bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer
Authors: Brodkin Jefim , Kaprio Tuomas , Hagström Jaana , Leppä Alli , Kokkola Arto , Haglund Caj , Böckelman Camilla
Published: December 2024

Introduction

Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications.

Methods

We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH.

Results

In the univariate survival analysis for disease-specific survival, the Epstein–Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19–5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA’s classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15–2.60], p = 0.009 and HR 1.74 [95% CI 1.06–2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial–mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30–2.77], p < 0.001) when compared with aberrant p53.

Conclusions

Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.
What is it all about? An explorative study of patients’ experiences with medication free treatment
Authors: Reitan Elisabeth C. Klæbo , Riley Henriette , Iversen Valentina C. , Høye Anne
Published: December 2024

Background

As a response to the political decision by the Norwegian Ministry of Health and Care Services to establish some kind of “medication free treatment” for patients with severe mental illness throughout the country, a 6-bed ward unit dedicated to offer such treatment was in 2017 established in Tromsø, Norway by the North Norway Health Care Region. The aim of the present study was to explore the experiences of patients admitted to this ward unit.

Method

Semi-structured interviews were conducted with 19 persons who had received treatment from the ward during the period January 2017 to October 2021. Analysis was done in line with Systematic Text Condensation and interviews were recorded, transcribed and analyzed using software NVivo.

Results

The importance of engaging in a dialogue about the possibilities of living a life without medication was unanimously validated, along with a focus on empowerment, motivation, activity and flexibility. Not everyone reported fulfillment of their own wishes or the ward’s goal of tapering down, and reflected upon emotions such as ambivalence or fear. Three core concepts were identified to describe the participants’ experiences: 1) Tapering off, 2) Relations, and 3) Frames and content. A fourth concept overarches the process formed by these concepts; 4) Processes across categories.

Conclusion

The study contributes to a deeper understanding of what "medication free" truly means, going beyond simply taking or not taking medications. It adds nuance to the debate surrounding medication free treatment. The ability to taper off medications is linked to intrapersonal factors, such as readiness and personal commitment, as well as the therapeutic environment, including the frames and values present on the ward. "Medication free" is more complex than it may initially appear, as many participants continue to use some form of psychotropic drugs. The sense of being part of something new and "exclusive" can be understood in light of what participants felt was lacking in previous treatment. It appears to be a need of rediscovering the significance of empowerment and empathic relationships in treatment of severe mental illness, in order to foster a sense of coherence and meaning.
All-cancer incidence and mortality in Pakistanis, Bangladeshis, and their descendants in England and Wales
Authors: Harrison Joseph , Sullivan Frank , Keenan Katherine , Kulu Hill
Published: December 2024

Background

This paper identifies differences in all-cancer incidence and mortality between Pakistani-born (PB), Bangladeshi-born (BB), their descendants, and the White British (WB) in England and Wales. Pakistanis and Bangladeshis are the most marginalised and disadvantaged groups in England and Wales yet, are found to have low cancer mortality and low all-cause mortality. Previous studies though have not looked at generational differences, applied individual-level data nor separated Pakistanis and Bangladeshis from each other and other Asian groups.

Methods

We use the Office for National Statistics Longitudinal Study of England and Wales which is a 1% representative sample of the population. We apply event history analysis on a study period from 1971 to 2016, following individuals from age 20 until a first cancer incidence, censoring at emigration or death. We observe 10,885,500 person-years and 71,926 cancer incidences for WB; 125,700 person-years and 295 events for PB; 53,900 person-years and 113 events for BB and 26,900 person-years and 24 events for descendants. Following incidence, we study a maximum of ten years until a death from cancer, or censoring. In this second analysis on mortality our sample has 329,700 person-years and 31,689 cancer deaths for WB; 1,200 person-years and 104 events for PB; 400 person-years and 50 events for BB and 100 person-years and 10 events for descendants.

Results

Results from the fully adjusted models show that the risk of cancer incidence is lower for PB, BB and descendants compared to the WB native group. Estimated hazard ratio (HR) equals 0.42 for PB (95% confidence interval (CI): 0.38–0.47), for BB HR is 0.38 (CI: 0.32–0.46) and, for descendants HR is 0.36 (CI: 0.24–0.54). Results for cancer mortality after incidence show HR for PB is 0.93 (CI: 0.76–1.12), for BB it is 0.95 (CI: 0.72–1.25) and for descendants HR equals 1.62 (CI: 0.87–3.02 - significant at 90%).

Conclusions

Using high quality representative data, we show that lower incidence of cancer and not better survival is the driver of the low cancer mortality previously found. This advantage persists across immigrant generations, but all-cancer mortality following incidence may be elevated for descendants.
Measuring domestic violence against Egyptian women and its consequent cost using a latent variable model
Authors: Hafez Mai Sherif , Mounir Carolin Sherif , El Zeini Laila Othman
Published: December 2024

Background

Domestic Violence is a threatening worldwide problem. Its consequences against women can be dramatic, as it negatively affects women’s quality of life reflected in their general wellbeing including physical, mental, emotional and sexual health, in addition to the economic cost. Both domestic violence and its cost are multidimensional constructs that cannot be directly measured.

