bluuebunny/crossref_metadata_2025 huggingface dataset:
The challenges of hepatic epithelioid hemangioendothelioma: the diagnosis and current treatments of a problematic tumor
Authors: Atyah Manar Mikhail , Sun Yongliang , Yang Zhiying
Published: November 2024

Background

Hepatic epithelioid hemangioendothelioma (HEHE) is a malignant vascular tumor known for its rarity. The different types of this hepatic tumor (single, multiple-nodular or diffused) indicate different prognosis and treatment plans. However, the heterogenic clinical manifestation creates a dilemma and a wide range of challenges when attending to HEHE patients. This review addresses the unique profile and clinical challenges that complicate the diagnosis and treatment of HEHE while focusing on current therapeutic strategies and their limitations.

Main text

The unclear etiology is a challenging feature of HEHE. The exact involvement of potential risk factors and mechanism of development are still undefined. Relevant genetic alterations like WWTR1–CAMTA1 fusion have been investigated; however, they are only applicable as diagnostic markers and their influence on therapeutic efficacy is largely unknown. Other characteristics include asymptomatic manifestation, lack of unique hepatic functional alterations, high rates of misdiagnosis and late-stage identification when metastases already exist. Currently, tissue biopsy is the main tool to establish a definite diagnosis but is challenged with the limited awareness to suspect HEHE at early stages and the lack of relevant guidelines due to the rarity and the insufficiency of relevant research. The absence of treatment guidelines is the greatest challenge of HEHE. Generally, Surgical approaches are recommended due to the benefits of prolonged survival and enhanced prognosis. Nonetheless, only a minority of patients are eligible for resections while liver transplants are faced with severe insufficiency of donor organs and long wait-lists. On the other hand, a variety of non-surgical treatments (like anti-angiogenic agents, interferon alpha-2B and sirolimus) are presented with a promising potential. However, relevant studies are challenged with limited sample-sizes and lack of prospective designs.

Conclusion

Regardless to decades passing since its discovery, HEHE still creates a dilemma due to its challenging clinical profile and lack of treatment guidelines. Raising awareness of HEHE in clinical practices improves the ability to diagnose this rare tumor at early stages and develop stronger research strategies and treatment guidelines to regulate the medical care provided to HEHE patients.
Quality of life and caregiving burden associated with parenting a person with Duchenne/Becker muscular dystrophy in Poland
Authors: Domaradzki Jan , Walkowiak Dariusz
Published: November 2024

Background

Duchenne and Becker muscular dystrophies (DBMD) are rare progressive, X-linked diseases of muscle wasting characterised by the early onset and prognosis of premature death. The aim of this study was to evaluate the impact of providing care for a person with DBMD on caregivers’ quality of life, perceived burden and financial well-being.

Results

202 Polish caregivers of a person with DBMD were included and completed a self-administered, computer-assisted online survey. Results show that DBMD affects the quality of life of caregivers who score significantly lower than the national average in every domain: 85.1% of DBMD caregivers scored below the national average in the physical health domain; in the environmental domain 83.7%; in the social relationships domain 82.2%; and in the psychological domain 72.3%. It also demonstrates that DBMD is a source of severe burden (mean score of 35.3). Finally, we report that while some dimensions of respondents’ quality of life and perceived burden were associated with patients’ age and caregivers’ educational status, financial well-being was the most important predictor of respondents’ quality of life and caregiving burden.

Conclusions

To improve DBMD caregivers’ quality of life and alleviate their burden, future intervention programs should promote resiliency and active coping and develop a social support system and respite care. Additionally, it is crucial to provide caregivers with adequate financial resources to fulfil their needs.
Pre-hospital management of penetrating neck injuries: derivation of an algorithm through a National Modified Delphi
Authors: Simpson Christopher , Tucker Harriet , Griggs Joanne , Gavrilovski Maja , Lyon Richard , Hudson Anthony ,   Air Ambulance Charity Kent Surrey Sussex, Breeze John , Hughes Michael , Leech Caroline , Watts Adam , Omeara Matt , Scurr Cosmo , Cowley Alan , ter Avest Ewoud , Brown Vicki , Russell Malcolm , Barnard Ed , Cowburn Phil , Hurst Tom , Dunne Andy , Walmsley Jim , Moore Fionna , Charlton Will , Lewis Simon , Hardy Pam , Edwards Tim , Yates James , Lang Nigel , Ingram Gordon , Bell Steve , Fitchett Clare , Curran Andy , Boylan Matthew , Battaloglu Emir , Nutbeam Tim , Taylor Matt , Smith Carl , Ley Erica , James Alex
Published: December 2024

Background

Timely and effective pre-hospital management of penetrating neck injuries (PNI) is critical to improve patient outcomes. Pre-hospital interventions in patients with PNI can be especially challenging due to the anatomical injury site coupled with a resource-limited environment. Nationally, in the United Kingdom, no consensus statement or expert agreed guidance exists on how to best manage PNI in the pre-hospital setting.

Method

We conducted a national modified e-Delphi study with subject matter experts (SMEs) from multiple professional specialities with experience in the management of PNI. Pre-identified SMEs were contacted and consented prior to participation allowing for a remotely conducted Delphi using REDCap and Microsoft Teams. In Round 1, statements drawn from the literature base were distributed to all SMEs. Round 2 comprised a facilitated and structured discussion of the statements and then an online survey provided final ratification in Round 3. Of the participating SMEs consensus was set a priori at 70%.

