bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction to the Evolution of New Working Spaces
Authors: Mariotti Ilaria , Tomaz Elisabete , Micek Grzegorz , Méndez-Ortega Carles
Published: February 2024

The chapter briefly describes the book structure and the contents of the chapters. Two sections compose the book: the first describes the main typologies of NeWSps and the evolution of this phenomenon, and the second focuses on NeWSps location and its evolution. The chapter also describes the methodological approaches to explore NeWSps, and underlines to what extent the book fills the gap in the literature on NeWSp typologies and geographical patterns.
University Hubs: Hybrid Spaces Between Campus, Work, and Social Spaces
Authors: Migliore Alessandra , Tagliaro Chiara , Schaumann Davide , Hua Ying
Published: February 2024

In recent years work and learning have radically changed to support community-focused, inter-professional, and interdisciplinary engagements. In response, companies and public administrations have been developing networked and dispersed workspaces to grant people access to a variety of places tailored to their needs. Likewise, university campuses have been evolving in the same direction. Aiming to expand into different geographical contexts, universities have been activating off-campus facilities that enact their mission of sustainable development, university-industry connection, and social inclusion. However, the phenomenon is still poorly understood even though evidence exists that it is an expanding trend. This study analyses this emergent phenomenon we call University Hubs by distinguishing it from other similar dynamics and discussing it in the context of the hybridization of spaces for study and work. Through a preliminary case study analysis, the paper reflects on University Hubs as an opportunity for the development of future university models. These spaces can pursue knowledge creation and sharing with diverse communities outside the campus boundaries, but they entail the risk of simply enhancing university visibility in different places without pursuing a true engagement with local communities.
Caring Practices in and Beyond Coworking Spaces
Authors: Merkel Janet , Belvončíková Eva , Zhurbas-Litvin Vika
Published: February 2024

Coworking and coworking spaces have proliferated over the last decade, and research has shown how these flexible, shared workspaces provide crucial resources for freelance and self-employed workers. This chapter aims to understand how care is practised in and through coworking spaces. Drawing on interviews with female hosts in different spaces across Europe, we apply Joan Tronto’s ethics of care framework (Tronto in Moral boundaries: A political argument for an ethic of care. Routledge [43]; Tronto in Caring democracy: Markets, equality, and justice. NYU Press [44]) to analyze caring practices in coworking spaces. This chapter adds to the literature on how coworking hosts and community managers provide care to “maintain, continue, and repair” (Fisher and Tronto in Work and identity in women’s lives. SUNY Press [18], p. 40) community and the hospitable atmosphere in coworking spaces across Europe.
Historical Snapshot
Authors: Breiding Paul , Kohn Kathlén , Sturmfels Bernd
Published: February 2024

Throughout this book, we will encounter the interplay of metric concepts with algebraic objects. In classical texts such as Salmon’s book [156], metric properties of algebraic varieties were essential. This includes the curvature of algebraic curves and computing their arc lengths and circumscribed areas using integral calculus. Conversely, many curves of interest were defined in terms of distances or angular conditions. This chapter provides an introduction to this classical approach to algebraic curves.
Computer Vision
Authors: Breiding Paul , Kohn Kathlén , Sturmfels Bernd
Published: February 2024

The field of computer vision studies how computers can gain understanding from images and videos, similar to human cognitive abilities. One of the classical challenges is to reconstruct a 3D object from images taken by several unknown cameras. While the resulting questions in multiview geometry [80] have a long history in computer vision, recent years have seen a confluence with ideas and algorithms from algebraic geometry.
Scales of Abstraction: The Kiel Conceptual Approach from Heterogeneous Data to Interpretations
Authors: Taylor Nicole , Rinne Christoph , Brozio Jan Piet , Kneisel Jutta , Wieckowska-Lüth Magdalena , Kleijne Jos , Gorbahn Hermann , Kirleis Wiebke , Müller Johannes
Published: February 2024