Methodology

In this study, a latent trait model is used by applying item response theory to measure both domestic violence and its consequent cost via thirty-five observed variables. Accordingly, the study fills a gap in the literature since it is the first attempt to examine the relationship between domestic violence and its consequent cost in Egypt using latent variable modelling rather than simple descriptive statistics. Each construct is considered as a multidimensional latent variable. The overall latent trait model also estimates the relationship between domestic violence and its consequent cost. The effect of a number of socioeconomic covariates on domestic violence is examined within the model. The proposed model is fitted to data from the 2015 Egypt Economic Cost of Gender-Based Violence Survey (ECGBVS) using Mplus software.

Results

The study shows that psychological violence is equally important in measuring domestic violence, as physical violence. The cost resulting from domestic violence relies in its measurement both on the reduced quality of life and the monetary cost endured by the violated woman and children. For socioeconomic covariates, it is shown that domestic violence is affected by women’s and husband’s age, educational level, and husband’s occupational status.

Conclusion

Domestic violence is measured by summarizing four forms of violence: physical, psychological, sexual and economic violence, in a single continuous latent variable measuring “Domestic Violence”. Similarly, Cost is measured by summarizing three forms of consequent cost of violence: economic cost, cost on children and cost on women’s quality of life, in another a single continuous latent variable “Cost”. Each of these dimensions is measured by a number of aspects, reflecting the multidimensional nature of the variables. The fitted latent trait model ensured the positive relationship between Domestic Violence and its consequent multidimensional cost.
Identification of critical residues at the C-terminal tip of ACKR4 regulating chemokine internalization and βarrestin involvement
Authors: Gerken Oliver J. , Catone Nicola , Legler Daniel F.
Published: December 2024

Background

Atypical chemokine receptors (ACKRs) play an important role in regulating the availability of chemokines and are responsible for the formation of chemokine gradients required for the directed migration of immune cells in health and disease. ACKR4 shapes gradients of the chemokines CCL19 and CCL21, which are essential for guiding leukocyte homing to lymphoid organs where they initiate an adaptive immune response against invading pathogens. How ACKRs internalize and scavenge chemokines on the molecular level remains poorly understood. Current state-of the art methods to study βarrestin recruitment, signaling and trafficking of ACKRs - and G-protein-coupled receptors in general - rely heavily on C-terminally tagged receptors with unknown consequences for receptor functions.

Methods

Fluorescently labelled CCL19 was used to quantify chemokine internalization by native and tagged receptors as assessed by flow cytometry and live cell confocal microscopy. Steady-state interaction and chemokine-driven recruitment of βarrestins was determined by NanoBiT bystander assays. βarrestin-dependency for CCL19 internalization was determined in wild-type versus βarrestin1/2-double deficient cell lines. Statistical significance was determined by unpaired t-test or one-way ANOVA with Dunnett’s or Tukey’s multiple comparison tests.

Results

Addition of a C-terminal tag selectively affected the function of ACKR4, but not other ACKRs. Fusing a short peptide tag or a fluorescent protein to ACKR4 significantly augmented its ability to internalize its cognate ligand CCL19. In comparison to native ACKR4, its C-terminal tagging provoked an elevated pre-association of βarrestins with the plasma membrane, yet a reduction in chemokine-driven βarrestin recruitment. Furthermore, the addition of a C-terminal tag led to a shift from a βarrestin-dependent towards a βarrestin-independent endocytosis pathway. Similar results on chemokine uptake and on βarrestin-dependency were obtained with ACKR4 variants, in which a putative class II PDZ-binding domain located at the C-terminal tip of the receptor was mutated.

Conclusion

This study identifies that the integrity of the C-terminus of ACKR4 is critical for receptor function. The addition of a C-terminal tag to ACKR4 enhances chemokine uptake and alters the involvement of βarrestins in receptor trafficking.
Clinical spectrum and molecular basis in 19 Chinese patients with 46, XY disorder of sexual development caused by NR5A1 mutations
Authors: Xu Yue , Liu Xuemeng , Liu Yang , Zhu Hui , Wu Jing , Han Bing , Ling Shiying , Cao Ren , Yao Haijun , Chen Yan , Liu Yu , Rao Yamin , Liu Xiaoyu , Zhao Shuangxia , Song Huaidong , Qiao Jie
Published: December 2024

Background

Nuclear receptor subfamily 5 group A member 1 (NR5A1) plays pivotal roles in steroidogenesis and gonadal development. 46, XY disorder of sexual development (DSD) caused by NR5A1 mutations is a rare genetic condition. This study aimed to provide a comprehensive analysis of the clinical characteristics and molecular defects observed in 19 Chinese patients with NR5A1 variants, including assessing the deleterious effects of novel variants in vitro and evaluating their functional impact on the gonad and adrenal glands in vivo.

Materials and methods

Subjects with NR5A1 variants were identified from 223 Chinese 46, XY DSD patients via next-generation sequencing. In-silico analysis and functional assays were performed to evaluate the transcriptional activity, expression levels and nuclear localization of novel NR5A1 variants. The histological structure of the gonads was evaluated via immunohistochemistry (IHC).

