bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrospun robust, biodegradable, bioactive, and nanostructured sutures to accelerate the chronic wound healing
Authors: Li Yiran , Xu Hongxing , Zhao Wenwen , Zhang Li , Wu Shaohua
Published: January 2025

The design and development of advanced surgical sutures with appropriate structure and abundant bio-functions are urgently required for the chronic wound closure and treatment. In this study, an integrated technique routine combining modified electrospinning with hot stretching process was proposed and implemented to fabricate poly(L-lactic acid) (PLLA) nanofiber sutures, and the Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SRHC) was encapsulated into PLLA nanofibers during the electrospinning process to enrich the biofunction of as-generated sutures. All the PLLA sutures loading without or with SRHC were found to exhibit bead-free and highly-aligned nanofiber structure. The addition of SRHC was found to have no significant influences on the fiber morphology, diameter, and the crystallinity of as-prepared PLLA sutures. Importantly, all the SRHC-contained PLLA nanofiber sutures possessed excellent tensile and knot strength, which were of significant importance for the surgical suture applications. Besides, the antioxidant and anti-inflammatory properties of these sutures obviously enhanced with the increasing of SRHC concentration. Furthermore, the in vitro cell tests illustrated that the high fiber orientation of the sutures was able to efficiently induce the human dermal fibroblasts (HDFs) to migrate in a rapid manner, and the sutures loaded with high content of SRHC could significantly promote the attachment and proliferation of HDFs in comparison. The in vivo diabetic mouse model experiments revealed that all the as-developed PLLA sutures could effectively close the wound, but the PLLA sutures containing high content of SRHC could dramatically promote the wound healing with high quality by shortening the healing time, improving the collagen deposition, neovascularization, and the regeneration of hair follicles, especially compared with commercial polyester (PET) suture. This study offers a simple and easily-handling strategy to develop robust, biodegradable, bioactive, and nanostructured PLLA sutures, which shows huge potential for the treatment of hard-to-heal diabetic wounds.
A highly polarization-sensitive near-infrared photodetector based on two-dimensional germanane/α-CdS heterostructure
Authors: Chen Zhengwang , Linghu Jiajun , Zhang Qiang , Che Junwei , Wang Xuezhi , Wei Songrui
Published: January 2025

Near-infrared (NIR) photodetectors have been widely used in imaging, remote sensing, communications, and medical fields. Emerging trends in the next-generation NIR photodetectors emphasize small size, low power consumption, and high polarization-sensitivity, thus demanding novel material compositions. Based on first-principles calculations, this paper proposes the two-dimensional Germanane/α-CdS vertically stacked van der Waals heterostructure as a polarization-sensitive NIR photodetector with superior performance. This structure exhibits thermodynamic stability at ambient temperatures, a type II band alignment, a tunable sensitive wavelength spanning 849–2296 nm, strong photocurrent and anisotropy, and remarkable polarization sensitivity with an extinction ratio of 6.74 under a nominal bias voltage of 0.2 V.
Towards wafer-scale 2D material sensors
Authors: Steeneken Peter G , Soikkeli Miika , Arpiainen Sanna , Rantala Arto , Jaaniso Raivo , Pezone Roberto , Vollebregt Sten , Lukas Sebastian , Kataria Satender , Houmes Maurits J A , Álvarez-Diduk Ruslan , Lee Kangho , Suryo Wasisto Hutomo , Anzinger Sebastian , Fueldner Marc , Verbiest Gerard J , Alijani Farbod , Hoon Shin Dong , Malic Ermin , van Rijn Richard , Nevanen Tarja K , Centeno Alba , Zurutuza Amaia , van der Zant Herre S J , Merkoçi Arben , Duesberg Georg S , Lemme Max C
Published: January 2025

The unique properties of two-dimensional (2D) materials bring great promise to improve sensor performance and realise novel sensing principles. However, to enable their high-volume production, wafer-scale processes that allow integration with electronic readout circuits need to be developed. In this perspective, we review recent progress in on-chip 2D material sensors, and compare their performance to the state-of-the-art, with a focus on results achieved in the Graphene Flagship programme. We discuss transfer-based and transfer-free production flows and routes for complementary metal-oxide-semiconductor integration and prototype development. Finally, we give an outlook on the future of 2D material sensors, and sketch a roadmap towards realising their industrial and societal impact.
Polariton manipulation using soliton angle in 2D moiré superlattices
Authors: Wang Kaiyuan , Lv Xinyu , Wen Lu , Yu Geliang , Li Zhiqiang , Wang Lei
Published: January 2025

