bluuebunny/crossref_metadata_2025 huggingface dataset:
On the usefulness of flying base stations in 5G and beyond scenarios
Authors: Cumino Pedro , Luís Miguel , Rosário Denis , Cerqueira Eduardo , Sargento Susana
Published: August 2023

Considering that one of the goals of the future network generations is to provide ubiquitous communication in the most diverse scenarios to achieve high connection coverage, it is foreseen that the use of unmanned aerial vehicles as flying base stations (UAV-BSs) can potentially extend the network and communication range. UAVs as flying base station can bring the potential to assist user devices and vehicles by carrying communication resources that can accommodate clients that were not previously planned by the ground infrastructure design due to flash crowd events, sudden natural disasters, or any other event that let to an overloaded environment. Allocating UAVs as flying base station still poses significant challenges in their deployment and the effectiveness of information transmission through UAVs as flying base station in the context of wireless communication since it is necessary to deal with both wireless communication capability and interference in the presence of terrestrial infrastructures already present. Besides, it is essential to understand how communication resources affect network performance. This paper studies the feasibility of using UAVs as flying base station in the assistance of wireless communication in a scenario where there is a sudden demand for data transmission due to possible congestion of local infrastructure. We show how the number of communication resources provided by the UAV-BS, the interference caused by the presence of multiple next generation node Bs (gNBs), and the UAV as flying base station positioning affect the network performance. We also highlight the need for a better next generation node B (gNB) and UAVs placement criteria since the received signal power prevents the user equipments (UEs) from using most of the available resources.
Combined effects of loneliness and inflammation on depression in people with HIV
Authors: Hussain Mariam A. , Watson C. Wei-Ming , Morgan Erin E. , Heaton Robert K. , Letendre Scott L. , Jeste Dilip V. , Moore David J. , Iudicello Jennifer E.
Published: August 2023

Objective

Loneliness is prevalent in people with HIV (PWH) and associated with adverse health-related consequences, including depression. Chronic inflammation has been linked to depression in PWH, though its association with loneliness is less well established. Simultaneous examination of inflammation, loneliness and depression is needed to clarify these relationships. This study investigated the relationship between loneliness and inflammation, and the effects of loneliness and inflammation on depression in PWH.

Methods

82 PWH who were on suppressive ART (mean age [SD] = 53.2 [9.0]) completed the UCLA Loneliness Scale-Version 3 and the Center for Epidemiologic Studies Depression Scale as part of a comprehensive evaluation. Biomarkers of systemic inflammation (CRP, IL-6, CCL2/MCP-1, sCD14) and coagulation (D-dimer) were measured in blood using commercial immunoassays.

Results

Multivariable linear regression analyses revealed that higher D-dimer, CCL2/MCP-1, and sCD14 were significant predictors of loneliness (ps < .05) while accounting for relevant covariates. Stepwise multiple linear regression models that included loneliness, biomarkers, and their interactions as predictors of depressive symptoms revealed significant main effects of loneliness and CCL2/MCP-1 levels (ps < .05), and a significant loneliness by D-dimer interaction (p < .05) whereby higher D-dimer was associated with increased depressive symptoms only at higher levels of loneliness.

Conclusions

Increased coagulation activity is associated with loneliness, and in the context of loneliness, may increase risk for depression. Increased inflammation was associated with depression suggesting potentially dissociable underlying biological processes. To the extent that these processes are modifiable, such findings could have important implications in the treatment of loneliness and depression in PWH.
Umgang mit Desinfektionsmitteln in Kleinbetrieben ausgewählter Branchen in Gesundheitsdienst und Wohlfahrtspflege
Authors: Michaelis Martina , Anhäuser Lea , Gerding Johannes , Nienhaus Albert , Stößel Ulrich
Published: August 2023

Hintergrund und Fragestellung

Die Desinfektion von Händen, Flächen und ggf. Arbeitsmitteln war insbesondere in Betrieben des Gesundheitsdienstes und der Wohlfahrtspflege schon immer wichtig und wurde seit Beginn der SARS-CoV-2-Pandemie noch wichtiger. Der Umgang mit Desinfektionsmitteln birgt auf der anderen Seite auch Gesundheitsgefahren. Insbesondere Klein- und Kleinstunternehmen (KKU) gelten hinsichtlich formaler Arbeitsschutzkriterien als schlechter aufgestellt als größere Betriebe. Zu unserer Hauptforschungsfrage „Wie wird in KKU mit Desinfektionsmitteln als Gefahrstoff umgegangen?“ lagen bislang keine empirischen Ergebnisse vor, so dass wir im Frühjahr 2022 Betriebsinhabende schriftlich befragten.

Material und Methoden

Es wurden zufällig ausgewählte Mitgliedsbetriebe der Berufsgenossenschaft für Gesundheitsdienst und Wohlfahrtspflege (BGW) in 5 KKU-Branchen angeschrieben. Die Datenauswertung erfolgte branchenvergleichend mittels bivariater Regressionsanalysen.