Results

Of the 67 pre-identified SMEs, 28 participated, resulting in a response rate of 42%. From the first two rounds, 19 statements were derived with every statement achieving consensus in Round 3. Subsequently, an algorithm for the pre-hospital management of PNI was developed and agreed with SME consensus.

Conclusion

Curation of national consensus statements from SMEs aims to provide principles and guidance for PNI management in a complicated patient group where pre-hospital evidence is lacking. Multi-professional national consensus on the best approach to manage these injuries alongside a novel PNI management algorithm aims to optimise time critical care and by extension improve patient outcomes.
EpiCHAOS: a metric to quantify epigenomic heterogeneity in single-cell data
Authors: Kelly Katherine , Scherer Michael , Braun Martina Maria , Lutsik Pavlo , Plass Christoph
Published: December 2024

Epigenetic heterogeneity is a fundamental property of biological systems and is recognized as a potential driver of tumor plasticity and therapy resistance. Single-cell epigenomics technologies have been widely employed to study epigenetic variation between—but not within—cellular clusters. We introduce epiCHAOS: a quantitative metric of cell-to-cell heterogeneity, applicable to any single-cell epigenomics data type. After validation in synthetic datasets, we apply epiCHAOS to investigate global and region-specific patterns of epigenetic heterogeneity across diverse biological systems. EpiCHAOS provides an excellent approximation of stemness and plasticity in development and malignancy, making it a valuable addition to single-cell cancer epigenomics analyses.
A multi-scene deep learning model for automated segmentation of acute vertebral compression fractures from radiographs: a multicenter cohort study
Authors: Zhang Hao , Yuan Genji , Zhang Ziyue , Guo Xiang , Xu Ruixiang , Xu Tongshuai , Zhong Xin , Kong Meng , Zhu Kai , Ma Xuexiao
Published: December 2024

Objective

To develop a multi-scene model that can automatically segment acute vertebral compression fractures (VCFs) from spine radiographs.

Methods

In this multicenter study, we collected radiographs from five hospitals (Hospitals A–E) between November 2016 and October 2019. The study included participants with acute VCFs, as well as healthy controls. For the development of the Positioning and Focus Network (PFNet), we used a training dataset consisting of 1071 participants from Hospitals A and B. The validation dataset included 458 participants from Hospitals A and B, whereas external test datasets 1–3 included 301 participants from Hospital C, 223 from Hospital D, and 261 from Hospital E, respectively. We evaluated the segmentation performance of the PFNet model and compared it with previously described approaches. Additionally, we used qualitative comparison and gradient-weighted class activation mapping (Grad-CAM) to explain the feature learning and segmentation results of the PFNet model.

Results

The PFNet model achieved accuracies of 99.93%, 98.53%, 99.21%, and 100% for the segmentation of acute VCFs in the validation dataset and external test datasets 1–3, respectively. The receiver operating characteristic curves comparing the four models across the validation and external test datasets consistently showed that the PFNet model outperformed other approaches, achieving the highest values for all measures. The qualitative comparison and Grad-CAM provided an intuitive view of the interpretability and effectiveness of our PFNet model.

Conclusion

In this study, we successfully developed a multi-scene model based on spine radiographs for precise preoperative and intraoperative segmentation of acute VCFs.

Critical relevance statement

Our PFNet model demonstrated high accuracy in multi-scene segmentation in clinical settings, making it a significant advancement in this field.

Key Points

This study developed the first multi-scene deep learning model capable of segmenting acute VCFs from spine radiographs.

The model’s architecture consists of two crucial modules: an attention-guided module and a supervised decoding module.

The exceptional generalization and consistently superior performance of our model were validated using multicenter external test datasets.

Graphical Abstract
Embracing sex-specific differences in engineered kidney models for enhanced biological understanding of kidney function
Authors: Veser Charlotte , Carlier Aurélie , Dubois Vanessa , Mihăilă Silvia M. , Swapnasrita Sangita
Published: December 2024

In vitro models serve as indispensable tools for advancing our understanding of biological processes, elucidating disease mechanisms, and establishing screening platforms for drug discovery. Kidneys play an instrumental role in the transport and elimination of drugs and toxins. Nevertheless, despite the well-documented inter-individual variability in kidney function and the multifaceted nature of renal diseases—spanning from their origin, trigger and which segment of the kidney is affected—to presentation, progression and prognosis, few studies take into consideration the variable of sex. Notably, the inherent disparities between female and male biology warrants a more comprehensive representation within in vitro models of the kidney. The omission of sex as a fundamental biological variable carries the substantial risk of overlooking sex-specific mechanisms implicated in health and disease, along with potential differences in drug responsiveness and toxicity profiles between sexes. This review emphasizes the importance of incorporating cellular, biological and functional sex-specific features of renal activity in health and disease in in vitro models. For that, we thoroughly document renal sex-specific features and propose a strategic experimental framework to integrate sex-based differences into human kidney in vitro models by outlining critical design criteria to elucidate sex-based features at cellular and tissue levels. The goal is to enhance the accuracy of models to unravel renal mechanisms, and improve our understanding of their impact on drug efficacy and safety profiles, paving the way for a more comprehensive understanding of patient-specific treatment modalities.
Exemplar Hospital Initiation Trial to Enhance Treatment Engagement (EXHIT ENTRE): protocol for CTN-0098 an open-label randomized comparative effectiveness trial of extended-release buprenorphine versus treatment as usual on post-hospital treatment engagement for hospitalized patients with opioid use disorder
Authors: Bart Gavin , Barth Kelly S. , Baukol Paulette , Enns Eva , Ghitza Udi E. , Harris Jacklyn , Jelstrom Eve , Liebschutz Jane M. , Magane Kara M. , Voronca Delia , Weinstein Zoe M. , Korthuis P. Todd
Published: December 2024

