bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunophenotyping identifies distinct cellular signatures for systemic lupus erythematosus and lupus nephritis
Authors: Aw Yi Tong V. , Whiley Phillip J. , Lorenzo Ayla May , Lea‐Henry Tom , Shanmuganandam Somasundhari , Stanley Maurice , Babu Sonia N. , Athanasopoulos Vicki , Cappello Jean , Ellyard Julia I. , Cook Matthew , Vinuesa Carola , Walters Giles , Fulcher David A. , Jiang Simon H.
Published: November 2022

Background

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by development of autoantibodies and multiorgan involvement. Kidney involvement, termed lupus nephritis, has major impact on life expectancy. It is increasingly recognized that SLE is likely a common clinical manifestation of pathophysiologically diverse processes, and lupus nephritis has similarly been associated with several distinct immunological processes. We compared the immune cell phenotypes of individuals with SLE in the presence or absence of nephritis.

Methods

Cryopreserved peripheral blood mononuclear cells from SLE patients with and without kidney involvement underwent flow cytometric analysis to identify major populations in T cells, B cells and myeloid lineages.

Results

We compared the frequencies of lymphocyte populations in 69 SLE patients without nephritis, 20 SLE patients with nephritis, and 92 healthy blood donors. Patients with SLE and lupus nephritis (LN) had reduced marginal zone B cells (P < 0.0001 in SLE; P = 0.001 in LN), memory B cells (P = 0.002 in SLE; P = 0.001 in LN) and circulating T follicular helper (Tfh) memory cells (P < 0.0001 in SLE and LN) compared to healthy donors. Patients with lupus nephritis had increase Th2 (P < 0.0001) and T regulatory cells (P < 0.0001) compared to both SLE patients without nephritis and healthy donors.

Conclusion

SLE patients with and without lupus nephritis have distinct immunologic differences that may reflect the unique pathophysiological processes contributing to disease manifestations.
Synchronous robotic repair of anterior diaphragmatic (Morgagni) hernia & low anterior resection for rectal cancer
Authors: Lambert Joel , Shugaba Abdul , Sheikh Adnan , Gill Michael
Published: November 2022

Background

We present the case report of synchronous trans‐fascial repair of a large congenital Morgagni hernia (MH) and low anterior resection using a fully robotic approach.

Methods

A 61‐year old female presented with fresh red blood in her stool. She had a previous history of abdominal hysterectomy and a performance status of 0. Imaging revealed a low rectal cancer and incidental large MH.

Results

Using the Da Vinci X platform the procedure was successfully performed; total operating time of 450 min, <200 ml blood loss and 5 days hospital stay. Post‐operative scan at 6 months, 1 and 2 years showed no evidence of hernia or cancer recurrence.

Conclusion

We have demonstrated that complex multi‐visceral procedures can be safely performed on fully robotic platforms, even in previously disturbed surgical fields. The robotic approach may provide the opportunity for seamless multi‐speciality operating simultaneously in multiple body cavities.
Print Learning: A Theoretical Framework for the Role of Children's Learning about the Orthography in the Development of Reading Skill
Authors: Conrad Nicole J. , Deacon S. Hélène
Published: November 2022

All dominant models of reading development ascribe a central role to learning about the orthography in reading acquisition, particularly as children transition to fluent word reading (e.g., Ehri, 2014; Share, 1995). And yet, we know far less about the contributions to word reading development of children's learning about the orthographic form of language than about its phonological dimensions. Through a focused review, we put forward a new conceptualization about the role of learning about the orthography in reading development. This new theoretical framework defines a broader conceptual and developmental scope of print learning, and it predicts bidirectional relations between print learning and word reading development. This theoretical framework both encompasses and expands traditional views on the role of learning about the orthography in reading development. We hope that this framework will both unify and guide theoretical conceptualizing and empirical research.
Success factors of global goal‐setting for sustainable development: Learning from the Millennium Development Goals
Authors: Hickmann Thomas , Biermann Frank , Spinazzola Matteo , Ballard Charlotte , Bogers Maya , Forestier Oana , Kalfagianni Agni , Kim Rakhyun E. , Montesano Francesco S. , Peek Tom , Sénit Carole‐Anne , van Driel Melanie , Vijge Marjanneke J. , Yunita Abbie
Published: November 2022

The Millennium Development Goals (MDGs) were an important precursor to the Sustainable Development Goals (SDGs). Hence, identifying the conditions that made the MDGs successful enhances our understanding of global goal‐setting and informs the global endeavour to achieve the SDGs. Drawing on a comprehensive review of 316 articles published between 2009 and 2018, we identify six factors that have enabled or hindered MDG implementation. Our analysis stresses the importance of path dependencies and shows that the MDGs catalysed changes only for those countries with sufficient resource availability, administrative capacity and economic development, as well as adequate support from external donors. National ownership and NGO pressure bolstered efforts to implement the MDGs. These findings suggest that globally agreed goals do not easily trickle down from the global to the national level. Thus, this article adopts a forward‐looking perspective and draws key lessons for the current implementation of the SDGs in developing countries.
Opportunities for circular bionutrient economy in Kenya: Sanitation and waste stream characterization
Authors: Midega Charles A. O.
Published: November 2022

