bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of retinal oxygen saturation during treatment of diabetic macular edema with a pre-defined regimen of aflibercept: a prospective study
Authors: Hasan Somar M. , Hammer Martin , Meller Daniel
Published: September 2021

Purpose

To study the effect of anti-VEGF therapy for diabetic macular edema (DME) on retinal oxygen saturation (O2S) and its correlation with functional and anatomical changes of retinal tissue.

Methods

An interventional prospective single group study. Included were 10 eyes of 10 patients with visually significant DME which received a fixed regimen of intravitreal aflibercept every 4 weeks for 5 months, followed by 3 injections every 8 weeks, and were controlled monthly. Visual acuity (VA), central retinal thickness (CRT), arterial (aO2S), venous (vO2S) and arterio-venous difference (AVdO2S) retinal oxygen saturation were noted monthly. Changes after 5th (V6) injection and on last follow-up (V12) were studied. Correlations of different parameters were analyzed.

Results

The aO2S did not change whereas vO2S decreased (62.2 ± 9.4 pre-op to 57.2 ± 10.5 on V6, p = 0.03). This remained unchanged at 59.4 ± 13.2 on V12 (p = 0.2) and was accompanied by an increase of AVdO2S (40.8 ± 8.3 pre-op to 44.8 ± 10.6, p = 0.03 on V6) which was followed by a non-significant decrease to 41.8 ± 11.3 on V12 (p = 0.06). We found no correlation between BCVA and aO2S. However, mild correlation between BCVA and both vO2S and AVdO2S (r = −0.2 p = 0.035 and r = 0.185 p = 0.05 respectively) was found. No correlation was found between CRT and aO2S, vO2S, or AVdO2S.

Conclusions

During DME treatment with fixed regimen of intravitreal aflibercept over 11 months, we observed a reduction of vO2S and increase of AVdO2S which correlated with BCVA but not CRT. This could be explained by increasing consumption of O2S in the central retina and, possibly, by re-perfusion process.
Evaluation of macular blood flow after intermittent intravenous infusion of high-dose corticosteroids (pulse therapy) in patients with thyroid-associated orbitopathy (TAO) using angio-OCT
Authors: Del Noce Chiara , Roda Matilde , Ferro Desideri Lorenzo , Traverso Carlo E. , Vagge Aldo
Published: September 2021

Purpose

The aim of this study is to evaluate the changes in macular blood flow index (BFI) in patients with moderate to severe thyroid-associated orbitopathy (TAO) before and after pulse therapy and their relationship with clinical features and disease activity using angio-OCT technology.

Methods

We analyzed twenty-four eyes. Every patient underwent a complete eye examination and angio-OCT analysis (OCT Topcon ImageNet 6; DRI OCT Triton, Topcon Corporation) before (T0) and two months (T2) after pulse therapy. We analyzed macular vascular blood flow in four angiographic levels: superficial plexus (SP), deep plexus (DP), external retina (ER), and choriocapillaris (CC). We used the clinical activity score (CAS) score to define TAO as moderate or severe.

Results

Macular BFI significantly increased at T2 in the DP, ER, and CC (p < 0.01). CAS score (5.8 ± 0.8 vs. 3.9 ± 0.9, p < 0.01) and Hertel exophthalmometry values (22.6 ± 2.3 mm vs. 21.2 ± 2,5 mm, p < 0.01) improved for all patients at T2 compared T0. Mean IOP increased from 13.3 ± 2.8 mmHg to 14.3 ± 2.1 mmHg (p < 0.01). No correlation was found between CAS score and macular BFI in all the analyzed levels.

Conclusions

Pulse therapy treatment can change macular BFI. In particular, two months alter pulse therapy, all the patients show an increase in macular vascular blood flow in each angiographic level. According to our results, angio-OCT analysis of the macular BFI may be a useful tool in the follow-up of TAO patients after pulse therapy.
Minimally invasive adrenalectomy for large pheochromocytoma: not recommendable yet? Results from a single institution case series
Authors: Arolfo Simone , Giraudo Giuseppe , Franco Caterina , Parasiliti Caprino Mirko , Seno Elisabetta , Morino Mario
Published: September 2021

Background

Minimally invasive adrenalectomy represents the treatment of choice of pheochromocytoma (PCC). For large or invasive PCCs, an open approach is currently recommended, in order to ensure complete tumor resection, prevent tumor rupture, avoid local recurrence, and limit perioperative hemodynamic instability. The aim of this study is to analyze perioperative outcomes of laparoscopic adrenalectomies (LAs) for large adrenal PCCs.

Methods

All consecutive LAs for PCC performed at a single institution between 1998 and 2020 were included. Two groups were defined: lesions larger (group 1) and smaller (group 2) than 5 cm. Short-term outcomes were compared in order to find any significant difference between the two groups.

Outcomes

One hundred fourteen patients underwent LA during the study period: 46 for lesions larger and 68 for lesions smaller than 5 cm. No significant differences were found in patients’ characteristics, median operative time, conversion rate, intraoperative hemodynamic and metabolic parameters, postoperative intensive care unit (ICU) admission rate, complications rate, and length of hospital stay. Long-term oncologic outcomes were similar, with a recurrence rate of 5.1% in group 1 vs 3.6% in group 2 (p = 1).

