bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of plasma start-up with high Z and low Z first wall in WEST
Authors: Guillemaut C. , Afonin K. , Bodner G. , Bucalossi J. , Corre Y. , Devynck P. , Diallo A. , Diez M. , Fedorczak N. , Gallo A. , Guillermin B. , Lapleigne V. , Lunsford R. , Maget P. , Morales J. , Moreau Ph. ,   the WEST Team,   the EUROfusion Tokamak Exploitation Team
Published: January 2025

The choice of first wall material is of paramount importance for the plasma start-up conditions in ITER and future fusion power plants. In this context, the present work focuses on the correlations between first wall impurity sources and total radiated power during plasma start-up in the tungsten (W) Environment in Steady-state Tokamak (WEST). The objective is to highlight experimental indications for a preferable combination of start-up plasma scenario and first wall materials. Until 2019, WEST featured a full high Z first wall with all limiters exposing only W surfaces to the plasma. To study the impact of a low Z first wall in WEST, boron nitride tiles were installed in the central part of the inner and outer limiters in 2020. Although visible spectroscopy and bolometry measurements show respectively a strong weakening of the WI line intensity on the limiters and a reduction of radiated power after the changeover, a degradation occurs with the accumulation of plasma exposure. In addition, the different plasma facing elements of the main chamber do not influence equally the radiated power during start-up. In both high Z and low Z environments, a clear non-linear dependence is found between the start-up radiated power and the outer limiter W impurity source. Since W seems to be the main cause for core radiation, correlation between outer limiter W sources and other impurity sources are investigated. Finally, analysis of the legacy of B powder drops on a number of start-up plasmas suggests that it is less effective at reducing radiated power when the first wall is covered with W.
Bridging the gap between defossilization and decarbonization to achieve net-zero industry
Authors: Griffiths Steven , Sovacool Benjamin , Iskandarova Marfuga , Walnum Hans Jakob
Published: January 2025

This paper examines the compatibility of broad decarbonization efforts, as embodied in the circular carbon economy (CCE) framework, with a narrower concept of defossilization in achieving net-zero industry. Through case studies of the United States, Norway, and the United Arab Emirates (UAE), we analyze national industrial decarbonization strategies and present findings from extensive fieldwork, including 139 expert interviews and 124 site visits supplemented with document analysis. Our results reveal that CCE and defossilization, which is defined as decarbonization through the elimination of fossil fuel extraction and use, are potentially compatible concepts in the long-term pursuit of net-zero industry. The CCE approach, which incorporates energy efficiency, renewable energy, electrification, low-carbon fuels, and carbon capture, utilization and storage, particularly offers a practical pathway for oil and gas (O&G) producing countries to transition towards net-zero industrial emissions. CCE allows these and similar countries to balance environmental goals with technical, economic, social and political challenges associated with defossilization. The case studies demonstrate that all three countries are adopting CCE strategies tailored to their unique contexts. The US emphasizes a portfolio approach integrating multiple technologies, the UAE focuses on leveraging existing fossil fuel infrastructure for CCE efforts, and Norway capitalizes on its abundant renewable resources while investing in carbon capture and storage and hydrogen projects utilizing its extensive O&G sector expertise and resources. Key policy recommendations include technology and policy leadership from countries pursuing a CCE framework, encouragement of public–private partnerships in the deployment of CCE technologies and ensuring social equity as net-zero industry is pursued in the near and long term. We also summarize existing approaches, pathways, and frameworks for industrial decarbonization, as well as barriers and challenges. We lastly call for further research on integration of CCE and defossilization visions, strategies and roadmaps and a strong focus on international cooperation in achieving net-zero industry.
Internal structure of gauge-invariant projected entangled pair states
Authors: Blanik David , Garre-Rubio José , Molnár András , Zohar Erez
Published: January 2025

Projected entangled pair states (PEPS) are very useful in the description of strongly correlated systems, partly because they allow encoding symmetries, either global or local (gauge), naturally. In recent years, PEPS with local symmetries have increasingly been used in the study of non-perturbative regimes of lattice gauge theories, most prominently as a way to construct variational ansatz states depending only on a small number of parameters and yet capturing the relevant physical properties. For the case of one-dimensional PEPS (matrix product states—MPS) a bidirectional connection was established between the internal structure of the tensor network, i.e. the mathematical properties of the constituent tensors, and the symmetry. In higher dimensions this has only been done for global symmetries, where in the local (gauge) case it is known only how to construct gauge-invariant states, but not what the symmetry implies on the internal structure of the PEPS. In the present work we complete this missing piece and study the internal structure of PEPS with a gauge symmetry. The PEPS we consider consist of matter and gauge field tensors placed on the vertices and edges, respectively, of arbitrary graphs.
Simulation of fluid flow with Cuprophan and AN69ST membranes in the dialyzer during hemodialysis
Authors: Ortega José Luis Velázquez , López Aldo Gómez , López Esteban Adrian Romero
Published: January 2025

