bluuebunny/crossref_metadata_2025 huggingface dataset:
The CARMENES search for exoplanets around M dwarfs
Authors: Shan Y. , Reiners A. , Fabbian D. , Marfil E. , Montes D. , Tabernero H. M. , Ribas I. , Caballero J. A. , Quirrenbach A. , Amado P. J. , Aceituno J. , Béjar V. J. S. , Cortés-Contreras M. , Dreizler S. , Hatzes A. P. , Henning Th. , Jeffers S. V. , Kaminski A. , Kürster M. , Lafarga M. , Morales J. C. , Nagel E. , Pallé E. , Passegger V. M. , Rodriguez-López C. , Schweitzer A. , Zechmeister M.
Published: August 2021

Context. M-dwarf spectra are complex and notoriously difficult to model, posing challenges to understanding their photospheric properties and compositions in depth. Vanadium (V) is an iron-group element whose abundance supposedly closely tracks that of iron, but has origins that are not completely understood.

Aims. Our aim is to characterize a series of neutral vanadium atomic absorption lines in the 800–910 nm wavelength region of high signal-to-noise, high-resolution, telluric-corrected M-dwarf spectra from the CARMENES survey. Many of these lines are prominent and exhibit a distinctive broad and flat-bottom shape, which is a result of hyperfine structure (HFS). We investigate the potential and implications of these HFS split lines for abundance analysis of cool stars.

Methods. With standard spectral synthesis routines, as provided by the spectroscopy software iSpec and the latest atomic data (including HFS) available from the VALD3 database, we modeled these striking line profiles. We used them to measure V abundances of cool dwarfs.

Results. We determined V abundances for 135 early M dwarfs (M0.0 V to M3.5 V) in the CARMENES guaranteed time observations sample. They exhibit a [V/Fe]–[Fe/H] trend consistent with that derived from nearby FG dwarfs. The tight (±0.1 dex) correlation between [V/H] and [Fe/H] suggests the potential application of V as an alternative metallicity indicator in M dwarfs. We also show hints that neglecting to model HFS could partially explain the temperature correlation in V abundance measurements observed in previous studies of samples involving dwarf stars with Teff ≲ 5300 K.

Conclusions. Our work suggests that HFS can impact certain absorption lines in cool photospheres more severely than in Sun-like ones. Therefore, we advocate that HFS should be carefully treated in abundance studies in stars cooler than ~5000 K. On the other hand, strong HFS split lines in high-resolution spectra present an opportunity for precision chemical analyses of large samples of cool stars. The V-to-Fe trends exhibited by the local M dwarfs continue to challenge theoretical models of V production in the Galaxy.
Highly performant CH3NH3PbI3 used in flexible micro and nanowires
Authors: Avachat Sayali S.
Published: August 2021

Great suppleness originates from the highly crystalline form of nanowires.
Resource nationalism and community engagement in extractive resource governance: insights from Tanzania
Authors: Poncian Japhace
Published: August 2021

Resource nationalism has dominated resource governance politics across Africa. Resource-rich states have sought to both relegitimise extraction and secure more economic benefits. However, there is a paucity of studies on the consequences of resource nationalism for community participation in resource-governance and decision-making processes. Drawing on three cases of community resistance and negotiation in three different eras, this paper compares two waves of resource nationalism, i.e. the second and third waves, to show whether and how resource nationalism promotes community participation. While presenting itself as pro-participatory governance, resource nationalism reproduces structural constraints on meaningful community engagement in extractive resource governance.
Compositionally graded AlGaN hole source layer for deep-ultraviolet nanowire light-emitting diode without electron blocking layer
Authors: Sharif Muhammad Nawaz , Usman Muhammad , Niass Mussaab Ibrahim , Liou Juin J , Wang Fang , Liu Yuhuai
Published: August 2021

The electron blocking layer (EBL) plays a vital role in blocking the electron overflow from an active region in the AlGaN-based deep-ultraviolet light-emitting diode (DUV-LED). Besides the blocking of electron overflow, EBL reduces hole injection toward the active region. In this work, we proposed a DUV nanowire (NW) LED structure without EBL by replacing it with a compositionally continuous graded hole source layer (HSL). Our proposed graded HSL without EBL provides a better electron blocking effect and enhanced hole injection efficiency. As a result, optical power is improved by 48% and series resistance is reduced by 50% with 4.8 V threshold voltage. Moreover, graded HSL without EBL offer reduced electric field within the active region, which leads to a significant increment in radiative recombination rate and enhancement of spontaneous emission by 34% at 254 nm wavelength, as a result, 52% maximum internal quantum efficiency with 24% efficiency drop is reported.
Validating frequency transfer via interferometric fiber links for optical clock comparisons
Authors: Koke Sebastian , Benkler Erik , Kuhl Alexander , Grosche Gesine
Published: August 2021