Conclusion

Minimally invasive adrenalectomy seems to be safe and effective even in large PCC. The recommendation to prefer an open approach for large PCCs should probably be reconsidered.
Effect of Personalized Messages Sent by a Health System’s Patient Portal on Influenza Vaccination Rates: a Randomized Clinical Trial
Authors: Szilagyi Peter G. , Albertin Christina S. , Casillas Alejandra , Valderrama Rebecca , Duru O. Kenrik , Ong Michael K , Vangala Sitaram , Tseng Chi-Hong , Humiston Sharon G. , Evans Sharon , Sloyan Michael , Bogard Jonathan E. , Fox Craig R. , Lerner Carlos
Published: September 2021

Background

Adult influenza vaccination rates are low. Tailored patient reminders might raise rates.

Objective

Evaluate impact of a health system’s patient portal reminders: (1) tailored to patient characteristics and (2) incorporating behavioral science strategies, on influenza vaccination rates among adults.

Design

Pragmatic 6-arm randomized trial across a health system during the 2019–2020 influenza vaccination season. The setting was one large health system—53 adult primary care practices.

Participants

All adult patients who used the patient portal within 12 months, stratified by the following: young adults (18–64 years, without diabetes), older adults (≥65 years, without diabetes), and those with diabetes (≥18 years).

Interventions

Patients were randomized within strata to either (1) pre-commitment reminder alone (1 message, mid-October), (2) pre-commitment + loss frame messages, (3) pre-commitment + gain frame messages, (4) loss frame messages alone, (5) gain frame messages alone, or (6) standard of care control. Patients in the pre-commitment group were sent a message in mid-October, asking if they planned on getting an influenza vaccination. Patients in loss or gain frame groups were sent up to 3 portal reminders (late October, November, and December, if no documented influenza vaccination in the EHR) about importance and safety of influenza vaccine.

Main Measures

Receipt of 1 influenza vaccine from 10/01/2019 to 03/31/2020.

Key Results

196,486 patients (145,166 young adults, 29,795 older adults, 21,525 adults with diabetes) were randomized. Influenza vaccination rates were as follows: for young adults 36.8%, for older adults 55.6%, and for diabetics 60.6%. On unadjusted and adjusted (for age, gender, insurance, race, ethnicity, and prior influenza vaccine history) analyses, influenza vaccination rates were not statistically different for any study group versus control.

Conclusions

Patient reminders sent by a health system’s patient portal that were tailored to patient demographics (young adults, older adults, diabetes) and that incorporated two behavioral economic messaging strategies (pre-commitment and loss/gain framing) were not effective in raising influenza vaccination rates.

Trial Registration

This trial was registered with ClinicalTrials.gov (NCT04110314).
Impact of olive mill wastewater (OMW) on the soil hydraulic and solute transport properties
Authors: Comegna A. , Dragonetti G. , Kodesova R. , Coppola A.
Published: September 2021

The Mediterranean area concentrates the world’s largest production area of olive oil. The olive oil industry represents, in this basin, one of the leading sectors of the agri-food economy. Olive mill water (OMW) is the principal waste effluent produced by the olive oil industry. Due to its high pollution load, this aqueous by-product cannot be directly disposed of in domestic wastewater treatment plants (especially those with a biological treatment unit). Untreated OMW is currently used for agronomic purposes in several countries, mainly because it is rich in valuable plant nutrients. However, OMW is characterized by toxic phenols, high organic matter, high salinity, suspended solids and several other components that may have possible negative effects on chemical and physical soil properties, as well as soil biological activities. In the present research, we focused on the effects of OMW application on transport and hydraulic soil properties. Three distinct soils from a pedological point of view were selected and a series of laboratory steady-state miscible flow tests were conducted under saturated conditions, on both OMW-treated and -untreated soil columns. Tests were conducted on disturbed and undisturbed soil columns. The approach proposed by Kachanoski, based on soil impedance (Z) measurements via the time domain reflectometry (TDR) technique, was used to monitor the leaching experiments. The breakthrough curves (BTCs) exhibited different shapes that allowed the repercussions of OMW applications on soil transport behaviour to be distinguished. Several additional tests conducted on OMW-treated and -untreated soil cores to determine water retention curves (SWRCs) and saturated hydraulic conductivity Ks allowed us to infer the probable mechanisms involved in soil hydrological behaviour changes under OMW treatments. The results show that when OMW leaches into the soil immediately after its disposal there is little effect on the evaluated hydraulic and hydrodispersive properties. By contrast, we demonstrated that a short incubation period (i.e. a short contact time between OMW and soil) of 10 days is enough to exert a great influence on all the values determined (e.g. soil pore velocity v and Ks reduced by up to one order of magnitude). These effects were especially evident in undisturbed soil samples.