Ergebnisse

Der Fragebogenrücklauf in therapeutischen Praxen (n = 127), Friseur- (n = 94) und Kosmetikstudios (n = 932), Kitas (n = 90) und ambulanten Pflegediensten (n = 129) war im Mittel 12 %. Eine unsachgemäße Lagerung von Desinfektionsmitteln war selten. Beim Umfüllen aus größeren Gebinden in kleinere Spender wurden in 73 % der Betriebe Schutzhandschuhe getragen und die Spenderflaschen sachgemäß gekennzeichnet. Fast immer wurden Beschäftigte zum sicheren Umgang mit Desinfektionsmitteln informiert, allerdings nur in 44 % der Betriebe durch Unterweisungen. Desinfektionspläne wurden in 82 % der Betriebe regelmäßig aktualisiert, Sicherheitsdatenblätter in 61 % verwendet und Gefährdungsbeurteilungen in 41 % durchgeführt. Fehler im Umgang mit Desinfektionsmitteln passierten aus der Sicht der Befragten nur selten. Ambulante Pflegedienste wiesen bei einigen Aspekten eine bessere Arbeitsschutzqualität auf als andere Betriebe.

Diskussion

Die Umsetzung von Unterweisungen und Gefährdungsbeurteilungen als Bestandteil des gesetzlich vorgeschriebenen Arbeitsschutzes ist – wie auch aus anderen Studien bekannt – in den untersuchten Betrieben defizitär, auch wenn auf der anderen Seite der sichere Umgang mit Desinfektionsmitteln in vielen KKU auf andere Weise informell thematisiert zu werden scheint. Das Gefahrstoffmanagement und der Umgang mit Desinfektionsmitteln selbst erscheinen im Großen und Ganzen unproblematisch. Limitationen: Angesichts des geringen Fragebogenrücklaufs hätte eine Verallgemeinerung der Ergebnisse vermutlich eine eher zu positive Einschätzung der Situation in der Grundgesamtheit zur Folge.
Machine learning for embodied carbon life cycle assessment of buildings
Authors: El Hafdaoui Hamza , Khallaayoun Ahmed , Bouarfa Ibtissam , Ouazzani Kamar
Published: August 2023

This paper addresses the significant issue of embodied carbon in buildings and presents a comprehensive approach to its assessment. A machine learning model is proposed, leveraging authentic databases and supervised learning techniques to estimate the environmental impacts of embodied carbon throughout the building life cycle. Validation of the model revealed average percentage errors of approximately 15.71% across different countries. The study also introduces a standardized algorithmic protocol and guidelines for assessing embodied carbon, demonstrated through a case study in Morocco. Results indicate that conventional residential buildings of 120 m2 emit 34.7 tons of embodied carbon, with floors contributing 55%, structure 27%, envelope 14%, and openings 4%. Notably, insulation accounts for 37.0% of the total embodied carbon. Recommendations include incorporating additional databases for learning, considering transportation emissions and primary materials sources, and training the model for different life cycle stages to enhance accuracy. This research provides valuable insights for reducing embodied carbon in buildings and promoting sustainable construction practices.
Not so simple
Authors: Caret Colin R.
Published: August 2023

In a recent series of articles, Beall has developed the view that FDE is the formal system most deserving of the honorific “Logic”. The Simple Argument for this view is a cost-benefit analysis: the view that FDE is Logic has no drawbacks and it has some benefits when compared with any of its rivals. In this paper, I argue that both premises of the Simple Argument are mistaken. I use this as an opportunity to further reflect on how such arguments can be bolstered to provide more substantial and productive support for revisionary theses about Logic.
Causation in the Law of the World Trade Organization
Authors: Gascoigne Catherine
Published: August 2023

Causation in the Law of the World Trade Organization: An Econometric Approach is for both scholars and practitioners of WTO law with an interest in the causal questions that WTO law raises. Assuming no prior knowledge of causal philosophy or statistical analysis, Dr Gascoigne discusses the problems in the current approach to causation in the WTO jurisprudence and proposes an alternative methodology that draws on causal philosophy and econometric analysis. The book demonstrates how this methodology could be harnessed to make causal determinations for the purpose of implementing trade remedies and to make out claims of serious prejudice. It also argues that the methodology could be helpful for assessing the impact of domestic legislation on policy objectives under the General Exceptions and the Technical Barriers to Trade Agreement as well as for calculating the amount of retaliation permissible under the Dispute Settlement Understanding.
Understanding Charles Darwin
Authors: Peterson Erik L.
Published: August 2023