The identification of individual palaeoecological and societal aspects allows the comparison of transformation processes across completely different ecological and historic situations. This basic concept proves, on the one hand, the comparability of transformation processes and the parameters involved in them, and shows on the other hand how diverse the appearance and expression of transformation can be. The investigation of transformations occurring across 15,000 years of human and environmental history is a complex undertaking and involves the consideration of archives of varying accessibility, handled by different disciplines using different analyses and approaches. This chapter demonstrates one approach used by Kiel Archaeology to integrate this heterogeneity in order to answer common research questions.
Conceptualising an Anatomy of Transformations: DPSIR, Theorisation, Semiotics and Emergence
Authors: Ribeiro Artur , Lattmann Claas , Schlicht Jan-Eric , Thalheim Bernhard , Sabnis Shikharani , Alliata Victoria , Ott Konrad
Published: February 2024

Transformation processes that affect past societies can be complex and difficult to understand when observed at larger scales, especially when many factors are involved. Furthermore, researching transformations can often become reductive, with too much focus on only some factors or aspects of past societies, to the detriment of others. This has been the challenge of large-scale socio-environmental projects of recent years, including our own.

In order to address this issue, this chapter develops a model of the anatomy of transformations that is built upon four main pillars. The first pillar is DPSIR (Driver-Pressure-State-Impact-Response). Originally used in ecological studies, DPSIR provides a flexible framework that allows us to recognise how societies and ecosystems affect one another in a dynamic manner. Within the DPSIR framework, a second pillar based on theorization allows us to contextualise human behaviour at different scales, for example, through practice theory or cultural evolutionary theory. The third pillar presupposes that human societies are built on meaning and uses semiotics to help us uncover the semantic dimension of past transformations. Finally, the fourth pillar is emergence, which conceives of transformations as diachronic processes in which ecosystems and societies develop new properties based on their interaction.

This anatomy has the aim of assembling different aspects of socio-environmental and archaeological research in order to produce a comprehensive picture of past transformations. At the same time, this overall framework is open-ended, which both makes it possible to adapt it to different chronological and geographical circumstances and allows adopters to add or remove elements as they see fit.
Sociolinguistic Aspects of Popular Abbreviations in Hong Kong Cantonese
Authors: Cheng Ken Siu-kei , Ho Ka-wai
Published: February 2024

This paper aims to study certain popular abbreviations in Hong Kong Cantonese in recent years from a sociolinguistic perspective so as to understand their characteristics and uniqueness. It was found that these abbreviations come from different languages and regions, and different strategies such as Cantonese romanization acronym and translation of foreign languages into Chinese characters were used in the process of abbreviation. In terms of grammar, they are mainly composed of adverb-verb and verb-object structures, and the part of speech may change in some cases. Some abbreviations also have rhetorical effects related to homonyms or taboos. These abbreviations are mastered by younger generations and are mostly used in informal domains. The main consideration for adopting abbreviations is of practical concern as well as their function of “insider communication”. Respondents rated Cantonese abbreviations as overall positive.
Color-kinematics duality with minimal deformation: two-loop four-gluon amplitudes in pure Yang-Mills revisited
Authors: Li Zeyu , Yang Gang
Published: February 2024

Abstract

The conjectured duality between color and kinematics has significantly advanced our understanding of both gauge and gravitational theories. However, constructing numerators that manifest the color-kinematics (CK) duality, even for the two-loop four-gluon amplitude in pure Yang-Mills, has been challenging. In this paper, we revisit this amplitude and show that the difficulty of applying CK duality can be overcome by introducing a simple deformation. Our approach distinguishes itself from previous studies by maximizing the use of off-shell CK duality while maintaining a compact ansatz. In particular, the deformation we introduce satisfies a subset of off-shell dual Jacobi relations. The resulting numerators are presented in d-dimensionally Lorentz invariant local form and are applicable to all helicities of external gluons. The solution we provide can be directly employed to construct the corresponding gravitational amplitude through double copy. Our findings suggest a novel and efficient strategy for constructing high-loop gauge and gravitational amplitudes using CK duality.
Killing spinors for finite temperature Euclidean solutions at the BPS bound
Authors: Hegde Subramanya , Virmani Amitabh
Published: February 2024

Abstract

In a recent paper [arXiv:2308.00038], Anupam, Chowdhury, and Sen conjectured that the finite temperature Euclidean five-dimensional Cvetic-Youm solution saturating the BPS bound is supersymmetric. In this paper, we explicitly construct Killing spinors for this solution in five-dimensional minimal supergravity. We also expand on the previous discussions of Killing spinors for the finite temperature Euclidean Kerr-Newman solution saturating the BPS bound. For both these cases, we show that the total charge gets divided into two harmonic sources on three-dimensional flat base space.
Anomalies and persistent order in the chiral Gross-Neveu model
Authors: Ciccone Riccardo , Di Pietro Lorenzo , Serone Marco
Published: February 2024