Graphic Abstract
Rational design of the inlet configuration of flow systems for enhanced mixing
Authors: Gao Yunhu , Zhu Di Fu , Han Yuan , Torrente-Murciano Laura
Published: September 2021

High mass transfer rate is a key advantage of microreactors however, under their characteristic laminar flow, it is dominated by slow diffusion rather than fast convection. In this paper, we demonstrate how the configuration of the inlet, i.e. mixers, can promote different flow patterns to greatly enhance mixing efficiency downstream. A systematic evaluation and comparison of different widely adopted mixers as well as advanced designs is presented using a combination of computational fluid dynamics (CFD) and backward particle tracking to accurately calculate diffusion, in the absence of numerical diffusion (false diffusion). In the method, the convection contributed concentration profile is obtained by tracking sampling points from a cross-sectional plane to the inlet point, and diffusion is estimated subsequently. In conventional T- and Y-mixers, the shape of channel, circular or square, is key with only the latter promoting engulfment flow. In cyclone mixers, the resulting average inlet velocity, independent of Reynolds number or geometry, is the dominating design parameter to predict mixing efficiency. This work will serve as a guideline for the design of efficient flow systems with predicted mixing as a way of maximising selectivity and product quality.
Influence of dynamic properties on scaffoldings safety
Authors: Błazik-Borowa Ewa , Bęc Jarosław
Published: September 2021

Scaffoldings are used for works at height and in places that are hard to reach, which makes such works dangerous to employees and accidents occur frequently. Loads generated by scaffolding users cannot be avoided. Moving workers excite low-frequency (1–2 Hz) vibrations and scaffoldings as slender structures are prone to such dynamic action. The method for determining the probability of vibrations excitation is presented here. The quantity representing this probability is called the predictor of occurrence of a dangerous situation due to vibrations induced by a walking employee. The predictor of resonance with ith natural frequency requires an analysis of the scaffolding dynamic behavior. The frequencies and the natural mode shapes of vibrations were determined. Numerical dynamic simulations of the worker's movement on the penultimate decks of two scaffoldings were carried out, as well. Predictor analysis was made for single frequencies and combinations of frequency pairs. The predictor values calculated for the first frequency or combinations with it are the highest ones, however the probability of resonance is not only affected by the first frequency. To improve safety, the natural frequencies should be increased. For longitudinal vibrations, this can be done by adding more bracing or reducing lengths of anchors. Increasing the number of anchors gives good results in both directions. During scaffolding design of both typical and atypical constructions, one must determine the natural frequencies and then, if the first natural frequency is less than 4.0 Hz, perform a dynamic scaffolding analysis.
Racial Integration and the Problem of Relational Devaluation
Authors: Matthew D. C.
Published: September 2021

This article argues that blacks should reject integration on self-protective and solidarity grounds. It distinguishes two aspects of black devaluation: a ‘stigmatization’ aspect that has to do with the fact that blacks are subject to various forms of discrimination, and an aesthetic aspect (‘phenotypic devaluation’) that concerns the aesthetic devaluation of characteristically black phenotypic traits. It identifies four self-worth harms that integration may inflict, and suggests that these may outweigh the benefits of integration. Further, it argues that, while the integrating process may reduce stigmatization, there is less reason to think that it can do the same for phenotypic devaluation.
Local Legitimacy and Tax Policy: Qaids as Part of a Composite State in Colonial Tunisia
Authors: Perrier Antoine
Published: September 2021

The colonial history of Tunisia has long been dictated by colonial sources that made the qaid (an official in charge of fiscal attributions), from the viewpoint of the capital city, a local notable and often a prevaricator. This study proposes to reconsider the relationship between government and regional power in the colonial context by drawing on the recent work of Ottoman studies about provincial elites. The article studies the fiscal reforms of the interwar period in a cereal-growing region of Tunisia, relying on sources in Arabic produced by the qaids, namely the administrative correspondence between local authorities, the prime minister, and colonial controllers. This article describes the role of qaids in the negotiation between national law and local specificities and finally highlights the role of decentralization and a local way of thinking about the state in the 1930s. It contributes to colonial history and the history of taxation by highlighting the territorial fractures in North Africa and the agency of local actors under the protectorate.
Geographically Targeted Spending in Mixed-Member Majoritarian Electoral Systems
Authors: Catalinac Amy , Motolinia Lucia
Published: September 2021

Can governments elected under mixed-member majoritarian (mmm) electoral systems use geographically targeted spending to increase their chances of staying in office, and if so, how? Although twenty-eight countries usemmmelectoral systems, scant research has addressed this question. The authors explain howmmm’s combination of electoral systems in two unlinked tiers creates a distinct strategic environment in which a large party and a small party can trade votes in one tier for votes in the other tier in a way that increases the number of seats won by both. They then explain how governing parties dependent on vote trading can use geographically targeted spending to cement it. These propositions are tested using original data from Japan (2003–2013) and Mexico (2012–2016). In both cases, municipalities in which the supporters of governing parties split their ballots as instructed were found to have received more money after elections. The findings have broad implications for research onmmmelectoral systems, distributive politics, and the politics of Japan and Mexico.
L’oralité mise en scène dans la bande dessinée: marques phonologiques et morphosyntaxiques dans Astérix et Titeuf
Authors: Grutschus Anke , Kern Beate
Published: September 2021

