Type ≤III rheumatoid swan-neck deformity without severe joint deterioration at the PIP joint. Aesthetic and functional improvements were observed and the patients were satisfied with the operation.
Clinical significance of HScore and MS score comparison in the prognostic evaluation of anti-MDA5-positive patients with dermatomyositis and interstitial lung disease
Authors: Zhao Shengnan , Ma Xiaolei , Zhang Xin , Jin Ziyi , Hu Wei , Hua Bingzhu , Wang Hong , Feng Xuebing , Sun Lingyun , Chen Zhiyong
Published: December 2021

Objectives

To evaluate the clinical significance of the HScore and MS score in the prognosis of anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with dermatomyositis (DM) and interstitial lung disease (ILD).

Methods

The clinical features as well as HScore and MS score were compared between the survivors (n = 61) and nonsurvivors (n = 36) among 97 anti-MDA5-positive DM-ILD patients. Potential prognostic factors were analysed.

Results

Compared with survivors, nonsurvivors had significantly older age, tended to be male, and had a significantly higher frequency of fever at disease onset, higher levels of aspartate transaminase, lactate dehydrogenase, and serum ferritin, as well as higher values of HScore and MS score but had a significantly lower frequency of arthritis at disease onset. Multivariate analysis revealed that age ≥50 years [hazard ratio (HR) = 2.70, p = .040, 95% confidence interval (CI) 1.05–6.97)], male gender (HR = 3.20, p = .017, 95% CI 1.23–8.28), and higher HScore (HR = 3.72, p = .003, 95% CI 1.56–8.86) were independent risk factors for mortality. Patients with more risk factors had significantly poorer survival (p < .001).

Conclusions

Older age, high HScore, and male gender are risk factors for poor survival among anti-MDA5-positive DM-ILD patients, suggesting the potential role of macrophage activation in the pathogenesis.
How reliable is assessment of joint swelling and tenderness over socks or stockings in patients with established rheumatoid arthritis?
Authors: Yano Koichiro , Tobimatsu Haruki , Ikari Katsunori , Okazaki Ken
Published: December 2021

Objectives

Physicians tend to omit examinations of the foot and ankle in routine practice because it consumes a lot of time when working within tight time constraints. Although barefoot examination is critical to assess disease activity of rheumatoid arthritis (RA), we think occasional examination of foot over socks or stockings is better than not examining foot at all. The aim of this study was to assess the accuracy of foot examinations over socks or stockings in patients with RA.

Methods

Sixty patients with RA were enrolled in this study. A rheumatologist and a senior resident performed foot examinations on each patient over socks, over stockings, and on bare foot to assess swelling and tenderness. Concordance rates between the barefoot examination and the examinations over socks or stockings by each examiner were investigated.

Results

The rheumatologist had a concordance rate of 94.4% over socks and 98.8% over stockings. The senior resident had a concordance rate of 95.6% over socks and 98.5% over stockings.

Conclusions

Foot examinations over socks and stockings had high concordance rates with the barefoot examination, and it may be an option for decreasing foot and ankle examination time in RA patients.
Protocol for mapping the variability in cell wall mechanical bending behavior in living leaf pavement cells
Authors: Li Wenlong , Keynia Sedighe , Belteton Samuel A , Afshar-Hatam Faezeh , Szymanski Daniel B , Turner Joseph A
Published: December 2021

Mechanical properties, size and geometry of cells, and internal turgor pressure greatly influence cell morphogenesis. Computational models of cell growth require values for wall elastic modulus and turgor pressure, but very few experiments have been designed to validate the results using measurements that deform the entire thickness of the cell wall. New wall material is synthesized at the inner surface of the cell such that full-thickness deformations are needed to quantify relevant changes associated with cell development. Here, we present an integrated, experimental–computational approach to analyze quantitatively the variation of elastic bending behavior in the primary cell wall of living Arabidopsis (Arabidopsis thaliana) pavement cells and to measure turgor pressure within cells under different osmotic conditions. This approach used laser scanning confocal microscopy to measure the 3D geometry of single pavement cells and indentation experiments to probe the local mechanical responses across the periclinal wall. The experimental results were matched iteratively using a finite element model of the experiment to determine the local mechanical properties and turgor pressure. The resulting modulus distribution along the periclinal wall was nonuniform across the leaf cells studied. These results were consistent with the characteristics of plant cell walls which have a heterogeneous organization. The results and model allowed the magnitude and orientation of cell wall stress to be predicted quantitatively. The methods also serve as a reference for future work to analyze the morphogenetic behaviors of plant cells in terms of the heterogeneity and anisotropy of cell walls.
Sleep talking versus sleep moaning: electrophysiological patterns preceding linguistic vocalizations during sleep
Authors: Mangiaruga Anastasia , D’Atri Aurora , Scarpelli Serena , Alfonsi Valentina , Camaioni Milena , Annarumma Ludovica , Gorgoni Maurizio , Pazzaglia Mariella , De Gennaro Luigi
Published: December 2021

