bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application to Older People
Authors: Bangash Ayesha 
Published: January 2025

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
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

ABSTRACT
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

Abstract
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

Abstract

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
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

Abstract
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

Abstract
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 &lt;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

Abstract

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

Abstract

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

Abstract
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

Abstract

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.