Hemodialysis is a crucial procedure for removing toxins and waste from the body when kidneys fail to perform this function effectively. This study addresses the need to improve the efficiency and biocompatibility of membranes used in dialyzers. We simulate fluid flow through two types of membranes, Cuprophan (cellulosic) and AN69ST (synthetic), to understand the complex mechanisms involved and quantify key variables such as pressure, concentration, and flow. This study presents a detailed model that applies mass conservation equations and Navier-Stokes principles adapted for porous media, along with heat and mass transfer considerations. The results revealed significant differences in the flow behavior and filtration efficiency between the two membranes, highlighting the superiority of the AN69ST membrane in terms of flow rate and toxin removal. This model serves as a valuable tool for characterizing new porous membranes in dialysis applications, enabling the prediction of the temperature, pressure, and concentration profiles. By providing this information without requiring extensive experimentation, the model complements the design and evaluation of new membranes and, optimizes their development. The ability to predict these profiles is crucial because they directly influence the parameters that determine treatment effectiveness. Moreover, this study underscores the importance of continued innovation in membrane materials and designs, contributing to improved clinical outcomes and treatment efficiency, representing a significant advancement in healthcare.
Quantum thermal machine as a rectifier
Authors: Santiago-García M , Pusuluk O , Müstecaplıoğlu Ö E , Çakmak B , Román-Ancheyta R
Published: January 2025

We study a chain of interacting individual quantum systems connected to heat baths at different temperatures on both ends. Starting with the two-system case, we thoroughly investigate the conditions for heat rectification (asymmetric heat transport), compute thermal conductance, and generalize the results to longer chains. We find that heat rectification in the weak coupling regime can be independent of the chain length and that negative differential thermal conductance occurs. We also examine the relationship between heat rectification with entanglement and the entropy production. In the strong coupling regime, the system exhibits an asymmetric Rabi-type splitting in the thermal conductance, leading to enhanced heat transport and improved rectification inaccessible in the weak coupling. This setup represents the simplest quantum thermal machine that consumes incoherent resources and delivers entanglement while acting as a rectifier and heat valve.
Fine pitch superconducting interconnects obtained with Nb–Nb direct bonding
Authors: Thomas Candice , Renaud Pablo , Guergour Meriem , Deschaseaux Edouard , Dubarry Christophe , Guillaume Jennifer , Vermande Elisa , Campo Alain , Fournel Frank , Hijazi Hadi , Papon Anne-Marie , Pellissier Catherine , Charbonnier Jean
Published: January 2025

For cryogenic systems, the development of superconducting interconnects is nowadays essential to reach large-scale integration schemes while addressing the associated challenges of signal dispersion and cross talk as well as thermal management. To achieve interconnects with micrometer and potentially sub-micrometer pitches, we investigate wafer-to-wafer direct bonding of Nb pads, using 200 mm processes developed for Cu/SiO2 hybrid bonding and for Nb routing levels. Contrarily to standard hybrid bonding, the Nb pads of these interconnects are surrounded by air instead of dielectric to reduce signal and thermal losses in between the wafers. We report on the fabrication and characterization of this technology using 20–7 μm-pitch direct bonded Nb pads. Transmission electron microscopy of the bonded interface and wafer-level parametric tests at 300 K of various daisy chains assess the bonding quality with a yield exceeding 90%. Low temperature electrical measurements in a cryostat demonstrate the promise of these interconnects with a critical temperature of 4.6 K, a critical magnetic field of 3.2 T and a critical current density of 1.25 kA/cm2 at 2 K and 0 T for 10 µm × 10 μm bonded Nb pads.
Para-hyper-Kähler Geometry of the Deformation Space of Maximal Globally Hyperbolic Anti-de Sitter Three-Manifolds
Authors: Mazzoli Filippo , Seppi Andrea , Tamburelli Andrea
Published: January 2025

In this paper we study the para-hyper-Kähler geometry of the deformation space of MGHC anti-de Sitter structures on

Σ
×

R

\Sigma \times \mathbb R

, for

Σ
\Sigma

a closed oriented surface. We show that a neutral pseudo-Riemannian metric and three symplectic structures coexist with an integrable complex structure and two para-complex structures, satisfying the relations of para-quaternionic numbers. We show that these structures are directly related to the geometry of MGHC manifolds, via the Mess homeomorphism, the parameterization of Krasnov-Schlenker by the induced metric on

K
K

-surfaces, the identification with the cotangent bundle

T
∗

T

(
Σ
)

T^*\mathcal T(\Sigma )

, and the circle action that arises from this identification. Finally, we study the relation to the natural para-complex geometry that the space inherits from being a component of the

P

S
L

(
2
,

B

)

\mathbb {P}\mathrm {SL}(2,\mathbb {B})

-character variety, where

B

\mathbb {B}

is the algebra of para-complex numbers, and the symplectic geometry deriving from Goldman symplectic form.
Arithmetic Quotients of the Bruhat-Tits Building for Projective General Linear Group in Positive Characteristic
Authors: Kondo Satoshi , Yasuda Seidai
Published: January 2025

Let

d
≥
1

d \ge 1

. We study a subspace of the space of automorphic forms of

G
L

d

\mathrm {GL}_d

over a global field of positive characteristic (or, a function field of a curve over a finite field). We fix a place

∞
\infty

of

F
F

, and we consider the subspace

A

S
t

\mathcal {A}_{\mathrm {St}}

consisting of automorphic forms such that the local component at

∞
\infty

of the associated automorphic representation is the Steinberg representation (to be made precise in the text).

We have two results.

One theorem (Theorem 5.4.2) describes the constituents of

A

S
t

\mathcal {A}_{\mathrm {St}}

as automorphic representation and gives a multiplicity one type statement.

