bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative virtual reality environment in disaster medicine: moving from single player to multiple learners
Authors: Abensur Vuillaume Laure , Goffoy Jonathan , Dubois Nadège , Almoyner Nathacha , Bardet Cécile , Dubreucq Evelyne , Klenkenberg Sophie , Donneau Anne-Françoise , Dib Camille , Ghuysen Alexandre ,   On Behalf Societe Francophone de Pédagogie Innovante en Santé and Medical Simulation Center of ULiège
Published: April 2024

Background

The use of virtual reality (VR) in healthcare education is on the increase. In disaster medicine, it could be a solution to the cost and logistic constraints for a “full-scale” scenarios. However, VR is mainly designed for single players, which is not appropriate for the objectives pursued in disaster medicine. We decided to evaluate the educational value of using individual VR simulation in disaster medicine on a group of learners.

Methods

The VR scenario used was a reproduction of a major train crash, with 21 victims and whose objectives were START triage and first aid techniques. The sessions were carried out in multi-participant groups with different roles (active and immersed with headset, paper triage without headset, and active for communications not immersed in the headset). Their perceived self-efficacy was assessed before (T0), after (T1) and 2 months (T2) after the training. Satisfaction and confidence in learning were also measured.

Results

The median levels of satisfaction and confidence in learning were of 21/25 and 32/40 respectively. Their perceived self-efficacy increased significantly between T0 and T1 (p < 0.001), and remained stable until T2. The different roles of participant showed no difference in terms of satisfaction, confidence in learning or changes in perceived self-efficacy. One third of the participants agreed that the number of participants had interfered with their learning. A significant negative correlation (rS = -0.51, p = 0.002) was found between satisfaction and the fact of having been hindered by the number of participants. Around 90% of participants found the activity entertaining and found the new technologies appropriate for learning technical skills.

Conclusions

This first experience of VR in a group setting is satisfactory and shows its positive effects. The limitations highlighted here will enable areas of improvement to be identified for the use of VR in disaster medicine, pending the development of multi-player tools. It would now be appropriate to analyse the impact of this type of simulation on learning and its retention over time.
Mitochondria protective and anti-apoptotic effects of peripheral benzodiazepine receptor and its ligands on the treatment of asthma in vitro and vivo
Authors: Liu Yurui , Zhang Zhengze , He Yuewen , Li Ruogen , Zhang Yuhao , Liu Hao , Wang Yong , Ma Wuhua
Published: April 2024

Background

Asthma is a prevalent respiratory inflammatory disease. Abnormal apoptosis of bronchial epithelial cells is one of the major factors in the progression of asthma. Peripheral benzodiazepine receptors are highly expressed in bronchial epithelial cells, which act as a component of the mitochondrial permeability transition pore to regulate its opening and closing and apoptosis of bronchial epithelial cells. We aimed to investigate the mechanisms by which peripheral benzodiazepine receptor and its ligands, agonist 4’-Chlorodiazepam (Ro5-4864) and antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11,195), modulate the mitochondrial function and cell apoptosis in the treatment of asthma.

Methods

In vitro study, Ro5-4864 and PK 11,195 were utilized to pretreat cells prior to the inflammatory injury induced by Lipopolysaccharide. The reactive oxygen species, the apoptosis of cell, the mitochondrial membrane potentials, the ultrastructures of the mitochondria and the expression levels of peripheral benzodiazepine receptors and apoptosis-related proteins and genes were detected. In vivo study, mice were administrated intraperitoneally with Ro5-4864 and PK 11,195 before sensitized and challenged by ovalbumin. Serum IgE and bronchoalveolar lavage fluid cytokines were detected, and lung tissues were underwent the histopathological examination.

Results

The ligands of peripheral benzodiazepine receptor counteracted the effects of the increase of reactive oxygen species, the elevated extent of apoptosis, the decrease of mitochondrial membrane potentials and the disruption of mitochondrial ultrastructures induced by Lipopolysaccharide. The ligands also promoted the expression of anti-apoptosis-related proteins and genes and inhibited the expression of pro-apoptosis-related proteins and genes. Besides, the ligands reduced the levels of serum IgE and bronchoalveolar lavage fluid cytokines in asthmatic mice and attenuated the histopathological damage of lungs.