The majority of people in low‐ and middle‐income countries, such as Kenya, lack effective sanitation and waste management systems. Circular bionutrient economy (CBE) is emerging as a framework to safely reuse organic wastes in agriculture. This study aimed to characterize waste and sanitation systems in Kisumu City, Kenya, with a view to exploring opportunities for CBE in the Lake Victoria basin. Sanitation was characterized through a case study approach in a populous informal settlement, and waste was quantified in two markets in the city. The main toilet facility was pit latrine, although there were also some urine‐diverting dry toilets (UDDTs). One toilet served about 36 people. Over a 1‐mo period, the UDDTs yielded approximately 64,400 L of urine, whereas about 67,500 L of fecal sludge was emptied from the pit latrines, out of which only about 33,000 L (48.9%) was properly disposed of. About 3 t of waste was generated daily from the markets, 95% of which was organic, and was disposed of at an open dumpsite. Organic waste, including human excreta, contains large amounts of organic matter and plant nutrients, and can be processed for agricultural nutrient cycles. Additionally, black soldierly larvae can effectively convert organic waste into nutrient‐rich fertilizer and high protein biomass for animal feeds. These results suggest an opportunity for a CBE system in the region for sustainable organic waste management and urban sanitation, and with opportunity to improve livelihoods and equity.
5G‐based remote magnetically controlled capsule endoscopy for examination of the stomach and small bowel
Authors: Zhang Ting , Chen Yi‐Zhi , Jiang Xi , He Chen , Pan Jun , Zhou Wei , Hu Jian‐Ping , Liao Zhuan , Li Zhao‐Shen
Published: November 2022

Background and aims

Remote endoscopy can improve diagnostic efficiency of gastrointestinal (GI) diseases for patients in remote areas. A novel remote magnetically controlled capsule endoscopy (MCE) system based on a 5G network was developed for real‐time remote GI examinations. We aimed to evaluate the feasibility and safety of the 5G‐based remote MCE for examination of the stomach and small bowel.

Methods

This was a prospective, nonrandomized, comparative study. Consecutive participants enrolled in the First People's Hospital of Yinchuan underwent remote MCE examinations performed by an endoscopist located in Changhai Hospital. Consecutive participants enrolled in Changhai Hospital underwent conventional MCE examinations performed by the same endoscopist. The main outcomes included the complete visualization rate of the stomach and small bowel, safety assessment and network latency time of remote MCE examinations.

Results

From March 2021 to June 2021, 20 participants in each group were enrolled. The complete visualization rate of the stomach and small bowel was 100% in both groups (p > 0.999) without any adverse event. The median network latency time of remote MCE group was 19.948 ms. Gastric examination time (8.96 vs. 8.92 min, p = 0.234), maneuverability (15.00 vs. 15.00, p = 0.317), image quality (1.00 vs. 1.00, p > 0.999) and diagnostic yields in the stomach and small bowel (55% vs. 30%, 5% vs. 0%, both p > 0.05) were comparable between remote and conventional MCE groups. All participants in remote MCE group considered remote MCE acceptable and necessary.

Conclusions

5G‐based remote MCE was a feasible and safe method for viewing the stomach and small bowel.
Immunotoxicity of nanomaterials in health and disease: Current challenges and emerging approaches for identifying immune modifiers in susceptible populations
Authors: Hofer Sabine , Hofstätter Norbert , Punz Benjamin , Hasenkopf Ingrid , Johnson Litty , Himly Martin
Published: November 2022

Nanosafety assessment has experienced an intense era of research during the past decades driven by a vivid interest of regulators, industry, and society. Toxicological assays based on in vitro cellular models have undergone an evolution from experimentation using nanoparticulate systems on singular epithelial cell models to employing advanced complex models more realistically mimicking the respective body barriers for analyzing their capacity to alter the immune state of exposed individuals. During this phase, a number of lessons were learned. We have thus arrived at a state where the next chapters have to be opened, pursuing the following objectives: (1) to elucidate underlying mechanisms, (2) to address effects on vulnerable groups, (3) to test material mixtures, and (4) to use realistic doses on (5) sophisticated models. Moreover, data reproducibility has become a significant demand. In this context, we studied the emerging concept of adverse outcome pathways (AOPs) from the perspective of immune activation and modulation resulting in pro‐inflammatory versus tolerogenic responses. When considering the interaction of nanomaterials with biological systems, protein corona formation represents the relevant molecular initiating event (e.g., by potential alterations of nanomaterial‐adsorbed proteins). Using this as an example, we illustrate how integrated experimental–computational workflows combining in vitro assays with in silico models aid in data enrichment and upon comprehensive ontology‐annotated (meta)data upload to online repositories assure FAIRness (Findability, Accessibility, Interoperability, Reusability). Such digital twinning may, in future, assist in early‐stage decision‐making during therapeutic development, and hence, promote safe‐by‐design innovation in nanomedicine. Moreover, it may, in combination with in silico‐based exposure‐relevant dose‐finding, serve for risk monitoring in particularly loaded areas, for example, workplaces, taking into account pre‐existing health conditions.