Background

Hospitalizations involving opioid use disorder (OUD) are increasing. Addiction consultation services (ACS) initiate medications for opioid use disorder (MOUD) in hospital settings and arrange post-hospital follow-up for ongoing MOUD care. Engagement in MOUD following hospital discharge is hampered by challenges in timely access to MOUD. This protocol describes an open-label randomized comparative effectiveness trial comparing ACS treatment as usual (TAU) to a single injection of a 28-day formulation extended-release buprenorphine (XR-BUP) on MOUD engagement 34-days following hospital discharge.

Methods

Six U.S. hospitals with ACS capable of prescribing all MOUD (i.e., methadone, buprenorphine, and extended-release naltrexone) recruit and randomize hospitalized patients with OUD who have not been on MOUD in the fourteen days prior to hospitalization. TAU may consist of any MOUD other than XR-BUP. Participants randomized to XR-BUP may receive any MOUD throughout their hospital stay and receive a 28-day XR-BUP injection within 72-hours of anticipated hospital discharge. There is no intervention beyond hospital stay. Participants are followed 34-, 90-, and 180-days following hospital discharge. The primary outcome is engagement in any MOUD 34-days following hospital discharge, which we hypothesize will be greater in the XR-BUP group. Randomizing 342 participants (171 per arm) provides 90% power to detect difference in the primary outcome between groups with an odds ratio of 2.1. Safety, secondary, and exploratory outcomes include: adverse events, MOUD engagement on days 90 and 180, opioid positive urine drug tests, self-reported drug use, hospital readmissions and emergency department visits, use of non-opioid drugs, fatal and non-fatal opioid overdose, all-cause mortality, quality of life, and cost-effectiveness. Data are analyzed by intention-to-treat, with pre-planned per-protocol and other secondary analyses that examine gender as an effect modifier, differences between groups, and impact of missingness.

Discussion

Engagement in MOUD care following hospitalization in individuals with OUD is low. This randomized comparative effectiveness trial can inform hospital ACS in medication selection to improve MOUD engagement 34-days following hospital discharge.

Trial registration

NCT04345718.
Regaining control over alcohol intake but not abstinence on disulfiram medication, as a harm reduction approach: 2 case reports
Authors: Schallenberg Max , Pilhatsch Maximilian , Petzold Johannes , Vogel-Blaschka Diana , Zimmermann Ulrich S. , Spreer Maik
Published: December 2024

Background

Alcohol use disorder (AUD) poses severe health risks, yet many affected individuals opt out of complete abstinence. Therefore, harm reduction strategies have become more prominent in treatment guidelines for AUD. Our two case reports illustrate how disulfiram, initially intended to enforce abstinence, was repurposed to support reduced drinking.

Case Presentations

A 41-year-old patient with a history of severe AUD successfully reduced his alcohol consumption to a low-risk level by leveraging the effects of the disulfiram-alcohol aversive reaction. Another patient, a 63-year-old woman with long histories of AUD and major depressive disorder, experienced fewer depressive episodes and hospitalizations with disulfiram therapy despite periodically intentional discontinuation of medication.

Conclusion

Individualized treatment strategies are critical in optimizing outcomes for patients with AUD. Continuous disulfiram therapy, despite its limitations in directly reducing alcohol intake, might offer a new avenue for harm reduction in exceptional cases even if alcohol consumption continues. The cases suggest that maintaining therapy, aiming at reduced drinking, can enhance the therapeutic alliance and help manage comorbid conditions. Regular medical monitoring is essential for safety and efficacy, warranting further study of possible long-term consequences and psychotropic effects of elevated acetaldehyde levels related to the disulfiram-alcohol interaction.
Inpatient detoxification for alcohol and other drug use: qualitative study of patients’ accounts of their relationships with staff
Authors: Neale Joanne , Cairns Beth , Gardiner Kevin , Livingston Wulf , McCarthy Trevor , Perkins Andrew
Published: December 2024

Background

The therapeutic alliance is an important predictor of treatment outcomes but people who use alcohol and other drugs report mixed views of treatment providers. We analysed patients’ accounts of inpatient detoxification staff to ascertain whether, and if so how, relationships with them, and thus the therapeutic alliance, might be improved.

Methods

Semi-structured qualitative interviews were conducted (in 2022/2023) with 20 people (14 males; 6 females) who had just completed inpatient detoxification in sixteen different facilities. Interviews were part of a larger longitudinal qualitative evaluation of an initiative to increase inpatient detoxification capacity across England.