We theoretically study the propagation and interference of plasmon polaritons in soliton superlattices in minimally twisted bilayer graphene (mTBG) with arbitrary soliton angle, which characterizes the local strain direction. We show that the band structures and local optical conductivity across the soliton evolve systematically with soliton angle, providing an important and tunable degree of freedom for tuning polariton-soliton interactions. Consequently, the plasmon polariton interference profile near single solitons can be significantly and continuously modulated through the soliton angle. Furthermore, our simulation reveals that the polariton interference profile can be designed and manipulated by changing the soliton angle profiles. Our study demonstrates that the modulating soliton angle profile in mTBG provides a valuable pathway to controlling polaritons for nanophotonic applications.
Grey relational analysis to identify the ideal combination of impact toughness and hardness for biodegradable quenched-tempered 42CrMo4 steel
Authors: Laxmi Bhagya , P K Jayashree , Rao U Sathish , Hegde Ananda , Sharma Sathyashankara
Published: January 2025

This work investigated the effect of different types of tempering on the hardness, impact toughness and microstructure of normalized and biodegradable-quenched 42CrMo4 steel. Specimens were normalised initially then hardened using green oil quenchants such as Pinnay oil, Karanja seed oil and blended oil (Equal volume percentage of Pinnay and Karanja seed oil) then subjected to single stage tempering process. Surface response methodology was used to obtain optimised conditions from single stage tempering process to carry out other types of the tempering processes such as multiple and step tempering processes. Grey relational analysis was used to select the tempering process that yield best balanced property condition. The two steps tempering process with hardness of 36 HRC, impact toughness of 56 Joules and with grey relational grade of 0.7 was considered as the process to get optimal mix of hardness and impact toughness in 42CrMo4 steel.
A systematic review of the impact of carbon reduction measures on human comfort: a human factors and ergonomics perspective
Authors: Fang Mingzhu , Kong Yue , Hu Jie , Wang Lingyu , Yan Xingyun , Guo Meixing , Wang Min , Wang Hairui , Liu Pinkuan
Published: January 2025

This systematic review uniquely explores the impact of carbon reduction measures on human comfort from a human factors and ergonomics perspective, focusing on human comfort. An analysis of 30 papers identifies key environmental factors requiring attention in contemporary carbon reduction strategies and their implications for human comfort. The results reveal a growing emphasis on thermal comfort and air quality in carbon reduction retrofits, while other environmental factors such as light and noise receive insufficient attention. While optimal ventilation and local environmental adjustments can yield positive outcomes, adverse effects like significant indoor temperature fluctuations and heightened carbon dioxide levels may arise from certain modifications. Moreover, the findings from the analysis of human comfort assessment methods indicate a lack of focus on human comfort evaluation in carbon emission reduction initiatives, with predominant reliance on subjective questionnaires. Most studies superficially mention human comfort assessment without delving into comprehensive research or employing systematic evaluation techniques. The findings indicate that although the implementation of carbon reduction measures is extensively covered in academic literature, the limited literature addressing human comfort assessment post-implementation implies a need for further comprehensive exploration and development within the field. This study furnishes researchers, practitioners, and policymakers with a comprehensive insight into the current landscape and proposes prospective research avenues within the domain.
Utilizing generative AI for crack detection in the marble industry
Authors: Vrochidou Eleni , Sidiropoulos George K , Ouzounis Athanasios G , Tsimperidis Ioannis , Kalpakis Vassilis , Stamkos Andreas , Papakostas George A
Published: January 2025

Recently, deep learning algorithms have achieved great accuracies in multiple computer vision tasks by using considerable amounts of annotated data. In the case of marble surface crack detection, the formation of such a dataset is challenging. Currently, there are limited marble crack-related datasets, obstructing the development of robust inspection models for automated industrial quality control. To resolve this problem, we propose a generative Artificial Intelligence (AI) approach, reporting the first synthetic marble crack texture image dataset using four generative adversarial networks (GANs). Each of the final four sub-datasets includes images of different cracks on marble surfaces. The quality of the synthetic datasets is comparatively evaluated; quantitative and qualitative experimental results are provided, highlighting the most efficient generative method. Moreover, to verify the effectiveness and significance of this work, two deep learning segmentation models are used to assess the quality of the synthetic marble crack image datasets. Results indicate that different training strategies using synthetic data could boost the performance of segmentation by up to 6.55% compared to conventional data augmentation techniques. Thus, the first step towards deep learning-based automated marble crack segmentation is delivered, aiming for the simultaneous robotic resin application for healing cracks on-site, in marble-processing industrial settings.
Crack detection based on GMM-Wasserstein distance under variable temperature environment
Authors: Zhang Xiaozhen , Wang Tiantian , Yang Jinsong , Xie Jingsong , Peng Chang , Xue Yuan
Published: January 2025