We investigate the validation of fiber-based optical frequency transfer for frequency comparison applications. We specifically consider the frequency transfer validation for remote optical clock comparisons and want to ensure interferometric fiber link uncertainty contributions below the combined uncertainty of the clocks under test. The validation is based on signals obtained via looping back from the remote end to the sender site and comparing the input with the output of the loop. These loop-back data need to be averaged over intervals for reaching the validation goal, as the short-term instability of long-distance interferometric fiber links is typically higher than that of optical clocks. We introduce a two-step validation approach and address the finding of a compromise between opposing aspects of averaging: reaching low uncertainties versus achieving a high data coverage of the validated data set via a high temporal resolution of the fault identification. We discuss the impact of different averaging types and of the tolerance of filtering criteria on the achievable estimated uncertainty and on the coverage of the validated data set. Data from four multiple-week-long measurement campaigns on the fiber link between Physikalisch-Technische Bundesansanstalt and University of Strasbourg are used for this assessment.
Erosion and redeposition patterns on entire erosion marker tiles after exposure in the first operation phase of WEST
Authors: Balden M , Mayer M , Bliewert B , Bernard E , Diez M , Firdaouss M , Missirlian M , Pégourié B , Richou M , Roche H , Tsitrone E , Martin C , Hakola A
Published: August 2021

The net erosion and deposition patterns in the inner and outer divertor of WEST were determined after different experimental campaigns (C3 and C4) of the first operational phase using ion beam analyses and scanning electron microscopy techniques. The analyses were performed on four entire tiles from inertially cooled, W-coated divertor units with an additional Mo marker coating covered with a further W coating. Strong erosion occurred at the expected location of the inner and outer strike line area with a campaign-averaged net erosion rate of >0.1 nm s−1. On the high field side of the inner strike line area, thick deposited layers were found (>10 μm; growth rate >1 nm s−1), mainly composed of B, C, O, and W. Additionally, strong arcing was observed in this region. At the end of the C4 campaign, He discharges were performed to study the He-W interaction. Although the conditions for nanotendrils, i.e. fuzz formation were fulfilled around the outer strike line position, neither nanotendrils nor He bubbles (>10 nm) were observed at this area.
Development of muon scattering tomography for a detection of reinforcement in concrete
Authors: Dobrowolska Magdalena , Velthuis Jaap , Kopp Anna , De Sio Chiara , Milne Ruaridh , Pearson Philip
Published: August 2021

Inspection of ageing, reinforced concrete structures is a world-wide challenge. Existing non-destructive evaluation techniques in civil and structural engineering have limited penetration depth and don’t allow to precisely ascertain the configuration of reinforcement within large concrete objects. The big challenge for critical infrastructure (bridges, dams, dry docks, nuclear bioshields etc.) is understanding the internal condition of the concrete and steel, not just the location of the reinforcement. In most new constructions the location should be known and recorded in the as-built drawings, where these might not exist due to poor record keeping for older structures. Muon scattering tomography is a non-destructive and non-invasive technique which shows great promise for high-depth 3D concrete imaging. Previously, we have demonstrated that individual bars with a diameter of 33.7 ± 7.3 mm can be located using muon scattering tomography. Here we present an improved method that exploits the periodicity of bar structures. With this new method, reinforcement with bars down to 6 mm thickness can be detected and imaged.
Arbitration, the World Trade Organization, and the Creation of a Multilateral Investment Court
Authors: Bjorklund Andrea K
Published: August 2021

The proliferation of international tribunals has reached the investment sphere. The European Union and its treaty partners have included an investment court system in the four individual investment agreements they have negotiated since the European Union took competence over foreign direct investment with the passage of the Lisbon Treaty. The United Nations Commission on International Trade Law (UNCITRAL), with the European Commission’s encouragement, is considering reform of investor-state arbitration with the front runner for reform the establishment of a multilateral investment court. Yet trade and investment law seem to be an oddly inverse relationship when it comes to preferred modes of dispute settlement. In the trade law realm, the survival of the ‘crown jewel’ of the World Trade Organisation (WTO)—its Dispute Settlement Body is uncertain. The appellate body has recently come in for special opprobrium. Arbitration is one of the suggested alternatives should existing dispute settlement procedures cease to function. Thus, in the investment law sphere, arbitration is apparently more and more disfavoured, and the preferred alternative is some kind of standing body with the pièce de résistance—an appellate body—at its apex. Why are these two regimes asynchronous? I hypothesize that states favour judicialization of disputes in the abstract but have reservations once judicialization becomes more concrete. Judicial or quasi-judicial decisions are hard for individual states to ignore or discredit, yet states have difficulty organizing multilateral responses to decisions they dislike.
Johnny Veeder and the Barcelona Traction Case
Authors: Bundy Rodman
Published: August 2021

Before his untimely death, Johnny Veeder had become fascinated with the Barcelona Traction case before the International Court of Justice, which in a sense was a precursor to modern investor-State arbitration. In Johnny’s honour, this article recounts the proceedings before the Court and the background of events involving a remarkable individual, Juan Antonias March, which led to the case being brought before the Court by Belgium against Spain as an espousal of the claims of Belgian nationals who had been shareholders in the Barcelona Traction company.
From Lena Goldfields to Crystallex: A Proposal For Collective Financing Of Sovereign Award Debt
Authors: Teitelbaum Ruth
Published: August 2021

The Lena Goldfields payment story must be recognized for upholding a critical principle: the notion that an arbitral award debt is a collective problem between sovereigns. The stories of payment in Lena Goldfields and Crystallex lead to the following inquiry: why should today’s system of investment treaty arbitration, based upon treaties providing for reciprocal obligations between sovereigns, treat the payment of arbitral awards as a one-sided obligation of only one sovereign, to be borne alone? If sovereigns are able to enter into treaties providing for mutual protections and benefits, including the mutual consent to arbitrate future investment disputes with foreign investors, why should they not also be able to collectively insure the future payment of awards owed to foreign investors in the future?
CDKN2B antisense RNA 1 suppresses tumor growth in human colorectal cancer by targeting MAPK inactivator dual-specificity phosphatase 1
Authors: Pan Jie , Lin Mengxin , Xu Zongbin , Xu Meifang , Zhang Junrong , Weng Zongqi , Lin Bingqiang , Lin Xiaoyan
Published: August 2021