Conclusion

Peripheral benzodiazepine receptor serves as a potential therapeutic target for the treatment of asthma, with its ligands exerting mitochondrial protective and anti-apoptotic effects on bronchial epithelial cells.
The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling
Authors: Ma Wenbo , Zhang Jinqiang , Chen Weina , Liu Nianli , Wu Tong
Published: April 2024

Background

Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with poor prognosis. Further mechanistic insights into the molecular mechanisms of CCA are needed to develop more effective target therapy.

Methods

The expression of the histone lysine acetyltransferase KAT2B in human CCA was analyzed in human CCA tissues. CCA xenograft was developed by inoculation of human CCA cells with or without KAT2B overexpression into SCID mice. Western blotting, ChIP-qPCR, qRT-PCR, protein immunoprecipitation, GST pull-down and RNA-seq were performed to delineate KAT2B mechanisms of action in CCA.

Results

We identified KAT2B as a frequently downregulated histone acetyltransferase in human CCA. Downregulation of KAT2B was significantly associated with CCA disease progression and poor prognosis of CCA patients. The reduction of KAT2B expression in human CCA was attributed to gene copy number loss. In experimental systems, we demonstrated that overexpression of KAT2B suppressed CCA cell proliferation and colony formation in vitro and inhibits CCA growth in mice. Mechanistically, forced overexpression of KAT2B enhanced the expression of the tumor suppressor gene NF2, which is independent of its histone acetyltransferase activity. We showed that KAT2B was recruited to the promoter region of the NF2 gene via interaction with the transcription factor SP1, which led to enhanced transcription of the NF2 gene. KAT2B-induced NF2 resulted in subsequent inhibition of YAP activity, as reflected by reduced nuclear accumulation of oncogenic YAP and inhibition of YAP downstream genes. Depletion of NF2 was able to reverse KAT2B-induced reduction of nuclear YAP and subvert KAT2B-induced inhibition of CCA cell growth.

Conclusions

This study provides the first evidence for an important tumor inhibitory effect of KAT2B in CCA through regulation of NF2-YAP signaling and suggests that this signaling cascade may be therapeutically targeted for CCA treatment.
Tolerance induction through early feeding to prevent food allergy in infants and children with sensitization against food allergens (TIFFANI): rationale, study design, and methods of a randomized controlled trial
Authors: Kalb Birgit , Meixner Lara , Heller Stephanie , Dölle-Bierke Sabine , Roll Stephanie , Tissen-Diabaté Tatjana , Lau Susanne , Forslund Sofia , Marenholz Ingo , Lee Young-Ae , Thiel Andreas , Babina Magda , Scheffel Jörg , Worm Margitta , Beyer Kirsten
Published: April 2024

Background

Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3–6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance.

Methods

In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen’s egg, cow’s milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3–6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period.

Discussion

Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the “window of opportunity” for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children.

Trial registration

German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.
Study protocol - assessing parkrun for walking rehabilitation for people living with, and beyond, cancer: acceptability, adherence, social support and physical function
Authors: Broadbent Suzanne , Buhmann Robert , Kriel Yuri , Coetzee Sonja , Jones Christian , Morris Michelle , Wright Hattie H
Published: April 2024

Introduction

Due to a variety of barriers, the majority of cancer survivors do not do enough physical activity to meet current recommendations. This study will assess the feasibility of participation in parkrun walk-run events as a novel mode of community rehabilitation exercise.

Methods

This protocol describes a single-arm intervention study with participants acting as their own controls. The study accepts adults diagnosed with any type of cancer, undergoing treatment or in remission. Participants must be able to walk and have medical clearance to exercise. A sample of 100 participants will be recruited across the Sunshine Coast over two years. Data will be collected over 9-months at 4 time points: Baseline (T1); after 4-weeks of usual daily activities and cancer management prior to parkrun participation(T2); after a 6-month parkrun intervention (T3); at 2-month follow-up (T4). The primary objectives are to assess the acceptability of, and adherence to, parkrun as rehabilitation exercise. Secondary outcomes include wellness, health-related quality of life, anxiety, depression, mood, physical function, parkrun metrics, dietary intake, and diet and exercise behaviour.

Conclusion

This study will be the first to examine the long-term effects of parkrun as a cancer rehabilitation modality with regard to physical function, psychosocial outcomes and dietary intake.