The operation of high-speed trains in dynamic temperature environments presents significant challenges for crack detection in critical aluminum alloy components. It has been demonstrated that temperature fluctuations significantly impact the performance of Lamb wave-based structural health monitoring (SHM) systems, thereby compromising the reliability of damage detection protocols. In response to these challenges, a novel crack detection methodology is introduced, leveraging GMM-Wasserstein distance metrics to address variable temperature conditions. Two innovative information entropy measures are developed: Energy Singular spectral entropy (ESE) and Power Singular spectral entropy (PSE), which are utilized to characterize the complex interactions between Lamb wave signals and crack propagation under thermal variations. To enhance feature extraction robustness, an integrated approach combining Ensemble Empirical Mode Decomposition (EEMD) and Singular Spectrum Analysis (SSA) has been implemented, effectively mitigating temperature-induced signal perturbations. Additionally, a sophisticated GMM-based probability migration analysis framework incorporating Wasserstein distance metrics has been developed to quantify structural damage state evolution. The efficacy of the proposed methodology has been rigorously validated through comprehensive experimentation on Al6061 aluminum plates subjected to temperatures ranging from −40 °C to 80 °C. Experimental results indicate that the proposed method achieves a classification accuracy of 95.83% in crack detection, representing a significant improvement over conventional approaches.
Tests of thermal macroeconomic theory on simulated microeconomies
Authors: Luo Yihang , MacKay R S , Chater Nick
Published: January 2025

In this paper, we test predictions of a new theory of macroeconomics, called ‘thermal macroeconomics.’ The theory aims to apply the mathematical structure of classical thermodynamics, including analogues of temperature and entropy, to predict aspects of the aggregate behaviour of populations of economic agents without analysing their detailed interactions. We test the theory by comparing its predictions with the behaviour of a variety of simulated micro-economies in which goods and money can be exchanged between agents, confirming the predictions of the theory. The paper serves also to illustrate and make more tangible the predictions of thermal macroeconomics.
Quantitative assessment of PINN inference on experimental data for gravity currents flows
Authors: Delcey Mickaël , Cheny Yoann , Schneider Jean , Becker Simon , Kiesgen De Richter Sébastien
Published: January 2025

In this paper, we apply physics informed neural networks (PINNs) to infer velocity and pressure field from light attenuation technique (LAT) measurements for gravity current induced by lock-exchange. In a PINN model, physical laws are embedded in the loss function of a neural network, such that the model fits the training data but is also constrained to reduce the residuals of the governing equations. PINNs are able to solve ill-posed inverse problems training on sparse and noisy data, and therefore can be applied to real engineering applications. The noise robustness of PINNs and the model parameters are investigated in a 2 dimensions toy case on a lock-exchange configuration, employing synthetic data. Then we train a PINN with experimental LAT measurements and quantitatively compare the velocity fields inferred to particle image velocimetry measurements performed simultaneously on the same experiment. The results state that accurate and useful quantities can be derived from a PINN model trained on real experimental data which is encouraging for a better description of gravity currents.
Quantum resources of quantum and classical variational methods
Authors: Spriggs Thomas , Ahmadi Arash , Chen Bokai , Greplova Eliska
Published: January 2025

Variational techniques have long been at the heart of atomic, solid-state, and many-body physics. They have recently extended to quantum and classical machine learning, providing a basis for representing quantum states via neural networks. These methods generally aim to minimize the energy of a given ansatz, though open questions remain about the expressivity of quantum and classical variational ansätze. The connection between variational techniques and quantum computing, through variational quantum algorithms, offers opportunities to explore the quantum complexity of classical methods. We demonstrate how the concept of non-stabilizerness, or magic, can create a bridge between quantum information and variational techniques and we show that energy accuracy is a necessary but not always sufficient condition for accuracy in non-stabilizerness. Through systematic benchmarking of neural network quantum states, matrix product states, and variational quantum methods, we show that while classical techniques are more accurate in non-stabilizerness, not accounting for the symmetries of the system can have a severe impact on this accuracy. Our findings form a basis for a universal expressivity characterization of both quantum and classical variational methods.
Trait Domain Specifiers
Authors: Bach Bo , Clark Lee Anna
Published: January 2025

This chapter defines and introduces the trait domain specifiers, including the rationale for their inclusion in the ICD-11 classification of personality disorder. The distinction and continuity between adaptive “Big Five” traits and maladaptive ICD-11 traits are described, followed by an overview of the clinical utility of codifying maladaptive trait domain. Each trait domain is characterized, along with tentative clinical interpretations and implications. Finally, the chapter highlights that combinations of trait domains are more informative for clinical practice than single domains considered separately. Thus, a number of trait domain combinations are comprehensively characterized, including their possible interpretations and implications for clinical practice.
Instruments and Other Sources of Diagnostic Information
Authors: Bach Bo , Sellbom Martin
Published: January 2025

ICD-11 Clinical Descriptions and Diagnostic Requirements for Personality Disorders and Related Traits should essentially be useful based on available clinical information without having to apply additional measures or instruments. However, for confident clinical use and research purposes, in which inter-rater reliability is often valued, standardized measurement may be important. In the present chapter we therefore provide an overview of available instruments, such as the Diagnostic Interview for Personality Pathology based on ICD-11 (DIPP-11) and the Personality Disorder Severity ICD-11 (PDS-ICD-11) scale, along with trait inventories such as the Personality inventory for ICD-11 (PiCD) and the Five-Factor inventory for ICD-11 (FFiCD). Additionally, we provide an overview of other instruments and sources of information that may inform severity determination and trait specifiers, including implicit association and projective tests.
Psychopathy and Interpersonal Harm
Authors: Somma Antonella , Fossati Andrea
Published: January 2025