The legend of Charles Darwin has never been more alive or more potent, but by virtue of this, his legacy has become susceptible to myths and misunderstandings. Understanding Charles Darwin examines key questions such as what did Darwin's work change about the world? In what ways is 'Darwinism' reflective of Darwin's own views? What problems were left unsolved? In our elevation of Darwin to this iconic status, have we neglected to recognise the work of other scientists? The book also examines Darwin's struggle with his religious beliefs, considering his findings, and whether he was truly an atheist. In this engaging account, Peterson paints an intimate portrait of Darwin from his own words in private correspondence and journals. The result is the Darwin you never knew.
Spacecraft attitude control based on generalised dynamic inversion with adaptive neural network
Authors: Jafri S. M. N. , Aslam M. I.
Published: August 2023

This paper proposes a robust generalised dynamic inversion (GDI) control system design with adaptive neural network (NN) estimation for spacecraft attitude tracking under the absence of knowledge of the spacecraft inertia parameters. The robust GDI control system works to enforce attitude tracking, and the adaptive NN augmentation compensates for the lack of knowledge of the spacecraft inertia parameters. The baseline GDI control law consists of a particular part and an auxiliary part. The particular part of the GDI control law works to realise a desired attitude dynamics of the spacecraft, and the auxiliary part works for finite-time stabilisation of the spacecraft angular velocity. Robustness against modeling uncertainties and external disturbances is provided by augmenting a siding mode control element within the particular part of the GDI control law. The singularity that accompanies GDI control is avoided by modifying the Moore-Penrose generalised inverse by means of a dynamic scaling factor. The NN weighting matrices are updated adaptively through a control Lyapunov function. A detailed stability analysis shows that the closed loop system is semi-global practically stable. For performance assessment, a spacecraft model is developed, and GDI-NN control is investigated for its attitude control problem through numerical simulations. Simulation results reveal the efficacy, robustness and adaptive attributes of proposed GDI-NN control for its application to spacecraft attitude control.
Was There an Administrative Revolution?
Authors: Qiao George Zhijian
Published: August 2023

This essay takes a close look at Maura Dykstra's monograph Uncertainty in the Empire of Routine (Harvard Asia Center, 2022). It analyzes the book's multitude of problems, such as its flawed conception, numerous factual blunders, failure to engage existing scholarship, problematic choice of primary sources, and dubious citation practices. Most significantly, this essay aims to provide ample evidence to demonstrate how the book systematically misrepresents the majority of its primary sources to support an untenable thesis. It argues that the book's central claims are ungrounded in evidence.
Stratified horizontal convection
Authors: Noto Daisuke , Ulloa Hugo N. , Yanagisawa Takatoshi , Tasaka Yuji
Published: August 2023

Surface differential heating on a stably stratified fluid body drives an overturning circulation confined to the upper fluid region – here coined stratified horizontal convection (SHC). In this manuscript, we investigate the dynamics of SHC via laboratory experiments, exploring local and global flow properties. By considering the available potential energy of the system, we derive a unique length scale of SHC and introduce the Péclet number

$Pe$

that captures both the stabilising effect of stratification and the destabilising effect of the baroclinic adjustment. We found that

$Pe$

characterises local and global flow properties, including the fluid transport of the overturning circulation, the available mechanical energy and the flow dimensionality. Our study provides insights into the fluid dynamics of stratified environments that experience horizontal convection, such as lakes, oceans and atmospheres.
The politics of (de)liberalization: studying partisan effects using mixed-effects models
Authors: Garritzmann Julian L. , Seng Kilian
Published: August 2023

Liberalization is a perennial topic in politics and political science. We first review a broad scholarly debate, showing that the mainstream theories make rival and contradictory claims regarding the role of political parties in (de)liberalization reforms. We then develop a framework of conditional partisan influence, arguing that and under what conditions parties matter. We test our (and rival) propositions with a new dataset on (de)liberalization reforms in 23 democracies since 1973 covering several policy areas. Methodologically, we argue that existing quantitative studies are problematic: They rely on time-series cross-section models using country-year observations; but governments do not change annually, so that the number of observations is artificially inflated, resulting in incorrect estimates. We propose mixed-effects models instead, with country-year observations nested in cabinets, which are nested in countries and years. The results show under what conditions parties matter for (de)liberalization. More generally, the paper argues that mixed-effects models should become the new standard for studying partisan influences.
Narratives of Racial Duty: Competitive Reality Television Series as Sites for Studying Racialized Social Obligations and Black Group-Based Decision-Making
Authors: Harbin M. Brielle
Published: August 2023

How do Black Americans practice a politics of racial group uplift while balancing their individual material interests? Traditionally, scholars have drawn on linked fate theory. However, more recent work argues that Black Americans remain politically unified because they feel race-based social pressure to conform more than a sense of linked fate. Employing a novel research design, I use the competitive reality television series, Survivor, to observe and analyze Black group-based decision-making. Through an inductive thematic content analysis of 13 Survivor episodes, I identified five themes in Black players’ discussions of racialized social obligations when playing the game—what I call narratives of racial duty. Claims that emerged in this storytelling suggested that similar to the political world, Black Survivor contestants were keenly aware of the racialized social obligations for them as contestants in the game. For some, this reality felt like a burden. For others, it presented an opportunity. These reactions led some Black players to work together and others to construct a rationale for defecting from race-based alliances. I conclude by making the case that analyzing entertainment programs offers race and politics scholars a new site for identifying common scripts used to adhere to (and sidestep) racialized social norms.
Eugenics and the Approval of Birth Control at the 1930 Lambeth Conference
Authors: MOELLER ANDREW
Published: August 2023