Study Objectives

Sleep talking (ST) has been rarely studied as an isolated phenomenon. Late investigations over the psycholinguistic features of vocal production in ST pointed to coherence with wake language formal features. Therefore, we investigated the EEG correlates of Verbal ST as the overt manifestation of sleep-related language processing, with the hypothesis of shared electrophysiological correlates with wake language production.

Methods

From a sample of 155 Highly frequent STs, we recorded 13 participants (age range 19–30 years, mean age 24.6 ± 3.3; 7F) via vPSG for at least two consecutive nights, and a total of 28 nights. We first investigated the sleep macrostructure of STs compared to 13 age and gender-matched subjects. We then compared the EEG signal before 21 Verbal STs versus 21 Nonverbal STs (moaning, laughing, crying, etc.) in six STs reporting both vocalization types in Stage 2 NREM sleep.

Results

The 2 × 2 mixed analysis of variance Group × Night interaction showed no statistically significant effect for macrostructural variables, but significant main effects for Group with lower REM (%), total sleep time, total bedtime, sleep efficiency index, and greater NREM (%) for STs compared to controls. EEG statistical comparisons (paired-samples Student’s t-test) showed a decrement in power spectra for Verbal STs versus Nonverbal STs within the theta and alpha EEG bands, strongly lateralized to the left hemisphere and localized on centro-parietal-occipitals channels. A single left parietal channel (P7) held significance after Bonferroni correction.

Conclusions

Our results suggest shared neural mechanisms between Verbal ST and language processing during wakefulness and a possible functional overlapping with linguistic planning in wakefulness.
A Simple and Rather Tender Thing? Laurence Housman’s Victoria Regina in 1930s Britain and America
Authors: Chernock Arianne
Published: December 2021

From 1935 to 1939, audiences on both sides of the Atlantic thronged theatres to see Laurence Housman’s play Victoria Regina, a series of vignettes about the life of Queen Victoria. Those unable to purchase tickets were able to read about the show in magazines and newspapers, listen to a radio production, and purchase clothing and home furnishings that reflected the revival of interest in the Victorian era. Yet to the extent that scholars have discussed this incredibly popular play and the Victorian revival that it spawned, they tend to ascribe its success to a nostalgic impulse, or what Alison Light has described as the phenomenon of ‘conservative modernity’. This article reframes Victoria Regina, by treating it as a site of provocation and meaning-making in a charged transatlantic context. As I show, Housman (1865–1959)—a free speech advocate, Quaker pacifist, committed internationalist, anti-imperialist, feminist, and nascent gay rights activist—wanted to use Victoria to goad, intentionally so. His Victoria may have been romantic and feminine, but she was still intended as a vehicle of dissent. Housman wrote Victoria Regina primarily to protest censorship laws in Britain, but also to provide a more woman-centered version of the nation’s past, and to promote conciliation over the conflict between Germany and Britain. It was in its capacity as a cultural bridge between the UK and the USA, however, that Victoria Regina ended up making its most sizeable impact. This article thus offers an important meditation not only on the relationship between theatre and politics in the interwar period but also on the Victorian inheritance and its continuing and sometimes surprising applications in the twentieth century—especially in facilitating the Anglo-American ‘special relationship’.
Using marine cargo traffic to identify countries in Africa with greatest risk of invasion by Anopheles stephensi
Authors: Ahn Jordan , Sinka Marianne , Irish Seth , Zohdy Sarah
Published: December 2021