La mise en scène du langage parlé est un élément central de la bande dessinée: les discours directs des protagonistes sont non seulement visuellement représentés par des bulles, mais leur langage se caractérise souvent aussi par les marques phonologiques et morpho-syntaxiques typiques de l’oral afin d’évoquer l’immédiat communicatif. Cet article se propose ainsi d’étudier, sur le plan phonologique, des phénomènes tels que les élisions, les aphérèses et même certaines marques prosodiques ainsi que, sur le plan morphosyntaxique, entre autres l’omission du ne de négation, les dislocations et l’absence du il impersonnel. On s’interrogera notamment sur les convergences entre l’oralité fictive des bandes dessinées et les résultats des études de l’oralité basées sur des corpus authentiques. L’analyse s’appuie sur un corpus de deux bandes dessinées francophones, comprenant un tome respectivement des séries Astérix et Titeuf. L’étude est basée sur une grille inspirée, entre autres, par la catégorisation des phénomènes de l’immédiat communicatif par Koch et Oesterreicher (2011) et complétée de manière inductive (corpus-driven). L’article montre que les deux sous-corpus révèlent des stratégies d’oralisation divergentes: alors que dans Astérix, on trouve un grand nombre de phénomènes phonologiques suprasegmentaux représentés, notamment au niveau de la typographie, Titeuf privilégie l’utilisation de marques morphosyntaxiques ainsi que de certains phénomènes phonologiques segmentaux.
Lake Erie Sediments: All Dredged Up with Nowhere to Grow
Authors: Besl J.
Published: September 2021

Agriculture is a key contributor to the algae mats that plague Lake Erie. With so many fertilizers entering the lake, could sediment from the lake floor be used to grow crops instead?
Energetic Charged Particles in the Terrestrial Magnetosphere: Cluster/RAPID Results
Authors: Kronberg E. A. , Daly P. W. , Grigorenko E. E. , Smirnov A. G. , Klecker B. , Malykhin A. Yu.
Published: September 2021

In this work, we review the results of observations by the Cluster/Research with Adaptive Particle Imaging Detectors (RAPID) energetic charged particle detector (40 keV–1 MeV). The origin of energetic ions in the region upstream of the Earth's bow shock is compared under different solar wind conditions. We give a brief overview of the acceleration mechanisms of charged particles in the plasma sheet. Effective acceleration is associated with (multiple) interaction(s) of charged particles with multiscale magnetic structures and/or electromagnetic fluctuations, which are the consequences of reconnection or other plasma instabilities. The necessity of such acceleration mechanisms to reproduce the distributions of energetic particles on closed magnetic field lines is discussed. We review empirical models describing the distributions of charged particles. Several aspects of the dynamics of energetic particles during substorms and their influence on the dynamics of magnetic storms are shown. We advise to consider including the energetic particles at 40 keV in calculations of the plasma temperature and pressure during these dynamic processes.
Influence of Aperiodic Non‐Tidal Atmospheric and Oceanic Loading Deformations on the Stochastic Properties of Global GNSS Vertical Land Motion Time Series
Authors: Gobron Kevin , Rebischung Paul , Van Camp Michel , Demoulin Alain , de Viron Olivier
Published: September 2021

Monitoring vertical land motions (VLMs) at the level of 0.1 mm/yr remains one of the most challenging scientific applications of global navigation satellite systems (GNSS). Such small rates of change can result from climatic and tectonic phenomena, and their detection is important to many solid Earth‐related studies, including the prediction of coastal sea‐level change and the understanding of intraplate deformation. Reaching a level of precision allowing to detect such small signals requires a thorough understanding of the stochastic variability in GNSS VLM time series. This paper investigates how the aperiodic part of non‐tidal atmospheric and oceanic loading (NTAOL) deformations influences the stochastic properties of VLM time series. Using the time series of over 10,000 stations, we describe the impact of correcting for NTAOL deformation on 5 complementary metrics, namely: the repeatability of position residuals, the power‐spectrum of position residuals, the estimated time‐correlation properties, the corresponding velocity uncertainties, and the spatial correlation of the residuals. We show that NTAOL deformations cause a latitude‐dependent bias in white noise plus power‐law model parameter estimates. This bias is significantly mitigated when correcting for NTAOL deformation, which reduces velocity uncertainties at high latitudes by 70%. Therefore, removing NTAOL deformation before the statistical analysis of VLM time series might help to detect subtle VLM signals in these areas. Our spatial correlation analysis also reveals a seasonality in the spatial correlation of the residuals, which is reduced after removing NTAOL deformation, confirming that NTAOL is a clear source of common‐mode errors in GNSS VLM time series.
Sensitivity of Middle Atmospheric Ozone to Solar Proton Events: A Comparison Between a Climate Model and Satellites
Authors: Nilsen K. , Kero A. , Verronen P. T. , Szeląg M. E. , Kalakoski N. , Jia J.
Published: September 2021