Results

Patients with NR5A1 gene variants presented with serious conditions, including micropenis, cryptorchidism, azoospermia, and radiological abnormalities of the spleen. Five novel NR5A1 variants were identified, including heterozygous p.Y5*, p.Q42E and p.L359_L363del, as well as copy number variation (CNV) of chr9:127213317–127570245_del and an exon 6 duplication. A total of 63.2% (12/19) of patients harbored additional variants other than NR5A1. Defective transcriptional regulatory activities and abnormal protein expression levels were observed in NR5A1 variants. The reduced levels of DHEA-S and 11-oxygenated steroids indicate a mild impairment in adrenal function among certain patients. The IHC analysis of the testis revealed intact expression levels of SOX9 in Sertoli cells, while significant differences were observed in the expression pattern of CYP17A1 in Leydig cells among patients. The preserved maturation of adult Leydig cells in the patients may trigger spontaneous puberty.

Conclusions

Patients with NR5A1 mutations exhibit complex phenotypes. The observed clinical heterogeneity may be attributed to oligogenic mutations, dysregulated Leydig cell function, as well as the impaired ability to modulate the transcription of target genes.
Use of mesoglycan in the acute phase of hemorrhoidal disease (the CHORMES study): study protocol for a double-blind, randomized controlled trial
Authors: Gallo Gaetano , Picciariello Arcangelo , Realis Luc Alberto , Salvatore Antonella , Di Vittori Angelo , Rinaldi Marcella , Trompetto Mario
Published: December 2024

Background

Hemorrhoidal disease (HD) is associated with substantial economic burden and negative effects on health-related quality of life (HRQoL). The aCute HaemORrhoids treatment with MESoglycan (CHORMES) study aims to evaluate the effects of orally administered mesoglycan, a natural preparation of glycosaminoglycans with antithrombotic and profibrinolytic properties, as an acute treatment in patients with HD.

Methods

CHORMES is a phase 2, double-blind, randomized controlled trial being conducted at two centers in Italy. Adults aged 18–75 years with Grade I–III HD according to Goligher classification or external thrombosed hemorrhoids, and a Hemorrhoidal Disease Symptom Score (HDSS) of ≥ 5, will be randomly allocated in a 1:1 ratio to mesoglycan or placebo and will be treated for 40 days (two capsules for the first 5 days and one capsule for the subsequent 35 days twice daily [after breakfast and dinner], equivalent to 200 mg in the first 5 days and 100 mg subsequently). Concomitant use of analgesics is permitted in both treatment groups. The trial aims to enroll 50 patients, with 25 patients in each treatment group. The primary objective of the trial is to evaluate the efficacy of mesoglycan in reducing symptoms of HD, assessed via change in HDSS from baseline (day 0) to day 40 in the intention-to-treat population. Secondary objectives include changes in HRQoL from baseline to day 40 using the Short Health Scale for Hemorrhoidal Disease, safety (adverse effects, physical assessments, vital signs and laboratory parameters in the safety population), fecal continence assessed using the Vaizey score, bleeding assessed using the Bleeding score, the amount and type of analgesic taken, and pain. Patient enrolment began on 11 December 2023, and trial completion is expected by December 2024.

Discussion

The CHORMES trial will evaluate the efficacy and safety of mesoglycan, in addition to its impact on HRQoL, analgesic use and pain, in patients with HD. The results of the trial will assist clinicians in determining the most effective treatment for patients with HD.

Trial registration

ClinicalTrials.gov NCT06101992. Prospectively registered on 26 October 2023 at https://clinicaltrials.gov/ct2/show/NCT06101992.
Relations between daily stressful events, exertion, heart rate variability, and thoracolumbar fascia deformability: a case report
Authors: Brandl Andreas , Engel Raimund , Egner Christoph , Schleip Robert , Schubert Christian
Published: December 2024

Background

The posture of performance-oriented sport climbers adapts in a way that likely promotes the development of low back pain. The thoracolumbar fascia, while also contributing to performance, seems to be involved in that process. Furthermore, there has been evidence of the stiffening of the fascial structures in disorders associated with negative affectivity. The study aims to investigate the relationship between the autonomic nervous system and the deformability of the thoracolumbar fascia in a sport climber in a natural setting.

Case presentation

Over a 30 day period, a 50-year-old German male reported daily morning resting heart rate variability and daily inventory of stressful events. The thoracolumbar fascia deformation was measured daily using ultrasound in a manual therapy clinic. A time series analysis was performed to detect possible time-delayed relationships between the variables.

A cluster analyses revealed two distinguishable heart rate variability clusters (heart rate variability clusters 1 and 2). Both clusters were correlated with thoracolumbar fascia deformation and daily inventory of stressful events. Higher heart rate variability cluster 1 immediately caused lower thoracolumbar fascia deformation. Heart rate variability cluster 1 parameters mediated the effect of daily inventory of stressful events on a decrease in thoracolumbar fascia deformation with a 2-day delay. One heart rate variability cluster 2 parameter mediated the effect of daily inventory of stressful events on an increase in thoracolumbar fascia deformation with a 7-day delay.