Aberrant expression of long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been detected in human colorectal cancer (CRC). This study aimed to investigate the role of CDKN2B-AS1 and the underlying mechanism in human CRC. Gain- and loss-of-function assays were performed to explore the role of CDKN2B-AS1 in the malignant behavior of HCT116 and SW480 CRC cells in vitro and in vivo. RNA pull-down assay was conducted to identify the target of CDKN2B-AS1 in CRC cells. The physical and functional interactions between CDKN2B-AS1 and the target were examined. CDKN2B-AS1 inhibited CRC cell proliferation and migration while promoting apoptosis in vitro via activation of mitogen-activated protein kinase kinases (MEK)/extracellular signal-regulated kinase (ERK)/p38 signaling. CDKN2B-AS1 bound to mitogen-activated protein kinase (MAPK) inactivator dual-specificity phosphatase 1 (DUSP1) in CRC cells. In contrast to CDKN2B-AS1, DUSP1 promoted CRC cell proliferation, suppressed apoptosis and inactivated MEK/ERK/p38 signaling in CRC cells. Furthermore, CDKN2B-AS1 overexpression attenuated DUSP1 expression in normal colonic myofibroblasts and CRC cells. Overexpression of DUSP1 effectively countered the activation of MEK/ERK/p38 signaling induced by CDKN2B-AS1 overexpression or further blocked MEK/ERK/p38 signaling suppressed by CDKN2B-AS1 silencing. In the mouse xenograft model, CDKN2B-AS1 suppressed CRC growth, whereas DUSP1 promoted CRC growth. CDKN2B-AS1 induced cell apoptosis while suppressing EMT (epithelial–mesenchymal transition), whereas DUSP1 suppressed cell apoptosis while inducing EMT in CRC, as evidenced by the alterations in the protein levels of apoptosis and EMT markers in tumor tissue samples. CDKN2B-AS1 regulates CRC cell growth and survival by targeting MAPK inactivator DUSP1.
COVID-19 and Everyday ICT Use: The Discursive Construction of Old Age in German Media
Authors: Köttl Hanna , Tatzer Verena C , Ayalon Liat
Published: August 2021

Background and Objectives

Media discourses have the power to construct and perpetuate positive and negative aging images and influence public and individuals’ attitudes. This study aims to critically examine the media portrayal of older persons’ everyday information and communication technology (EICT) usage during the first and second waves of the coronavirus disease 2019 pandemic.

Research Design and Methods

A total of 51 articles published in 3 leading German newspapers between March 2020 and November 2020 were identified from the LexisNexis Academic database. Data were analyzed employing critical discourse and thematic analysis.

Results

EICT use was associated with youthful, consumption-orientated, and active lifestyles, while nonuse was constructed as failures on the policy or individual level. The pandemic seemed to have acted as an amplifier, further exacerbating and perpetuating stereotypical, dichotomous, but also empowering aging images.

Discussion and Implications

Neoliberal rational and binary distinctions of active users and nonusers opened and encouraged critical discussions on positive aging trends, the concept of the third and fourth ages, and aging-and-innovation discourses. Moreover, the crucial educative role of the media in raising awareness about power imbalances and reducing EICT-related ageism is stressed.
Bringing Disciplines and People Together to Characterize the Plastic and Genetic Responses of Molluscs to Environmental Change
Authors: Matoo Omera B , Neiman Maurine
Published: August 2021

Molluscs are remarkably diverse and are found across nearly all ecosystems, meaning that members of this ancient animal phylum provide a powerful means to study genomic-phenotype connections in a climate change framework. Recent advances in genomic sequencing technologies and genome assembly approaches finally allow the relatively cheap and tractable assembly of high-quality mollusc genome resources. After a brief review of these issues and advances, we use a case-study approach to provide some concrete examples of phenotypic plasticity and genomic adaptation in molluscs in response to environmental factors expected to be influenced by climate change. Our goal is to use molluscs as a “common currency” to demonstrate how organismal and evolutionary biologists can use natural systems to make phenotype-genotype connections in the context of changing environments. In parallel, we emphasize the critical need to collaborate and integrate findings across taxa and disciplines in order to use new data and information to advance our understanding of mollusc biology in the context of global environmental change. We end with a brief synthetic summary of the papers inspired by the 2021 SICB Symposium “Genomic Perspectives in Comparative Physiology of Molluscs: Integration across Disciplines”.
Rapid Shifts in Mitochondrial tRNA Import in a Plant Lineage with Extensive Mitochondrial tRNA Gene Loss
Authors: Warren Jessica M , Salinas-Giegé Thalia , Triant Deborah A , Taylor Douglas R , Drouard Laurence , Sloan Daniel B
Published: August 2021