Energetic particle precipitation (EPP) impact on the middle atmospheric ozone chemistry potentially plays an important role in the connection between space weather and Earth's climate system. A variant of the Whole Atmosphere Community Climate Model (WACCM‐D) implements a detailed set of ionospheric D‐region chemistry instead of a simple parameterization used in the earlier WACCM versions. This allows WACCM‐D to capture the impact of EPP in more detail. Here, we validate the ion chemistry of the WACCM‐D by analyzing the middle atmospheric ozone response to the EPP forcing during well‐known solar proton events (SPEs). We use a multi‐satellite approach to derive the middle atmospheric sensitivity for the SPE forcing as a statistical relation between the solar proton flux and the consequent ozone change. An identical sensitivity analysis is carried out for the WACCM‐D model results, enabling one‐to‐one comparison with the results derived from the satellite observations. Our results show a good agreement in the sensitivity between satellites and the WACCM‐D for nighttime conditions. For daytime conditions, we find a good agreement for the satellite data sets that include the largest SPEs (maximum proton flux pfu). However, for those satellite data‐sets with only minor and moderate SPEs, WACCM‐D tends to underestimate the sensitivity in daytime conditions. In summary, the WACCM‐D with its full ion chemistry and transportation demonstrates a realistic representation of the SPE sensitivity of ozone, and thus provides a conservative platform for long‐term EPP impact studies.
Formation of a Mesospheric Inversion Layer and the Subsequent Elevated Stratopause Associated With the Major Stratospheric Sudden Warming in 2018/19
Authors: Okui Haruka , Sato Kaoru , Koshin Dai , Watanabe Shingo
Published: August 2021

Since 2004, following prolonged stratospheric sudden warming (SSW) events, it has been observed that the stratopause disappeared and reformed at a higher altitude, forming an elevated stratopause (ES). The relative roles of atmospheric waves in the mechanism of ES formation are still not fully understood. We performed a hindcast of the 2018/19 SSW event using a gravity‐wave (GW) permitting general circulation model that resolves the mesosphere and lower thermosphere (MLT) and analyzed dynamical phenomena throughout the entire middle atmosphere. An ES formed after the major warming on January 1, 2019. There was a marked temperature maximum in the polar upper mesosphere around December 28, 2018 prior to the disappearance of the descending stratopause associated with the SSW. This temperature structure is referred to as a mesospheric inversion layer (MIL). We show that adiabatic heating from the residual circulation driven by GW forcing (GWF) causes barotropic and/or baroclinic instability before the MIL formation, causing in situ generation of planetary waves (PWs). These PWs propagate into the MLT and exert negative (westward) forcing, which contributes to the MIL formation. Both GWF and PW forcing (PWF) above the recovered eastward jet play crucial roles in ES formation. The altitude of the recovered eastward jet, which regulates GWF and PWF height, is likely affected by the MIL structure. Simple vertical propagation from the lower atmosphere is insufficient to explain the presence of the GWs observed in this event.
Appreciation of Peer Reviewers for 2020
Authors: Zhang Minghua , Fu Rong , Giorgi Filippo , Leung Ruby , Mellouki AbdelWahid , Randel William , Rogers Robert , Russell Lynn , Yang Ping , Zhang Chidong
Published: September 2021

Key Point

Appreciation of peer reviewers for 2020
Ozone and Nitrogen Dioxide Pollution in a Coastal Urban Environment: The Role of Sea Breezes, and Implications of Their Representation for Remote Sensing of Local Air Quality
Authors: Geddes Jeffrey A. , Wang Bo , Li Dan
Published: September 2021

We present an analysis of sea breeze conditions for the Boston region and examine their impact on the concentration of local air pollutants over the past decade. Sea breezes occur about one‐third of the days during the summer and play an important role in the spatial distribution and temporal evolution of NO2 and O3 across the urban area. Mornings preceding a sea breeze are characterized by low horizontal wind speeds, low background O3, and an accumulation of local primary emissions. Air pollution is recirculated inland during sea breezes, frequently coinciding with the highest O3 measured at the urban center. We use “Ox” (= NO2 + O3) to account for temporary O3 suppression by NO and find large horizontal gradients (differences in Ox greater than 30 ppb across less than 15 km), which are not observed on otherwise westerly or easterly prevailing days. This implies a challenge in surface monitoring networks to adequately represent the spatial variability of secondary air pollution in coastal urban areas. We investigate satellite‐based climatologies of tropospheric NO2, and find evidence of selection biases due to cloud conditions, but show that sea breeze days are well observed due to the fair weather conditions generally associated with these events. The fine scale of the sea breeze in Boston is not reliably represented by meteorological reanalyses products commonly used in chemical transport models required to provide inputs for the satellite‐based retrievals. This implies a higher systematic error in the operational retrievals on sea breeze days compared to other days.
Biobehavioral correlates of an fMRI index of striatal tissue iron in depressed patients
Authors: Price Rebecca B. , Tervo-Clemmens Brenden C. , Panny Benjamin , Degutis Michelle , Griffo Angela , Woody Mary
Published: September 2021