Abstract

We study the 2d chiral Gross-Neveu model at finite temperature T and chemical potential μ. The analysis is performed by relating the theory to a SU(N) × U(1) Wess-Zumino-Witten model with appropriate levels and global identifications necessary to keep track of the fermion spin structures. At μ = 0 we show that a certain ℤ2-valued ’t Hooft anomaly forbids the system to be trivially gapped when fermions are periodic along the thermal circle for any N and any T > 0. We also study the two-point function of a certain composite fermion operator which allows us to determine the remnants for T > 0 of the inhomogeneous chiral phase configuration found at T = 0 for any N and any μ. The inhomogeneous configuration decays exponentially at large distances for anti-periodic fermions while it persists for T > 0 and any μ for periodic fermions, as expected from anomaly considerations. A large N analysis confirms the above findings.
BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response
Authors: Ji Rui , Zhang Zhimo , Yang Zhe , Chen Xin , Yin Tailang , Yang Jing
Published: February 2024

Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS.
The impact of VPS35 D620N mutation on alternative autophagy and its reversal by estrogen in Parkinson's disease
Authors: Shiraishi Tomotaka , Bono Keiko , Hiraki Hiromi , Manome Yoko , Oka Hisayoshi , Iguchi Yasuyuki , Okano Hirotaka James
Published: February 2024

VPS35 plays a key role in neurodegenerative processes in Alzheimer’s disease and Parkinson’s disease (PD). Many genetic studies have shown a close relationship between autophagy and PD pathophysiology, and specifically, the PD-causing D620N mutation in VPS35 has been shown to impair autophagy. However, the molecular mechanisms underlying neuronal cell death and impaired autophagy in PD are debated. Notably, increasing evidence suggests that Rab9-dependent “alternative” autophagy, which is driven by a different molecular mechanism that driving ATG5-dependent “conventional” autophagy, also contributes to neurodegenerative process. In this study, we investigated the relationship between alternative autophagy and VPS35 D620N mutant-related PD pathogenesis. We isolated iPSCs from the blood mononuclear cell population of two PD patients carrying the VPS35 D620N mutant. In addition, we used CRISPR-Cas9 to generate SH-SY5Y cells carrying the D620N variant of VPS35. We first revealed that the number of autophagic vacuoles was significantly decreased in ATG5-knockout Mouse Embryonic Fibroblast or ATG5-knockdown patient-derived dopaminergic neurons carrying the VPS35 D620N mutant compared with that of the wild type VPS35 control cells. Furthermore, estrogen, which activates alternative autophagy pathways, increased the number of autophagic vacuoles in ATG5-knockdown VPS35 D620N mutant dopaminergic neurons. Estrogen induces Rab9 phosphorylation, mediated through Ulk1 phosphorylation, ultimately regulating alternative autophagy. Moreover, estrogen reduced the apoptosis rate of VPS35 D620N neurons, and this effect of estrogen was diminished under alternative autophagy knockdown conditions. In conclusion, alternative autophagy might be important for maintaining neuronal homeostasis and may be associated with the neuroprotective effect of estrogen in PD with VPS35 D620N.
Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity
Authors: Bläsius Katharina , Ludwig Lena , Knapp Sarah , Flaßhove Charlotte , Sonnabend Friederike , Keller Diandra , Tacken Nikola , Gao Xintong , Kahveci-Türköz Selcan , Grannemann Caroline , Babendreyer Aaron , Adrain Colin , Huth Sebastian , Baron Jens Malte , Ludwig Andreas , Düsterhöft Stefan
Published: February 2024

The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.
High-resolution mapping of Ryd4Hb, a major resistance gene to Barley yellow dwarf virus from Hordeum bulbosum
Authors: Pidon Hélène , Ruge-Wehling Brigitte , Will Torsten , Habekuß Antje , Wendler Neele , Oldach Klaus , Maasberg-Prelle Anja , Korzun Viktor , Stein Nils
Published: February 2024

Key message

We mapped Ryd4Hb in a 66.5 kbp interval in barley and dissociated it from a sublethality factor. These results will enable a targeted selection of the resistance in barley breeding.