Psychopathy represents a personality disorder that is characterized by a pattern of attributes including affectiveand interpersonal features, and impulsive and antisocial behaviors. Although the rates of psychopathic individuals are particularly elevated in correctional settings, psychopathy can be observed also in clinical and community settings. This chapter provides a review of psychopathy models and major personality dimensions involved in its presentation. It specifically provides a detailed guide to using the ICD-11 dimensional model of personality disorders to capture essential features of psychopathy in clinical populations. Finally, a case vignette is provided to help the reader to translate theoretical descriptions of psychopathy-related dimensions and their ICD-11 counterparts into clinical observation of their manifestations.
Schema Therapy
Authors: Rafaeli Eshkol , Shuv-Ami Itay
Published: January 2025

This chapter introduces schema therapy (ST), an integrative theory- and evidence-based clinical approach for the treatment of personality disorders (PDs) and other enduring psychological difficulties. ST deliberately employs few technical terms, and instead relies on concepts that allow clinicians from diverse orientations to find common ground. Moreover, ST’s straightforward language helps therapists share their case conceptualization and treatment goals with their patients. To illustrate this, we introduce ST’s basic concepts and link them to the ICD-11 model of PDs. We define three early ST concepts (needs, schemas, and coping styles) and link these to ICD-11’s (dimensional) trait domains. We then expand on the ST concept of modes, which we link to ICD-11’s PD severity dimension, and note how it takes a further step toward attending to fluctuating states and within-person changes. The focus on modes also guides schema therapists’ differential use of therapeutic stances, on which we elaborate. These include limited reparenting, which helps address patients’ unmet primary needs, soothe their distressed or hyper-aroused child modes, help them return into a window of tolerance (Ogden & Minton, 2000), and (ultimately) serve as a model for their self-care (i.e., their Healthy Adult mode). They also include the dialectic stance of empathic confrontation, which helps address the ill effects of well-intentioned but often maladaptive coping modes (e.g., detachment, avoidance, hostility, dependence, perfectionism, etc.). We use two case examples to explore ST conceptualizations and interventions.
Psychoeducation and Case-formulation
Authors: Hutsebaut Joost , Kamphuis Jan H
Published: January 2025

Psychoeducation and case-formulation can be powerful clinical tools to engage a client in treatment by offering a destigmatizing and validating translation of current symptoms and problems into foci for treatment. This chapter will illustrate this translational process by offering a jargon-free reformulation of core features of the ICD-11 model for personality disorders. Using a case illustration, it will offer clinicians an experience-near translation of the general diagnostic requirements; the core impairments in self and interpersonal functioning; the emotional, cognitive, and behavioral manifestations of these impairments; and the trait domains. In addition, the chapter will illustrate how this diagnostic information can be used to identify treatment goals, and to reach consensus with a client on the goals and tasks of treatment, which we consider one of the main goals of an assessment.
Application to Children and Young People
Authors: Sharp Carla , Bo Sune , Chanen Andrew
Published: January 2025

In this chapter, we argue that the publication of the International Classification of Diseases 11th revision (ICD-11) paves the way for both the description of a developmental pathway for personality disorder, and the prevention, early identification, and treatment of personality challenges in young people. We propose a developmental pathway for personality disorder that integrates both personality functioning (maladaptive self and interpersonal functioning) and maladaptive trait domain. We then translate this developmental pathway into an ICD-11 informed “clinical staging” model for the prevention and treatment of personality disorder. We conclude that the ICD-11 holds much promise for prevention and early intervention, given its developmental relevance.
Application to Older People
Authors: Bangash Ayesha
Published: January 2025

With an aging population, the number of older adults with personality disorders is expected to increase in the near future. There is a clinical need for adequate assessment of this group. Previous diagnostic manuals have used a categorical approach to diagnosing personality disorders with little evidence to support their use in older people. The ICD-11 is the current diagnostic manual which makes use of a dimensional model. This chapter discusses the presentation and management of late life personality disorders with relevance to the dimensional model. It also examines the applicability of the personality disorder features of the ICD-11 in later life.
Neuroscientific Considerations
Authors: Bertsch Katja , Herpertz Sabine C
Published: January 2025

Neurobiological findings neither support categorical entities nor provide specific biological landmarks for particular disorders; they rather support the existence of key capacities needed for self and interpersonal functioning. In this chapter, we provide an overview of such capacities, their underlying neural correlates, and current findings on alterations in individuals with personality disorders. Important neurobiological mechanisms for self-functioning include self-awareness, self-referential thinking, self-appraisal, and self-control, while for interpersonal functioning we consider social perception, empathy, theory of mind, social reward processing, and intimacy in close relationships as relevant. Although neurobiological findings may help to provide a deeper, mechanistic understanding of dysfunctions and therapeutic change, a major limitation of the existing literature is the reliance on categorical diagnoses in previous studies.
Health Policies Informed by Severity Classification
Authors: Monk-Cunliffe Jonathan , Dale Oliver
Published: January 2025