For the other theorem (Theorem 4.5.1), we construct, using the geometry of the Bruhat-Tits building, an analogue of modular symbols in

A

S
t

\mathcal {A}_{\mathrm {St}}

integrally (that is, in the space of

Z

\mathbb {Z}

-valued automorphic forms). We show that the quotient is finite when a level is fixed and give a bound on the exponent of this quotient.
Stochasticity and invasion fronts
Authors: Phillips Ben
Published: January 2025

This chapter shows that chance events (stochasticity) can play a major role in invasions. This chapter explains the ecological sources of stochasticity, and how we might incorporate this stochasticity into our understanding. This chapter shows that chance events in reproduction and dispersal all combine to make real-world invasions difficult to predict. In aggregate, these chance events can also cause invasions to move slower, or faster, than they would otherwise.
Pushed and pulled waves
Authors: Phillips Ben
Published: January 2025

This chapter introduces the idea of pushed invasions. The chapter explains the difference between pushed and pulled invasions, and steps through a myriad of circumstances that can cause pushed invasions. This chapter examines how this class of invasion affects the theory that has been developed thus far, and examines dynamics that are peculiar to pushed invasions, such as range pinning.
The French Divergence
Authors: Briggs Jonathyne
Published: January 2025

This chapter lays out the historical context for the interpretation of autism in France, detailing the influence of psychoanalysis in defining aspects and diagnosis since the first cases were recognized. The norms of family, the influence of the natalist movement, and the belief in the regenerative properties of youth in the postwar period were challenged by autistic persons, especially children who received attention from professionals. Coupled with approaches that concerned the role of the mother in the development of autism, psychoanalysis became the accepted intervention and entrenched the experience of autism in childhood. This combination led parents to become activists against psychoanalysis after their initial support of the efforts of analysts. The strength of psychoanalysis led to a divergence of treatment from psychological norms elsewhere in the Western world.
Inclusion of health equity language in recruitment materials for postgraduate pharmacy residencies
Authors: Vas Sarah , Kumar Akshara , Schowe Jessica , Reyes Jasmine , Krout Taylor , Miller Monica L , Karwa Rakhi
Published: January 2025

Purpose

The study objective was to analyze the use of health equity (HE)– and social determinants of health (SDOH)–related language within pharmacy residency websites and recruitment materials.

Methods

Using the ASHP residency directory of 2022, a randomly selected sample of postgraduate year 1 (PGY1) and PGY1/PGY2 programs from each state were analyzed. After search terms were selected from HE/SDOH resources, each program’s residency-specific webpages (RSWs) and institution-specific webpages (ISWs) were searched and given a score based on the frequency of identified terms. The primary outcome was the number of programs with at least one identified instance of HE/SDOH terms. Additional outcomes included the frequency of HE/SDOH terms on ISWs or RSWs and program score distribution. Outcomes were also evaluated among programs in medically underserved areas (MUAs).

Results

Three hundred eighteen programs were included, of which 205 (64%) included HE/SDOH language within RSWs, ISWs, or both. Of these 205 programs, 126 programs (61%) included language only on ISWs. The number of programs that only had one instance of HE/SDOH terms on either category of webpages, or had a score of 1, was 128 programs (40.2% of the total of 318 programs). Of the 111 programs in MUAs (35%), 66 (59.5%) included HE/SDOH language within the ISWs.

Conclusion

Most evaluated programs, including those in MUAs, lacked language specifically identifying their focus and work around HE/SDOH within their residency promotional materials.
Gene-ius at work: Hemophilia B treatment enters a new era
Authors: Northington Madison W , Rice Sarah E , Holmes Abigail L , Watts Alexander Courtney S
Published: January 2025

Disclaimer

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Purpose

Hemophilia B is a rare, hereditary bleeding disorder characterized by a deficiency in clotting factor IX (FIX). Traditional therapeutic strategies involve an economically and physically burdensome combination of prophylactic and episodic (ie, on-demand) administration of clotting factor concentrates (CFCs). The first gene therapy for hemophilia B, etranacogene dezaparvovec (Hemgenix), was approved by the Food and Drug Administration (FDA) in November 2022, with approval for fidanacogene elaparvovec (Beqvez) following in April 2024, produced by CSL Behrig and Pfizer, respectively. This literature review aims to provide an overview of current therapeutic strategies for the treatment of hemophilia B, introducing and focusing on the efficacy and safety of the novel gene therapies etranacogene dezaparvovec and fidanacogene elaparvovec.

Both FDA-approved hemophilia B gene therapies, etranacogene dezaparvovec and fidanacogene elaparvovec, utilize adeno-associated virus (AAV) vectors for delivery of the gene encoding FIX. Each of these medications has a distinct AAV serotype, but they have the same treatment modality, with the goal of curing the disease and reducing or eliminating prophylactic CFC requirements. Despite their different AAV serotypes, both products deliver a functional copy of the gene encoding the Padua variant (variant R338L) of human FIX. Recent clinical trials have demonstrated efficacy in increasing FIX concentrations leading to reduced frequency of spontaneous bleeding episodes; however, safety and response durability remain concerns.