Conclusion

Heart rate variability cluster 1 values, which probably indicate sympathetic nervous system activity, are directly related to thoracolumbar fascia. Presumably, the sympathetic nervous system mediated the effect of daily inventory of stressful events on a lower thoracolumbar fascia deformation with a 2-day delay, followed by a supercompensation, most likely parasympathetically mediated. Coaches and trainers should be aware of these mechanisms and consider monitoring during training to minimize potential additional risk factors for impaired performance and health.
Significance of bleeding control in hemorrhagic cyst infection in autosomal dominant polycystic kidney disease: a case presentation with literature review
Authors: Takayanagi Shunsuke , Mori Keita P. , Kubo Shigeto , Mishima Natsumi , Watanabe Tomoka , Asou Mea , Taniguchi Misaki , Miyauchi Miho , Higashi Yoshiaki , Handa Takaya , Endo Tomomi , Matsubara Takeshi , Tsukamoto Tatsuo
Published: December 2024

Background

In patients with autosomal dominant polycystic kidney disease (ADPKD), renal and hepatic cystic infections are common complications, sometimes frequent and refractory. Hemorrhagic complications are often present in these cases. Owing to the diversity of patient backgrounds, the treatment of these complications has not been standardized. Here we report three cases that suggest the significance of detecting and treating hemorrhagic complications in cases of cyst infection.

Case presentation

Case 1: A 46-year-old man on low-dose aspirin for antiphospholipid antibody syndrome presented with fever, left flank pain, and gross hematuria. He had a history of frequent renal cyst infections. Imaging studies revealed a hemorrhagic cyst infection of the left kidney and acute kidney injury. He was treated with ciprofloxacin and tranexamic acid, and aspirin was discontinued. Subsequently, infection and bleeding successfully improved after treatment for 2 months. To date, cyst infection has not recurred. Case 2: A 70-year-old man on eicosapentaenoic acid for dyslipidemia presented with fever and left flank pain which was diagnosed as a hemorrhagic cyst infection of the left kidney. He had a history of renal cyst infection. Hemorrhagic cyst infection of the left kidney was made with imaging studies and positive blood cultures. Ciprofloxacin and metronidazole were administered, and eicosapentaenoic acid was discontinued. The infection and bleeding resolved after treatment for 1 month. To date, cyst infection has not recurred. Case 3: A 63-year-old man on chronic maintenance hemodialysis receiving warfarin for atrial fibrillation and cardiogenic cerebral embolism presented with fever, back pain, and hypotension. On magnetic resonance imaging (MRI) and computerized tomography (CT), he was diagnosed with hemorrhagic cyst infection of the liver. Despite multidrug antibiotic therapy and discontinuation of warfarin, the bleeding tendency did not improve, and he died after 3 months.

Conclusions

Since cyst hemorrhage might be an aggravating complication in the treatment of refractory and recurrent cyst infections in patients with ADPKD, we believe that a careful imaging evaluation should be performed to detect cyst hemorrhage in these cases.
Reflection on a professional advisory group to inform the use of patient empowerment tools within an implementation science research project
Authors: Woolley Katherine E. , Jones Nia J. , Letchford Robert , Withers Kathleen L.
Published: December 2024

Professional advisory groups, with patient and public involvement (PPI) representatives, can be used for co-production within research projects. This paper aims to document the benefits and challenges of undertaking stakeholder and participant engagement for an implementation research project within NHS (National Health Service) Wales. A patient focused research project, initiated by clinicians, on the use of patient empowerment tools within standard patient care, used a professional advisory group to identify appropriate tools to use within the research proposal. The professional advisory group was made up of therapists, NHS stakeholders, academics and PPI representatives. A hybrid-meeting style was employed to optimise participation for all members of the group. Benefits of the professional advisory group included increased engagement and ownership of the study due to co-creation, and obtaining important contextual information and lived experience. However, challenges included keeping the discussion on topic due to pre-conceived agendas, pleasing everyone in the room due to varied backgrounds, and technological issues. Future professional advisory groups should consider how to facilitate the full involvement of PPI representatives within the discussion and having a variety of resources to present the topic of discussion. Furthermore, clearly communicating what the purpose and direction of the research project is and how it fits into the wider system, should be carefully considered. Overall, it was recognised that the professional advisory group was of significant value to shape the research proposal. Due to the situational challenges faced by healthcare professional within the NHS and preconceived ideas for solutions, it is hoped that by involving stakeholders early in the process there will be greater acceptance and usability of the research findings.
Imaging of intraluminal duodenal diverticulum in adults, an infrequent entity: pictorial essay
Authors: Whittle Carolina , Maldonado Ignacio , Campos Oscar , Orellana Franco
Published: December 2024

Background

An intraluminal duodenal diverticulum (IDD) is an infrequent abnormality consisting of a sac-like projection within the duodenum secondary to a congenital web of the membrane in the second portion of the duodenum near the papilla of Vater, due to incomplete lumen recanalization of the embryological foregut, with a typical imaging appearance of a “windsock.”

The purpose is to present the radiological and tomographic findings characteristics of “IDD.”