Dopaminergic function is a critical transdiagnostic neurophysiological dimension with broad relevance in psychiatry. Normalized T2*-weighted (nT2*w) imaging has been previously investigated as a method to quantify biological properties of tissue in the striatum (e.g., tissue iron), providing a widely available, in vivo marker with potential relevance to dopaminergic function; but no prior study to our knowledge has examined this neuroimaging marker in clinical depression. In a treatment-seeking, clinically depressed sample (n = 110), we quantified tissue iron (nT2*w) in striatal regions. We assessed test-retest reliability and correlated values with dimensional features across levels of analysis, including demographic/biological (sex, age, Body Mass Index), neuroanatomical (hippocampal atrophy, which was quantified using a recently validated machine-learning algorithm), and performance-based (Affective Go/NoGo task performance) indices with relevance to depressive neurocognition. Across patients, decreased tissue iron concentration (as indexed by higher nT2*w) in striatal regions correlated with indices of decreased cognitive-affective function on the Affective Go/NoGo task. Greater caudate nT2*w also correlated with greater hippocampal atrophy. Striatal tissue iron concentrations were robustly lower in female patients than males but gender differences did not explain relations with other neurocognitive variables. A widely available fMRI index of striatal tissue properties, which exhibited strong psychometric properties and can be readily quantified from most fMRI datasets irrespective of study-specific features such as task design, showed relevance to multiple biobehavioral markers of pathophysiology in the context of moderate-to-severe, treatment-resistant depression. Striatal tissue iron may play a role in dimensional and subgroup-specific features of depression, with implications for future research on depression heterogeneity.
Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection
Authors: Smith Nikaïa , Goncalves Pedro , Charbit Bruno , Grzelak Ludivine , Beretta Maxime , Planchais Cyril , Bruel Timothée , Rouilly Vincent , Bondet Vincent , Hadjadj Jérôme , Yatim Nader , Pere Helene , Merkling Sarah H. , Ghozlane Amine , Kernéis Solen , Rieux-Laucat Frederic , Terrier Benjamin , Schwartz Olivier , Mouquet Hugo , Duffy Darragh , Di Santo James P.
Published: September 2021

Coordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.
Deep learning for distinguishing normal versus abnormal chest radiographs and generalization to two unseen diseases tuberculosis and COVID-19
Authors: Nabulsi Zaid , Sellergren Andrew , Jamshy Shahar , Lau Charles , Santos Edward , Kiraly Atilla P. , Ye Wenxing , Yang Jie , Pilgrim Rory , Kazemzadeh Sahar , Yu Jin , Kalidindi Sreenivasa Raju , Etemadi Mozziyar , Garcia-Vicente Florencia , Melnick David , Corrado Greg S. , Peng Lily , Eswaran Krish , Tse Daniel , Beladia Neeral , Liu Yun , Chen Po-Hsuan Cameron , Shetty Shravya
Published: September 2021

Chest radiography (CXR) is the most widely-used thoracic clinical imaging modality and is crucial for guiding the management of cardiothoracic conditions. The detection of specific CXR findings has been the main focus of several artificial intelligence (AI) systems. However, the wide range of possible CXR abnormalities makes it impractical to detect every possible condition by building multiple separate systems, each of which detects one or more pre-specified conditions. In this work, we developed and evaluated an AI system to classify CXRs as normal or abnormal. For training and tuning the system, we used a de-identified dataset of 248,445 patients from a multi-city hospital network in India. To assess generalizability, we evaluated our system using 6 international datasets from India, China, and the United States. Of these datasets, 4 focused on diseases that the AI was not trained to detect: 2 datasets with tuberculosis and 2 datasets with coronavirus disease 2019. Our results suggest that the AI system trained using a large dataset containing a diverse array of CXR abnormalities generalizes to new patient populations and unseen diseases. In a simulated workflow where the AI system prioritized abnormal cases, the turnaround time for abnormal cases reduced by 7–28%. These results represent an important step towards evaluating whether AI can be safely used to flag cases in a general setting where previously unseen abnormalities exist. Lastly, to facilitate the continued development of AI models for CXR, we release our collected labels for the publicly available dataset.
A fructosylated peptide derived from a collagen II T cell epitope for long-term treatment of arthritis (FIA-CIA) in mice
Authors: Wenhart Clara , Holthoff Hans-Peter , Reimann Andreas , Li Zhongmin , Faßbender Julia , Ungerer Martin
Published: August 2021

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease which affects primarily the joints. Peptides of several proteins have shown an effect in some experimental animal models of RA. We investigated arthritis development in male DBA/1 mice which were injected with bovine collagen II (bCII) and human fibrinogen (hFib) on days 0 and 21, leading to stable and reproducible disease induction in 100% of immunized mice (FIA-CIA). In a second study, two bCII—derived peptides were given three times in the course of 6 weeks after FIA-CIA induction to test for impact on arthritis. Mice were scored weekly for arthritis and anti-citrullinated peptide antibodies (ACPAs) were determined in the sera taken on days 0, 14, 35, 56 and 84. Histology of the hind paws was performed at the end of the experiment. Intravenous administration of peptide 90578, a novel fructosylated peptide derived from the immunodominant T cell epitope of bCII, at a dosage of 1 mg/kg resulted in significant beneficial effects on clinical outcome parameters and on the arthritis histology scores which was sustained over 12 weeks. Survival tended to be improved in peptide 90578-treated mice. Intravenous administration of pure soluble peptide 90578 without adjuvants is a promising approach to treat RA, with treatment starting at a time when ACPAs are already present. The results complement existing data on peptide “vaccination” of healthy animals, or on treatment using recombinant peptide expressing virus or complex biological compounds.
Functional data analysis characterizes the shapes of the first COVID-19 epidemic wave in Italy
Authors: Boschi Tobia , Di Iorio Jacopo , Testa Lorenzo , Cremona Marzia A. , Chiaromonte Francesca
Published: August 2021