Results

Patients described how treatment was delivered by professionals with diverse roles. They rated staff highly and appreciated their personal qualities; the standard of medical care and non-medical services they provided; their willingness to provide privacy, freedom and choice; the support given at key points in the treatment journey; and the positive impact staff relationships had on their substance use and lives more generally. Criticisms of staff were infrequent, mostly related to specific individuals or events, and potentially more common when detoxification occurred within general hospitals rather than within specialist services.

Conclusions

Patients’ accounts of staff in this study were more positive than documented in previous literature. However, the characteristics that patients appreciated (and disliked) were consistent with earlier research. There was scope to improve in some services and patient groups not interviewed may have held more negative views of staff. Overall, the holistic and patient-centred approach that staff adopted, and patients valued, appears to contribute to a good therapeutic alliance.
Shear Strengthening of RC Beams Using Partial-Length Near-Surface Mounted (PLNSM) CFRP Strips
Authors: Khol Senghong , Seo Soo-Yeon , Van Tran Hai , Hanif Muhammad Usman
Published: December 2024

Shear strengthening of reinforced concrete beams using near-surface mounting (NSM) method with fiber-reinforced polymer (FRP) strips is more effective because of improved bond strength, better fire resistance and high maintainability. However, the surface preparation for NSM method is a difficult process where the beam–slab corner is not accessible by the rotary blade of the groove-making equipment. Consequently, the application of NSM method becomes more difficult to apply. Therefore, in this study, the effect of reducing in NSM length on the shear strength has been investigated by reinforcing only a part of the height, not the entire web of beam, referred to as the partial-length NSM method (PLNSM). Half scaled five RC T-beams were made and tested under symmetrical four-point static loading system. All except one was strengthened in shear in which the effect of reduced NSM length was balanced by inclining the partial-length NSM strips (IPLNSM). Furthermore, to mitigate the detrimental effect of reduced lengths of NSM strips, the retrofitting was enhanced by additional externally bonded reinforcement (EBR) method using CFRP sheets. The results showed that there was no significant negative effect of reduced NSM length on the strength of the strengthened specimens, and by providing inclined NSM strips, significant improvement in the strength was observed. Additionally, the hybrid approach combining the inclined partial length NSM (IPLNSM) and EBR method showed improvement in strength and deflection capacity. Lastly, when compared with the currently available design procedures, it was found that the available formulation can predict the design strength of PLNSM and IPLNSM reinforcement, thus making them a viable option for retrofitting reinforced concrete beams.
Early predictors of unfavorable outcomes in pediatric acute respiratory failure
Authors: Miura Shinya , Michihata Nobuaki , Isogai Toshiaki , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: December 2024

Objective

Acute respiratory failure is a leading cause of critical illness in children. However, patient outcomes and early predictors of unfavorable outcomes are not well understood. This study aimed to describe composite unfavorable outcomes, defined as in-hospital death or discharge with new comorbidities, and to identify early predictors in children with acute respiratory failure in acute care hospitals.

Design

Retrospective cohort study using a national inpatient database in Japan.

Setting

All acute care hospitals registered in the database.

Patients

This study included children under 20 years of age who were admitted with acute respiratory diseases between July 2010 and March 2022 and received ventilatory support within the first three days of hospitalization.

Intervention

None.

Measurements and main results

Among 29,362 eligible children, the median age was 1.2 (interquartile range, 0.3–3.7) years and 28.8% had underlying conditions. The highest level of ventilatory support within the first three days was invasive ventilation (69.4%), noninvasive ventilation (1.0%), and high-flow nasal cannula (29.7%). Respiratory diagnoses included pneumonia (58.6%), bronchiolitis (29.0%), and asthma (11.1%). Among these children, 669 (2.3%) died and 1994 (6.8%) were discharged with new comorbidities, resulting in 2663 (9.1%) children experiencing unfavorable outcomes. In the logistic regression model, older age, underlying conditions, pneumonia, and low hospital volume were associated with unfavorable outcomes after adjusting for covariates.

Conclusions

A significant proportion of pediatric patients with acute respiratory failure experienced unfavorable outcomes, warranting future efforts to improve acute care services for at-risk children. Early predictors identified from national database analyses could inform risk stratification and optimize the provision of acute care services for vulnerable pediatric patients.
Interfacial charge transfer on hierarchical synergistic shell wall of MXene/MoS2 on CdS nanospheres: heterostructure integrity for visible light responsive photocatalytic H2 evolution
Authors: Ranjith Kugalur Shanmugam , Mohammadi Ali , Raju Ganji Seeta Rama , Huh Yun Suk , Han Young-Kyu
Published: December 2024