Conclusion

For the first time in history, individuals with hemophilia B have access to potentially curative therapies through gene therapy. Both etranacogene dezaparvovec and fidanacogene elaparvovec offer significant efficacy, reducing the number of bleeding episodes and raising FIX concentrations with a single lifetime administration. While concerns remain regarding long-term safety and durability, these therapies represent a major advancement in reducing treatment burden and improving quality of life for patients. The future of hemophilia B management now holds the promise of greater independence from frequent prophylactic treatments.
Contrasting habitat associations and ecophysiological adaptations drive interspecific growth differences among Himalayan high-mountain plants
Authors: Chondol Thinles , Klimeš Adam , Hiiesalu Inga , Altman Jan , Čapková Kateřina , Jandová Veronika , Kopecký Martin , Macek Martin , Řeháková Klára , Doležal Jiří
Published: January 2025

Background and Aims

Understanding interspecific differences in plant growth rates and their internal and external drivers is key to predicting species responses to ongoing environmental changes. Annual growth rates vary among plants based on their ecological preferences, growth forms, ecophysiological adaptations and evolutionary history. However, the relative importance of these factors remains unclear, particularly in high-mountain ecosystems experiencing rapid changes.

Methods

We examined how habitat associations, elevational optima, growth forms, and ecophysiological and anatomical traits influence interspecific differences in radial growth rates among 324 vascular dicot species naturally occurring in the western Himalayas. Growth rates were determined from annual ring width measurements on the oldest plant sections of over 7800 individuals from a range of habitats (desert, steppe, wetland, alpine, subnival), growth forms (perennial tap-rooted, rhizomatous, cushiony, woody) and climatic gradients (elevations of 2650–6150 m).

Key Results

Habitat associations accounted for 24 % of the variability in interspecific growth rates. Adding growth form and height increased the explanation to 42 %, and incorporating plant functional traits further improved predictions to 46 %. Growth rates were higher in warmer, drier conditions and lower in cold, wet environments. Subnival cushion plants had the slowest growth, while ruderal plants grew the fastest. Desert plants showed higher growth rates, reflecting their drought adaptive strategies, while wetland forbs had lower growth rates due to increased resource competition. Growth was positively correlated with leaf nitrogen content and non-structural carbohydrates (mainly fructans), due to enhanced photosynthesis and stress tolerance, and negatively correlated with leaf carbon and root nitrogen content.

Conclusion

Our study of 324 dicot species in the western Himalayas suggests that plant growth in high elevations is determined by a combination of habitat conditions, morphological traits and ecophysiological adaptations. Growth variations among the highest-growing angiosperms reflect adaptive strategies along the global ‘fast–slow’ and ‘acquisitive–conservative’ spectrums. These results underscore the importance of habitat-specific studies for predicting plant growth responses to environmental changes, emphasizing a species-specific approach for effective conservation in fragile ecosystems.
Advances of computational methods enhance the development of multi-epitope vaccines
Authors: Wei Yiwen , Qiu Tianyi , Ai Yisi , Zhang Yuxi , Xie Junting , Zhang Dong , Luo Xiaochuan , Sun Xiulan , Wang Xin , Qiu Jingxuan
Published: January 2025

Vaccine development is one of the most promising fields, and multi-epitope vaccine, which does not need laborious culture processes, is an attractive alternative to classical vaccines with the advantage of safety, and efficiency. The rapid development of algorithms and the accumulation of immune data have facilitated the advancement of computer-aided vaccine design. Here we systemically reviewed the in silico data and algorithms resource, for different steps of computational vaccine design, including immunogen selection, epitope prediction, vaccine construction, optimization, and evaluation. The performance of different available tools on epitope prediction and immunogenicity evaluation was tested and compared on benchmark datasets. Finally, we discuss the future research direction for the construction of a multiepitope vaccine.
Effects of endometrial embryokines on the preimplantation bovine embryo to create a gene expression signature consistent with a high competence phenotype
Authors: Maldonado Mariângela Bueno Cordeiro , Rabaglino Maria Belen , Cannon Gabrielle Heather , Hansen Peter James
Published: January 2025

Optimal embryonic development depends upon cell-signaling molecules released by the maternal reproductive tract called embryokines. The identity of specific embryokines that enhance the competence of the embryo for sustained survival is largely lacking. The current objective was to evaluate the effects of three putative embryokines in cattle on embryonic development to the blastocyst stage. The molecules tested were vascular endothelial growth factor A (VEGFA), C-X-C motif chemokine ligand 12 (CXCL12), and interleukin-6 (IL6). Molecules were added from day 4 to 7.5 of culture at 50 ng/mL (VEGFA and CXCL12) or 100 ng/mL (IL6). Endpoints were development to the blastocyst stage and transcript abundance for 94 specific genes involved in lineage commitment, epigenetic regulation, and other functions. Among the genes examined were eight whose transcript abundance has been related to embryo competence for survival after embryo transfer. None of the molecules increased the proportion of putative zygotes or cleaved embryos becoming blastocysts at day 7.5 of development. An embryo competence index based on a Bayesian multiple regression formula to weigh transcript abundance of the eight biomarker genes was not affected by treatment with VEGFA but was increased by both CXCL12 and IL6. The transcript abundance of 5 genes was modified by VEGFA, 19 by CXCL12, and 19 by IL6. A total of 11 genes were modified in a similar manner by CXCL12 and IL6. Most differentially expressed genes for CXCL12 and IL6 were downregulated, suggesting that the embryokines may promote a less energetically demanding metabolic state than would be the case in their absence.
White matter connections within the central sulcus subserving the somato-cognitive action network
Authors: Skandalakis Georgios P , Viganò Luca , Neudorfer Clemens , Rossi Marco , Fornia Luca , Cerri Gabriella , Kinsman Kelsey P , Bajouri Zabiullah , Tavakkoli Armin D , Koutsarnakis Christos , Lani Evgenia , Komaitis Spyridon , Stranjalis George , Zadeh Gelareh , Barrios-Martinez Jessica , Yeh Fang-Cheng , Serletis Demitre , Kogan Michael , Hadjipanayis Constantinos G , Hong Jennifer , Simmons Nathan , Gordon Evan M , Dosenbach Nico U F , Horn Andreas , Bello Lorenzo , Kalyvas Aristotelis , Evans Linton T
Published: January 2025