Results

The IDD in barium upper gastrointestinal imaging and computed tomography (CT) was presented. On upper barium gastrointestinal examination, it is possible to detect an intraluminal duodenal image, that can be distended with gas or barium contrast and delimited by a thin wall (halo sign), mimicking a windsock or a double lumen. On CT, it is possible to identify a windsock sign on the duodenum, most often on the second part, distended by gas and contrast agent.

Conclusion

IDD imaging in barium upper gastrointestinal imaging and CT is pathognomonic of this infrequent entity in adults that needs to be recognized by the radiologist. In our small series, IDD images of the windsock sign on barium studies and the characteristic presentation on CT can help to exclude another duodenal conditions, guiding appropriate management.
Delineating resilience in children with cleft lip and palate (CL/P): a cross-sectional study
Authors: Yusof Muhammad Safwan , Ibrahim Hasherah Mohd
Published: December 2024

Background

Resilience refers to an individual’s ability to thrive despite adversity. Children with cleft lip and/or palate (CL/P) face numerous challenges during school age due to speech and aesthetic differences compared to typically developing (TD) children. This study aims to compare the resilience levels between Malaysian children with CL/P and TD children, utilizing the Malay-translated Resilience Scale-10 (RS-10)© ([Wagnild, Resilience scale for children (RS10) user’s guide 2015, n.d]).

Results

A total of 121 Malaysian children comprising 52 CL/P and 69 TD children between the ages of 7 to 12 years participated in this study. Among the children with CL/P, 49 exhibited intelligible speech with mild to moderate differences, while three had severely reduced intelligibility. Participants completed the RS-10 online with parental assistance. The total mean scores of resilience for TD and CL/P were 30.80 ± 4.28 and 33.15 ± 6.01 respectively. The t-test results showed no significant differences in resilience scores between groups and across genders. The analysis of variance showed no significant difference between age groups. Regression analysis revealed that age and group were marginally significant predictors of resilience scores. Specifically, each additional year of age was associated with a 0.47-point reduction in RS-10 scores highlighting coping difficulties associated with CL/P in older children.

Conclusions

The findings highlight the resilience of Malaysian children with CL/P, showing they can achieve resilience levels similar to their TD peers, particularly when speech outcomes are favourable.
Sarcopenia and low prognostic nutritional index as markers of disease activity in patients with inflammatory bowel disease and predictors of poor outcome: a cohort longitudinal study
Authors: Sherif Mirella , Fouad Rabab , Elbaz Tamer , Awadalla Maryse , Tantawi Omnia , Negm Mohamed , El-kareem Dalia Abd , Naguib Ibrahim , Shehab Hany , Badary Hedy A.
Published: December 2024

Background

Inflammatory Bowel Diseases (IBD) are the gastro-intestinal diseases of the current century. They are described by alternating periods of activity & remission. The assessment of severity is classically done by scoring systems for each disease which depend on patients’ symptoms, inflammatory markers, endoscopic findings, and disease impact on functional activities. The current study focused on some of the potentially modifiable risk factors for activity, not involved in classic scoring systems like sarcopenia & Prognostic Nutritional Index (PNI) in a group of IBD studied cases.

Results

A prospective study on 146 patients with established diagnosis of IBD; divided into two groups; Group1 were studied cases in activity; and Group 2 were patients in remission. Both groups were subjected to clinical assessment, laboratory tests, endoscopies, cross-sectional imaging with specific attention to psoas muscle indices. Both groups were followed up clinically for at least 6 months by clinical activity scores. In this research, the mean patients’ age was 35 years and 45% were females; the prevalence of sarcopenia in studied cases with active IBD had been 49.3% & 6.8% in remission. It was more prevalent in Crohn’s disease. Sarcopenia and low PNI were significantly related to disease activity, & poor clinical outcome in studied cases with IBD with a p- value < 0.05.

Conclusion

Sarcopenia and low PNI can be used as markers of activity of IBD. They are associated with worse outcomes. It is recommended to early detect and manage sarcopenia and malnutrition in IBD patients to improve outcomes.
Common and specific factors in psychological treatment of personality pathology
Authors: Keulen-de Vos Marije , Clercx Maartje
Published: December 2024

Cognitive–behavioural therapy (CBT) has been widely used for a broad range of mental health problems for several decades and has been researched extensively. Its techniques are relatively easy to learn and follow in treatment protocols. Many new CBT-based psychotherapies have been developed that go further than traditional CBT, some specifically addressing personality disorders. These so-called third-wave approaches target emotional responses to situations by using strategies such as mindfulness exercises and acceptance of unpleasant thoughts and feelings (observing thoughts as ‘from afar’). In this article, we discuss the historical context of these therapies, dissect common and specific factors in some treatment modalities often used to treat personality disorders, and suggest potential future directions for research and treatment.
Securing the base: the need for attachment-informed interventions in the perinatal period
Authors: Ayre Karyn , McLoughlin Caoimhe
Published: December 2024

‘Each has shaped the other.’1

Evidence abounds on the salience of attachment to early development and beyond. In 2018, Adshead distilled the relevance of 20 years of attachment theory to psychiatric practice.2 We argue research funders must move one step further: develop the evidence around perinatal attachment-informed interventions.
Lewy Body Dementia
Authors: Galvin James E.
Published: December 2024

OBJECTIVE

Lewy body dementia (LBD) is an umbrella term describing two closely related conditions: Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB). LBD is the second most common cause of neurodegenerative dementia but is often underrecognized in clinical practice. This review covers the key epidemiologic, clinical, cognitive, behavioral, and biomarker features of LBD and discusses current treatment options.