Energy scarcity and environmental pollution have prompted research in hydrogen generation from solar to develop clean energy through highly efficient, effective, and long-lasting photocatalytic systems. Designing a catalyst with robust stability and an effective carrier separation rate was achieved through heterostructure assembly, but certain functionalities must be explored. In this paper we designed a ternary heterostructure assembly of CdS nanospheres wrapped with hierarchical shell walls of layered MXene-tagged MoS2 nanoflakes, forming intimate interfaces through an in-situ growth process. An in-layered shell wall of MXene with surface-wrapped MoS2 nanoflakes as a core–shell assembly improved the photo-corrosion resistance and accelerated the production of photocatalytic H2 (38.5 mmol g−1 h−1), which is 10.7, 3.1, and 1.9 times faster than that of CdS, CdS–MXe, and CdS–MoS2 nanostructures, respectively. The apparent quantum efficiency of the CdS–MXe2.4/MoS2 heterostructure was calculated to be 34.6% at λ = 420 nm. X-ray and ultraviolet photoelectron spectroscopies validated the electronic states, energy band alignment, and work function of the heterostructures, whilst time-resolved photoluminescence measured the carrier lifespan to evaluate the effective charge migration in the CdS-MXe/MoS2 heterostructure. The dual surface wrapping of MXe/MoS2 over CdS nanospheres confirmed the structural durability that remained intact throughout the photocatalytic reaction, promoting approximately 93.1% of its catalytic property even after five repeatable cycles. This study examined how the MXene heterostructure template improves the catalytic efficiency and opens a new way to design MXene-based durable heterostructure catalysts for solar-energy conversion.

Graphical Abstract
Comparable postoperative outcomes in patients treated with either open or arthroscopic trochleoplasty for patella dysplasia
Authors: Riedl Georg , Holzer Lukas A. , Smekal Vinzenz
Published: December 2024

Background

The aim of this study was to compare the clinical and radiologic results of the arthroscopic and the open trochleoplasty techniques.

Methods

A total of 83 trochleoplasties in 83 patients were performed between 2014 and 2021 in one institution. Surgical indications for trochleoplasty were recurrent patellofemoral instability and a lateral trochlear inclination angle (LTI) ≤ 11˚ and a trochlear depth ≤ 6 mm. Of the trochleoplasties, 40 were done by open technique (OT) and 43 by arthroscopic technique (AT). In every case an additional medial patellofemoral ligament (MPFL) reconstruction was performed. Additional tuberosity tibia transfer and/or de-rotation of the femur were done when indicated. Pre- and postoperative magnetic resonance imaging (MRI) were analyzed in respect to LTI, trochlear depth, and lateralization of the patella. Postoperative subjective clinical assessment was done using the Kujala Score, Banff II Score, Tegner Score, and Marx Score.

Results

Of the patients, 15 with OT and 20 with AT were available for follow-up. The mean follow-up was 29.9 months in the OT group and 12.7 months in the AT group. No re-dislocation was observed in either groups. A significant reduction of LTI, increase of trochlear depth, and a reduction of lateralization of the patella was observed between the pre- and postoperative MRI scans in both groups. No significant difference in the observed MRI parameters was found between the two groups. Neither was there a difference in the postoperative Kujala Score, Banff II Score, Tegner Score, and Marx Score between the two groups. Length of stay was on average 6.2 days in the AT group and 8.1 days in the OT group. The surgical time was on average 141 min in the OT group and 160 min in the AT group.

Conclusion

We found that patients undergoing an arthroscopic trochleoplasty had a comparable outcome with respect to clinical and radiological parameters compared with patients treated by open trochleoplasty.
A self-reported questionnaire for screening of hearing impairment in older
Authors: Aakash Mishra , Nikita Nanavati
Published: December 2024

Introduction

Hearing loss is a prevalent concern for older adults aged 60 years and above, making early intervention essential. Accurate diagnosis relies on calibrated instruments, soundproof environments, and qualified audiologists. While these resources are often available, certain situations may limit access. This study investigates the potential of self-assessment tools as an alternative screening method for older adults to identify those who may require further audiological evaluation.

Aim

To study the efficacy of self-reported questionnaire in identifying hearing loss among older adults and its potential application in clinical practice.

Method

This cross-sectional study included a total of 160 older adults. Participants were divided into two groups: Group I with normal hearing sensitivity and Group II with mild to moderately severe sensorineural hearing loss. Pure-tone audiometry was used to measure hearing thresholds, followed by administering a questionnaire.

Result

It was observed that there was significant difference between scores of the self-awareness and communication difficulties for different degrees of hearing loss among older adults (p-value < 0.05). The cut-off score was observed to be increasing with the increase of the hearing loss, and also, it was observed that there is a positive strong correlation between scores of self-awareness domain and communication difficulties domain across different degrees of hearing loss.

Conclusion

Thus, this questionnaire could be an effective tool for screening of hearing loss and assessing its severity, from mild to moderately severe in older adults. This will facilitate early detection and intervention, potentially enhancing their quality of life.
Neuropsychiatric Symptoms in Dementia
Authors: Marshall Gad A.
Published: December 2024

OBJECTIVE

This article discusses the prevalence, pathophysiology, assessment, and management of neuropsychiatric symptoms in patients with dementia.

LATEST DEVELOPMENTS

There is a growing body of evidence localizing neuropsychiatric symptoms in dementia to frontal circuits in the brain, as well as relating them to pathologic changes seen in different dementias. Although very few medications have been approved by the US Food and Drug Administration (FDA) for the treatment of neuropsychiatric symptoms in dementia, there are more clinical trials showing the benefit of antidepressants, stimulants, and antipsychotics. In line with that trend, in 2023, the FDA approved the use of brexpiprazole, an atypical antipsychotic, for the treatment of agitation in Alzheimer disease dementia.