In most eukaryotes, transfer RNAs (tRNAs) are one of the very few classes of genes remaining in the mitochondrial genome, but some mitochondria have lost these vestiges of their prokaryotic ancestry. Sequencing of mitogenomes from the flowering plant genus Silene previously revealed a large range in tRNA gene content, suggesting rapid and ongoing gene loss/replacement. Here, we use this system to test longstanding hypotheses about how mitochondrial tRNA genes are replaced by importing nuclear-encoded tRNAs. We traced the evolutionary history of these gene loss events by sequencing mitochondrial genomes from key outgroups (Agrostemma githago and Silene [=Lychnis] chalcedonica). We then performed the first global sequencing of purified plant mitochondrial tRNA populations to characterize the expression of mitochondrial-encoded tRNAs and the identity of imported nuclear-encoded tRNAs. We also confirmed the utility of high-throughput sequencing methods for the detection of tRNA import by sequencing mitochondrial tRNA populations in a species (Solanum tuberosum) with known tRNA trafficking patterns. Mitochondrial tRNA sequencing in Silene revealed substantial shifts in the abundance of some nuclear-encoded tRNAs in conjunction with their recent history of mt-tRNA gene loss and surprising cases where tRNAs with anticodons still encoded in the mitochondrial genome also appeared to be imported. These data suggest that nuclear-encoded counterparts are likely replacing mitochondrial tRNAs even in systems with recent mitochondrial tRNA gene loss, and the redundant import of a nuclear-encoded tRNA may provide a mechanism for functional replacement between translation systems separated by billions of years of evolutionary divergence.
Effects of increasing dietary inclusion of camelina cake on growth performance of growing-finishing pigs
Authors: Hilbrands A M , Johnston L J , Cox R B , Forcella F , Gesch R , Li Y Z
Published: August 2021

The objective of this experiment was to determine the dietary inclusion rate of camelina cake (CC) that would support the growth performance of growing-finishing pigs similar to that of a corn-soybean meal-based diet. Pigs (n = 192; BW = 35.2 kg; Duroc x (Yorkshire x Landrace)), balanced for sex and initial weight, were assigned to pens (8 pigs/pen) and pens were assigned randomly to one of four dietary treatments (6 pens/treatment). Treatments consisted of a non GMO corn-soybean meal control diet (CON), or CON containing 5% (5CC), 10% (10CC), or 15% (15CC) camelina cake. Feed disappearance on a pen basis and individual body weights of pigs were recorded every other week to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) on a pen basis. Prior to harvest, real-time ultrasonic measurements of back fat depth and loin eye area were collected on all live pigs. Pigs were harvested as a single group at about 23 weeks of age at a commercial abattoir. Data were analyzed using Proc Glimmix with dietary treatment as a fixed effect and pen serving as the experimental unit. Growth performance data collected over time were analyzed using repeated measures within the Proc Glimmix procedure. Overall, pigs fed CON exhibited similar ADG to those consuming 5CC and higher ADG than pigs consuming 10CC and 15CC diets (1.10 kg vs. 1.05 kg for 10CC and 1.02 kg for 15CC; P < 0.05 for both mean comparisons). Pigs fed CON consumed more feed than pigs fed any of the CC diets (ADFI = 2.66 kg for CON vs. 2.46 kg for 5CC, 2.46 kg for 10CC and 2.47 kg for 15CC; P < 0.05 for all). These differences resulted in heavier (P < 0.05) CON-fed pigs at marketing than 10CC or 15CC-fed pigs. There were no differences in any carcass traits analyzed. From these data, we conclude that feeding up to 5% CC in corn-soybean meal-based diets did not negatively influence growth performance, or carcass traits of growing-finishing pigs.
Alphabetical Mnemonic to Assist in the Treatment of an Acute Ischemic Stroke
Authors: Toufic El Hussein Mohamed , Green Tyler
Published: August 2021

Determining the treatment plan and how to successfully manage a patient suffering from an acute ischemic stroke can be challenging for a registered nurse (RN) in the emergency department. Using a mnemonic in the treatment process assists in reducing medical errors and increases the likelihood of making positive clinical outcomes. Mnemonics sum up complex strategies into relevant information that can be comprehensible for users. The authors have created a mnemonic strategy to provide RNs in the emergency department with a structured approach to the pharmacotherapeutic strategies used in treating patients with an acute ischemic stroke. All guidelines used throughout the article are in concurrence.
Rapid Response System Restructure
Authors: Winterbottom Fiona A. , Webre Heather
Published: August 2021

This article describes the staged restructure of the rapid response program into a dedicated 24/7 proactive rapid response system in a quaternary academic medical center in the southern United States. Rapid response nurses (RRNs) completed clinical leadership training on artificial intelligence, electronic risk stratification alerts, expert nurse rounding, emergency response, teamwork, closed-loop communication, and outcome measurement. The program goal was to reduce preventable deaths and resuscitation events outside the intensive care unit (ICU). Program outcomes between 2017 and 2019 included a 65% decrease in cardiac arrests outside the ICU, a 27% decrease of cardiac arrests inside the ICU, a 4.7% decrease in patients admitted to the ICU from inpatient beds, and a 27% reduction in the risk-adjusted mortality index for patients with expert proactive rounding encounters. Hospital peer group ranking on the Hospital Survey of Patient Safety improved in the areas of events reported, actions promoting patient safety, and continuous improvement suggesting a positive cultural shift. Implementation of a dedicated 24/7 RRN model of care integrating proactive rounding, technology, and ART can improve outcomes for patients and staff.
Blood pressure response during treadmill exercise testing and the risk for future cardiovascular events and new-onset hypertension
Authors: Zafrir Barak , Aker Amir , Asaf Yosi , Saliba Walid
Published: August 2021

Objective:

The physiologic response to exercise may provide valuable prognostic information. We investigated the association of blood pressure (BP) measurements during exercise stress testing (EST) with long-term risk of myocardial infarction, stroke or death (major adverse cardiovascular event, MACE), as well as the development of new-onset hypertension.