Trial registration

Australian and New Zealand Clinical Trials Registry ACTRN12623000473662 registered 09/05/2023.Approved by UniSC Human Research Ethics Committee (A221828) and the UK parkrun Research Board. Original protocol. Authors SB, RB, HHW, MM, YK.
Enhancing lung cancer diagnosis with data fusion and mobile edge computing using DenseNet and CNN
Authors: Zhang Chengping , Aamir Muhammad , Guan Yurong , Al-Razgan Muna , Awwad Emad Mahrous , Ullah Rizwan , Bhatti Uzair Aslam , Ghadi Yazeed Yasin
Published: April 2024

The recent advancements in automated lung cancer diagnosis through the application of Convolutional Neural Networks (CNN) on Computed Tomography (CT) scans have marked a significant leap in medical imaging and diagnostics. The precision of these CNN-based classifiers in detecting and analyzing lung cancer symptoms has opened new avenues in early detection and treatment planning. However, despite these technological strides, there are critical areas that require further exploration and development. In this landscape, computer-aided diagnostic systems and artificial intelligence, particularly deep learning methods like the region proposal network, the dual path network, and local binary patterns, have become pivotal. However, these methods face challenges such as limited interpretability, data variability handling issues, and insufficient generalization. Addressing these challenges is key to enhancing early detection and accurate diagnosis, fundamental for effective treatment planning and improving patient outcomes. This study introduces an advanced approach that combines a Convolutional Neural Network (CNN) with DenseNet, leveraging data fusion and mobile edge computing for lung cancer identification and classification. The integration of data fusion techniques enables the system to amalgamate information from multiple sources, enhancing the robustness and accuracy of the model. Mobile edge computing facilitates faster processing and analysis of CT scan images by bringing computational resources closer to the data source, crucial for real-time applications. The images undergo preprocessing, including resizing and rescaling, to optimize feature extraction. The DenseNet-CNN model, strengthened by data fusion and edge computing capabilities, excels in extracting and learning features from these CT scans, effectively distinguishing between healthy and cancerous lung tissues. The classification categories include Normal, Benign, and Malignant, with the latter further sub-categorized into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In controlled experiments, this approach outperformed existing state-of-the-art methods, achieving an impressive accuracy of 99%. This indicates its potential as a powerful tool in the early detection and classification of lung cancer, a significant advancement in medical imaging and diagnostic technology.
Multi-sector stakeholder consensus on tackling the complex health and social needs of the growing population of people leaving prison in older age
Authors: Hwang Ye In , Hampton Stephen , Withall Adrienne Lee , Snoyman Phillip , Forsyth Katrina , Butler Tony
Published: April 2024

Background

As populations age globally, cooperation across multi-sector stakeholders is increasingly important to service older persons, particularly those with high and complex health and social needs. One such population is older people entering society after a period of incarceration in prison. The ‘ageing epidemic’ in prisons worldwide has caught the attention of researchers, governments and community organisations, who identify challenges in servicing this group as they re-enter the community. Challenges lie across multiple sectors, with inadequate support leading to dire consequences for public health, social welfare and recidivism. This is the first study to bring together multi-sector stakeholders from Australia to form recommendations for improving health and social outcomes for older people re-entering community after imprisonment.

Results

A modified nominal group technique was used to produce recommendations from N = 15 key stakeholders across prison health, corrections, research, advocacy, aged care, community services, via online workshops. The importance and priority of these recommendations was validated by a broader sample of N = 44 stakeholders, using an online survey. Thirty-six recommendations for improving outcomes for this population were strongly supported. The key issues underlying the recommendations included: improved multi-stakeholder systems and services, targeted release preparation and practices that ensure continuity of care, advocacy-focused initiatives in the community, and extended funding for effective programs.

Conclusions

There is consensus across stakeholders on ways forward, with intervention and policy updates required at the individual, systems and community levels. These recommendations entail two important findings about this population: (1) They are a high-needs, unique, and underserved group at risk of significant health and social inequity in the community, (2) Multi-sector stakeholder cooperation will be crucial to service this growing group.
Scoping review of military veterans involved in the criminal legal system and their health and healthcare: 5-year update and map to the Veterans-Sequential Intercept Model
Authors: Singh Kreeti , Timko Christine , Yu Mengfei , Taylor Emmeline , Blue-Howells Jessica , Finlay Andrea K.
Published: April 2024

Background

A previous scoping review of legal-involved veterans’ health and healthcare (1947–2017) identified studies and their limitations. Given the influx of literature published recently, this study aimed to update the previous review and map articles to the Veterans-Sequential Intercept Model (V-SIM) – a conceptual model used by key partners, including Veterans Health Administration, veteran advocates, criminal justice practitioners, and local governments to identify intercept points in the criminal legal system where resources and programming can be provided. Developing an updated resource of literature is essential to inform current research, discover gaps, and highlight areas for future research.