ESSENTIAL POINTS

Neuropsychiatric symptoms are a core feature of all dementias and often emerge before cognitive symptoms manifest. They are highly clinically significant symptoms that disrupt the lives of patients and care partners and greatly influence the decision to place patients in long-term care facilities. The first line of treatment for neuropsychiatric symptoms in dementia is nonpharmacologic behavioral modification, but clinicians often must supplement this intervention with medications using an empiric approach.
Atypical Presentations of Alzheimer Disease
Authors: Jones David , Pelak Victoria , Rogalski Emily
Published: December 2024

OBJECTIVE

This article provides a comprehensive review of the distinct features of four atypical Alzheimer disease (AD) variants: dysexecutive AD, behavioral variant AD, posterior cortical atrophy, and the logopenic variant of primary progressive aphasia. It also elucidates their clinical presentations, underlying pathophysiologic pathways, diagnostic indicators, and management requirements.

LATEST DEVELOPMENTS

Recent research has revealed that these atypical AD forms vary not only in clinical manifestations but in their functional neuroanatomy spanning a common pathophysiologic spectrum. Imaging techniques, such as MRI, fludeoxyglucose positron emission tomography (FDG-PET), and tau PET, have identified distinct abnormalities in specific brain regions associated with each variant. This same variability is less tightly coupled to amyloid imaging. Emerging diagnostic and therapeutic strategies should be tailored to each variant's unique features.

ESSENTIAL POINTS

Atypical forms of AD often present with symptoms that are predominantly nonmemory related, distinguishing them from the more common memory-centric presentation of the disease. Two distinct clinical and pathologic entities, dysexecutive AD and behavioral variant AD, have replaced the outdated term frontal AD. Posterior cortical atrophy is another variant that mainly affects higher-order visual functions, which can lead to misdiagnoses because of its atypical symptom profile. Logopenic primary progressive aphasia is marked by difficulties in word retrieval, a challenge that may not be readily apparent if the person compensates by using circumlocution. Modern diagnostic techniques, such as MRI, PET, and biomarker analysis, have proven crucial for the accurate diagnosis and differentiation of these atypical AD variants. In treating these forms, it is critical to use tailored therapeutic interventions that combine pharmacotherapy with nonpharmacologic strategies to effectively manage the disease.
Diagnosing Alzheimer Disease
Authors: Day Gregory S.
Published: December 2024

OBJECTIVE

This article reviews the current understanding of Alzheimer disease (AD), including the natural history, common risk factors, and expected progression of AD neuropathologic change so that neurologists can apply this knowledge to identify patients with symptoms, signs, and findings on common diagnostic tests consistent with AD.

LATEST DEVELOPMENTS

The advent of potential disease-modifying therapies emphasizes the need to develop and deploy a practical and efficient approach to diagnose patients with cognitive impairment due to AD.

ESSENTIAL POINTS

The accumulation and spread of cerebral amyloid plaques and tau tangles in patients with AD leads to synaptic dysfunction, neuronal loss, and the eventual emergence and progression of cognitive impairment. A pragmatic and organized approach is needed to recognize patients with symptomatic AD in clinical practice, stage the level of impairment, confirm the clinical diagnosis, and apply this information to advance therapeutic decision making.
Neuroimaging in Dementia
Authors: Risacher Shannon L.
Published: December 2024

OBJECTIVE

This article captures the current literature regarding the use of neuroimaging measures to study neurodegenerative diseases, including early- and late-onset Alzheimer disease, vascular cognitive impairment, frontotemporal lobar degeneration disorders, dementia with Lewy bodies, and Parkinson disease dementia. In particular, the article highlights significant recent changes in novel therapeutics now available for the treatment of Alzheimer disease and in defining neurodegenerative disease using biological frameworks. Studies summarized include those using structural and functional MRI (fMRI) techniques, as well as metabolic and molecular emission tomography imaging (ie, positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]).

LATEST DEVELOPMENTS

Neuroimaging measures are considered essential biomarkers for the detection and diagnosis of most neurodegenerative diseases. The recent approval of anti-amyloid antibody therapies has highlighted the importance of MRI and PET techniques in treatment eligibility and monitoring for associated side effects. Given the success of the initial biomarker-based classification system for Alzheimer disease (the amyloid, tau, neurodegeneration [A/T/N] framework), researchers in vascular cognitive impairment have created similar techniques for biomarker-based diagnosis. Further, the A/T/N framework for Alzheimer disease has been updated to include several pathologic targets for biomarker detection.

ESSENTIAL POINTS

Neurodegenerative diseases have a major health impact on millions of patients around the world. Neuroimaging biomarkers are rapidly becoming major diagnostic tools for the detection, monitoring, and treatment of neurodegenerative diseases. This article educates readers about the current literature surrounding the use of neuroimaging tools in neurodegenerative diseases along with recent important developments in the field.
Castor is a temporal transcription factor that specifies early born central complex neuron identity
Authors: Dillon Noah R. , Doe Chris Q.
Published: December 2024