We investigate patterns of COVID-19 mortality across 20 Italian regions and their association with mobility, positivity, and socio-demographic, infrastructural and environmental covariates. Notwithstanding limitations in accuracy and resolution of the data available from public sources, we pinpoint significant trends exploiting information in curves and shapes with Functional Data Analysis techniques. These depict two starkly different epidemics; an “exponential” one unfolding in Lombardia and the worst hit areas of the north, and a milder, “flat(tened)” one in the rest of the country—including Veneto, where cases appeared concurrently with Lombardia but aggressive testing was implemented early on. We find that mobility and positivity can predict COVID-19 mortality, also when controlling for relevant covariates. Among the latter, primary care appears to mitigate mortality, and contacts in hospitals, schools and workplaces to aggravate it. The techniques we describe could capture additional and potentially sharper signals if applied to richer data.
Soluble urokinase plasminogen activator receptor (suPAR) predicts critical illness and kidney failure in patients admitted to the intensive care unit
Authors: Reisinger Alexander C. , Niedrist Tobias , Posch Florian , Hatzl Stefan , Hackl Gerald , Prattes Juergen , Schilcher Gernot , Meißl Anna-Maria , Raggam Reinhard B. , Herrmann Markus , Eller Philipp
Published: September 2021

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker and risk factor for kidney diseases, with a potential prognostic value in critically ill patients. In this monocentric prospective study, we measured plasma suPAR levels immediately after ICU admission in unselected 237 consecutive patients using a turbidimetric assay. Primary objective was the prognostic value for ICU- and 28-day mortality. Secondary objectives were association with sequential organ failure assessment (SOFA) score, coagulation and inflammation markers, AKI-3 and differences in prespecified subgroups. Median suPAR levels were 8.0 ng/mL [25th-75th percentile 4.3–14.4], with lower levels in ICU survivors than non-survivors (6.7 vs. 11.6 ng/mL, p < 0.001). SuPAR levels were higher in COVID-19, kidney disease, moderate-to-severe liver disease, and sepsis. ICU mortality increased by an odds ratio (OR) of 4.7 in patients with the highest compared to lowest quartile suPAR. Kaplan–Meier overall survival estimates at 3 months were 63% and 49%, in patients with suPAR below/above 12 ng/mL (log-rank p = 0.027). Due to an observed interaction between SOFA score and suPAR, we performed a random forest method identifying cutoffs. ICU mortality was 53%, 17% and 2% in patients with a SOFA score > 7, SOFA ≤ 7 & suPAR > 8 ng/mL, and SOFA score ≤ 7 & suPAR ≤ 8 ng/mL, respectively. suPAR was a significant predictor for AKI-3 occurrence (OR per doubling 1.89, 95% CI: 1.20–2.98; p = 0.006). suPAR levels at ICU admission may offer additional value for risk stratification especially in ICU patients with moderate organ dysfunction as reflected by a SOFA score ≤ 7.
Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy
Authors: Kovács Zsuzsanna Z. A. , Szűcs Gergő , Freiwan Marah , Kovács Mónika G. , Márványkövi Fanni M. , Dinh Hoa , Siska Andrea , Farkas Katalin , Kovács Ferenc , Kriston András , Horváth Péter , Kővári Bence , Cserni Bálint Gábor , Cserni Gábor , Földesi Imre , Csont Tamás , Sárközy Márta
Published: September 2021

Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects. We aimed to compare the antiremodeling effects of the angiotensin-II receptor blocker losartan and the β3-AR agonist mirabegron in uremic cardiomyopathy. Chronic kidney disease (CKD) was induced by 5/6th nephrectomy in male Wistar rats. Five weeks later, rats were randomized into four groups: (1) sham-operated, (2) CKD, (3) losartan-treated (10 mg/kg/day) CKD, and (4) mirabegron-treated (10 mg/kg/day) CKD groups. At week 13, echocardiographic, histologic, laboratory, qRT-PCR, and Western blot measurements proved the development of uremic cardiomyopathy with DD, LVH, fibrosis, inflammation, and reduced eNOS levels, which were significantly ameliorated by losartan. However, mirabegron showed a tendency to decrease DD and fibrosis; but eNOS expression remained reduced. In uremic cardiomyopathy, β3-AR, sarcoplasmic reticulum ATPase (SERCA), and phospholamban levels did not change irrespective of treatments. Mirabegron reduced the angiotensin-II receptor 1 expression in uremic cardiomyopathy that might explain its mild antiremodeling effects despite the unchanged expression of the β3-AR.
Characterizing the dielectric properties of carbon fiber at different processing stages
Authors: Chao Hsien-Wen , Hsu Hung-Chun , Chen Yen-Ren , Chang Tsun-Hsu
Published: September 2021