LATEST DEVELOPMENTS

Indicative biomarkers of LBD improve the ability to make a diagnosis and include single-photon emission computed tomography (SPECT) of the dopamine system (brain) and the noradrenergic system (cardiac), and polysomnography. α-Synuclein–specific biomarkers in spinal fluid, skin, plasma, and brain imaging are in active development with some available for clinical use. Prodromal stages of PDD and DLB have been contextualized, and diagnostic criteria have been published. An emerging theme is whether an integrated staging system focusing on protein aggregation, rather than clinical symptoms, may advance research efforts.

ESSENTIAL POINTS

LBD is a common cause of cognitive impairment in older adults but is often subject to significant delays in diagnosis and treatment, increasing the burden on patients and family care partners. Understanding key features of disease and the use of biomarkers will improve recognition. Earlier detection may also facilitate the development of new therapeutics and enrollment in clinical trials.
LATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy
Authors: Ramanan Vijay K. , Graff-Radford Jonathan
Published: December 2024

OBJECTIVE

Although Alzheimer disease (AD) is the most common neurodegenerative cause of dementia, neurologists must be aware of other etiologies that can mimic the amnestic-predominant syndrome and medial temporal brain involvement typically associated with AD. This article reviews recent updates surrounding limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE), hippocampal sclerosis, and primary age-related tauopathy.

LATEST DEVELOPMENTS

LATE neuropathologic change occurs in approximately 40% of autopsied older adults, including occurrences in isolation in some older individuals with amnestic cognitive impairment. LATE neuropathologic change is often, but not always, associated with hippocampal sclerosis (neuronal loss and gliosis in the hippocampus and associated structures) and frequently coexists with AD and other neurodegenerative pathologies. Although there is no direct clinical biomarker for TDP-43 pathology, recent studies suggest that a clinical diagnosis of LATE can be achieved through the integration of multiple data points. Primary age-related tauopathy refers to the pathologic finding (in some cognitively unimpaired older adults as well as some individuals with cognitive impairment) of medial temporal–predominant neurofibrillary tangles in the absence of amyloid-β (Aβ) plaques. Recent consensus frameworks have attempted to resolve ambiguities of nomenclature and diagnosis for these entities, and efforts toward in vivo biomarkers are ongoing.

ESSENTIAL POINTS

LATE, with or without hippocampal sclerosis, and primary age-related tauopathy belong in the differential diagnosis (along with AD, argyrophilic grain disease, and other disorders) for slowly progressive amnestic-predominant cognitive impairment, particularly in individuals older than 75 years. Accurate recognition of clinical and diagnostic test features supportive of these non-AD entities is vital to optimize patient counseling, therapeutic selection, and novel biomarker development.
Implementing New Dementia Care Models in Practice
Authors: Ramanan Vijay K.
Published: December 2024

Care for patients with Alzheimer disease and related neurodegenerative causes of dementia is in the midst of a transformation. Recent advancements in diagnostics and therapeutics reflect a rapidly evolving knowledge base and represent positive steps for patients and clinicians facing these progressive diseases; however, the complexities of emerging biomarkers and treatment options present challenges that will require systematic adaptations to routine care to facilitate effective incorporation of these options. This article reviews ongoing updates in the assessment and management of neurodegenerative causes of dementia, focusing on practical models for innovation that practices and health care systems can use to implement these new tools. In particular, sustainable adaptation in the field will benefit from a comprehensive approach implemented at local levels, including (1) education of clinicians and communities to refine perceptions about dementia care, (2) multifaceted stakeholder engagement to optimize infrastructure and workflows to the new era, and (3) investments in personnel to address existing and exacerbated gaps.
Treatment of Alzheimer Disease
Authors: Geldmacher David S.
Published: December 2024

OBJECTIVE

Symptom-oriented treatment has been the mainstay of Alzheimer disease (AD) pharmacotherapy for decades. This article reviews the evidence basis for symptomatic treatments for AD and the emerging data on amyloid-lowering therapies with possible disease-slowing effects.

LATEST DEVELOPMENT

Amyloid-lowering monoclonal antibody therapies entered clinical use in 2021. In July 2023, lecanemab became the first of these to gain full US Food and Drug Administration (FDA) approval and limited Medicare payment coverage. Donanemab gained similar approval status in July 2024. The approved agents remove amyloid plaque from the brain and appear to slow clinical disease progression but can produce significant adverse events known as amyloid-related imaging abnormalities with cerebral edema or effusion and with cerebral hemorrhages. Extensive safety monitoring is therefore required, including scheduled MRI scans. Also in 2023, brexpiprazole became the first agent specifically approved by the FDA for agitation associated with AD. Suvorexant, an orexin receptor antagonist, previously was approved for the treatment of insomnia in people with mild and moderate AD.