This article is categorized under:

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Early correction of base deficit decreases late mortality in polytrauma
Authors: van Wessem Karlijn J. P. , Hietbrink Falco , Leenen Luke P. H.
Published: November 2022

Introduction

Physiology-driven resuscitation has become the standard of care in severely injured patients. This has resulted in a decrease in acute deaths by hemorrhagic shock. With increased survival from hemorrhage, focus shifts towards death later during hospital stay. This population based cohort study investigated the association of initial physiology derangement correction and (late) mortality.

Methods

Consecutive polytrauma patients aged > 15 years with deranged physiology who were admitted to a level-1 trauma center intensive care unit (ICU) from 2015 to 2021, and requiring surgical intervention < 24 h were included. Patients who acutely (< 48 h) died were excluded. Demographics, treatment, and outcome parameters were analyzed. Physiology was monitored by serial base deficits (BD) during the first 48 h. Correction of physiology was defined as BD return to normal values. Area under the curve (AUC) of BD in time was used as measurement for the correction of physiological derangement and related to mortality 3–6 days (early), and > 7 days (late).

Results

Two hundred thirty-five patients were included with a median age of 44 years (70% male), and Injury Severity Score (ISS) of 33. Mortality rate was 16% (71% due to traumatic brain injury (TBI)). Median time to death was 11 (6–17) days; 71% died > 7 days after injury. There was no difference between the single base deficit measurements in the emergency department(ED), operating room (OR), nor ICU between patients who died and those who did not. However, patients who later died were more acidotic at 24 and 48 h after arrival, and had a higher AUC of BD in time. This was independent of time and cause of death.

Conclusion

Early physiological restoration based on serial BD measurements in the first 48 h after injury decreases late mortality.
Postprimäre frühelektive Totalprothetik bei schweren Frakturen des oberen Sprunggelenks
Authors: Pflüger Patrick , Schlickewei Carsten , Barg Alexej , Valderrabano Victor
Published: November 2022

Die Versorgung des oberen Sprunggelenks (OSG) mithilfe einer Totalprothese (TP) ist heutzutage eine etablierte und sichere operative Therapie der Arthrose am OSG. Moderne Implantate haben geringe Revisionsraten und sind der Arthrodese des Sprunggelenks hinsichtlich des von Patienten berichteten Ergebnisses überlegen. Der Stellenwert der primären endoprothetischen Versorgung von Frakturen am OSG ist unklar. Aktuell finden sich diesbezüglich in der Literatur keine Studien. In Anbetracht der steigenden Fallzahlen instabiler Sprunggelenkfrakturen, insbesondere bei älteren Patienten und aufgrund wachsender funktioneller Ansprüche auch bis ins hohe Lebensalter, gilt es zukünftig beim Management dieser Frakturen auch eine endoprothetische Versorgung zu berücksichtigen. Klinische Studien sind notwendig, um die Versorgung von Frakturen des OSG mithilfe einer TP zu evaluieren.
Multimodale Therapiekonzepte lokaler Verfahren mit der Immuntherapie
Authors: Eckert Franziska
Published: November 2022

Immuntherapien haben sich in der Behandlung onkologischer Erkrankungen i. Allg. sowie in der Uroonkologie etabliert. Die Rationale, diese Therapien mit Bestrahlung zu kombinieren, basieren auf den biologischen Effekten von Tumorbestrahlung, die weit über ein „physikalisches“ Abtöten von Tumorzellen hinausgeht. Abhängig von Dosis und Fraktionierung der Bestrahlung sowie dem verwendeten Tumormodell oder der Tumorentität können immunaktivierende und immunsupprimierende Effekte ausgelöst werden. Da eine Antitumorimmunantwort nicht lokal im Tumor sondern systemisch erfolgt, kann eine erfolgreich ausgelöste Antitumorimmunität in einer bestrahlten Metastase zu einem systemischen Ansprechen führen (abskopaler Effekt). In klinischen Studien werden Kombinationsschemata für lokal fortgeschrittene Tumorerkrankungen in der kurativen Situation zur Erhöhung der Heilungsraten sowie in der metastasierten Situation zur Verlängerung des Überlebens in der palliativen Situation eingesetzt. Ein weiteres Einsatzgebiet ist die lokale Behandlung von Oligometastasen oder in der Oligoprogression unter laufender Systemtherapie.
Combination of GNSS orbits using least-squares variance component estimation
Authors: Mansur Gustavo , Sakic Pierre , Brack Andreas , Männel Benjamin , Schuh Harald
Published: November 2022

Over the past years, the International GNSS Service (IGS) has been putting efforts into extending its service by setting up and running the Multi-GNSS experiment and pilot project (MGEX). Several MGEX analysis centers (ACs) contribute by providing solutions containing not only GPS and GLONASS but also Galileo, BeiDou, and QZSS. As the current IGS combination software can only handle the orbits of one constellation at a time, it requires substantial modifications to obtain a consistent MGEX orbit product. In this contribution, we present a least-squares framework for a Multi-GNSS orbit combination, where the weights used to combine the ACs’ orbits are determined by least-squares variance component estimation. We introduce and compare two weighting strategies, where either AC-specific weights or AC and constellation-specific weights are used. An automated Z-score test is implemented yielding a common set of core satellites that are used to determine the weights. Both strategies are tested using MGEX orbit solutions for a period of two and a half years. They yield similar results with an agreement with the ACs’ orbits at the one centimeter level for GPS and up to a few centimeters for the other constellations. The 3D-RMS is generally slightly better with the AC and constellation weighting. A comparison of our combination approach with the official IGS combination using three years of GPS and GLONASS orbits shows an agreement of better than 5 mm and 12 mm for GPS and GLONASS, respectively, while the agreement of the official IGS combination with the ACs’ GPS solutions is only around $$15\,\textrm{mm}$$