Virus diseases are causing high yield losses in crops worldwide. The Barley yellow dwarf virus (BYDV) complex is responsible for one of the most widespread and economically important viral diseases of cereals. While no gene conferring complete resistance (immunity) has been uncovered in the primary gene pool of barley, sources of resistance were searched and identified in the wild relative Hordeum bulbosum, representing the secondary gene pool of barley. One such locus, Ryd4Hb, has been previously introgressed into barley, and was allocated to chromosome 3H, but is tightly linked to a sublethality factor that prevents the incorporation and utilization of Ryd4Hb in barley varieties. To solve this problem, we fine-mapped Ryd4Hb and separated it from this negative factor. We narrowed the Ryd4Hb locus to a corresponding 66.5 kbp physical interval in the barley ‘Morex’ reference genome. The region comprises a gene from the nucleotide-binding and leucine-rich repeat immune receptor family, typical of dominant virus resistance genes. The closest homolog to this Ryd4Hb candidate gene is the wheat Sr35 stem rust resistance gene. In addition to the fine mapping, we reduced the interval bearing the sublethality factor to 600 kbp in barley. Aphid feeding experiments demonstrated that Ryd4Hb provides a resistance to BYDV rather than to its vector. The presented results, including the high-throughput molecular markers, will permit a more targeted selection of the resistance in breeding, enabling the use of Ryd4Hb in barley varieties.
Elevated ITGA1 levels in type 2 diabetes: implications for cardiac function impairment
Authors: Su Mengqi , Hou Yilin , Cai Sidong , Li Wenpeng , Wei Yinxia , Wang Run , Wu Min , Liu Mingya , Chang Junlei , Yang Kelaier , Yiu Kaihang , Chen Cong
Published: February 2024

Aims/hypothesis

Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies.

Methods

Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals’ left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF.

Results

Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF.

Conclusions/interpretation

ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes.

Data availability

The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org.

Graphical Abstract
Generic vanishing, 1-forms, and topology of Albanese maps
Authors: Dutta Yajnaseni , Hao Feng , Liu Yongqiang
Published: February 2024

Given a bounded constructible complex of sheaves $$\mathcal {F}$$
F
on a complex Abelian variety, we prove an equality relating the cohomology jump loci of $$\mathcal {F}$$
F
and its singular support. As an application, we identify two subsets of the set of holomorphic 1-forms with zeros on a complex smooth projective irregular variety X; one from Green-Lazarsfeld’s cohomology jump loci and one from the Kashiwara’s estimates for singular supports. This result is related to Kotschick’s conjecture about the equivalence between the existence of nowhere vanishing global holomorphic 1-forms and the existence of a fibre bundle structure over the circle. Our results give a conjecturally equivalent formulation using singular support, which is equivalent to a criterion involving cohomology jump loci proposed by Schreieder. As another application, we reprove a recent result proved by Schreieder and Yang; namely if X has simple Albanese variety and admits a fibre bundle structure over the circle, then the Albanese morphism cohomologically behaves like a smooth morphism with respect to integer coefficients. In a related direction, we address the question whether the set of 1-forms that vanish somewhere is a finite union of linear subspaces of $$H^0(X,\Omega _X^1)$$

H
0

(
X
,

Ω
X
1

)

. We show that this is indeed the case for forms admitting zero locus of codimension 1.
S-Duality and the Universal Isometries of Instanton Corrected q-Map Spaces
Authors: Cortés Vicente , Tulli Iván
Published: February 2024

Given a conical affine special Kähler manifold together with a compatible mutually local variation of BPS structures, one can construct a quaternionic-Kähler (QK) manifold. We call the resulting QK manifold an instanton corrected c-map space. Our main aim is to study the isometries of a subclass of instanton corrected c-map spaces associated to projective special real manifolds with a compatible mutually local variation of BPS structures. We call the latter subclass instanton corrected q-map spaces. In the setting of Calabi–Yau compactifications of type IIB string theory, instanton corrected q-map spaces are related to the hypermultiplet moduli space metric with perturbative corrections, together with worldsheet, D(-1) and D1 instanton corrections. In the physics literature, it has been shown that the hypermultiplet metric with such corrections must have an $$\textrm{SL}(2,{\mathbb {Z}})$$