In this chapter we set out key principles to guide health policy in supporting people who have received a diagnosis of personality disorder. We begin by describing the landscape of personality disorder services in the United Kingdom, and then discuss how these may be impacted by the changes brought by ICD-11. We believe a severity-based classification lends itself to the adoption of a public health approach to personality disorder, considering the broad range of services that people may interact with. This change mirrors an existing tiered model of services. The term “personality disorder,” and the construct it describes, is increasingly contested within the United Kingdom. Some consider the construct itself harmful and, whilst not universally agreed, almost all believe service provision requires improvement. We will not address those concerns here and instead offer a pragmatic approach which we hope informs an ever-evolving diagnostic system.
Fc gamma receptor polymorphisms in antibody therapy: implications for bioassay development to enhance product quality
Authors: Twomey Julianne D , George Sasha , Zhang Baolin
Published: January 2025

The effectiveness of therapeutic antibodies is often associated with their Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. These functions rely on interactions between Fc gamma receptors (FcγRs) on immune cells and the Fc region of antibodies. Genetic variations in these receptors, known as FcγR polymorphisms, can influence therapeutic outcomes by altering receptor expression levels, affinity, and function. This review examines the impact of FcγR polymorphisms on antibody therapy, emphasizing their role in developing and optimizing functional bioassays to assess product quality. Understanding these polymorphisms is essential for refining bioassays, which are crucial for accurately characterizing antibody products and ensuring consistency in manufacturing processes.
Early Stone Tool Technology in Hominin Evolution
Authors: Finestone Emma
Published: January 2025

The appearance of the first stone artifacts in the archaeological record marked a significant behavioral shift in hominin evolution. Historically, early tools were attributed exclusively to toolmakers belonging to the genus Homo. However, subsequent discoveries have pushed back the origin of stone tools to precede the appearance of early Homo in the fossil record. The chronology and distribution of early archaeological sites suggest that cumulative lithic culture was not a behavior practiced by a single hominin species but instead emerged across multiple taxa over time.

The precise taxonomic identities of early tool users remain uncertain. It is possible that members of the hominin genera Homo, Paranthropus, and perhaps Australopithecus all engaged in tool-assisted foraging. These genera coincide with the time frame and regions where Early Stone Age tools are found. Fossils attributed to Homo and Paranthropus often co-occur at the same Oldowan localities. However, fossils of the genus Paranthropus are more commonly associated with stone tools south of the Omo-Turkana basin, and artifacts are exclusively associated with genus Homo north of the Omo-Turkana basin. Homo erectus is linked to several important technological milestones, including the oldest Acheulean toolkits and the earliest dispersals out of Africa. While much attention has been paid to the implications of tool manufacture for genus Homo, an integrated technological perspective should also be considered when evaluating the potential diet and behavior of australopiths.
Improving estimation efficiency for survival data analysis by integrating a coarsened time-to-event outcome from an external study
Authors: Deng Daxuan , Zhang Lijun , Feng Hao , Chinchilli Vernon M , Chen Chixiang , Wang Ming
Published: January 2025

In the era of big data, increasing availability of data makes combining different data sources to obtain more accurate estimations a popular topic. However, the development of data integration is often hindered by the heterogeneity in data forms across studies. In this paper, we focus on a case in survival analysis where we have primary study data with a continuous time-to-event outcome and complete covariate measurements, while the data from an external study contain an outcome observed at regular intervals, and only a subset of covariates is measured. To incorporate external information while accounting for the different data forms, we posit working models and obtain informative weights by empirical likelihood, which will be used to construct a weighted estimator in the main analysis. We have established the theory demonstrating that the new estimator has higher estimation efficiency compared to the conventional ones, and this advantage is robust to working model misspecification, as confirmed in our simulation studies. To assess its utility, we apply our method to accommodate data from the National Alzheimer’s Coordinating Center to improve the analysis of the Alzheimer’s Disease Neuroimaging Initiative Phase 1 study.
Contemporary management of phyllodes tumours of the breast: proposal for recommendations from the UK Association of Breast Surgery
Authors: Bishr Mai K , Humphreys Alex , Ahmed Mahbubl , Cox Karina , Hughes Adam , Isherwood Jennifer , Pinder Sarah , Remoundos Dionysios Dennis , Sawyer Elinor , Tamimy Muhammad Sarmad , Whisker Lisa
Published: January 2025

Phyllodes tumours of the breast are rare fibroepithelial neoplasms classified histologically into benign, borderline, or malignant; each requiring different treatment strategies. The infrequency of presentation can result in diagnostic and management variability. The aim is to provide evidence-based or expert consensus recommendations for multidisciplinary teams managing patients with phyllodes tumours.
Gastric partitioning versus gastrojejunostomy for gastric outlet obstruction due to unresectable gastric cancer: randomized clinical trial
Authors: Ramos Marcus Fernando Kodama Pertille , Pereira Marina Alessandra , Dias André Roncon , Yagi Osmar Kenji , Zilberstein Bruno , Ribeiro-Junior Ulysses
Published: January 2025

Background

Gastric outlet obstruction due to unresectable tumours is usually managed with a gastrojejunostomy. Unfortunately, the unsatisfactory outcomes of this procedure have led to the search for alternatives, including gastric partitioning.