Following the vote in favour of birth control at the 1930 Lambeth Conference, the Church of England became the first major Christian denomination explicitly to condone the use of birth control. This paper argues that the bishop of Winchester, Theodore Woods, was the previously unheralded principal actor responsible for reversing the position of the Church. Woods was convinced that the Church needed to ‘modernise’ its position in order to secure a receptive audience for its higher-ordered teachings on marriage, sex and especially procreation. In turn, he hoped to bring about an increased birthrate amongst the eugenically ‘desirable’ English middle and upper classes.
National survey sampling exercise on current practice in channelled local anaesthetic biopsy in suspected head and neck cancer
Authors: Lim Alison E , Moen Christy M , Montgomery Jenny
Published: August 2023

Objective

Out-patient channelled endoscopic local anaesthetic biopsy reduces the time to diagnosis and wider use may improve cancer pathway times. This study aimed to assess the practice of ENT surgeons using channelled local anaesthetic biopsy.

Method

A survey was distributed nationally, containing questions about out-patient local anaesthetic biopsy.

Results

In total, 58 responses were returned; only 12 per cent of respondents (n = 7) used general anaesthetic biopsy. The advantages of local anaesthetic biopsy were: the avoidance of general anaesthetic for patients with poor performance scores (95 per cent, n = 55) and faster cancer pathway times (91 per cent, n = 53). Disadvantages were: clinics running late (29 per cent, n = 17) and complications (24 per cent, n = 14). The main barrier to using local anaesthetic was access to channelled flexible endoscopy (38 per cent, n = 22), with 43 per cent (n = 25) reporting they were not using out-patient channelled endoscopes but would be interested in using them.

Conclusion

Surgeons are interested in using channelled endoscopic local anaesthetic biopsy, but they are limited by access to equipment. Increased use of channelled endoscopes may improve national cancer pathway times and avoid challenging general anaesthetics.
Prospective association of attachment style with suicide attempts among US Army soldiers
Authors: Naifeh James A. , Ursano Robert J. , Stein Murray B. , Wang Jing , Mash Holly B. Herberman , Aliaga Pablo A. , Fullerton Carol S. , Dinh Hieu M. , Kao Tzu-Cheg , Sampson Nancy A. , Kessler Ronald C.
Published: August 2023

Background

Insecure attachment styles are associated with retrospectively reported suicide attempts (SAs). It is not known if attachment styles are prospectively associated with medically documented SAs.

Methods

A representative sample of US Army soldiers entering service (n = 21 772) was surveyed and followed via administrative records for their first 48 months of service. Attachment style (secure, preoccupied, fearful, dismissing) was assessed at baseline. Administrative medical records identified SAs. Discrete-time survival analysis examined associations of attachment style with future SA during service, adjusting for time in service, socio-demographics, service-related variables, and mental health diagnosis (MH-Dx). We examined whether associations of attachment style with SA differed based on sex and MH-Dx.

Results

In total, 253 respondents attempted suicide. Endorsed attachment styles included secure (46.8%), preoccupied (9.1%), fearful (15.7%), and dismissing (19.2%). Examined separately, insecure attachment styles were associated with increased odds of SA: preoccupied [OR 2.5 (95% CI 1.7–3.4)], fearful [OR 1.6 (95% CI 1.1–2.3)], dismissing [OR 1.8 (95% CI 1.3–2.6)]. Examining attachment styles simultaneously along with other covariates, preoccupied [OR 1.9 (95% CI 1.4–2.7)] and dismissing [OR 1.7 (95% CI 1.2–2.4)] remained significant. The dismissing attachment and MH-Dx interaction was significant. In stratified analyses, dismissing attachment was associated with SA only among soldiers without MH-Dx. Other interactions were non-significant. Soldiers endorsing any insecure attachment style had elevated SA risk across the first 48 months in service, particularly during the first 12 months.