SL
(
2
,
Z
)

acting by isometries, related to S-duality. We give a mathematical treatment of this result, specifying under which conditions instanton corrected q-map spaces carry an action by isometries by $$\textrm{SL}(2,{\mathbb {Z}})$$

SL
(
2
,
Z
)

or some of its subgroups. We further study the universal isometries of instanton corrected q-map spaces, and compare them to the universal isometries of tree-level q-map spaces. Finally, we give an explicit example of a non-trivial instanton corrected q-map space with full $$\textrm{SL}(2,{\mathbb {Z}})$$

SL
(
2
,
Z
)

acting by isometries and admitting a quotient of finite volume by a discrete group of isometries.
Production of recombinant vesicular stomatitis virus-based vectors by tangential flow depth filtration
Authors: Göbel Sven , Pelz Lars , Silva Cristina A. T. , Brühlmann Béla , Hill Charles , Altomonte Jennifer , Kamen Amine , Reichl Udo , Genzel Yvonne
Published: February 2024

Cell culture-based production of vector-based vaccines and virotherapeutics is of increasing interest. The vectors used not only retain their ability to infect cells but also induce robust immune responses. Using two recombinant vesicular stomatitis virus (rVSV)-based constructs, we performed a proof-of-concept study regarding an integrated closed single-use perfusion system that allows continuous virus harvesting and clarification.

Using suspension BHK-21 cells and a fusogenic oncolytic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV), a modified alternating tangential flow device (mATF) or tangential flow depth filtration (TFDF) systems were used for cell retention. As the hollow fibers of the former are characterized by a large internal lumen (0.75 mm; pore size 0.65 μm), membrane blocking by the multi-nucleated syncytia formed during infection could be prevented. However, virus particles were completely retained. In contrast, the TFDF filter unit (lumen 3.15 mm, pore size 2–5 μm) allowed not only to achieve high viable cell concentrations (VCC, 16.4–20.6×106 cells/mL) but also continuous vector harvesting and clarification. Compared to an optimized batch process, 11-fold higher infectious virus titers were obtained in the clarified permeate (maximum 7.5×109 TCID50/mL).

Using HEK293-SF cells and a rVSV vector expressing a green fluorescent protein, perfusion cultivations resulted in a maximum VCC of 11.3×106 cells/mL and infectious virus titers up to 7.1×1010 TCID50/mL in the permeate. Not only continuous harvesting but also clarification was possible. Although the cell-specific virus yield decreased relative to a batch process established as a control, an increased space-time yield was obtained.

Key points

• Viral vector production using a TFDF perfusion system resulted in a 460% increase in space-time yield

• Use of a TFDF system allowed continuous virus harvesting and clarification

• TFDF perfusion system has great potential towards the establishment of an intensified vector production
Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial)
Authors: Zhu Hai-Dong , Li Xiao , Sun Jun-Hui , Zhu Xu , Liu Zhao-Yu , Li Hai-Liang , Lu Jian , Yan Zhi-Ping , Shao Guo-Liang , He Xiao-Feng , Chao Min , Lu Li-Gong , Zhong Bin-Yan , Li Rui , Zhang Qi , Teng Gao-Jun
Published: February 2024

Purpose

While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin.

Materials and Methods

This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30–50), 75 (range, 60–90), or 100 (range, 75–125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events.

Results

Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death.

Conclusion

DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC.

Trial Registration

Clinicaltrials.gov NCT03113955; registered April 14, 2017.

Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017.

Level of evidence

2, Prospective, Non-randomized, Single-arm, study.