15

mm

. An external validation using satellite laser ranging shows that the mean residuals of our combined products are around $$-3\,\textrm{mm}$$

-
3

mm

for Galileo, $$6\,\textrm{mm}$$

6

mm

for GLONASS, $$-8\,\textrm{mm}$$

-
8

mm

for BeiDou, and $$-31\,\textrm{mm}$$

-
31

mm

for QZSS.
Oxidation processes and thermal stability of actinolite
Authors: Rösche Constanze , Waeselmann Naemi , Petrova Nadia , Malcherek Thomas , Schlüter Jochen , Mihailova Boriana
Published: November 2022

Understanding the thermal behaviour of iron-containing amphiboles (AB2C5T8O22W2, C5 = M(1)2 M(2)2 M(3)) at atomic-level scale may have important implications in several fields, including metamorphic petrology, geophysics, and environmental sciences. Here, the thermally induced oxidation and decomposition of actinolite are studied by in situ high-temperature Raman spectroscopy and complementary thermogravimetric/mass-spectrometry analyses as well as X-ray diffraction of the products of amphibole decomposition. The effect of CFe2+ on dehydrogenation/dehydroxylation is followed by comparing the results on actinolite with those for tremolite. We show that mobile charge carriers, namely polarons (conduction electrons coupled to FeO6 phonons) and H+ cations, exist in actinolite at elevated temperatures ~ 1150–1250 K. The temperature-induced actinolite breakdown is a multistep process, involving (i) delocalization of e− from CFe2+ as well as of H+ from hydroxyl groups shared by Fe-containing M(1)M(1)M(3) species, which, however, remain in the crystal bulk; (ii) dehydrogenation and ejection of e− between 1250 and 1350 K, where actinolite can be considered as “oxo-actinolite”, as H+ also from hydroxyl groups next to M(1,3)(MgMgMg) configurations become delocalized and mostly remain in the crystal bulk; (iii) complete dehydroxylation and consequent structure collapse above 1350 K, forming an Fe3+-bearing defect-rich augitic pyroxene. The dehydrogenation of tremolite occurs at 1400 K, triggering immediately a disintegration of the silicate double-chain into single SiO4-chains and followed by a rearrangement of the amphibole octahedral strips and BCa2+ cations into pyroxene-type octahedral sheets at 1450 K. The result of tremolite decomposition is also a single-phase defect-rich clinopyroxene with an intermediate composition on the diopside–clinoenstatite join.
Mental illness rates among employees with fixed-term versus permanent employment contracts: a Danish cohort study
Authors: Hannerz Harald , Burr Hermann , Nielsen Martin Lindhardt , Garde Anne Helene , Flyvholm Mari-Ann
Published: November 2022

Purpose

It has been hypothesized that employment in a fixed-term instead of permanent contract position is associated with an increased risk of development of mental health problems. The present study aimed at estimating rate ratios between fixed-term and permanent employees in the Danish labor force, for use of psychotropic drugs and psychiatric hospital treatment due to mood, anxiety or stress-related disorders, respectively.

Methods

Employment data were drawn from the Danish Labor Force Survey of 2001–2013, which is a part of the European Labor Force Survey. Full-time employed survey participants without mental illness at the baseline interview (N = 106,501) were followed in national health registers for up to 5 years. Poisson regressions were used to estimate rate ratios for redeemed prescriptions of psychotropic drugs and psychiatric hospital treatments due to mood, anxiety or stress-related disease. The analyses were controlled for age, gender, industrial sector, nighttime work, level of education, calendar year, disposable family income and social transfer payments within 1 year prior to the baseline interview.

Results

The rate ratio for hospital diagnosed mood, anxiety or stress-related disorders among employees with fixed-term vs. permanent employment contracts was estimated at 1.39 (99.5% CI 1.04–1.86), while the corresponding rate ratio for redeemed prescriptions of psychotropic drugs was estimated at 1.12 (99.5% CI 1.01–1.24).

Conclusion

The present study supports the hypothesis that employment in a fixed-term rather than permanent contract position is associated with an increased risk of developing mental health problems.