The generation of neuronal diversity is important for brain function, but how diversity is generated is incompletely understood. We used the development of the Drosophila central complex (CX) to address this question. The CX develops from eight bilateral Type 2 neuroblasts (T2NBs), which generate hundreds of different neuronal types. T2NBs express broad opposing temporal gradients of RNA-binding proteins. It remains unknown whether these protein gradients are sufficient to directly generate all known neuronal diversity, or whether there are temporal transcription factors (TTFs) with narrow expression windows that each specify a small subset of CX neuron identities. Multiple candidate TTFs have been identified, but their function remains uncharacterized. Here, we show that: (1) the adult E-PG neurons are born from early larval T2NBs; (2) the candidate TTF Castor is expressed transiently in early larval T2NBs when E-PG and P-EN neurons are born; and (3) Castor is required to specify early born E-PG and P-EN neuron identities. We conclude that Castor is a TTF in larval T2NB lineages that specifies multiple, early born CX neuron identities.
The co-chaperone DNAJA2 buffers proteasomal degradation of cytosolic proteins with missense mutations
Authors: Baker Heather A. , Bernardini Jonathan P. , Csizmók Veronika , Madero Angel , Kamat Shriya , Eng Hailey , Lacoste Jessica , Yeung Faith A. , Comyn Sophie , Hui Elizabeth , Calabrese Gaetano , Raught Brian , Taipale Mikko , Mayor Thibault
Published: December 2024

Mutations can disrupt the native function of protein by causing misfolding, which is generally handled by an intricate protein quality control network. To better understand the triaging mechanisms for misfolded cytosolic proteins, we screened a human mutation library to identify a panel of unstable mutations. The degradation of these mutated cytosolic proteins is largely dependent on the ubiquitin proteasome system. Using BioID proximity labelling, we found that the co-chaperones DNAJA1 and DNAJA2 are key interactors with one of the mutated proteins. Notably, the absence of DNAJA2 increases the turnover of the mutant but not the wild-type protein. Our work indicates that specific missense mutations in cytosolic proteins can promote enhanced interactions with molecular chaperones. Assessment of the broader panel of cytosolic mutant proteins shows that the co-chaperone DNAJA2 exhibits two distinct behaviours – acting to stabilize a wide array of cytosolic proteins, including wild-type variants, and to specifically ‘buffer’ some mutant proteins to reduce their turnover. Our work illustrates how distinct elements of the protein homeostasis network are utilized in the presence of a cytosolic misfolded protein.
Η πολιτική των Γερμανών έναντι των Ορθοδόξων Εκκλησιών στην κατεχόμενη Ουκρανία (1941-1944)
Authors: Χέι Σβιτλάνα
Published: December 2024

Η παρούσα διδακτορική διατριβή εξετάζει την πολιτική του Γ΄ Ράιχ έναντι των δύο Ορθοδόξων Εκκλησιών στην Ουκρανία κατά τη διάρκεια του Β΄ Παγκοσμίου Πολέμου. Η εργασία αποτελείται από επτά κεφάλαια. Συγκεκριμένα, στο πρώτο κεφάλαιο εξετάζονται τα σχέδια των ηγετών της ναζιστικής Γερμανίας για την Ουκρανία και οι σχέσεις τους με τους Ουκρανούς εθνικιστές, κυρίως τα μέλη της Οργάνωσης των Ουκρανών Εθνικιστών. Το δεύτερο κεφάλαιο μελετά την θρησκευτική αναβίωση που παρατηρήθηκε κατά τη διάρκεια της γερμανικής κατοχής· το τρίτο κεφάλαιο επικεντρώνεται στο ρόλο της Ορθόδοξης Εκκλησίας κατά τη γερμανική κατοχή στην Ουκρανία· το τέταρτο εστιάζει στη δημιουργία της Ουκρανικής Αυτόνομης Ορθόδοξης Εκκλησίας και της Ουκρανικής Αυτοκέφαλης Ορθόδοξης Εκκλησίας· το πέμπτο κεφάλαιο αφορά την πολιτική των γερμανικών κατοχικών αρχών προς τις δύο Ουκρανικές Ορθόδοξες Εκκλησίες· το έκτο μελέτα την ιδιοτελή στάση των γερμανικών κατοχικών αρχών προς τις Ορθόδοξες Εκκλησίες και, τέλος, το έβδομο κεφάλαιο εξετάζει την απόπειρα εγκαθίδρυσης της «νέας θρησκείας» στα ουκρανικά κατεχόμενα εδάφη.
Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator and a pilot study in orthopaedic-trauma patients.
Authors: Saranteas Theodosios , Poulogiannopoulou Eleni , Riga Maria , Panagouli Konstantina , Mavrogenis Andreas , Papadimos Thomas
Published: December 2024