Graphical Abstract
Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms
Authors: Streuer Alexander , Jann Johann-Christoph , Boch Tobias , Mossner Maximilian , Riabov Vladimir , Schmitt Nanni , Altrock Eva , Xu Qingyu , Demmerle Marie , Nowak Verena , Oblaender Julia , Palme Iris , Weimer Nadine , Rapp Felicitas , Metzgeroth Georgia , Hecht Anna , Höger Thomas , Merz Christian , Hofmann Wolf-Karsten , Nolte Florian , Nowak Daniel
Published: February 2024

In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response. Bone marrow samples of n = 12 low-risk MDS patients from the above referenced clinical trial were analyzed by serial deep whole exome sequencing in a total of n = 58 time points. We could distinguish a mean of 3.5 molecularly defined subclones per patient (range 2–6). We observed a molecular response defined as reductions of dominant clone sizes by a variant allele frequency (VAF) decrease of at least 10% (mean 20%, range: 10.5–39.2%) in dependency of Asunercept treatment in 9 of 12 (75%) patients. Most of this decline in clonal populations was observed after completion of 12 weeks treatment. Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation.
Pediatric ping-pong skull fractures treated with vacuum-assisted elevation
Authors: Ahmed Syed D. , Allhusen Virginia D. , Muhonen Michael G. , Magge Suresh N.
Published: February 2024

Purpose

Depressed (“ping-pong”) skull fractures can be treated by different means, including observation, non-surgical treatments, or surgical intervention. The authors describe their experience with vacuum-assisted elevation of ping-pong skull fractures and evaluate variables associated with surgical outcomes.

Methods

The authors present a retrospective review of all ping-pong skull fractures treated with vacuum-assisted elevation at the Children’s Hospital of Orange County in 2021–2022. Variables included patient age, mechanism of injury, fracture depth, bone thickness at the fracture site, and degree of elevation.

Results

Seven patients underwent vacuum-assisted elevation of ping-pong fractures at the bedside without the use of anesthesia. Fractures caused by birth-related trauma were deeper than those caused by falls (p < 0.001). There was no significant difference between groups in bone thickness at the fracture site (2.10 mm vs 2.16 mm, n.s). Six of the seven patients experienced significant improvement in fracture site depression, with four displaying a complete fracture reduction and two displaying a significant reduction. The degree of fracture reduction was modestly related to the depth of fracture, with the two deepest fractures failing to achieve full reduction. Age appeared to be related to fracture reduction, with the lowest reduction observed in one of the oldest patients in this sample. No complications were observed in any patient other than temporary mild swelling at the suction site, and no re-treatment or surgery for the fractures was required.

Conclusion

Vacuum-assisted elevation of ping-pong skull fractures is a safe and effective noninvasive treatment option for infants that can be used under certain circumstances. The procedure can be done safely at the bedside and is a relatively quick procedure. It avoids the need for open surgical intervention, anesthesia, or hospital admission, and can lead to excellent outcomes.
Effect of preoperative oral carbohydrates on insulin resistance in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial
Authors: Wang Xiaohan , Zhuang Jingwen , Cheng Jianxin , Wang Zeyang , Sheng Jingyi , Guo Shanshan , Wang Rui , Wang Zhiping
Published: February 2024

Purpose

The present research seeks to clarify the consequences of two specific preoperative oral carbohydrate (POC) amounts on insulin resistance (IR) and stomach evacuation in laparoscopic cholecystectomy (LC) patients.

Methods

A total of 129 patients set for elective LC procedures were randomly assigned to a control group (C, n = 45), a 200 mL POC group (P1, n = 42), and a 400 mL POC group (P2, n = 42). The C group was fasted from midnight until surgery, whereas the P1 and P2 groups received their respective carbohydrate volumes 2–4 h before anesthesia. Fasting blood glucose, insulin, and glucagon concentrations were measured at three junctures. IR metrics were derived by employing the homeostasis model assessment. Gastric volume was measured before anesthesia using gastric ultrasound. Inter-group comparisons included IR indicators, subjective comfort scores, and hemodynamic data.

Results

At T2, the C group exhibited reduced glucose concentrations compared to the P2 group (4.73 ± 0.64 vs. 5.26 ± 1.02 mmol/L, p < 0.05). The Perlas grading indicated that grade 1 was more prevalent in the P2 group than in the P1 and C groups (18 [42.9%] vs. 6 [14.3%] and 1 [2.2%], p < 0.05). Additionally, thirst and hunger metrics for the P2 group were notably reduced compared to the C group at both T2 and T3.

Conclusion

Administering either 200 mL or 400 mL of carbohydrates 2–4 h pre-surgery had no detectable impact on IR or gastric volume in LC patients.