Methods

Monocentric, randomized, parallel, open-label trial that included patients with obstructive, unresectable distal gastric tumours. The objective was to compare gastric partitioning to gastrojejunostomy, considering the gastric outlet obstruction scoring system scale as the main outcome. Randomization was performed using computer-generated software available online and after the application of the informed consent term, the allocation group was revealed to the surgeon before the surgical procedure.

Results

Over 7 years, 90 patients were initially randomized. After applying the inclusion and exclusion criteria, 25 patients were included in the gastrojejunostomy group and 27 in the partitioning group. Both groups were similar regarding initial clinical characteristics including sex, age, weight, clinical performance, and the acceptance of oral diet. Surgery duration, length of hospital stay, postoperative complications, and 30- and 90-day mortality rates were similar between groups. Acceptance of normal diet was more frequently reached by patients in the partitioning group (96% versus 72%; P = 0.022). During outpatient follow-up, maintenance of oral intake and weight was similar between groups. Patients in the partitioning group received more frequent red blood cell transfusions (81% versus 52%; P = 0.024). There was no difference regarding the administration of palliative chemotherapy lines and survival. In the multivariable analysis, the inability to eat a full diet (P = 0.035) and the absence of palliative chemotherapy after the procedure (P = 0.001) were associated with worse survival.

Conclusions

Gastric partitioning provided a better return of the ability to accept food orally. There was no difference regarding postoperative complications and long-term survival.

Trial registration

NCT02065803, clinicaltrials.gov
Distinct roles of mTORC2 in excitatory and inhibitory neurons in inflammatory and neuropathic pain
Authors: He Wei , Ge Xin , Ji Ru-Rong
Published: January 2025

This scientific commentary refers to ‘Targeting spinal mechanistic target of rapamycin complex 2 alleviates inflammatory and neuropathic pain’ by Wong et al. (https://doi.org/10.1093/brain/awae275).
Neural pathway activation in the subthalamic region depends on stimulation polarity
Authors: Borgheai Seyyed Bahram , Opri Enrico , Isbaine Faical , Cole Eric R , Jafari Deligani Roohollah , Laxpati Nealen G , Risk Benjamin B , Willie Jon T , Gross Robert E , AuYong Nicholas , McIntyre Cameron C , Miocinovic Svjetlana
Published: January 2025

Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease; however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic versus anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioural responses, but anodic DBS broadens the therapeutic window. This suggests that neural pathways involved respond preferentially depending on stimulus polarity. To experimentally compare the activation of therapeutically relevant pathways during cathodic and anodic subthalamic nucleus (STN) DBS, pathway activation was quantified by measuring evoked potentials resulting from antidromic or orthodromic activation in 15 Parkinson’s disease patients undergoing DBS implantation. Cortical evoked potentials (cEPs) were recorded using subdural electrocorticography, DBS local evoked potentials (DLEPs) were recorded from non-stimulating contacts, and electromyography activity was recorded from arm and face muscles. We measured (i) the amplitude of short-latency cEP, previously demonstrated to reflect activation of the cortico-STN hyperdirect pathway, (ii) DLEP amplitude thought to reflect activation of STN-globus pallidus (GP) pathway and (iii) amplitudes of very short-latency cEPs and motor evoked potentials for activation of corticospinal/bulbar tract (CSBT). We constructed recruitment and strength–duration curves for each EP/pathway to compare the excitability for different stimulation polarities. We compared experimental data with the most advanced DBS computational models. Our results provide experimental evidence that subcortical cathodic and anodic stimulation activate the same pathways in the STN region and that cathodic stimulation is in general more efficient. However, relative efficiency varies for different pathways so that anodic stimulation is the least efficient in activating CSBT, more efficient in activating the hyperdirect pathway and as efficient as cathodic in activating STN-GP pathway. Our experiments confirm biophysical model predictions regarding neural activations in the central nervous system and provide evidence that stimulus polarity has differential effects on passing axons, terminal synapses, and local neurons. Comparison of experimental results with clinical DBS studies provides further evidence that the hyperdirect pathway may be involved in the therapeutic mechanisms of DBS.
Evaluating conversion from mild cognitive impairment to Alzheimer’s disease with structural MRI: a machine learning study
Authors: Vecchio Daniela , Piras Federica , Natalizi Federica , Banaj Nerisa , Pellicano Clelia , Piras Fabrizio
Published: January 2025