Backround/Objectives We investigated a technique that facilitates the coiling of a regular straight catheter (with integral stylet) behind the sciatic nerve in an ultrasound (US) regional anaesthesia simulator, and then applied our findings to a series of orthopedic-trauma patients. Methods We conducted a randomized study of two methods of perineural catheter advancement in a sciatic nerve block Blue Phantom simulator. Two groups of twenty catheters each (method A and method B) were evaluated under real-time ultrasound imaging. The needle in-plane/nerve in-short-axis technique was applied. In method A the catheter was advanced beyond the needle tip with the integral stylet extending along its entire length; in method B the catheter was advanced after its integral stylet was retracted by 6 cm, thus providing flexibility to the catheter’s distal end. Additionally, to assess the procedural effectiveness of method B coiling technique, a pilot study was conducted examining 25 perineural catheters coiled underneath the sciatic nerve in trauma-orthopaedic patients to document any catheter tip displacement from their initial position (for 36 hours postoperatively). Results In the simulation study, method B led to a significantly higher percentage (18/20:90%) of coiled catheters than method A (3/20:15%). Two coiled catheters of method B were found kinked/obstructed. In our patients, after catheter insertion, the distal end of 2/25 (8%) coiled catheters was obstructed. One perineural catheter was dislodged. For the remaining 22 (88%) catheters, ultrasound imaging demonstrated that local anaesthetic infusion made contact with the sciatic nerve, indicating no displacement of the catheter’s distal end postoperatively. Conclusion Regular straight perineural catheters can be coiled if their integral stylet is partially retracted. This coiling method offers extra catheter length adjacent to the nerve structure which potentially mitigates catheter tip displacement. Trial registration clinicaltrials.gov, registration No: NCT06568510, 23/08/2024, registration URL: https://clinicaltrials.gov/study/NCT06568510?intr=coiling%20of%20echogenic%20sciatic%20nerve&rank=1#study-overview
Kinetics of naturally induced binding and neutralising anti-SARS-CoV-2 antibody levels and potencies among SARS-CoV-2 infected Kenyans with diverse grades of COVID-19 severity: an observational study
Authors: Kimotho John , Sein Yiakon , Sayed Shahin , Shah Reena , Mwai Kennedy , Saleh Mansoor , Wanjiku Perpetual , Mwacharo Jedidah , Nyagwange James , Karanja Henry , Kutima Bernadette , Gitonga John N. , Mugo Daisy , Karanu Ann , Moranga Linda , Oluoch Viviane , Shah Jasmit , Mutiso Julius , Mburu Alfred , Nneka Zaitun , Betti Peter , Usyu Mutinda Wanzila , Issak Abdi Abdirahman , Bejon Philip , Isabella Ochola-Oyier Lynette , M.Warimwe George , Nduati Eunice W. , M. Ndungu Francis
Published: December 2024

Background Given the low levels of coronavirus disease 2019 (COVID-19) vaccine coverage in sub-Saharan Africa (sSA), despite high levels of natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of naturally acquired immunity. Methods We measured whole-spike immunoglobulin G (IgG) and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody-neutralising potency against the wild-type (Wuhan) SARS-CoV-2 pseudovirus in a subset of 51 patients over three successive time points. Binding and neutralising antibody levels and potencies were then tested for correlations with COVID-19 severities. Results Rates of seroconversion increased from day 0 (day of PCR testing) to day 180 (six months) (63.6% to 100 %) and (69.3 % to 97%) for anti-spike-IgG and anti-spike-RBD binding Igs, respectively. Levels of these binding antibodies peaked at day 28 (p<0.01) and were subsequently maintained for six months without significant decay (p>0.99). Similarly, antibody-neutralising potencies peaked at day 28 (p<0.01) but declined by three-fold, six months after COVID-19 diagnosis (p<0.01). Binding antibody levels were highly correlated with neutralising antibody potencies at all the time points analysed (r>0.60, p<0.01). Levels and potencies of binding and neutralising antibodies increased with disease severity. Conclusions Most COVID-19 patients generated SARS-CoV-2 specific binding antibodies that remained stable in the first six months of infection. However, the respective neutralising antibodies decayed three-fold by month-six of COVID-19 diagnosis suggesting that they are short-lived, consistent with what has been observed elsewhere in the world. Thus, regular vaccination boosters are required to sustain the high levels of anti-SARS-CoV-2 naturally acquired neutralising antibody potencies in our population.
ВЛИЯНИЕ РАЗВИТИЯ ИНФОРМАЦИОННЫХ ТЕХНОЛОГИЙ НА ФОРМИРОВАНИЕ ПОКОЛЕНИЙ СОТРУДНИКОВ В ИТ-СФЕРЕ РОССИЙСКИХ ОРГАНИЗАЦИЯХ
Authors: Mekhtiev Roman F.
Published: November 2024

Цель. Сфера информационных технологий (ИТ) стремительно развивается и активно интегрируется во все процессы социума. В связи с этим, современное общество должно обладать необходимыми ИТ-навыками и находиться в постоянной цифровой трансформации, в том числе в рабочей среде. Это приводит к возникновению проблемы цифровой адаптации сотрудников, прежде всего старшего возраста. Особо остро проблема отражается в ИТ-подразделениях. Целью данного исследования является оценка влияния развития отрасли ИТ в СССР и России на цифровое развитие сотрудников. В качестве объекта исследования рассматривались сотрудники ИТ-подразделений крупной российской компании из топливно-энергетического комплекса.
Метод и методология проведения работы. При проведении исследования использовался количественный метод анализа статистических данных о сотрудниках российской компании, а также метод экспертного интервьюирования руководящего и подчиненного состава ИТ-подразделений.
Результаты. По результатам проведенного анализа установлено влияние развития ИТ-отрасли на формирование возрастных (поколенческих) особенностей российского общества. Выстроена взаимосвязь между возрастными особенностями сотрудников и их должностными обязанностями.
Область применения результатов. Результаты исследований можно использовать при формировании кадровой политики в ИТ-подразделениях российских организаций.