Trial registration

ChiCTR, ChiCTR2200065648. Registered January 13, 2023, http://www.chictr.org.cn.
Clinicopathological features and prognosis of primary small bowel adenocarcinoma: a large multicenter analysis of the JSCCR database in Japan
Authors: Yamashita Ken , Oka Shiro , Yamada Takeshi , Mitsui Keigo , Yamamoto Hironori , Takahashi Keiichi , Shiomi Akio , Hotta Kinichi , Takeuchi Yoji , Kuwai Toshio , Ishida Fumio , Kudo Shin-Ei , Saito Shoichi , Ueno Masashi , Sunami Eiji , Yamano Tomoki , Itabashi Michio , Ohtsuka Kazuo , Kinugasa Yusuke , Matsumoto Takayuki , Sugai Tamotsu , Uraoka Toshio , Kurahara Koichi , Yamaguchi Shigeki , Kato Tomohiro , Okajima Masazumi , Kashida Hiroshi , Akagi Yoshito , Ikematsu Hiroaki , Ito Masaaki , Esaki Motohiro , Kawai Masaya , Yao Takashi , Hamada Madoka , Horimatsu Takahiro , Koda Keiji , Fukai Yasumori , Komori Koji , Saitoh Yusuke , Kanemitsu Yukihide , Takamaru Hiroyuki , Yamada Kazutaka , Nozawa Hiroaki , Takayama Tetsuji , Togashi Kazutomo , Shinto Eiji , Torisu Takehiro , Toyoshima Akira , Ohmiya Naoki , Kato Takeshi , Otsuji Eigo , Nagata Shinji , Hashiguchi Yojiro , Sugihara Kenichi , Ajioka Yoichi , Tanaka Shinji
Published: February 2024

Background

The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan.

Methods

We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum.

Results

The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7–100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA.

Conclusions

Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.
Examining the impact of a change in maternity leave policy in Canada on maternal mental health care visits to the physician
Authors: Larose Marie-Pier , Haeck Catherine , Lefebvre Pierre , Merrigan Philip
Published: February 2024

Purpose

Maternity leave is a critical employee benefit that allows mothers to recover from the stress of pregnancy and childbirth and bond with their new baby. We aimed to examine the association between the extension of a maternity leave policy and maternal use of mental health services and prescription drugs in a universal public healthcare system.

Methods

This study uses administrative medical records from 18,000 randomly selected women who gave birth three months before and after an extension of the maternity leave policy. More specifically, mothers who gave birth after January 1st 2001, were entitled to 50 weeks of paid maternity leave, while mothers who gave birth before that date were entitled to only 26 weeks of paid maternity leave. Medical records were analyzed over a seven-year period (i.e., from October 1998 to March 2006). We examined the number and costs of mothers’ medical visits for mental health care in the five years following delivery, as well as maternal use of prescribed medication for mental health problems.

Results

We found that mothers with extended maternity leave had − 0.12 (95%CI=-0.21; -0.02) fewer medical visits than mothers without a more generous maternity leave and that the cost of mental health services was Can$5 less expensive per women. These differences were found specifically during the extended maternity leave period.

Conclusions

The extra time away from work may help mothers to balance new family dynamics which may result in less demand on the healthcare system.
Virtual reality environments for stress reduction and management: a scoping review
Authors: Ladakis Ioannis , Filos Dimitrios , Chouvarda Ioanna
Published: February 2024

Virtual reality, a cutting-edge innovation in the realm of digital experiences, though more frequently employed for entertainment and education, can also serve as a tool for immersing users in therapeutic settings that promote relaxation and mindfulness. An increasing number of research attempts investigate its usability and impact on stress evaluation, management and reduction. This scoping review aims to depict the current role of virtual reality in stress reduction and identify common methods and practice, technology patterns as well as gaps. Results depict the emerging research interest in the domain of VR-based stress reduction systems. The developed systems included in this review were basically addressed to the general public (59%) for daily life stress reduction utilizing a commercial VR headset often combined with supportive sensors. Guided imagery emerged as the most implemented method, but it is also noteworthy that almost all studies implicitly used this method. According to the analysis, most studies performed evaluation of the proposed VR system including both subjective and objective measurements to provide evidence on its efficiency and its actual impact on stress levels. Finally, validation methodologies attempt to point out the potential of VR technology in the direction of providing an efficient solution for the alleviation of stress burdens. Even though numerous studies report the usefulness and efficiency of VR technology regarding stress reduction, several challenges still need to be addressed, mainly because of the difficult definition, detection and evaluation of stress. An approach integrating the existing knowledge regarding signals that can act as biomarkers of stress and qualitative measurements could open new pathways toward the development of more impactful VR-based stress reduction systems.
Virtual reality natural experiences for mental health: comparing the effects between different immersion levels
Authors: Yen Hsin-Yen , Hsu Hsuan , Huang Wen-Hsin
Published: February 2024