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield’s motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the ‘plis de passage’ of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.

Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space to seed functional MRI connectivity across 9000 resting-state functional MRI scans, which demonstrated the connectivity of these sites with the somato-cognitive action network. Intraoperative recordings during direct electrical central sulcus stimulation further identified inter-effector regions corresponding to plis de passage locations.

This work provides a critical step towards an improved understanding of the somato-cognitive action network in both structural and functional terms. Furthermore, our work has the potential to guide the development of refined motor cortex stimulation techniques for treating brain disorders and operative resective techniques for complex surgery of the motor cortex.
Unmasking paramagnetic rim multiple sclerosis lesions: the advantages of quantitative susceptibility mapping over phase imaging
Authors: Rovira Àlex , Pareto Deborah
Published: January 2025

This scientific commentary refers to ‘Quantitative susceptibility mapping is more sensitive and specific than phase imaging in detecting chronic active multiple sclerosis lesion rims: pathological validation’, by Gillen et al. (https://doi.org/10.1093/braincomms/fcaf011).
Cortical involvement of lateral trunk flexion and verticality misperception in Parkinson’s disease
Authors: Kohsaka Masayuki , Oeda Tomoko , Takaya Shigetoshi , Tomita Satoshi , Park Kwiyoung , Yamamoto Kenji , Fukuyama Hidenao , Sawada Hideyuki
Published: January 2025

Lateral trunk flexion is a common form of postural abnormality in Parkinson’s disease and could be associated with verticality misperception. However, the mechanisms underlying lateral trunk flexion and verticality misperception in Parkinson’s disease remain unclear. In the current study, we examined whether lateral trunk flexion is associated with verticality misperception in patients with Parkinson’s disease. We also identified the brain regions involved in lateral trunk flexion and altered verticality perception. In this cross-sectional study, we evaluated the verticality perception using the subjective visual vertical test in 81 patients with Parkinson’s disease and 14 age-matched healthy controls. According to the 97.5th percentile upper reference limit of the body tilt angle in the healthy controls, patients with Parkinson’s disease were grouped into 37 patients with lateral trunk flexion and 44 patients without lateral trunk flexion. The mean of absolute subjective visual vertical angles was compared between patients with Parkinson’s disease with lateral trunk flexion, those without lateral trunk flexion, and the healthy controls, and the impact of verticality misperception on lateral trunk flexion was evaluated using multivariate logistic regression models. We further performed a voxel-wise comparison of regional cerebral blood flow using N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography (height threshold of P < 0.001, uncorrected for multiple comparisons, extent threshold of 100 voxels) to identify the brain regions associated with lateral trunk flexion, and to investigate the relationship between verticality misperception and regional hypoperfusion. The mean of absolute subjective visual vertical angles was larger in patients with Parkinson’s disease with and without lateral trunk flexion than in healthy controls (P < 0.001 and P < 0.001). Additionally, the subjective visual vertical angle was associated with the presence of lateral trunk flexion (odds ratio 2.25, 95% confidence interval 1.51–3.36, P < 0.001). The regional cerebral blood flow in patients with Parkinson’s disease with lateral trunk flexion was decreased in the right inferior parietal lobule, right superior parietal lobule, right superior temporal gyrus, and right dorsal posterior cingulate cortex compared with those without lateral trunk flexion. The subjective visual vertical angle was inversely correlated with regional cerebral blood flow in these regions, except for the dorsal posterior cingulate cortex. Our study reveals that hypofunction in the right temporoparietal association cortices is involved in verticality misperception and the development of lateral trunk flexion in patients with Parkinson’s disease. These results provide insights into potential therapeutic targets for addressing lateral trunk flexion.
A spectrum of BAP1 expression from nevus to melanoma in a patient with BAP1 tumor predisposition syndrome
Authors: Ogura Yasuaki , Shimauchi Takatoshi , Sugiyama Tomoko , Sugimura Yuki , Nakagawa Masahiro , Osawa Harumo , Kojima Risa , Iwaizumi Moriya , Honda Tetsuya
Published: January 2025

BAP1 tumor predisposition syndrome (BAP1-TPDS) is a rare autosomal dominant disorder characterized by germline loss-of-function mutations in the BAP1 tumor suppressor gene, and patients with BAP1-TPDS are at an increased risk of developing various tumors, including melanoma. we report a case of melanoma on the scalp in a patient with BAP1-TPDS. Based on BAP1 expression pattern and cell morphology, we identified four distinct melanocytic populations within the lesion. We believe these findings provide us with important clues to understand the developmental mechanism of melanoma arising from nevi following a BAP1 mutation.
Optimizing arrhythmia identification using chaos theory and deep learning analysis
Authors: Eldakhly Nabil M
Published: January 2025