Alzheimer’s disease is a disabling neurodegenerative disorder for which no effective treatment currently exists. To predict the diagnosis of Alzheimer’s disease could be crucial for patients’ outcome, but current Alzheimer’s disease biomarkers are invasive, time consuming or expensive. Thus, developing MRI-based computational methods for Alzheimer’s disease early diagnosis would be essential to narrow down the phenotypic measures predictive of cognitive decline. Amnestic mild cognitive impairment (aMCI) is associated with higher risk for Alzheimer’s disease, and here, we aimed to identify MRI-based quantitative rules to predict aMCI to possible Alzheimer’s disease conversion, applying different machine learning algorithms sequentially. At baseline, T1-weighted brain images were collected for 104 aMCI patients and processed to obtain 146 volumetric measures of cerebral grey matter regions [regions of interest (ROIs)]. One year later, patients were classified as converters (aMCI-c = 32) or non-converters, i.e. clinically and neuropsychologically stable (aMCI-s = 72) based on cognitive performance. Feature selection was performed by random forest (RF), and the identified seven ROIs volumetric data were used to implement support vector machine (SVM) and decision tree (DT) classification algorithms. Both SVM and DT reached an average accuracy of 86% in identifying aMCI-c and aMCI-s. DT found a critical threshold volume of the right entorhinal cortex (EC-r) as the first feature for differentiating aMCI-c/aMCI-s. Almost all aMCI-c had an EC-r volume <1286 mm3, while more than half of the aMCI-s patients had a volume above the identified threshold for this structure. Other key regions for the classification between aMCI-c/aMCI-s were the left lateral occipital (LOC-l), the middle temporal gyrus and the temporal pole cortices. Our study reinforces previous evidence suggesting that the morphometry of the EC-r and LOC-l best predicts aMCI to Alzheimer’s disease conversion. Further investigations are needed prior to deeming our findings as a broadly applicable predictive framework. However, here, a first indication was derived for volumetric thresholds that, being easy to obtain, may assist in early identification of Alzheimer’s disease in clinical practice, thus contributing to establishing MRI as a useful non-invasive prognostic instrument for dementia onset.
Functional validation of a novel STAT3 ‘variant of unknown significance’ identifies a new case of STAT3 GOF syndrome and reveals broad immune cell defects.
Authors: Mackie Joseph , Suan Daniel , McNaughton Peter , Haerynck Filomeen , O’Sullivan Michael , Guerin Antoine , Ma Cindy S , Tangye Stuart G
Published: January 2025

Introduction

Signal transducer and activator of transcription 3 (STAT3) orchestrates crucial immune responses through its pleiotropic functions as a transcription factor. Patients with germline monoallelic dominant negative or hypermorphic STAT3 variants, who present with immunodeficiency and/or immune dysregulation, have revealed the importance of balanced STAT3 signaling in lymphocyte differentiation and function, and immune homeostasis. Here, we report a novel missense variant of unknown significance in the DNA-binding domain of STAT3 in a patient who experienced hypogammaglobulinemia, lymphadenopathy, hepatosplenomegaly, immune thrombocytopenia, eczema, and enteropathy over a 35-year period.

Methods

In vitro demonstration of prolonged STAT3 activation due to delayed dephosphorylation, and enhanced transcriptional activity, confirmed this to be a novel pathogenic STAT3 gain-of-function variant. Peripheral blood lymphocytes from this patient, and patients with confirmed STAT3 Gain-of-function Syndrome, were collected to investigate mechanisms of disease pathogenesis.

Results

B cell dysregulation was evidenced by a loss of class-switched memory B cells and a significantly expanded CD19hiCD21lo B cell population, likely influenced by a skewed CXCR3+ TFH population. Interestingly, unlike STAT3 dominant negative variants, cytokine secretion by activated peripheral blood STAT3 GOF CD4+ T cells and frequencies of Treg cells were intact, suggesting CD4+ T cell dysregulation likely occurs at sites of disease rather than the periphery

Conclusion

This study provides an in-depth case study in confirming a STAT3 gain-of-function variant and identifies lymphocyte dysregulation in the peripheral blood of patients with STAT3 gain-of-function syndrome. Identifying cellular biomarkers of disease provides a flow cytometric-based screen to guide validation of additional novel STAT3 gain-of-function variants as well as provide insights into putative mechanisms of disease pathogenesis.
Dedicator of cytokinesis 2 regulates cytoskeletal actin dynamics and is essential for platelet biogenesis and functions
Authors: Ji Jiani , Xu Xulin , Zhang Lili , Liu Shuang , Chen Jiayi , Gao Huihui , Xiang Limin , Li Yaofeng , Xu Hui , Chen Yaobing , Xiang Huiqin , Chen Shuai , Han Yunyun , Tang Zhaoming , Wang Xuanbin , Shi Xiaofeng , Mao Jianhua , Xi Xiaodong , Wang Jinyu , Fang Chao
Published: January 2025

Aims

Dedicator of cytokinesis 2 (DOCK2), a member of the DOCK family of guanine nucleotide exchange factors that specifically act on the Rho GTPases including Rac and Cdc42, plays pivotal roles in the regulation of leukocyte homeostasis. However, its functions in platelets remain unknown.