Methods

A systematic search of 5 databases identified articles related to legal-involved veterans’ health and healthcare published between December 2017 through December 2022. The first and senior authors conducted abstract reviews, full-text reviews, and data extraction of study characteristics. Finally, each article was sorted by the various intercept points from the V-SIM.

Results

Of 903 potentially relevant articles, 107 peer-reviewed publications were included in this review, most related to mental health (66/107, 62%) and used an observational quantitative study design (95/107, 89%). Although most articles did not explicitly use the V-SIM to guide data collection, analyses, or interpretation, all could be mapped to this conceptual model. Half of the articles (54/107, 50%) collected data from intercept 5 (Community Corrections and Support Intercept) of the V-SIM. No articles gathered data from intercepts 0 (Community and Emergency Services Intercept), 1 (Law Enforcement Intercept), or 2 (Initial Detention and Court Hearings Intercept).

Conclusions

There were 107 articles published in the last five years compared to 190 articles published in 70 years covered in the last review, illustrating the growing interest in legal-involved veterans. The V-SIM is widely used by front-line providers and clinical leadership, but not by researchers to guide their work. By clearly tying their research to the V-SIM, researchers could generate results to help guide policy and practice at specific intercept points. Despite the large number of publications, research on prevention and early intervention for legal-involved veterans is lacking, indicating areas of great need for future studies.
Lung cancer cell-intrinsic IL-15 promotes cell migration and sensitizes murine lung tumors to anti-PD-L1 therapy
Authors: Hu Shaojie , Meng Kelin , Wang Tianlai , Qu Rirong , Wang Boyu , Xi Yu , Yu Taiyan , Yuan Zhiwei , Cai Zihao , Tian Yitao , Zeng Chenxi , Wang Xue , Zou Wenbin , Fu Xiangning , Li Lequn
Published: April 2024

Background

IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells.

Methods

Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay. NCG and C57BL/6 mouse models were used to evaluate the functions of IL-15 in vivo.

Results

Cancer cell-intrinsic IL-15 promoted cell motility and migration in vitro and metastasis in vivo via activation of the AKT-mTORC1 pathway; however, exogenous IL-15 inhibited cell motility and migration via suppression of the RhoA-MLC2 axis. Mechanistic analysis revealed that both the intracellular and extracellular IL-15-mediated effects required the expression of IL-15Rα by tumor cells. Detailed analyses revealed that the IL-2/IL-15Rβ and IL-2Rγ chains were undetected in the complex formed by intracellular IL-15 and IL-15Rα. However, when exogenous IL-15 engaged tumor cells, a complex containing the IL-15Rα, IL-2/IL-15Rβ, and IL-2Rγ chains was formed, indicating that the differential actions of intracellular and extracellular IL-15 on tumor cells might be caused by their distinctive modes of IL-15 receptor engagement. Using a Lewis lung carcinoma (LLC) metastasis model, we showed that although IL-15 overexpression facilitated the lung metastasis of LLC cells, IL-15-overexpressing LLC tumors were more sensitive to anti-PD-L1 therapy than were IL-15-wild-type LLC tumors via an enhanced antitumor immune response, as evidenced by their increased CD8+ T-cell infiltration compared to that of their counterparts.

Conclusions

Cancer cell-intrinsic IL-15 and exogenous IL-15 differentially regulate cell motility and migration. Thus, cancer cell-intrinsic IL-15 acts as a double-edged sword in tumor progression. Additionally, high levels of IL-15 expressed by tumor cells might improve the responsiveness of tumors to immunotherapies.
Systematic review on the impacts of agricultural interventions on food security and nutrition in complex humanitarian emergency settings
Authors: Al Daccache Melodie , Abi Zeid Berthe , Hojeij Leila , Baliki Ghassan , Brück Tilman , Ghattas Hala
Published: April 2024