ESSENTIAL POINTS

There is robust evidence for the use of acetylcholinesterase inhibitors for patients with mild, moderate, and severe dementia due to AD, including outcomes beyond changes in cognitive screening test scores. More limited studies support the use of memantine in moderate and severe stages. These agents have a primary effect of delaying decline in cognition and function and postponing the emergence of adverse behaviors. Pharmacotherapy for behavioral and psychological symptoms is less predictable, and most clinical trials have had negative results. Anti-amyloid therapies provide the first FDA-approved option to alter AD pathology, but an understanding of overall utility and value to patients remains in its infancy.
Genetics and Neuropathology of Neurodegenerative Dementias
Authors: Scholz Sonja W. , Cobos Inma
Published: December 2024

OBJECTIVE

This article provides an overview of the current understanding of the genetic and pathologic features of neurodegenerative dementias, with an emphasis on Alzheimer disease and related dementias.

LATEST DEVELOPMENTS

In recent years, there has been substantial progress in genetic research, contributing significant knowledge to our understanding of the molecular risk factors involved in neurodegenerative dementia syndromes. Several genes have been linked to monogenic forms of dementia (eg, APP, PSEN1, PSEN2, SNCA, GRN, C9orf72, MAPT) and an even larger number of genetic variants are known to influence susceptibility for developing dementia. As anti-amyloid therapies for patients with early-stage Alzheimer disease have entered the clinical arena, screening for the apolipoprotein E ε4 high-risk allele has come into focus, emphasizing the importance of genetic counseling. Similarly, advances in the pathologic classifications of neurodegenerative dementia syndromes and molecular pathology highlight their heterogeneity and overlapping features and provide insights into the pathogenesis of these conditions.

ESSENTIAL POINTS

Recent progress in neurogenetics and molecular pathology has improved our understanding of the complex pathogenetic changes associated with neurodegenerative dementias, facilitating improved disease modeling, enhanced diagnostics, and individualized counseling. The hope is that this knowledge will ultimately pave the way for the development of novel therapeutics.
Homecoming After Brexit: Evidence on Academic Migration From Bibliometric Data
Authors: Sanlitürk Ebru , Aref Samin , Zagheni Emilio , Billari Francesco C.
Published: December 2024

This study assesses the initial effects of the 2016 Brexit referendum on the mobility of academic scholars to and from the United Kingdom (UK). We leverage bibliometric data from millions of Scopus publications to infer changes in the countries of residence of published researchers by the changes in their institutional affiliations over time. We focus on a selected sample of active and internationally mobile researchers whose movements are traceable for every year between 2013 and 2019 and measure the changes in their migration patterns. Although we do not observe a brain drain following Brexit, we ﬁnd evidence that scholars’ mobility patterns changed after Brexit. Among the active researchers in our sample, their probability of leaving the UK increased by approximately 86% if their academic origin (country of ﬁrst publication) was an EU country. For scholars with a UK academic origin, their post-Brexit probability of leaving the UK decreased by approximately 14%, and their probability of moving (back) to the UK increased by roughly 65%. Our analysis points to a compositional change in the academic origins of the researchers entering and leaving the UK as one of the ﬁrst impacts of Brexit on the UK and EU academic workforce.
Tango6 regulates HSPC proliferation and definitive haematopoiesis via Ikzf1 and Cmyb in caudal haematopoietic tissue
Authors: Liu Shengnan , Feng Zhi , Su Ming , Liu Chenchen , Xi Yuan , Chen Huan , Luo Lingfei , Tian Xin , Zhao Fangying , Li Li
Published: December 2024

Haematopoietic stem and progenitor cells (HSPCs) arise from the aorta-gonad-mesonephros and migrate to the caudal haematopoietic tissue (CHT) in zebrafish, where nascent HSPCs undergo tightly controlled proliferation and differentiation to promote definitive haematopoiesis. Effective expansion of HSPCs requires the coordination of well-established vesicle trafficking systems and appropriate transcription factors. However, the underlying molecules are yet to be identified. Using large-scale genetic screening of zebrafish larvae, Tango6 of the coat protein complex I (COPI) vesicle trafficking system was found to be indispensable for HSPC proliferation and definitive haematopoiesis. Homozygous tango6cq72 mutants display defective expansion of HSPCs in the CHT and compromised haematopoiesis. However, haematopoietic overexpression of Tango6 promoted haematopoietic expansion. tango6 deficiency caused a decline in RNA polymerase II subunit B and accumulation of DNA damage, which suppressed cell expansion in a P53-dependent manner. ikzf1 and cmyb (myb), two indispensable haematopoietic transcription factors, are targets of P53 and are used by tango6 in haematopoiesis. The haematopoietic phenotype was partially recovered by compensating for loss of ikzf1 and cmyb in tango6cq72 mutants. This study reveals a vesicle trafficking-mediated Tango6-P53-Ikzf1/Cmyb axis in zebrafish definitive haematopoiesis.
Maintenance of niche architecture requires actomyosin and enables proper stem cell signaling and oriented division in the Drosophila testis
Authors: Vida Gabriela S. , Botto Elizabeth , DiNardo Stephen
Published: December 2024