Methods:

A retrospective analysis of treadmill ESTs (years 2005–2019) performed by the Bruce protocol in patients aged 35–75 years without a history of cardiovascular disease (n = 14 792; 48% women). BP was documented at rest, submaximal exercise (Bruce stage-2), peak exercise and recovery (2 min). Association of SBP measures with study outcomes during median follow-up of 6.5 years was investigated.

Results:

Highest vs. lowest SBP quartile at rest (≥140 vs. <120 mmHg), submaximal-exercise (≥170 vs. <130 mmHg), peak-exercise (≥180 vs. ≤145 mmHg) and recovery (≥160 vs. <130 mmHg) was associated with an increase in the adjusted hazard ratio and 95% confidence interval (CI) for MACE: 1.53 (1.23–1.88), 1.33 (1.01–1.76), 1.30 (1.05–1.61), 1.35 (1.09–1.68), respectively. The association between SBP at submaximal exercise and recovery with MACE displayed a J-shaped pattern. Among nonhypertensive patients (n = 8529), excessive SBP response to peak exercise (≥190 mmHg in women and ≥210 mmHg in men) was an independent predictor of hypertension [hazard ratio (95% CI)]: 1.87 (1.41–2.48), as were SBPs during submaximal exercise [>160 vs. ≤130 mmHg: 2.44 (1.97–3.03)] and recovery [≥140 vs. ≤120 mmHg: 1.65 (1.37–1.98)].

Conclusion:

BP measurement during rest, exercise and recovery phases of EST provides incremental prognostic information regarding long-term risk for cardiovascular events and the probability for developing hypertension.
Lens Opacities Classification System III–based artificial intelligence program for automatic cataract grading
Authors: Lu Qiang , Wei Ling , He Wenwen , Zhang Keke , Wang Jinrui , Zhang Yinglei , Rong Xianfang , Zhao Zhennan , Cai Lei , He Xixi , Wu Jun , Ding Dayong , Lu Yi , Zhu Xiangjia
Published: August 2021

Purpose:

To establish and validate an artificial intelligence (AI)-assisted automatic cataract grading program based on the Lens Opacities Classification System III (LOCS III).

Setting:

Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China.

Design:

AI training.

Methods:

Advanced deep-learning algorithms, including Faster R-CNN and ResNet, were applied to the localization and analysis of the region of interest. An internal dataset from the EENT Hospital of Fudan University and an external dataset from the Pujiang Eye Study were used for AI training, validation, and testing. The datasets were automatically labeled on the AI platform regarding the capture mode and cataract grading based on the LOCS III.

Results:

The AI program showed reliable capture mode recognition, grading, and referral capability for nuclear and cortical cataract grading. In the internal and external datasets, 99.4% and 100% of automatic nuclear grading, respectively, had an absolute prediction error of ≤1.0, with a satisfactory referral capability (area under the curve [AUC]: 0.983 for the internal dataset; 0.977 for the external dataset); 75.0% (internal dataset) and 93.5% (external dataset) of the automatic cortical grades had an absolute prediction error of ≤1.0, with AUCs of 0.855 and 0.795 for referral, respectively. Good consistency was observed between automatic and manual grading when both nuclear and cortical cataracts were evaluated. However, automatic grading of posterior subcapsular cataracts was impractical.

Conclusions:

The AI program proposed in this study showed robust grading and diagnostic performance for both nuclear and cortical cataracts, based on LOCS III.
Validating a biosignature-predicting placebo pill response in chronic pain in the settings of a randomized controlled trial
Authors: Vachon-Presseau Etienne , Abdullah Taha B. , Berger Sara E. , Huang Lejian , Griffith James W. , Schnitzer Thomas J. , Apkarian A. Vania
Published: August 2021

The objective of this study is to validate a placebo pill response predictive model—a biosignature—that classifies chronic pain patients into placebo responders (predicted-PTxResp) and nonresponders (predicted-PTxNonR) and test whether it can dissociate placebo and active treatment responses. The model, based on psychological and brain functional connectivity, was derived in our previous study and blindly applied to current trial participants. Ninety-four chronic low back pain (CLBP) patients were classified into predicted-PTxResp or predicted-PTxNonR and randomized into no treatment, placebo treatment, or naproxen treatment. To monitor analgesia, back pain intensity was collected twice a day: 3 weeks baseline, 6 weeks of treatment, and 3 weeks of washout. Eighty-nine CLBP patients were included in the intent-to-treat analyses and 77 CLBP patients in the per-protocol analyses. Both analyses showed similar results. At the group level, the predictive model performed remarkably well, dissociating the separate effect sizes of pure placebo response and pure active treatment response and demonstrating that these effects interacted additively. Pain relief was about 15% stronger in the predicted-PTxResp compared with the predicted-PTxNonR receiving either placebo or naproxen, and the predicted-PTxNonR successfully isolated the active drug effect. At a single subject level, the biosignature better predicted placebo nonresponders, with poor accuracy. One component of the biosignature (dorsolateral prefrontal cortex–precentral gyrus functional connectivity) could be generalized across 3 placebo studies and in 2 different cohorts—CLBP and osteoarthritis pain patients. This study shows that a biosignature can predict placebo response at a group level in the setting of a randomized controlled trial.
Remote physical examination for temporomandibular disorders
Authors: Exposto Fernando G. , Castrillon Eduardo E. , Exposto Cristina R. , Costa Dyna Mara F. , Gøkhan Muhammed A. , Svensson Peter , Costa Yuri M.
Published: August 2021