Optimal heart function is crucial for quality life. Electrocardiograms are indispensable for diagnosing cardiac irregularities and analyzing heartbeat signals. This study unveils three novel machine learning (ML) techniques enhancing diagnostic precision. The first method scrutinizes raw ECG data and its time-series metrics, while the second incorporates historical patient health data for direct ECG classification. The third technique transforms ECG signals into insightful features, focusing on QRS complex waves. Uniquely combining these strategies, our research pioneers in advanced feature selection for cardiac diagnosis. Experiments were conducted to compare the integration of clinical data, QRS characteristics, and chaos preprocessing impact on the diagnosis. For classification assessment, five algorithms were utilized: Support Vector Machine, Decision Tree, Naïve Bayes, Neural Network, and Convolutional Neural Networks (CNNs). Implementing chaos theory, we converted QRS features into deterministic metrics. Notably, our Chaos-Enhanced CNN model exhibited outstanding performance, achieving a remarkable 99.8% accuracy rate, outshining other models.
Certolizumab Pegol Treatment in Patients With Crohn’s Disease: Final Safety Data From the SECURE Registry
Authors: Lichtenstein Gary R , Lee Scott D , Feagan Brian G , Loftus Edward V , Ng Samson , Dehlin Kaitlin , Quinn Paul , Coarse Jason , Rosario-Jansen Theresa , Arendt Catherine , Stark Jeffrey L
Published: January 2025

Background

Crohn’s disease (CD) treatment is associated with increased risks of infection and malignancies. Although the safety of certolizumab pegol (CZP) is well established, long-term data from community-based observational studies are lacking.

Aim

This study aimed to evaluate long-term safety outcomes of patients from the SECURE registry receiving CZP relative to other CD treatments, including corticosteroids, immunosuppressants, and biologics. The primary outcome of this observational study was the evaluation of malignancies.

Methods

Adult patients with CD were prospectively monitored for up to 8 years. Pre-specified data were collected for all enrolled patients. Adverse events of interest (AEoIs) were reported per 100 patient-years (PY) of exposure. Incidence rate ratios (IRRs) were calculated for AEoIs using multivariate regression analysis accounting for exposure to multiple treatments. Malignancies reported after any exposure to CZP were attributed to CZP. Post-hoc analyses were conducted to evaluate non-melanoma skin cancer (NMSC), lymphoma, and pregnancy outcomes.

Results

A total of 3072 patients were enrolled in the study. The risk of AEoIs was similar between patients with only CZP exposure versus comparator exposure. Among patients with any CZP exposure, there was a higher frequency of serious infections (IRR: 2.56 [95% confidence interval (CI): 2.00, 3.29]) and hypersensitivity or anaphylactic reactions (IRR: 4.11 [95% CI: 1.80, 9.38]) versus patients with comparator exposure. Malignancy rates were similar across groups; however, concomitant use of thiopurines was associated with higher odds of NMSC (odds ratio: 2.30 [95% CI: 1.09, 4.89]). Most cases of lymphoma (5/7) occurred in patients with exposure to thiopurines. Pregnancy outcomes were similar across groups.

Conclusions

No new safety signals were identified for CZP; the use of thiopurines was identified as a risk factor for NMSC.

Trial registration

NCT00844285.
Prognostic significance of subcarinal lymph node involvement in patients with Siewert type I and II gastro-esophageal junctional adenocarcinoma: an analysis of 698 patients undergoing Ivor-Lewis esophagectomy
Authors: Walmsley James A , Abdelrahman Mohamed , Ariyarathenam Arun , Berrisford Richard , Humphreys Lee , Sanders Grant , Tham Ji Chung , Wheatley Tim , Chan David S Y
Published: January 2025

Gastro-esophageal junction (GOJ) adenocarcinoma is increasingly common and despite significant changes in management over the past decade, overall survival remains poor. Determining factors that influence survival is important for optimizing curative surgery. The prognostic significance of subcarinal lymph node involvement is unclear. The purpose of this study was to assess the prognostic significance of subcarinal lymph node involvement in patients undergoing curative resection of GOJ adenocarcinoma. Consecutive patients undergoing curative 2-stage Ivor-Lewis esophagectomy between February 2010 and January 2022 were analyzed retrospectively from a prospectively maintained database for Siewert type I and II GOJ adenocarcinoma confirmed on histopathology. Outcomes were compared based on subcarinal node involvement confirmed on histopathology. A total of 698 patients with Siewert type I (n = 314) and II (n = 384) adenocarcinoma were analyzed [median age 68 (31–85), 604 males (87%) neo-adjuvant use 491 (74.4%)]. Eighteen patients (2.6%) had subcarinal lymph node involvement. These patients had more advanced overall stage of disease and positive node involvement than those without and a significantly lower median survival of 6 months (<1–25) compared to 53 months (41–65) (p < 0.001). On multivariate analysis, pathological T stage, para-gastric and subcarinal lymph node involvement were found to be the independent and significant factors influencing survival. Subcarinal lymph node involvement is an indicator of advanced disease and high positive node burden. It is an independent prognostic factor in patients undergoing curative surgery for Siewert type I and II GOJ adenocarcinoma.
Impact of a personalized, strike early and strong lipid-lowering approach on low-density lipoprotein-cholesterol levels and cardiovascular outcome in patients with acute myocardial infarction
Authors: Patti Giuseppe , Cumitini Luca , Bosco Manuel , Marengo Alessandra , D'Amario Domenico , Mennuni Marco , Solli Martina , Grisafi Leonardo
Published: January 2025