Anopheles stephensi is an efficient malaria vector commonly found in South Asia and the Arabian Peninsula, but in recent years it has established as an invasive species in the Horn of Africa (HoA). In this region, An. stephensi was first detected in a livestock quarantine station near a major seaport in Djibouti in 2012, in Ethiopia in 2016, in Sudan in 2018 and Somalia in 2019. Anopheles stephensi often uses artificial containers as larval habitats, which may facilitate introduction through maritime trade as has been seen with other invasive container breeding mosquitoes. If An. stephensi is being introduced through maritime traffic, prioritization exercises are needed to identify locations at greatest risk of An. stephensi introduction for early detection and rapid response, limiting further invasion opportunities. Here, we use UNCTAD maritime trade data to 1) identify coastal African countries which were most highly connected to select An. stephensi endemic countries in 2011, prior to initial detection in Africa, 2) develop a ranked prioritization list of countries based on likelihood of An. stephensi introduction for 2016 and 2020 based on maritime trade alone and maritime trade and habitat suitability, and 3) use network analysis to describe intracontinental maritime trade and eigenvector centrality to determine likely paths of further introduction on the continent if An. stephensi is detected in a new location. Our results show that in 2011, Sudan and Djibouti were ranked as the top two countries with likelihood of An. stephensi introduction based on maritime trade alone, and these were indeed the first two coastal countries in the HoA where An. stephensi was detected. Trade data from 2020 with Djibouti and Sudan included as source populations identify Egypt, Kenya, Mauritius, Tanzania, and Morocco as the top five countries with likelihood of An. stephensi introduction. When factoring in habitat suitability, Egypt, Kenya, Tanzania, Morocco, and Libya are ranked highest. Network analysis revealed that the countries with the highest eigenvector centrality scores, and therefore highest degrees of connectivity with other coastal African nations were South Africa (0.175), Mauritius (0.159), Ghana (0.159), Togo (0.157), and Morocco (0.044) and therefore detection of An. stephensi in any one of these locations has a higher potential to cascade further across the continent via maritime trade than those with lower eigenvector centrality scores. Taken together, these data could serve as tools to prioritize efforts for An. stephensi surveillance and control in Africa. Surveillance in seaports of countries at greatest risk of introduction may serve as an early warning system for the detection of An. stephensi, providing opportunities to limit further introduction and expansion of this invasive malaria vector in Africa.
Electrically Controlling and Optically Observing the Membrane Potential of Supported Lipid Bilayers
Authors: Yudovich Shimon , Marzouqe Adan , Kantorovitsch Joseph , Teblum Eti , Chen Tao , Enderlein Jörg , Miller Evan W. , Weiss Shimon
Published: December 2021

Supported lipid bilayers are a well-developed model system for the study of membranes and their associated proteins, such as membrane channels, enzymes, and receptors. These versatile model membranes can be made from various components, ranging from simple synthetic phospholipids to complex mixtures of constituents, mimicking the cell membrane with its relevant physiochemical and molecular phenomena. In addition, the high stability of supported lipid bilayers allows for their study via a wide array of experimental probes. In this work, we describe a platform for supported lipid bilayers that is accessible both electrically and optically. We show that the polarization of the supported membrane can be electrically controlled and optically probed using voltage-sensitive dyes. Membrane polarization dynamics is understood through electrochemical impedance spectroscopy and the analysis of the equivalent electrical circuit. We also describe the effect of the conducting electrode layer on the fluorescence of the optical probe through metal-induced energy transfer. We conclude with a discussion on possible applications of this platform for the study of voltage-dependent membrane proteins and other processes in membrane biology and surface science.
Cognitive experience alters cortical involvement in navigation decisions
Authors: Arlt Charlotte , Barroso-Luque Roberto , Kira Shinichiro , Bruno Carissa A. , Xia Ningjing , Chettih Selmaan N. , Soares Sofia , Pettit Noah L. , Harvey Christopher D.
Published: December 2021

The neural correlates of decision-making have been investigated extensively, and recent work aims to identify under what conditions cortex is actually necessary for making accurate decisions. We discovered that mice with distinct cognitive experiences, beyond sensory and motor learning, use different cortical areas and neural activity patterns to solve the same task, revealing past learning as a critical determinant of whether cortex is necessary for decision-making. We used optogenetics and calcium imaging to study the necessity and neural activity of multiple cortical areas in mice with different training histories. Posterior parietal cortex and retrosplenial cortex were mostly dispensable for accurate decision-making in mice performing a simple navigation-based decision task. In contrast, these areas were essential for the same simple task when mice were previously trained on complex tasks with delay periods or association switches. Multi-area calcium imaging showed that, in mice with complex-task experience, single-neuron activity had higher selectivity and neuron-neuron correlations were weaker, leading to codes with higher task information. Therefore, past experience sets the landscape for how future tasks are solved by the brain and is a key factor in determining whether cortical areas have a causal role in decision-making.