There is a need to further develop telemedicine approaches because of the immediate and perhaps long-term consequences of the coronavirus disease 2019. Thus, a remote protocol for assessment of patients with temporomandibular disorders (TMD) was developed, and the agreement of this protocol was compared with the guidelines of the Diagnostic Criteria for TMD (DC/TMD). A total of 16 individuals were first assessed by a reference standard examination (RSE) and 3 other examinations applied in a random order by 3 examiners: standard physical examination (standard examination), physical examination keeping 2-m distance (physical distanced examination), and examination conducted with the aid of video communication technology (video communication examination). The primary outcomes were the diagnoses of myalgia of the masseter and temporalis muscles and arthralgia. The diagnoses of intra-articular joint disorders were considered secondary outcomes because of a less impact on psychosocial functioning and quality of life when compared with the pain-related diagnoses. The Fleiss kappa coefficient and its 95% confidence interval were computed to determine the level of agreement in diagnoses between each examination protocol and the RSE. There was substantial to almost perfect agreement between the RSE and all the examination protocols for the diagnoses of myalgia (0.86-1.00) and arthralgia (0.74-0.87) (P < 0.001). On the other hand, there was an overall poor agreement (0.30-0.58) between the RSE and all the protocols for the diagnosis of disk displacement with reduction. Remote assessment of patients with pain-related TMD is feasible and presents a high degree of accuracy.
Nerve injury induces transient locus coeruleus activation over time: role of the locus coeruleus–dorsal reticular nucleus pathway
Authors: Camarena-Delgado Carmen , Llorca-Torralba Meritxell , Suárez-Pereira Irene , Bravo Lidia , López‐Martín Carolina , Garcia-Partida Jose A. , Mico Juan A. , Berrocoso Esther
Published: August 2021

The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. Using the chronic constriction injury of the sciatic nerve as a model of neuropathic pain in male Sprague–Dawley rats, we identified time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion, hypothesizing that the LC→dorsal reticular nucleus (DRt) pathway is involved in the pathological nociception associated with chronic pain. LCipsi inactivation with lidocaine increased cold allodynia 2 days after nerve injury but not later. However, similar blockade of LCcontra reduced cold allodynia 7 and 30 days after inducing neuropathy but not earlier. Furthermore, lidocaine blockade of the LCipsi or LCcontra reversed pain-induced depression 30 days after neuropathy. Long-term pain enhances phosphorylated cAMP-response element binding protein expression in the DRtcontra but not in the DRtipsi. Moreover, inactivation of the LCcontra→DRtcontra pathway using dual viral-mediated gene transfer of designer receptor exclusively activated by designer drugs produced consistent analgesia in evoked and spontaneous pain 30 days postinjury. This analgesia was similar to that produced by spinal activation of α2-adrenoreceptors. Furthermore, chemogenetic inactivation of the LCcontra→DRtcontra pathway induced depressive-like behaviour in naïve animals, but it did not modify long-term pain-induced depression. Overall, nerve damage activates the LCipsi, which temporally dampens the neuropathic phenotype. However, the ensuing activation of a LCcontra→DRtcontra facilitatory pain projection contributes to chronic pain, whereas global bilateral LC activation contributes to associated depressive-like phenotype.
Potential Clinical Utility of a Targeted Circulating Tumor DNA Assay in Esophageal Adenocarcinoma
Authors: Cabalag Carlos S. , Yates Michael , Corrales Mariana Benitez , Yeh Paul , Wong Stephen Q. , Zhang Bonnie Z. , Fujihara Kenji M. , Chong Lynn , Hii Michael W. , Dawson Sarah-Jane , Phillips Wayne A. , Duong Cuong P. , Clemons Nicholas J.
Published: August 2021

Objective:

To explore the clinical utility of circulating tumor DNA (ctDNA) in esophageal adenocarcinoma (EAC) by developing a cost-effective and rapid technique utilising targeted amplicon sequencing.

Summary of background data:

Emerging evidence suggests that levels of ctDNA in the blood can be used to monitor treatment response and in the detection of disease recurrence in various cancer types. Current staging modalities for EAC such as computerised tomography of the chest/abdomen/pelvis (CT) and positron emission tomography (PET) do not reliably detect occult micro-metastatic disease, the presence of which signifies a poor prognosis. After curative-intent treatment, some patients are still at high risk of recurrent disease, and there is no widely accepted optimal surveillance tool for patients with EAC.

Methods:

Sixty-two patients with EAC were investigated for the presence of ctDNA using a tumor-informed approach. We designed a custom targeted amplicon sequencing panel of target specific primers covering mutational foci in 9 of the most commonly mutated genes in EAC. Serial blood samples were taken before and after neoadjuvant treatment (NAT), and during surveillance.