Aims

Considering the lack of evidence, we evaluated the impact on cardiovascular outcome of the systematic introduction in our institution of a personalized strike early and strong (SES) approach for lipid-lowering therapy (LLT) in patients admitted for acute myocardial infarction (MI).

Methods and results

We retrospectively analysed data from 500 consecutive patients hospitalized across three periods: Period A (N = 198, January–June 2019), when the low-density lipoprotein cholesterol (LDL-C) goal was <70 mg/dL and a stepwise LLT approach was recommended; Period B (N = 180, January–June 2021), when the LDL-C goal was <55 mg/dL and a stepwise approach was recommended; Period C (N = 122, January–June 2023), when the LDL-C goal was <55 mg/dL and our SES protocol was implemented. Primary endpoints were achievement of the LDL-C goal during follow-up and 1-year incidence of major adverse cardiovascular events (MACE). Compared to the other periods, in Period C, there was a higher use of potent statins, alone or in combination with ezetimibe, and of proprotein convertase subtilisin/kexin type 9 inhibitor inhibitors at discharge. This translated into higher achievement of the LDL-C goal (83% vs. 55% in Period A and 43% in Period B; P < 0.001) and reduced incidence of MACE (3% vs. 12% and 11%; P = 0.026). MACE rates were lowest in patients with early and sustained LDL-C <55 mg/dL and in those achieving both LDL-C <55 mg/dL and ≥50% LDL-C reduction.

Conclusion

The systematic introduction of a personalized, SES strategy for LLT in patients with acute MI led to greater achievement of LDL-C goal and lower risk of MACE at 1 year vs. the stepwise approach.
Prognostic value of computed tomography-derived myocardial extracellular volume in aortic stenosis: a meta-analysis of all-cause mortality and heart failure hospitalization
Authors: Kirigaya Jin , Kato Shingo , Matsushita Kensuke , Horita Nobuyuki , Utsunomiya Daisuke , Hibi Kiyoshi
Published: January 2025

Aims

Pre-existing myocardial fibrosis before aortic valve replacement (AVR) is a major cause of postoperative heart failure (HF). Evaluation of fibrosis by computed tomography extracellular volume (CT-ECV) may allow risk stratification for patients with severe aortic stenosis (AS) scheduled for transaortic AVR (TAVR) or surgical AVR (SAVR). We performed a meta-analysis to determine the prognostic value of CT-ECV for the prediction of adverse events in patients with severe AS scheduled for AVR.

Methods and results

Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. A comprehensive literature review was conducted to examine the association between CT-ECV and prognosis in patients with severe AS who underwent AVR. The diagnostic performance of CT-ECV for predicting composite adverse events (all-cause death and hospitalization for HF) was assessed using a pooled odds ratio (OR). Data from 902 patients with severe AS were extracted from six studies, including 881 TAVR and 21 SAVR cases. The pooled OR of abnormal CT-ECV for predicting adverse events was 4.53 [95% confidence interval (CI): 3.13–6.57 (I2 = 10%, P for heterogeneity = 0.50)]. We performed an OR meta-analysis on five studies with only TAVR cases (n = 807). The pooled OR of abnormal CT-ECV for predicting adverse events in TAVR patients was 4.85 [95% CI: 3.26–7.21 (I² = 0%, P < 0.001)].

Conclusion

Considering the high prognostic ability and versatility of CT-ECV, it may be used to predict postoperative adverse events in patients with severe AS who underwent AVR.
Impact of cardiac position, morphology and operative technique on long-term Fontan outcomes in heterotaxy
Authors: Kadowaki Sachiko , Fan Chun-Po Steve , Zahiri Yasmin , Yap Kok Hooi , Tocharoenchok Teerapong , Dipchand Anne I , Honjo Osami , Barron David J
Published: January 2025

OBJECTIVES

This study aimed to assess the outcomes of heterotaxy patients who underwent the Fontan operation, focusing on morphological features and surgical techniques.

METHODS

Eighty-two consecutive heterotaxy patients who underwent the Fontan operation from 1985 to 2021 were compared to 150 patients with tricuspid atresia (TA) and 144 patients with hypoplastic left heart syndrome (HLHS). The Kaplan–Meier method and Cox proportional hazard model were used to analyse transplant-free survival and predictor of outcomes.