Virtual nature is an innovative approach for promoting mental health. The purpose of this study was to compare the effects on mental health outcomes between two immersion levels of virtual reality natural experiences. The study design was a cluster trial. Healthy adults were allocated to two experimental groups. Identical pre-recorded 360° videos of natural scenes and sounds were played on the two virtual reality devices, one with a higher immersive level via a head-mounted display and the other one with a lower immersive level via a smartphone. The intervention was conducted for 30 min per session, once a week for 12 weeks. Data were collected by self-reported questionnaires at the baseline and post-intervention. In total, 54 participants completed the interventions. A significantly greater effect was revealed on improving happiness, self-rated health, and physical, mental, social, and environmental quality of life, and ameliorating distress, depression, and somatization in participants who experienced the higher immersive level compared to participants who experienced the lower immersive level. Virtual reality natural experiences with high immersion are recommended to promote mental health.
Using problem-based exploratory training to improve pilot understanding of autopilot functions
Authors: Leeuwen Jordy K. van , Landman Annemarie , Groen Eric L. , Mumaw Randall J. , Stroosma Olaf , Paassen Marinus M. van , Mulder Max
Published: February 2024

Previous research indicated a need to improve pilot training with regard to understanding of autopilot logic and behavior, especially in non-routine situations. Therefore, we tested the effect of problem-based exploratory training on pilots’ understanding of autopilot functions. Using a moving-base flight simulator, general aviation pilots (n = 45) were trained to diagnose failures either without foreknowledge and guidance (exploratory group), without foreknowledge but with some guidance (exploratory-guidance group) or with foreknowledge and full guidance (control group). They subsequently performed six test scenarios in which their understanding of the effects of failures was tested by requiring them to deduce the failures and select autopilot modes that were still functioning. Those who received exploratory training with guidance were significantly more likely than the other groups to diagnose failures correctly. The exploratory training group also selected the most appropriate functioning autopilot modes significantly faster than the control group. The results suggest that exploratory training with an appropriate level of guidance is useful for gaining a practical understanding of autopilot logic and behavior. Exploratory training may help to improve transfer of training to operational practice, and prevent automation surprises and accidents.
The role of budget impact and its relationship with cost-effectiveness in reimbursement decisions on health technologies in the Netherlands
Authors: Reckers-Droog Vivian , Enzing Joost , Brouwer Werner
Published: February 2024

Health authorities using cost-effectiveness analysis (CEA) for informing reimbursement decisions on health technologies increasingly require economic evaluations encompassing both CEA and budget impact analysis (BIA). Good Research Practices advocate that the economic and clinical assumptions underlying these analyses are aligned and consistently applied. Nonetheless, CEAs and BIAs often are stand-alone analyses used in different stages of the decision-making process. This article used policy reports and Ministerial correspondence to discuss and elucidate the role of budget impact and its relationship with cost-effectiveness in reimbursement decisions in the Netherlands. The results indicate that CEAs and BIAs are both considered important for informing these decisions. While the requirements regarding CEAs—and application of the associated decision rule—are consistent across the different stages, the same does not hold for BIAs. Importantly, the definition of and evidence on budget impact differs between stages. Some important aspects (e.g. substitution and saving effects) typically are considered in the assessment and appraisal stages but are seemingly not considered in price negotiations and the final reimbursement decision. Further research is warranted to better understand why BIAs are not aligned with CEAs (e.g. in terms of underlying assumptions), vary in form and importance between stages, and do not have a clear relationship with the results of CEAs in the decision-making framework. Improving the understanding of the circumstances under which decision-makers attach a relatively larger or smaller weight to (different aspects of) budget impact may contribute to increasing the transparency, consistency, and optimality of reimbursement decisions in the Netherlands.