Results:

Somatic mutations were detected in pre-treatment biopsy samples of 55 out of 62 (89%) EAC patients. Mutations in TP53 (80%) were the most common. Out of these 55 patients, 20 (36%) had detectable ctDNA at baseline. The majority (90%) of patients with detectable ctDNA had either locally advanced tumors, nodal involvement or metastatic disease. In patients with locally advanced tumors, disease free survival (DFS) was more accurately stratified using pre-treatment ctDNA status [HR 4.34 (95% CI 0.93–20.21); P = 0.05] compared to nodal status on PET-CT. In an exploratory subgroup analysis, patients who are node negative but ctDNA positive have inferior DFS [HR 11.71 (95% CI 1.16-118.80) P = 0.04]. In blood samples taken before and following NAT, clearance of ctDNA after NAT was associated with a favourable response to treatment. Furthermore, patients who are ctDNA positive during post-treatment surveillance are at high risk of relapse.

Conclusions:

Our study shows that ctDNA has potential to provide additional prognostication over conventional staging investigation such as CT and PET. It may also have clinical utility in the assessment of response to NAT and as a biomarker for the surveillance of recurrent disease.
American Society of Anesthesiologists-Physical Status Classification As An Independent Risk Factor of Surgical Site Infection After Infra-Inguinal Arterial Bypass
Authors: Tresson Philippe , Quiquandon Samuel , Rivoire Emeraude , Boibieux André , Vanhems Philippe , Bordet Marine , Long Anne
Published: August 2021

Objectives:

The present study aimed to assess whether high-risk American Society of Anesthesiologists (ASA)-Physical Status was an independent risk factor for the development of surgical site infection (SSI) after infra-inguinal lower extremity bypass (LEB).

Summary of Background Data:

The ASA-Physical Status Classification System assesses the overall physical status preoperatively. ASA-Physical Status is associated with postoperative morbidity and mortality. However, limited data are available on how ASA-Physical Status Class affects the development of SSI after infra-inguinal LEB.

Methods:

Patients who had undergone infra-inguinal LEB from January 1, 2015 to December 31, 2018, for obliterative arteriopathy or popliteal aneurysm at our university hospital were included. SSI risk factors were identified using multivariable logistic regression. The length of hospital stay, major limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality were compared for patients with SSI versus those without SSI 3 months and 1- year of follow-up after the index surgery.

Results:

Among the 267 patients included, 30 (11.2%) developed SSI during the 3-month period and 32 (12%) at 1 year. ASA-Physical Status ≥3 [odds ratio (OR): 3.7, 95% confidence interval CI) 1.5–11.1], emergency surgery (OR: 2.7, 95% CI 1.2–6.0), general anesthesia (OR: 2.8, 95% CI 1.3–6.1), and procedure performed by a junior surgeon (OR: 2.7, 95% CI 1.3–6.0) were independently associated with SSI. At 3 months and 1 year, SSI was significantly associated with MALE (including surgical wound debridement, subsequent thrombectomy, major amputation), length of hospital stay, and all-cause mortality.

Conclusion:

The ASA-Physical Status should be considered in medical management when an infra-inguinal LEB is considered in frail patients, to prevent surgical complications.
Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma
Authors: Newhook Timothy E. , Vreeland Timothy J. , Griffin James F. , Tidwell Rebecca S. S. , Prakash Laura R. , Koay Eugene J. , Ludmir Ethan B. , Smaglo Brandon G. , Pant Shubham , Overman Michael , Wolff Robert A. , Ikoma Naruhiko , Maxwell Jessica , Kim Michael P. , Lee Jeffrey E. , Katz Matthew H. G. , Tzeng Ching-Wei D.
Published: August 2021

Objective:

To characterize associations between carbohydrate antigen 19–9 (CA19–9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC).

Background:

Although normalization of CA19–9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19–9 dynamics during NT can improve prognostication.

Methods:

Characteristics for patients with PDAC undergoing NT (July 2011–October 2018) with ≥3 CA19–9 results (bilirubin<2mg/dL) were collected and grouped by CA19–9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups.

Results:

Of 431 patients, 166 had eligible CA19–9 values. Median baseline CA19–9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19–9 dynamics during NT were analyzed by shape, direction, and normalization creating response types (“A-B-C-D-E”). Type A was “Always” decreasing to normalization, B “Bidirectional” with eventual normalization, C “Consistently” normal, D any “Decrease” without normalization, and E “Elevating” without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19–9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19–9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01).

Conclusions:

This novel A-B-C-D-E classification of CA19–9 dynamics during NT was associated with postresection outcomes more precisely than CA19–9 normalization alone.
Retrospective mortality and prevalence of SARS-CoV-2 antibodies in greater Omdurman, Sudan: a population–based cross–sectional survey
Authors: Moser Wendelin , Fahal Mohammed Ahmed Hassan , Abualas Elamin , Bedri Shahinaz , Elsir Mahgoub Taj , Mohamed Mona Fateh El Rahman Omer , Mahmoud Abdelhalim Babiker , Ahmad Amna Ismail Ibrahim , Adam Mohammed A. , Altalib Sami , DafaAllah Ola Adil , Hmed Salahaldin Abdallah , Azman Andrew S. , Ciglenecki Iza , Gignoux Etienne , González Alan , Mwongera Christine , Albela Manuel
Published: August 2021

Background

Even after adjusting for the expected lower severity due to the younger age of the population, relatively low SARS-CoV-2 incidence and mortality rates have been reported throughout Africa. For investigating whether this is truly the case, we conducted a survey to estimate the COVID-19 related mortality and cumulative incidence of SARS-CoV-2 infections in Omdurman the most populated city of the tripartite metropolis Khartoum in Sudan.