Stem cells are essential to repair and regenerate tissues, and often reside in a niche that controls their behavior. Here, we use the Drosophila testis niche, a paradigm for niche–stem cell interactions, to address the cell biological features that maintain niche structure and function during its steady-state operation. We report enrichment of Myosin II (MyoII) and a key regulator of actomyosin contractility (AMC), Rho Kinase (ROK), within the niche cell cortex at the interface with germline stem cells (GSCs). Compromising MyoII and ROK disrupts niche architecture, suggesting that AMC in niche cells is important to maintain its reproducible structure. Furthermore, defects in niche architecture disrupt GSC function. Our data suggest that the niche signals less robustly to adjacent germ cells yet permits increased numbers of cells to respond to the signal. Finally, compromising MyoII in niche cells leads to increased misorientation of centrosomes in GSCs as well as defects in the centrosome orientation checkpoint. Ultimately, this work identifies a crucial role for AMC-dependent maintenance of niche structure to ensure a proper complement of stem cells that correctly execute divisions.
Strategies to improve the social skills in students with autism spectrum disorder in the mainstream education
Authors: Μπαξεβανίδης Θεόδωρος
Published: December 2024

Η διατριβή με τίτλο «Στρατηγικές για τη βελτίωση των κοινωνικών δεξιοτήτων σε μαθητές με Διαταραχή Αυτιστικού Φάσματος (ΔΑΦ) στην τυπική εκπαίδευση» εστιάζει στη διερεύνηση πρακτικών και αποτελεσματικών εκπαιδευτικών παρεμβάσεων για την ενίσχυση των κοινωνικών δεξιοτήτων μαθητών με ΔΑΦ σε γενικά σχολεία. Η αύξηση του αριθμού μαθητών με ΔΑΦ στην τυπική εκπαίδευση δημιουργεί πρόσθετες προκλήσεις για τους εκπαιδευτικούς, ενώ παράλληλα υπογραμμίζει την ανάγκη για προσαρμοσμένες εκπαιδευτικές στρατηγικές που να γεφυρώνουν το χάσμα μεταξύ θεωρίας και εκπαιδευτικής πρακτικής. Η διατριβή αρχικά εξετάζει τη φύση της Διαταραχής Αυτιστικού Φάσματος, παρέχοντας μια λεπτομερή ανασκόπηση για την ιστορία, τα συμπτώματα, τις διαγνωστικές προσεγγίσεις και τις επιδημιολογικές τάσεις. Αναφέρεται στα σημαντικά ελλείμματα που αντιμετωπίζουν οι μαθητές με ΔΑΦ στην κοινωνική αλληλεπίδραση, στην έκφραση συναισθημάτων και στις δεξιότητες επικοινωνίας. Αυτά τα ελλείμματα οδηγούν σε δυσκολίες ένταξης στην τάξη, περιορισμένη συμμετοχή σε δραστηριότητες και συχνά αρνητικές κοινωνικές εμπειρίες. Η έρευνα βασίζεται σε διάφορες στρατηγικές παρέμβασης, όπως η θεωρία της κοινωνικής μάθησης, η μέθοδος TEACCH, οι κοινωνικές ιστορίες και οι εντατικές συμπεριφορικές παρεμβάσεις. Οι παρεμβάσεις αυτές στοχεύουν στην ενίσχυση της κοινωνικής αλληλεπίδρασης και της έκφρασης συναισθημάτων, προωθώντας τη συμπερίληψη και τη βελτίωση της ποιότητας ζωής των μαθητών με ΔΑΦ. Μέσα από δράσεις όπως η υποστήριξη από συνομηλίκους και εξατομικευμένα προγράμματα παρέμβασης, οι μαθητές μπορούν να αναπτύξουν ουσιαστικές κοινωνικές σχέσεις και δεξιότητες αυτορρύθμισης.Η ανάλυση των αποτελεσμάτων της μελέτης, η οποία περιλαμβάνει μελέτες περίπτωσης μαθητών με ΔΑΦ στην πρωτοβάθμια εκπαίδευση, αποκαλύπτει ότι οι εκπαιδευτικές παρεμβάσεις έχουν σημαντικά θετικά αποτελέσματα. Οι μαθητές βελτίωσαν τις κοινωνικές τους δεξιότητες, τη συμμετοχή σε δραστηριότητες και τη γενική τους συμπεριφορά. Επιπλέον, η μελέτη τονίζει την ανάγκη για συνεχή εκπαίδευση των εκπαιδευτικών και τη δημιουργία ενός συμπεριληπτικού σχολικού περιβάλλοντος.Η συμβολή της διατριβής είναι διττή: αφενός προσφέρει θεωρητική γνώση για τη φύση και τις ανάγκες των μαθητών με ΔΑΦ, αφετέρου παρέχει πρακτικές κατευθύνσεις για την εφαρμογή στρατηγικών που βελτιώνουν την εκπαίδευση και την κοινωνική τους ένταξη. Τέλος, η διατριβή υποστηρίζει τη σημασία της εξατομίκευσης στις εκπαιδευτικές παρεμβάσεις και ενθαρρύνει τη συνεργασία μεταξύ εκπαιδευτικών, μαθητών και οικογενειών για τη δημιουργία ενός υποστηρικτικού και αποτελεσματικού εκπαιδευτικού συστήματος.