International registered report identifier (IRRID)

DERR2-10.2196/24392.
Counting mitoses in gastrointestinal stromal tumours (GISTs): variable practices in the real-world setting and their clinical implications
Authors: Campora Michela , Paudice Michele , Gambella Alessandro , Comandini Danila , Parente Paola , Sbaraglia Marta , Dei Tos Angelo Paolo , Grillo Federica , Mastracci Luca
Published: November 2022

Mitotic count (MC) is an important prognostic indicator in gastrointestinal stromal tumours (GISTs). Though MC evaluation was initially proposed in 50 HPFs, recent international guidelines recommend that MC be performed on 5 mm2 because HPFs may have different areas depending on the ocular field number (FN) of the utilized light microscope. Performing MC on different areas leads to a non-standardized evaluation and erroneous risk stratification. The aim of the study was to audit real-life MC practices with special emphasis on possible risk stratification errors. A survey was administered to Italian pathologists to evaluate the following: method used for MC (5 mm2 versus 50 HPF); FN of the light microscope; prognostic scheme for risk stratification. Based on the results of the survey, 100 GISTs (25/risk class using Miettinen prognostic scheme) were retrieved and MC performed using 5 mm2 versus the corresponding mm2 area sizes of 50 HPFs with variable FNs (18, 20, 22). The survey demonstrated that the majority of pathologists (64.5%) use 50 HPFs with various FNs leading to excessive area size. The most frequently used prognostic scheme is that by Miettinen. Using this prognostic scheme and counting mitoses in 5 mm2 versus 50 HPFs with FNs 18, 20 and 22, a change in risk class was identified ranging from 10 to 41%, depending on FN. In conclusion, this study demonstrates that MC is still frequently performed on 50 HPF, with area sizes exceeding the specified 5 mm2 by far.
Deformation of planar ring mesh under static in-plane tensile loads
Authors: Dries Fabian W. , Wallmersperger Thomas , Kessler Jörg
Published: November 2022

A ring mesh is a large-scale manufacturable structure with versatile applications in architecture and for protective systems. However, the static and dynamic numerical simulation of a large-scale ring mesh is a resource-intensive task due to the many nonlinear contact points between the individual rings. To characterize the rigid body behavior of the ring mesh, in this paper, a representative volume element is loaded under different in-plane directions. The Green-Lagrangian strain tensor components are obtained as a result. An implicit one-step algorithm is used for this dynamic relaxation issue, modified by the use of stiff springs. Static convergence positions of a representative volume element are determined in several multiaxial tensile directions. The obtained deformation parameters can be used to simulate large deformations of large-scaled ring meshes.
The Roles of the Moss Layer in Mediating Tree Seedling Environmental Stress, Mercury Exposure, and Regeneration in High-Elevation Conifer Forests
Authors: Berdugo Monica B. , Dovciak Martin , Kimmerer Robin W. , Driscoll Charles T.
Published: November 2022

The persistence of future forests depends on the success of tree seedlings which are experiencing increasing physiological stress from changing climate and air pollution. Although the moss layer can serve as an important substrate for tree seedlings, its potential for reducing environmental stress and enhancing the establishment of seedlings remains poorly understood. We tested if the moss layer decreased environmental stress and increased the abundance of balsam fir seedlings dominant in high-elevation forests of northeastern United States that are sensitive to changing climate and mercury deposition. We surveyed balsam fir seedling density by substrate (moss, litter, other) on 120 quadrats (1 × 1 m) in two contrasting canopy environments (in gaps and under canopies), measured seedling stress, and quantified mercury content in seedlings and substrates. We observed that, in both canopy environments, tree seedlings established on moss exhibited (i) increased density, (ii) decreased physiological stress, and (iii) higher potential to recruit into larger size classes, compared to seedlings established in litter. Regardless of canopy environment, seedling foliar mercury levels did not correspond to substrate mercury despite large differences in substrate mercury concentrations (relative to moss, litter concentrations were ~ 4-times greater and soil concentrations were ~ 6-times greater), likely reflecting the dominance of foliar over root uptake of mercury. Because the moss layer appeared to mitigate seedling drought stress, and to increase seedling establishment and recruitment compared to other substrates, these microsite effects should be considered in models predicting forest regeneration and dynamics under increased drought stress associated with the ongoing climate warming.
Cyber risk management for autonomous passenger ships using threat-informed defense-in-depth
Authors: Amro Ahmed , Gkioulos Vasileios
Published: November 2022

Recent innovations in the smart city domain have led to the proposition of a new mode of transportation utilizing Autonomous Passenger Ships (APS) or ferries in inland waterways. The novelty of the APS concept influenced the cyber risk paradigm and led to different considerations regarding attack objectives, techniques as well as risk management approaches. The main factor that has led to this is the autoremote operational mode, which refers to autonomous operations and remote supervision and control in case of emergency. The autoremote operational mode influences the risk of cyber attacks due to the increased connectivity and reliance on technology for automating navigational functions. On the other hand, the presence of passengers without crew members imposes a safety risk factor in cyber attacks. In this paper, we propose a new cyber risk management approach for managing the cyber risks against cyber physical systems in general and Autonomous Passenger Ships in particular. Our proposed approach aims to improve the Defense-in-Depth risk management strategy with additional components from the Threat-Informed Defense strategy allowing for more evolved cyber risk management capabilities. Moreover, we have utilized the proposed cyber risk management approach for the proposition of a cybersecurity architecture for managing the cyber risks against an APS use case named milliAmpere2. Additionally, we present our results after conducting a Systematic Literature Review (SLR) in cybersecurity evaluation in the maritime domain. Then, the findings of the SLR were utilized for a suitable evaluation of the proposed risk management approach. Our findings suggest that our proposed risk management approach named Threat-Informed Defense-in-Depth is capable of enriching several risk management activities across different stages in the system development life cycle. Additionally, a comprehensive evaluation of the cybersecurity posture of milliAmpere2 has been conducted using several approaches including risk evaluation, simulation, checklist, and adversary emulation. Our evaluation has uncovered several limitations in the current cybersecurity posture and proposed actions for improvement.
Utilizing a Digital Swarm Intelligence Platform to Improve Consensus Among Radiologists and Exploring Its Applications
Authors: Shah Rutwik , Astuto Arouche Nunes Bruno , Gleason Tyler , Fletcher Will , Banaga Justin , Sweetwood Kevin , Ye Allen , Patel Rina , McGill Kevin , Link Thomas , Crane Jason , Pedoia Valentina , Majumdar Sharmila
Published: November 2022