Conclusions

Insecure attachment styles, particularly preoccupied and dismissing, are associated with increased future SA risk among soldiers. Elevated risk is most substantial during first year of service but persists through the first 48 months. Dismissing attachment may indicate risk specifically among soldiers not identified by the mental healthcare system.
Experimentation-based Policymaking for Urban Regeneration in Shenzhen, China
Authors: Tong De , Yang Shuang , Lai Yani
Published: August 2023

A growing appreciation of the potential benefits of experimentation to tame the complexities of urban transformation has led to an increase in related research activity. Building on a “practice-to-policy” experimentation-based framework, this paper investigates the adaptive policymaking process for urban regeneration in Shenzhen since the 2000s. It finds that “explorative experimentation” is used to identify a general direction in the absence of a clear route for the policy process, while “generative experimentation” is sequentially dedicated to specific issues for the improvement of the entire policy package within a particular reform. We argue that understanding the successive roles or hybrid functions of these two types of experiment adds new insights to the development rationales for Shenzhen's urban regeneration and provides inspiration for an experimental model of urban governance. Governments and policymakers can benefit from the experimentation-based approach, as presented in the Shenzhen case, to pursue policy innovation embedded in local contexts.
‘Translating’ Classics for Generations Z and Alpha
Authors: Bozia Eleni , Pantazopoulou Anastasia , Smith Anthony J.
Published: August 2023

This paper presents a public outreach program developed by the Department of Classics at the University of Florida to introduce school-age children to Classics. The main goal is to emphasise the value of Classics and the practical skills it teaches by engaging students with hands-on exercises and materialising connections between the past and the present. The paper focuses on the importance of Classics and the humanities in the development of engaged citizens, the types of programs and their content, and ways to ensure the sustainability of such initiatives through the involvement of graduate students, faculty, and administrators.
The Politics of Time: The Political Origins of Working-Time Regulation
Authors: Rasmussen Magnus Bergli
Published: August 2023

Towards the end of the nineteenth century, leisure was reserved for the few. By the end of the twentieth century, however, most workers had a regulated normal working time of 40 or fewer hours per week, annual paid leave, and overtime compensation. In this paper, I investigate which political parties brought forth these changes – which party constellations supported or opposed working-time reforms and argue that sector and class differences drive party preferences. Lower-class and urban middle-class workers demanded regulation as demand for leisure increased with income. In contrast, employers and farmers opposed such reforms. Accordingly, the study argues that socialist and social-liberal parties were inclined to support leisure-securing working-time reforms, whereas conservative and farmer parties opposed them. Due to their linkages with workers and farmers, liberal parties may be divided into a rural constituency that tends to oppose working-time reforms and an urban constituency that supports them. I test these expectations using parliamentary data: 65 roll-call votes from Norway between 1880 and 1940, combined with analysis of major reforms and legislative appeals. Finally, I undertake a generalization test using country-level reform data from 33 democracies between 1880 and 2010. Results generally fall in line with expectations, and the pattern is stable over time.
Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake
Authors: Bojsen-Møller Kirstine Nyvold , Svane Maria Saur , Martinussen Christoffer , Dirksen Carsten , Jørgensen Nils Bruun , Jensen Jens-Erik Beck , Jensen Christian Zinck , Torekov Signe Sørensen , Kristiansen Viggo Bjerregaard , Rehfeld Jens Frederik , Bork-Jensen Jette , Grarup Niels , Hansen Torben , Hartmann Bolette , Holst Jens Juul , Madsbad Sten
Published: August 2023

Background/Objectives

After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.

Subjects/Methods

Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.

Results

On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (−1% [−13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).

Conclusions

Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.
Deciphering pathogenic cellular module at single-cell resolution in checkpoint inhibitor-related pneumonitis
Authors: Cui Pengfei , Li Jinfeng , Tao Haitao , Li Xiaoyan , Wu Liangliang , Ma Junxun , Wang Huanhuan , Liu Tingting , Zhang Min , Hu Yi
Published: August 2023

Checkpoint inhibitor pneumonitis (CIP) is the most common fatal immune-related adverse event; however, its pathophysiology remains largely unknown. Comprehensively dissecting the key cellular players and molecular pathways associated with CIP pathobiology is critical for precision diagnosis and develop novel therapy strategy of CIP. Herein, we performed a comprehensive single-cell transcriptome analysis to dissect the complexity of the immunological response in the bronchoalveolar lavage fluid (BALF) microenvironment. CIP was characterized by a dramatic accumulation of CXCL13+ T cells and hyperinflammatory CXCL9+ monocytes. T-cell receptor (TCR) analysis revealed that CXCL13+ T cells exhibited hyperexpanded- TCR clonotypes, and pseudotime analysis revealed a potential differentiation trajectory from naïve to cytotoxic effector status. Monocyte trajectories showed that LAMP3+ DCs derived from CXCL9+ monocytes possessed the potential to migrate from tumors to the BALF, whereas the differentiation trajectory to anti-inflammatory macrophages was blocked. Intercellular crosstalk analysis revealed the signaling pathways such as CXCL9/10/11-CXCR3, FASLG-FAS, and IFNGR1/2-IFNG were activated in CIP+ samples. We also proposed a novel immune signature with high diagnostic power to distinguish CIP+ from CIP− samples (AUC = 0.755). Our data highlighted key cellular players, signatures, and interactions involved in CIP pathogenesis.
Liquid-activated quantum emission from pristine hexagonal boron nitride for nanofluidic sensing
Authors: Ronceray Nathan , You Yi , Glushkov Evgenii , Lihter Martina , Rehl Benjamin , Chen Tzu-Heng , Nam Gwang-Hyeon , Borza Fanny , Watanabe Kenji , Taniguchi Takashi , Roke Sylvie , Keerthi Ashok , Comtet Jean , Radha Boya , Radenovic Aleksandra
Published: August 2023