The polyacrylonitrile (PAN) fibers go through a series of chemical reactions in various processing temperatures/stages and finally turn into the so-called carbon fibers. Oxidization is the first stage, and it takes the largest proportion of the entire processing time for the tremendous change from a chain texture to a ladder texture. The pre-carbonization of carbon fibers is then achieved using a furnace with a higher processing temperature (typically at 700–900 °C). During the reaction processes, the color of the fibers changes from white (PAN) to light black (oxidation), and eventually to black (pre-carbonization). Characterizing the complex permittivity helps us determine the carbonization status of the fibers. This work employed the enhanced-field method (EFM) and the contour mapping method to determine the fibers’ dielectric properties for the first time. Results show that both the real and imaginary parts of permittivity increase as the processing temperature rises. The dielectric constants change from 2.82 (PAN) to 6.50 (pre-carbonization), and the loss tangents increase from 0.007 (lossless) to 0.089 (lossy). This study provides a simple and effective method for characterizing carbon fibers’ processing status and can be applied to the measurement of other fibrous materials.
Comparative analysis of therapeutic effects between medium cut-off and high flux dialyzers using metabolomics and proteomics: exploratory, prospective study in hemodialysis
Authors: Kim Hyo Jin , Seong Eun Young , Lee Wonho , Kim Suhkmann , Ahn Hee-Sung , Yeom Jeonghun , Kim Kyunggon , Kwon Chae Hwa , Song Sang Heon
Published: August 2021

In this single-center prospective study of 20 patients receiving maintenance hemodialysis (HD), we compared the therapeutic effects of medium cut-off (MCO) and high flux (HF) dialyzers using metabolomics and proteomics. A consecutive dialyzer membrane was used for 15-week study periods: 1st HF dialyzer, MCO dialyzer, 2nd HF dialyzer, for 5 weeks respectively. 1H-nuclear magnetic resonance was used to identify the metabolites and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was used to identify proteins. To compare the effects of the HF and MCO dialyzers, orthogonal projection to latent structure discriminant analysis (OPLS-DA) was performed. OPLS-DA showed that metabolite characteristics could be significantly classified by 1st HF and MCO dialyzers. The Pre-HD metabolites with variable importance in projection scores ≥ 1.0 in both 1st HF versus MCO and MCO versus 2nd HF were succinate, glutamate, and histidine. The pre-HD levels of succinate and histidine were significantly lower, while those of glutamate were significantly higher in MCO period than in the HF period. OPLS-DA of the proteome also substantially separated 1st HF and MCO periods. Plasma pre-HD levels of fibronectin 1 were significantly higher, and those of complement component 4B and retinol-binding protein 4 were significantly lower in MCO than in the 1st HF period. Interestingly, as per Ingenuity Pathway Analysis, an increase in epithelial cell proliferation and a decrease in endothelial cell apoptosis occurred during the MCO period. Overall, our results suggest that the use of MCO dialyzers results in characteristic metabolomics and proteomics profiles during HD compared with HF dialyzers, which might be related to oxidative stress, insulin resistance, complement-coagulation axis, inflammation, and nutrition.
A learning-based tip contact force estimation method for tendon-driven continuum manipulator
Authors: Feng Fan , Hong Wuzhou , Xie Le
Published: September 2021

Although tendon-driven continuum manipulators have been extensively researched, how to realize tip contact force sensing in a more general and efficient way without increasing the diameter is still a challenge. Rather than use a complex modeling approach, this paper proposes a general tip contact force-sensing method based on a recurrent neural network that takes the tendons’ position and tension as the input of a recurrent neural network and the tip contact force of the continuum manipulator as the output and fits this static model by means of machine learning so that it may be used as a real-time contact force estimator. We also designed and built a corresponding three-degree-of-freedom contact force data acquisition platform based on the structure of a continuum manipulator designed in our previous studies. After obtaining training data, we built and compared the performances of a multi-layer perceptron-based contact force estimator as a baseline and three typical recurrent neural network-based contact force estimators through TensorFlow framework to verify the feasibility of this method. We also proposed a manually decoupled sub-estimators algorithm and evaluated the advantages and disadvantages of those two methods.
A novel specimen shape for measurement of linear strain fields by means of digital image correlation
Authors: Amraish Nedaa , Reisinger Andreas , Pahr Dieter
Published: September 2021

Strains on the surface of engineering structures or biological tissues are non-homogeneous. These strain fields can be captured by means of Digital Image Correlation (DIC). However, DIC strain field measurements are prone to noise and filtering of these fields influences measured strain gradients. This study aims to design a novel tensile test specimen showing two linear gradients, to measure full-field linear strain measurements on the surface of test specimens, and to investigate the accuracy of DIC strain measurements globally (full-field) and locally (strain gauges’ positions), with and without filtering of the DIC strain fields. Three materials were employed for this study: aluminium, polymer, and bovine bone. Normalized strain gradients were introduced that are load independent and evaluated at two local positions showing 3.6 and 6.9% strain change per mm. Such levels are typically found in human bones. At these two positions, two strain gauges were applied to check the experimental strain magnitudes. A third strain gauge was applied to measure the strain in a neutral position showing no gradient. The accuracy of the DIC field measurement was evaluated at two deformation stages (at $$\approx $$
≈
500 and 1750 μstrain) using the root mean square error (RMSE). The RMSE over the two linear strain fields was less than 500 μstrain for both deformation stages and all materials. Gaussian low-pass filter (LPF) reduced the DIC noise between 25% and 64% on average. As well, filtering improved the accuracy of the local normalized strain gradients measurements with relative difference less than 20% and 12% for the high- and low-gradient, respectively. In summary, a novel specimen shape and methodological approach are presented which are useful for evaluating and improving the accuracy of the DIC measurement where non-homogeneous strain fields are expected such as on bone tissue due to their hierarchical structure.