Radiologists today play a central role in making diagnostic decisions and labeling images for training and benchmarking artificial intelligence (AI) algorithms. A key concern is low inter-reader reliability (IRR) seen between experts when interpreting challenging cases. While team-based decisions are known to outperform individual decisions, inter-personal biases often creep up in group interactions which limit nondominant participants from expressing true opinions. To overcome the dual problems of low consensus and interpersonal bias, we explored a solution modeled on bee swarms. Two separate cohorts, three board-certified radiologists, (cohort 1), and five radiology residents (cohort 2) collaborated on a digital swarm platform in real time and in a blinded fashion, grading meniscal lesions on knee MR exams. These consensus votes were benchmarked against clinical (arthroscopy) and radiological (senior-most radiologist) standards of reference using Cohen’s kappa. The IRR of the consensus votes was then compared to the IRR of the majority and most confident votes of the two cohorts. IRR was also calculated for predictions from a meniscal lesion detecting AI algorithm. The attending cohort saw an improvement of 23% in IRR of swarm votes (k= 0.34) over majority vote (k= 0.11). Similar improvement of 23% in IRR (k= 0.25) in 3-resident swarm votes over majority vote (k= 0.02) was observed. The 5-resident swarm had an even higher improvement of 30% in IRR (k= 0.37) over majority vote (k= 0.07). The swarm consensus votes outperformed individual and majority vote decision in both the radiologists and resident cohorts. The attending and resident swarms also outperformed predictions from a state-of-the-art AI algorithm.
Cognitive changes are associated with increased blood-brain barrier leakage in non-brain metastases lung cancer patients
Authors: Zhang Da-Fu , Li Zhen-Hui , Zhang Zhi-Ping , He Yin-Fu , Shang Bin-Li , Xu Xiu-Feng , Ding Ying-Ying , Cheng Yu-Qi
Published: November 2022

To explore the relationship between cognitive function and blood–brain barrier leakage in non-brain metastasis lung cancer and healthy controls. 75 lung cancers without brain metastasis and 29 healthy controls matched with age, sex, and education were evaluated by cognitive assessment, and the Patlak pharmacokinetic model was used to calculate the average leakage in each brain region according to the automated anatomical labeling atlas. After that, the relationships between cognitive and blood–brain barrier leakage were evaluated. Compared with healthy controls, the leakage of bilateral temporal gyrus and whole brain gyrus were higher in patients with lung cancers (P < 0.05), mainly in patients with advanced lung cancer (P < 0.05), but not in patients with early lung cancer (P > 0.05). The cognitive impairment of advanced lung cancers was mainly reflected in the damage of visuospatial/executive, and delayed recall. The left temporal gyrus with increased blood–brain barrier leakage showed negative correlations with delayed recall (r = -0.201, P = 0.042). An increase in blood–brain barrier leakage was found in non-brain metastases advanced lung cancers that corresponded to decreased delayed recall. With progression in lung cancer staging, blood–brain barrier shows higher leakage and may lead to brain metastases and lower cognitive development.
Anisotropic Continuum-Molecular Models: A Unified Framework Based on Pair Potentials for Elasticity, Fracture and Diffusion-Type Problems
Authors: Diana Vito
Published: November 2022

This paper presents a unified framework for continuum-molecular modeling of anisotropic elasticity, fracture and diffusion-based problems within a generalized two-dimensional peridynamic theory. A variational procedure is proposed to derive the governing equations of the model, that postulates oriented material points interacting through pair potentials from which pairwise generalized actions are computed as energy conjugates to properly defined pairwise measures of primary field variables. While mass is considered as continuous function of volume, we define constitutive laws for long-range interactions such that the overall anisotropic behavior of the material is the result of the assigned elastic, conductive and failure micro-interaction properties. The non-central force assumption in elasticity, together with the definition of specific orientation-dependent micromoduli functions respecting material symmetries, allow to obtain a fully anisotropic non-local continuum using a purely pairwise description of deformation and constitutive properties. A general and consistent micro-macro moduli correspondence principle is also established, based on the formal analogy with the classic elastic and conductivity tensors. The main concepts presented in this work can be used for further developments of anisotropic continuum-molecular formulations to include other mechanical behaviors and coupled phenomena involving different physics.
Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction
Authors: Li Xuying , Zhai Qian , Gou Xingchun , Quan Minxue , Li Yansong , Zhang Xiaohua , Deng Bin , Tian Yi , Wang Qiang , Hou Lichao
Published: November 2022