Liquids confined down to the atomic scale can show radically new properties. However, only indirect and ensemble measurements operate in such extreme confinement, calling for novel optical approaches that enable direct imaging at the molecular level. Here we harness fluorescence originating from single-photon emitters at the surface of hexagonal boron nitride for molecular imaging and sensing in nanometrically confined liquids. The emission originates from the chemisorption of organic solvent molecules onto native surface defects, revealing single-molecule dynamics at the interface through the spatially correlated activation of neighbouring defects. Emitter spectra further offer a direct readout of the local dielectric properties, unveiling increasing dielectric order under nanometre-scale confinement. Liquid-activated native hexagonal boron nitride defects bridge the gap between solid-state nanophotonics and nanofluidics, opening new avenues for nanoscale sensing and optofluidics.
Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma
Authors: Lee Holly , Ahn Sungwoo , Maity Ranjan , Leblay Noemie , Ziccheddu Bachisio , Truger Marietta , Chojnacka Monika , Cirrincione Anthony , Durante Michael , Tilmont Remi , Barakat Elie , Poorebrahim Mansour , Sinha Sarthak , McIntyre John , M.Y. Chan Angela , Wilson Holly , Kyman Shari , Krishnan Amrita , Landgren Ola , Walter Wencke , Meggendorfer Manja , Haferlach Claudia , Haferlach Torsten , Einsele Hermann , Kortüm Martin K. , Knop Stefan , Alberge Jean Baptiste , Rosenwald Andreas , Keats Jonathan J. , Rasche Leo , Maura Francesco , Neri Paola , Bahlis Nizar J.
Published: August 2023

B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy. In two cases, MM relapse post-TCE/CAR T therapy was driven by BCMA-negative clones harboring focal biallelic deletions at the TNFRSF17 locus at relapse or by selective expansion of pre-existing subclones with biallelic TNFRSF17 loss. In another five cases of relapse, newly detected, nontruncating, missense mutations or in-frame deletions in the extracellular domain of BCMA negated the efficacies of anti-BCMA TCE therapies, despite detectable surface BCMA protein expression. In the present study, we also report four cases of MM relapse with biallelic mutations of GPRC5D after anti-GPRC5D TCE therapy, including two cases with convergent evolution where multiple subclones lost GPRC5D through somatic events. Immunoselection of BCMA- or GPRC5D-negative or mutant clones is an important tumor-intrinsic driver of relapse post-targeted therapies. Mutational events on BCMA confer distinct sensitivities toward different anti-BCMA therapies, underscoring the importance of considering the tumor antigen landscape for optimal design and selection of targeted immunotherapies in MM.
Sex differences in brain protein expression and disease
Authors: Wingo Aliza P. , Liu Yue , Gerasimov Ekaterina S. , Vattathil Selina M. , Liu Jiaqi , Cutler David J. , Epstein Michael P. , Blokland Gabriëlla A. M. , Thambisetty Madhav , Troncoso Juan C. , Duong Duc M. , Bennett David A. , Levey Allan I. , Seyfried Nicholas T. , Wingo Thomas S.
Published: August 2023

Most complex human traits differ by sex, but we have limited insight into the underlying mechanisms. Here, we investigated the influence of biological sex on protein expression and its genetic regulation in 1,277 human brain proteomes. We found that 13.2% (1,354) of brain proteins had sex-differentiated abundance and 1.5% (150) of proteins had sex-biased protein quantitative trait loci (sb-pQTLs). Among genes with sex-biased expression, we found 67% concordance between sex-differentiated protein and transcript levels; however, sex effects on the genetic regulation of expression were more evident at the protein level. Considering 24 psychiatric, neurologic and brain morphologic traits, we found that an average of 25% of their putatively causal genes had sex-differentiated protein abundance and 12 putatively causal proteins had sb-pQTLs. Furthermore, integrating sex-specific pQTLs with sex-stratified genome-wide association studies of six psychiatric and neurologic conditions, we uncovered another 23 proteins contributing to these traits in one sex but not the other. Together, these findings begin to provide insights into mechanisms underlying sex differences in brain protein expression and disease.
Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results
Authors: Chalkias Spyros , Whatley Jordan L. , Eder Frank , Essink Brandon , Khetan Shishir , Bradley Paul , Brosz Adam , McGhee Nichole , Tomassini Joanne E. , Chen Xing , Zhao Xiaoping , Sutherland Andrea , Shen Xiaoying , Girard Bethany , Edwards Darin K. , Feng Jing , Zhou Honghong , Walsh Stephen , Montefiori David C. , Baden Lindsey R. , Miller Jacqueline M. , Das Rituparna
Published: August 2023