RESULTS

The 20-year transplant-free survival rates were comparable between right atrial isomerism (RAI, n = 45) and left atrial isomerism (LAI, n = 37) [RAI versus LAI, 76% (95% confidence interval, 57–87%) vs 68% (47–82%), P = 0.22], although more pulmonary vein interventions at Fontan were needed in RAI. Surgical techniques included extracardiac conduit in 66%, intra-atrial conduit in 9% and lateral tunnel in 18% of the cases. Cardiac position and apicocaval juxtaposition did not influence outcomes, but the inferior vena cava (IVC)-contralateral pulmonary artery (PA) Fontan was associated with 100% survival, while the IVC-ipsilateral PA Fontan at the cardiac apex showed a 67% (34–87%) survival rate at 20 years. In-hospital mortality was higher in heterotaxy [9.8% (5–19%)] compared to TA [1.3% (0.3–5.3%), P<0.01) and HLHS [2.8% (1.1–7.3%), P = 0.02], with no early death after 2000 in any group. The 20-year transplant-free survival in heterotaxy [72% (59–82%)] was similar to that in HLHS [80% (69–87%), P = 0.11].

CONCLUSIONS

Various routing techniques can be successfully applied to overcome anatomical challenges in heterotaxy. Despite higher in-hospital mortality, overall survival was similar to HLHS. RAI had comparable survival to LAI with more pulmonary vein interventions at Fontan.
One-minute sit-to-stand test cut-offs for risk stratification based on six-minute walk test thresholds in pulmonary hypertension
Authors: Kronberger Christina , Mousavi Roya Anahita , Ermolaev Nikita , Willixhofer Robin , Rassoulpour Nima , Kaya Musa Bedirxan , Poledniczek Michael , Eslami Mahshid , Krall Christoph , Litschauer Brigitte , Grzeda Mariusz Tadeusz , McKenna Ian , Badr Eslam Roza
Published: January 2025

Aims

We aimed to establish 1-min sit-to-stand test (1-min STST) cut-off values that align with the guideline-recommended 6-min walk test (6MWT) thresholds (165 and 440 m) for 1-year mortality risk stratification in pulmonary hypertension (PH) patients. Furthermore, we aimed to compare clinical characteristics and long-term mortality among patients stratified by these proposed 1-min STST cut-offs.

Methods and results

All patients performed the 1-min STST and 6MWT. Receiver operating characteristics analysis was performed to determine 1-min STST cut-offs corresponding to the 6MWT thresholds. Patients were stratified into three groups based on these cut-offs. Among 114 PH patients (mean age 66 ± 14 years, 57% female), the mean number of 1-min STST repetitions was 17 ± 6 and the mean 6MWT distance was 354 ± 133 m. The aligning 1-min STST cut-off for the <165 m 6MWT threshold was 14 repetitions (sensitivity 69%; specificity 100%) with an area under the curve (AUC) of 0.90 [95% confidence interval (CI) 0.84–0.97]. For the >440 m threshold, 20 repetitions (sensitivity 81%; specificity 84%) aligned with an AUC of 0.85 (95% CI 0.75–0.94). Patients performing ≤14 repetitions had worse N-terminal prohormone of brain natriuretic peptide levels (P < 0.001), World Health Organization functional class (P < 0.001), mean pulmonary artery pressure (P = 0.050), and health-related quality of life (P < 0.001) and a higher rate of mortality than those performing ≥20 repetitions (P = 0.020).

Conclusion

The 1-min STST cut-offs aligning with the 6MWT thresholds of 165 and 440 m are 14 and 20 repetitions, respectively. Patients performing ≤14 repetitions demonstrated worse clinical parameters and higher mortality rates, making the 1-min STST a potential risk stratification tool in PH patients.

Lay summary

This study identified cut-off values for the 1-min sit-to-stand test (1-min STST) that align with the 6-min walk test (6MWT) thresholds used to predict 1-year mortality risk in pulmonary hypertension (PH) patients, proposing the 1-min STST as a practical alternative for risk stratification.
Management of intrahepatic cholangiocarcinoma: a review for clinicians
Authors: Colangelo Matteo , Di Martino Marcello , Polidoro Michela Anna , Forti Laura , Tober Nastassja , Gennari Alessandra , Pagano Nico , Donadon Matteo
Published: January 2025

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy that arises from second-order biliary epithelial cells. Its incidence is gradually increasing worldwide. Well-known risk factors have been described, although in many cases, they are not identifiable. Treatment options are continuously expanding, but the prognosis of iCCA remains dismal. R0 liver resection remains the only curative treatment, but only a limited number of patients can benefit from it. Frequently, major hepatectomies are needed to completely remove the tumour. This could contraindicate surgery or increase postoperative morbidity in patients with chronic liver disease and small remnant liver volume. In cases of anticipated inadequate future liver remnant, regenerative techniques may be used to expand resectability. The role and extent of lymphadenectomy in iCCA are still matters of debate. Improvements in iCCA diagnosis and better understanding of genetic profiles might lead to optimized surgical approaches and drug therapies. The role of neoadjuvant and adjuvant therapies is broadening, gaining more and more acceptance in clinical practice. Combining surgery with locoregional therapies and novel drugs, such as checkpoint-inhibitors and molecular-targeted molecules, might improve treatment options and survival rates. Liver transplantation, after very poor initial results, is now receiving attention for the treatment of patients with unresectable very early iCCA (i.e. <2 cm) in cirrhotic livers, showing survival outcomes comparable to those of hepatocellular carcinoma. Ongoing prospective protocols are testing the efficacy of liver transplantation for patients with unresectable, advanced tumours confined to the liver, with sustained response to neoadjuvant treatment. In such a continuously changing landscape, the aim of our work is to review the state-of-the-art in the surgical and medical treatment of iCCA.