Sleep loss is often associated with cognitive dysfunction. Alterations in the structure and function of synapses in the hippocampus are thought to underlie memory storage. Paired immunoglobulin-like receptor B (PirB) plays a negative role in various neurological diseases by inhibiting axon regeneration and synaptic plasticity. However, the contributions of PirB to the mechanisms underlying the changes in synaptic plasticity after sleep loss that ultimately promote deficits in cognitive function have not been well elucidated. Here, we showed that chronic sleep restriction (CSR) mice displayed cognitive impairment and synaptic deficits accompanied by upregulation of PirB expression in the hippocampus. Mechanistically, PirB caused the dysregulation of actin through the RhoA/ROCK2/LIMK1/cofilin signalling pathway, leading to abnormal structural and functional plasticity, which in turn resulted in cognitive dysfunction. PirB knockdown alleviated synaptic deficits and cognitive impairment after CSR by inhibiting the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Moreover, we found that fasudil, a widely used ROCK2 inhibitor, could mimic the beneficial effect of PirB knockdown and ameliorate synaptic deficits and cognitive impairment, further demonstrating that PirB induced cognitive dysfunction after CSR via the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Our study sheds new light on the role of PirB as an important mediator in modulating the dysfunction of synaptic plasticity and cognitive function via the RhoA/ROCK2/LIMK1/cofilin signalling pathway, which indicated that hippocampal PirB is a promising therapeutic target for counteracting cognitive impairment after CSR.

Graphical Abstract

This illustration depicts the signalling pathway by PirB in mediating cognitive impairment and synaptic deficits in CSR mice. In the hippocampus of CSR mice, the expression level of PirB was significantly increased. In addition, CSR increases RhoA and ROCK2 levels and reduces levels of both LIMK1 and cofilin phosphorylation. PirB knockdown reverses cognitive impairment and synaptic plasticity disorders caused by CSR through the RhoA/ROCK2/LIMK1/cofilin signalling pathway
Has the IPCC’s revised vulnerability concept been well adopted?
Authors: Estoque Ronald C. , Ishtiaque Asif , Parajuli Jagadish , Athukorala Darshana , Rabby Yasin Wahid , Ooba Makoto
Published: November 2022

In the Third and Fourth Assessment Reports (TAR and AR4, respectively) by the Intergovernmental Panel on Climate Change (IPCC), vulnerability is conceived as a function of exposure, sensitivity, and adaptive capacity. However, in its Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX) and Fifth Assessment Report (AR5), the IPCC redefined and separated exposure, and it reconceptualized vulnerability to be a function of sensitivity and capacity to cope and adapt. In this review, we found that the IPCC’s revised vulnerability concept has not been well adopted and that researchers’ preference, possible misinterpretation, possible confusion, and possible unawareness are among the possible technical and practical reasons. Among the issues that need further clarification from the IPCC is whether or not such a reconceptualization of vulnerability in the SREX/AR5 necessarily implies nullification of the TAR/AR4 vulnerability concept as far as the IPCC is concerned.
A comprehensive study of buckwheat husk co-pelletization for utilization via combustion
Authors: Joka Yildiz Magdalena , Cwalina Paweł , Obidziński Sławomir
Published: November 2022

Buckwheat husks are a valuable source of carbon and show the potential to be used as an energy source. However, due to low bulk density and low susceptibility to compaction, it is beneficial to use them in the form of co-pellets. The study presents comprehensive research detailing buckwheat husks’ potential for co-pelletization with oily (peanut husks) and dusty (senna leaves) agri-food wastes, whereas the effect of material parameters such as the amount of additive (10, 15, 20%) and the process parameters as the die rotational speed (170, 220, 270 rpm) on pellets’ quality (kinetic durability, bulk and particle density, degree of compaction) and the energy consumption of the pelletization process were examined. Ten percent of potato pulp as a binder was added to each pelletized mixture. It was found that an increase in the senna leaf content affects positively the kinetic durability of pellets. The fatty peanut husks have a negative effect on the pellets’ quality (measured by the kinetic durability and bulk density); however, both additions of senna leaves and peanut husks are lowering the energy consumption of the pelletizer. The highest quality pellets and the addition of 10% peanut husks to buckwheat husks (kinetic durability of 96%) and 20% of senna leaves to buckwheat husks (kinetic durability of 92%) obtained at 170 rpm were subjected to combustion in a fixed-bed unit, and the content of CO, CO2, NO, SO2, HCl, and O2 in the fuel gases was measured. The emission factors were higher than the Ecodesign limitations (CO > 500 mg·Nm−3, NO > 200 mg·Nm−3). The obtained results indicate that buckwheat husks can be successfully co-pelletized with other waste biomass; however, the pellets to be combusted require a boiler with improved air-supplying construction.
Identification of potential diagnostic and prognostic biomarkers for papillary thyroid microcarcinoma (PTMC) based on TMT-labeled LC–MS/MS and machine learning
Authors: Li J. , Mi L. , Ran B. , Sui C. , Zhou L. , Li F. , Dionigi G. , Sun H. , Liang N.
Published: November 2022

Objectives

To explore the molecular mechanisms underlying aggressive progression of papillary thyroid microcarcinoma and identify potential biomarkers.