This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received mRNA-1273 as primary vaccination series and booster doses were enrolled in a sequential, nonrandomized manner and received single-second boosters of mRNA-1273 (n = 376) or bivalent mRNA-1273.222 (n = 511). Primary objectives were safety and the noninferiority or superiority of neutralizing antibody (nAb) responses against Omicron BA.4/BA.5 and ancestral SARS-CoV-2 with the D614G mutation (ancestral SARS-CoV-2 (D614G)), 28 days post boost. Superiority and noninferiority were based on prespecified success criteria (lower bounds of 95% CI > 1 and < 0.677, respectively) of the mRNA-1273.222:mRNA-1273 geometric mean ratios. Bivalent Omicron BA.4/BA.5-containing mRNA-1273.222 elicited superior nAb responses against BA.4/BA.5 versus mRNA-1273 and noninferior responses against ancestral SARS-CoV-2 (D614G) at day 29 post boost in participants without detectable prior SARS-CoV-2 infection. Day 29 seroresponses against Omicron BA.4/BA.5 were higher for mRNA-1273.222 than for mRNA-1273 and similar against ancestral SARS-CoV-2 (D614G), both meeting noninferiority criterion. The safety profile of mRNA-1273.222 was similar to that previously reported for mRNA-1273 with no new safety concerns identified. Continued monitoring of neutralization and real-world vaccine effectiveness are needed as additional divergent-virus variants emerge. ClinicalTrials.gov registration: NCT04927065.
Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization
Authors: Taquet Maxime , Skorniewska Zuzanna , Hampshire Adam , Chalmers James D. , Ho Ling-Pei , Horsley Alex , Marks Michael , Poinasamy Krisnah , Raman Betty , Leavy Olivia C. , Richardson Matthew , Elneima Omer , McAuley Hamish J. C. , Shikotra Aarti , Singapuri Amisha , Sereno Marco , Saunders Ruth M. , Harris Victoria C. , Houchen-Wolloff Linzy , Greening Neil J. , Mansoori Parisa , Harrison Ewen M. , Docherty Annemarie B. , Lone Nazir I. , Quint Jennifer , Sattar Naveed , Brightling Christopher E. , Wain Louise V. , Evans Rachael E. , Geddes John R. , Harrison Paul J. ,   PHOSP-COVID Study Collaborative Group
Published: August 2023

Post-COVID cognitive deficits, including ‘brain fog’, are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.
Biomolecular characterization of 3500-year-old ancient Egyptian mummification balms from the Valley of the Kings
Authors: Huber B. , Hammann S. , Loeben C. E. , Jha D. K. , Vassão D. G. , Larsen T. , Spengler R. N. , Fuller D. Q. , Roberts P. , Devièse T. , Boivin N.
Published: August 2023

Ancient Egyptian mummification was practiced for nearly 4000 years as a key feature of some of the most complex mortuary practices documented in the archaeological record. Embalming, the preservation of the body and organs of the deceased for the afterlife, was a central component of the Egyptian mummification process. Here, we combine GC–MS, HT-GC–MS, and LC–MS/MS analyses to examine mummification balms excavated more than a century ago by Howard Carter from Tomb KV42 in the Valley of the Kings. Balm residues were scraped from now empty canopic jars that once contained the mummified organs of the noble lady Senetnay, dating to the 18th dynasty, ca. 1450 BCE. Our analysis revealed balms consisting of beeswax, plant oil, fats, bitumen, Pinaceae resins, a balsamic substance, and dammar orPistaciatree resin. These are the richest, most complex balms yet identified for this early time period and they shed light on balm ingredients for which there is limited information in Egyptian textual sources. They highlight both the exceptional status of Senetnay and the myriad trade connections of the Egyptians in the 2nd millennium BCE. They further illustrate the excellent preservation possible even for organic remains long removed from their original archaeological context.
Regulatory role of PI3K/Akt/WNK1 signal pathway in mouse model of bone cancer pain
Authors: Fu Xiao , Zhang Yanhong , Zhang Rui
Published: August 2023