Methods

A retrospective, cross–sectional, mortality and seroprevalence survey was conducted in Omdurman, Sudan, from March 1, until April 10 2021. A two–stage cluster sampling method was used to investigate the death rate for the pre–pandemic (January 1, 2019–February 29, 2020) and pandemic (March 1, 2020 – day of the survey) period using questionnaires. The seroprevalence survey was performed in a subset of households and all consenting members were tested with a rapid serological test (SD–Biosensor) and a subgroup additionally with ELISA (EUROIMMUN). Fisher’s exact test was used to assess differences between the pre–and pandemic periods and a random effect and Bayesian latent class model to adjust for test performance.

Findings

Data from 27315 people (3716 households) for the entire recall period showed a 67% (95% CI 32–110) increase in death rate between the pre–pandemic (0.12 deaths/10000 people/day [95% CI 0.10–0.14]) and pandemic (0.20 [0.16–0.23]) periods. Notably, a 74% (30–133) increase in death was observed among people aged ≥50 years. The adjusted seroprevalence of SARS-CoV-2 was 54.6% (95% CI 51.4–57.8). The seroprevalence was significantly associated with age, increasing up to 80.7% (71.7–89.7) for the oldest age group (≥50 years).

Interpretation

Our results showed a significant elevated mortality for the pandemic period with a considerable excess mortality in Omdurman, Sudan. The overall high seroprevalence indicated a different age pattern compared to other countries, with a significant increase by age.

Funding

Medécins Sans Frontières
Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at ER monitoring and regulating fatty acids
Authors: Han Song-iee , Nakakuki Masanori , Nakagawa Yoshimi , Wang Yunong , Araki Masaya , Yamamoto Yuta , Tokiwa Hiroaki , Takeda Hiroyuki , Mizunoe Yuhei , Motomura Kaori , Ohno Hiroshi , Murayama Yuki , Aita Yuichi , Takeuchi Yoshinori , Osaki Yoshinori , Miyamoto Takafumi , Sekiya Motohiro , Matsuzaka Takashi , Yahagi Naoya , Sone Hirohito , Kawano Hiroyuki , Shimano Hitoshi
Published: August 2021

The ER-embedded transcription factors, sterol-regulatory element-binding proteins (SREBPs), master regulators of lipid biosynthesis, are transported to Golgi for proteolytic activation to tune cellular cholesterol levels and regulate lipogenesis. However, mechanisms by which the cell responds to the levels of saturated or unsaturated fatty acids remain underexplored. Here we show that RHBDL4/RHBDD1, a rhomboid family protease, directly cleaves SREBP-1c at ER. The p97/VCP, AAA-ATPase complex then acts as an auxiliary segregase to extract the remaining ER-embedded fragment of SREBP-1c. Importantly, the enzymatic activity of RHBDL4 is enhanced by saturated fatty acids (SFAs), but inhibited by polyunsaturated fatty acids (PUFAs). Genetic deletion of RHBDL4 in mice fed on a Western diet enriched in SFAs and cholesterol prevented SREBP-1c from inducing genes for lipogenesis, particularly for synthesis and incorporation of PUFAs, and secretion of lipoproteins. The RHBDL4–SREBP-1c pathway reveals a regulatory system for monitoring fatty acid composition and maintaining cellular lipid homeostasis.

Graphical Abstract
Enhanced circularity in aftermarkets: logistics tradeoffs
Authors: Gatenholm Gabriella , Halldórsson Árni , Bäckstrand Jenny
Published: August 2021

Purpose

The purpose of this paper is to identify requirements and tradeoffs on logistics services for enhanced circularity of materials and resources.

Design/methodology/approach

Based on multiple case study design and abductive reasoning, the study investigates 13 different product categories. The data were analyzed based on theoretical,a prioricodes from the literature review. Inductive, emerging codes were added to the coding scheme during the analysis.

Findings

Requirements of logistics services to support slowing of resource flows are categorized with respect to initiator, location of the service, single or multiple actors, and transportation of parts, products and people. Moreover, the study identifies new logistics tradeoffs: material and people, knowledge and people, and information and knowledge. Transportation of product, people and parts can be reduced by increasing local knowledge and improve information sharing.

Research limitations/implications

This review contributes to the understanding of the relationship between logistics services and enhancement of circularity by highlighting requirements on logistics services in the aftermarket supply chain that support slowing of resource flows. To enhance circularity, logistics services must extend the traditional material information flow with the flow of people and knowledge, respectively.

Practical implications

The categorization provides practitioners and researchers with an overview of requirements and tradeoffs on logistics services to enhance circularity of a particular circular cycle. The implications will provide an opportunity to address environmental impact of transportation and improve the utilization of scarce materials.

Social implications

Variety of tradeoffs in logistics services can enhance slowing and hence circularity of scarce materials.

Originality/value

First, the authors illustrate how traditional tradeoffs in logistics such as flow of materials, resources and people need to be addressed to enhance circularity through slowing. Second, the authors identify two new tradeoffs in logistics services: knowledge flow and degree of customer involvement.