Methods

Samples were collected and sequenced using tandem mass tag-labeled liquid chromatography–tandem mass spectrometry. Differentially expressed proteins (DEPs) were identified and further analyzed using Mfuzz and protein–protein interaction analysis (PPI). Parallel reaction monitoring (PRM) and immunohistochemistry (IHC) were performed to validate the DEPs.

Results

Five thousand, two hundred and three DEPs were identified and quantified from the tumor/normal comparison group or the N1/N0 comparison group. Mfuzz analysis showed that clusters of DEPs were enriched according to progressive status, followed by normal tissue, tumors without lymphatic metastases, and tumors with lymphatic metastases. Analysis of PPI revealed that DEPs interacted with and were enriched in the following metabolic pathways: apoptosis, tricarboxylic acid cycle, PI3K-Akt pathway, cholesterol metabolism, pyruvate metabolism, and thyroid hormone synthesis. In addition, 18 of the 20 target proteins were successfully validated with PRM and IHC in another 20 paired validation samples. Based on machine learning, the five proteins that showed the best performance in discriminating between tumor and normal nodules were PDLIM4, ANXA1, PKM, NPC2, and LMNA. FN1 performed well in discriminating between patients with lymph node metastases (N1) and N0 with an AUC of 0.690. Finally, five validated DEPs showed a potential prognostic role after examining The Cancer Genome Atlas database: FN1, IDH2, VDAC1, FABP4, and TG. Accordingly, a nomogram was constructed whose concordance index was 0.685 (confidence interval: 0.645–0.726).

Conclusions

PDLIM4, ANXA1, PKM, NPC2, LMNA, and FN1 are potential diagnostic biomarkers. The five-protein nomogram could be a prognostic biomarker.
Biosafety of inorganic nanomaterials for theranostic applications
Authors: Kang Moon Sung , Kwon Mina , Jang Hee Jeong , Jeong Seung Jo , Han Dong-Wook , Kim Ki Su
Published: November 2022

Recent advances in inorganic nanomaterial-based theranostics enabled imaging-guided molecular targeting and drug delivery, and various combinations of theranostic systems. The term “theranostics” is defined as diagnosis processed with therapy simultaneously with a specific connection between therapy and diagnosis. The inorganic nanomaterials, representatively carbon, metal, ceramic, and semiconductor-based nanomaterials, exhibit their unique characteristics to be used in theranostic applications. However, the unveiled human biosafety of nanomaterials for clinical use has become a major concern. Therefore, in this review, we compiled recent research on in vitro and in vivo biosafety of inorganic nanomaterials in various theranostic applications, along with a discussion of how the particle formulation, size, surface functionalization, test species, and test condition affect biocompatibility. Furthermore, the progress and challenges of the development of biocompatible inorganic nanomaterials for theranostic applications were discussed. In conclusion, with appropriate precautions on the biosafe condition to be administered, inorganic nanomaterials can be proposed to have excellent potential in the future theranostic application.
Using Macroeconomic Indicators to Enact an Ambitious Circular Economy
Authors: Pinyol Alberich Josep , Llorente-González Leandro J. , Ramezankhani Mohammad Javad , Bimpizas-Pinis Meletios , Lowe Benjamin H.
Published: November 2022

The circular economy has the potential to promote systemic change towards a sustainable future. However, the dominance of technical and market-oriented considerations has placed the circular economy as part of an eco-modernist agenda, which retains growth in gross domestic product as the overarching priority. In this context, we analyse 12 existing macroeconomic indicators, developed and implemented by governments and international organisations, and determine if they could enact alternative notions of circularity. Specifically, we focus on the performative role that indicators can play in both defining and surmounting such reductionist views, thus helping us to address the world we want to create. We find that many of these indicators are agents of the status quo, but that some could disrupt the omnipotence of GDP thereby getting the macroeconomic conditions right for a more ambitious understanding of the circular economy.
Democracy, epistemic agency, and AI: political epistemology in times of artificial intelligence
Authors: Coeckelbergh Mark
Published: November 2022

Democratic theories assume that citizens have some form of political knowledge in order to vote for representatives or to directly engage in democratic deliberation and participation. However, apart from widespread attention to the phenomenon of fake news and misinformation, less attention has been paid to how they are supposed to acquire that knowledge in contexts shaped by artificial intelligence and related digital technologies. While this topic can also be approached from an empirical angle, this paper contributes to supporting concerns about AI and democracy by looking at the issue through the lens of political epistemology, in particular using the concept of epistemic agency. It argues that artificial intelligence (AI) endangers democracy since it risks to diminish the epistemic agency of citizens and thereby undermine the relevant kind of political agency in democracy. It shows that next to fake news and manipulation by means of AI analysis of big data, epistemic bubbles and the defaulting of statistical knowledge endanger the epistemic agency of citizens when they form and wish to revise their political beliefs. AI risks to undermine trust in one’s own epistemic capacities and hinder the exercise of those capacities. If we want to protect the knowledge basis of our democracies, we must address these problems in education and technology policy.