In the advanced stage of cancer, the pain caused by bone metastasis is unbearable, but the mechanism of bone cancer pain (BCP) is very complicated and remains unclear. In this study, we used 4T1 mouse breast cancer cells to establish a bone cancer pain model to study the mechanism of BCP. Then the paw withdrawal mechanical threshold (PWMT) and the hematoxylin-eosin staining were used to reflect the erosion of cancer cells on tibia tissue. We also determined the role of proinflammatory factors (TNF-α, IL-17, etc.) in BCP by the enzyme-linked immunosorbent assay in mouse serum. When GSK690693, a new Akt inhibitor, was given and the absence of intermediate signal dominated by Akt is found, pain may be relieved by blocking the transmission of pain signal and raising the PWMT. In addition, we also found that GSK690693 inhibited the phosphorylation of Akt protein, resulting in a significant decrease in with-nolysinekinases 1 (WNK1) expression in the spinal cord tissue. In the BCP model, we confirmed that GSK690693 has a relieving effect on BCP, which may play an analgesic effect through PI3K-WNK1 signal pathway. At the same time, there is a close relationship between inflammatory factors and PI3K-WNK1 signal pathway. The PI3K/Akt pathway in the dorsal horn of the mouse spinal cord activates the downstream WNK1 protein, which promotes the release of inflammatory cytokines, which leads to the formation of BCP in mice. Inhibition of Akt can reduce the levels of IL-17 and TNF-α, cut off the downstream WNK1 protein signal receiving pathway, increase the PWMT and relieve BCP in mice. To clarify the analgesic target of BCP, to provide reference and theoretical support for the clinical effective treatment of BCP and the development of new high-efficiency analgesics.
Association of extracellular water/total body water ratio with protein-energy wasting and mortality in patients on hemodialysis
Authors: Yajima Takahiro , Yajima Kumiko
Published: August 2023

Bioimpedance analysis-assessed extracellular water/total body water (ECW/TBW) ratio may be a marker for mortality and poor nutritional status in hemodialysis patients. In 193 maintenance hemodialysis patients, we retrospectively investigated the relationships among ECW/TBW ratio, mortality, and protein-energy wasting (PEW). Four components—body mass index, normalized protein catabolic rate, normalized serum creatinine level, and serum albumin level—constitute the simple PEW score; this score was calculated based on the positive number of items concerning malnutrition among these four components. A score ≥ 3 indicated PEW. Patients were stratified by an ECW/TBW ratio cut-off value (0.40) and by PEW versus non-PEW status. The simple PEW score, cardiothoracic ratio, and log-transformed C-reactive protein level were independently correlated with the ECW/TBW ratio. Eighty-four patients died during follow-up (median 4.3 years). After adjustments for sex, age, hemodialysis vintage, histories of cardiovascular events and diabetes, and C-reactive protein level, a higher ECW/TBW ratio and PEW were independently related to elevated risks of all-cause death. Adding the ECW/TBW ratio to a baseline risk model including PEW significantly increased C-statistics from 0.788 to 0.835. In conclusion, the ECW/TBW ratio may be an indicator of PEW and may be a predictor of death even accounting for PEW, in hemodialysis patients.
Thermoelectric properties of ballistic Normal–Weyl semimetal-Normal junction
Authors: Lotfi Jafar , Abdollahipour Babak
Published: August 2023

Weyl semimetals are a new class of topological materials possessing outstanding physical properties. We investigate the thermoelectric properties of a ballistic Weyl semimetal specimen connected to two normal contacts. We introduce a model to evaluate the thermoelectric coefficients of the junction and analyze its features along two distinct directions, one along the chiral axis of the Weyl semimetal and the other perpendicular to it. We demonstrate that the thermoelectric response of this junction depends on whether it is along the chiral axis of the Weyl semimetal or not. Electrical and thermal conductances of this junction reveal considerable dependence on the length and chemical potential of the Weyl semimetal layer. In particular, we observe that, decreasing the chemical potential in the normal contacts enhances the Seebeck coefficient and thermoelectric figure of merit of the junction to substantial values. Hence, we unveil that a ballistic junction of Weyl semimetal can serve as a fundamental segment for application in future thermoelectric devices for thermal energy harvesting.
System of models for simulation and optimization of operating modes of a delayed coking unit in a fuzzy environment
Authors: Orazbayev Batyr , Orazbayeva Kulman , Uskenbayeva Gulzhan , Dyussembina Elmira , Shukirova Aliya , Rzayeva Leila , Tuleuova Raigul
Published: August 2023

The purpose of this study is to develop a method for synthesizing mathematical models of interconnected units of fuzzy chemical-technological systems (CTS) used for system modeling and optimization of their operating modes in a fuzzy environment. Since many CTSs in practice consist of many interconnected units, the development of their mathematical models combined into a single system of models, which allows systematic modeling and optimization of CTS parameters, is an urgent scientific and practical task. To develop a system of models of fuzzy described CTS, consisting of interconnected units, a system of methods is used that combines formal (experimental-statistical) and informal methods (methods of peer review, fuzzy set theory). A method for developing a system of mathematical models of CTS units under conditions of uncertainty due to the random and fuzzy nature of the available information is proposed. In the proposed method, mathematical models of various CTS units, depending on the nature of the initial and available information, are developed by various methods. Accordingly, various types of models are obtained, which are then combined into a single system of models, taking into account the interconnections of the system’s units. These results make it possible to develop more adequate models and determine the optimal CTS operating modes in a fuzzy environment by using the experience, knowledge and intuition of the decision maker, subject matter experts. Based on the proposed method, models of coke chambers and the main rectification column are developed in the form of combined models, including statistical and fuzzy models. The results obtained on the example of delayed coking units can be exported to similar CTS in oil refining, petrochemicals and other industries.