Methods and results

Using mice with genetic deficiency of DOCK2 (Dock2−/−), we showed that Dock2−/− mice exhibited a macrothrombocytopenic phenotype characterized as decreased platelet count and enlarged platelet size by transmission electron microscopy. Dock2−/− megakaryocytes had reduced polyploidization determined by propidium iodide staining and defective proplatelet formation by confocal microscopy. DOCK2 deficiency led to enriched F-actin level in resting platelets but defective F-actin assembly in activated platelets by phalloidin staining, and mechanistically, attenuated activity of Rac1, unchanged Cdc42 but enhanced RhoA measured by immunoprecipitation of GTP-bound proteins. Immunoblotting analysis showed that Dock2−/− platelets had reduced immunoreceptor tyrosine-based activation motif signaling downstream of impaired clustering of GPVI receptors determined by stochastic optical reconstruction microscopy. Further, DOCK2 deficiency resulted in reduced density and branches of fibrin fibres in the clots in vitro and diminished platelet aggregation in a microfluidic chamber ex vivo. Dock2−/− platelets exhibited impaired incorporation into a growing thrombus in cremaster arterioles following allogeneic transfusion into a WT recipient and defective heterotypic interactions with neutrophils in cremaster venules as reflected by decreased platelet-neutrophil aggregate formation in vitro under stirring condition. In addition, myeloid deficiency of DOCK2 caused prolonged tail bleeding times. Finally, pharmacological inhibition of DOCK2 using a small-molecular inhibitor CPYPP suppressed actin dynamics leading to impaired responses to GPVI activation and defects in platelet spreading, clot retraction, and thrombus formation.

Conclusion

DOCK2 plays critical roles in the regulation of platelet biogenesis and functions by controlling Rac1 activity and cytoskeletal actin dynamics and may be a novel target for the treatment of thrombotic and thrombo-inflammatory diseases.
End-of-life issues in the intensive therapy unit: 10 important points to remember
Authors: Vincent Jean-Louis
Published: January 2025

End-of-life (EOL) issues have become increasingly common in intensive therapy units (ITUs), largely due to advances in critical care that enable patients to be kept alive for extended periods. Death in the ITU now generally follows an EOL decision, which can pose ethical, emotional, and practical challenges. Our approach to such issues should be based on adherence to the four bioethical principles − autonomy, beneficence, non-maleficence, and distributive justice − as well as the concept of proportionate care, and requires careful and effective communication with the whole ITU team, including the patient and their family. In this article, we discuss 10 key considerations related to EOL care in the ITU, in an attempt to highlight some critical aspects of EOL decision-making for intensivists navigating this sensitive and multifaceted area of practice.
Role of exercise stress echocardiography in systemic sclerosis: pathophysiological and prognostic significance of the systemic sclerosis with a heart failure and preserved ejection fraction phenotype
Authors: Yuasa Naoki , Harada Tomonari , Kagami Kazuki , Sorimachi Hidemi , Saito Yuki , Naito Ayami , Tani Yuta , Kato Toshimitsu , Endo Yukie , Takama Noriaki , Wada Naoki , Motegi Sei-Ichiro , Ishii Hideki , Obokata Masaru
Published: January 2025

Aims

Left ventricular (LV) diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are common cardiac complications of patients with systemic sclerosis (SSc). Exercise stress echocardiography is often used in symptomatic patients with SSc to detect abnormal increases in pulmonary pressures during exercise, but the pathophysiologic and prognostic significance of exercise stress echocardiography to assess the presence of HFpEF in these patients is unclear.

Methods and results

Patients with SSc (n = 140) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. The HFA-PEFF score ≥ 5 points was used to diagnose HFpEF. Thirty-five patients met the HFpEF criteria (prevalence 25%). Compared with patients with SSc-non-HFpEF, those with SSc-HFpEF were older and had a higher prevalence of coronary artery disease, more severe LV diastolic dysfunction (by definition), depressed right ventricular systolic function, reduced exercise capacity (lower peak oxygen consumption), and poorer ventilatory efficiency. Exercise right heart catheterization was performed in 25 patients and it confirmed elevated pulmonary capillary wedge pressure during peak exercise in patients with SSc-HFpEF. Participants were followed up to assess the primary composite endpoint: all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or oral diuretic intensification. Compared with SSc-non-HFpEF, SSc-HFpEF had a 5.3-fold increased risk of the composite outcomes (hazard ratio 5.29, confidence intervals 2.06–13.5, P = 0.0005).

Conclusion

In addition to pulmonary haemodynamics, exercise stress echocardiography may be useful to identify the HFpEF phenotype that has different pathophysiology and clinical outcomes in patients with SSc.