Complex humanitarian emergencies are a main driver of food and nutritional insecurity. Agricultural interventions are key to improving nutrition and food security, and their positive impacts are well-documented in stable developing countries. However, it is unclear if their positive effects on food security hold in complex emergency settings, too. In this paper, we systematically review empirical articles that apply rigorous designs to assess the causal impacts of agricultural interventions on food security, nutrition, or health outcomes in complex humanitarian emergencies. We only find six articles matching these criteria, which have mixed results on dietary diversity and food security, and little evidence on child nutrition. Our review underscores the need for more rigorous research on the impacts of agricultural interventions in complex humanitarian emergency settings.
Minimum acceptable diet and associated factors among 6–23 months children in rural households with irrigated users and non-irrigated users in Ethiopia: a comparative cross-sectional study
Authors: Mengistu Welelaw , Birhanu Dereje , Seid Omer
Published: April 2024

Introduction

Poor quality of complementary foods is a key contributor to undernutrition even with optimal breastfeeding. Minimum Acceptable Diet (MAD) has tremendous health and nutrition benefits but only 12% of Ethiopian children’s feeding practices meet its standards. The Ethiopian government has recently increased efforts to expand nutrition-sensitive irrigation to improve child nutrition. However, the impact that irrigation has brought on the minimum acceptable diet practice of children below two years has not yet been studied. The aim of this study was to compare the magnitude of MAD practice and associated factors among children aged 6–23 months in households with irrigated users and non-users of North Mecha district, Ethiopia.

Methods

A community-based comparative cross-sectional study was employed among 824 mother-child pairs. For infant and young child feeding practices, the data collection tools were adapted from the World Health Organization’s standardized questionnaire developed in 2010. X2 test was used to compare the MAD practices of irrigated users’ and non-irrigated users. Bivariate and multivariable logistic regression analyses were performed to see the predictor variables. p-value < 0.05 was taken to declare statistical significance.

Results

The present study showed that the MAD practice of under two children in irrigated users is significantly higher than non-users (X2 = 13.91, P <.001). Maternal involvement in decision-making [AOR = 4.37, 95% CI: (2.05,9.33)], initiation of breastfeeding [AOR = 5.29, 95% CI: (2.393,11.672)], and history of illness [AOR = 4.10, 95%CI: (1.48,11.38)] were independent predictors for MAD practice among irrigated users. Whereas, maternal involvement in decision making [AOR = 4.71, 95% CI: ( 2.28, 9.75)], place of delivery [AOR = 2.51, 95% CI: ( 1.14, 5.55)], postnatal care (PNC) follow-up [AOR = 3.01, 95%CI: (1.57, 5.77)] and growth monitoring and promotion (GMP) service utilization [AOR = 4.64, 95% CI: (2.40, 8.95)] were the independent predictors among the non-users.

Conclusion

MAD practice was much higher in irrigated users than in non-irrigated users. Involvement in a decision, place of delivery, PNC, and GMP are independent predictors of MAD in children from non-irrigated households. The study suggested that expanding access to irrigation to households may be the best approach to improve child nutrition.
Nonbacterial thrombotic endocarditis of mitral valve associated with a lymphoproliferative malignancy: case report and literature review
Authors: Duarte Fabiana , Barradas Maria Inês , Dias Ana Raquel , Faria Carlos , Machado Carina , Pavão Carolina
Published: April 2024

Background

Non-bacterial thrombotic endocarditis (NBTE) is a rare condition marked by sterile vegetations on cardiac valves, often linked to rheumatologic diseases, autoimmune disorders, and advanced solid malignancies. An early diagnosis and treatment of the associated clinical condition are mandatory, although they do not usually eliminate valvular vegetations, making anticoagulation essential to prevent embolic events. Despite variability, the prognosis of NBTE is usually unfavorable due to recurrent embolic events and the severity of the primary condition, typically advanced cancer.

Case presentation

We present a case of a 57 years-old male who presented to the emergency department with a 5-day history of painful bilateral digital edema and color change episodes (from pallor to cyanosis). Physical examination revealed erythrocyanosis in the distal extremities, prompting consideration of secondary Raynaud syndrome.

Despite medical therapy, progressive digital ischemia led to multiple finger amputations. During etiological investigation, anticoagulation tests and autoimmune analysis yielded negative results. A transesophageal echocardiogram was performed, revealing an irregular hyperechogenic mass on the anterior leaflet of the mitral valve without valve dysfunction, and a thoracic computed tomography scan with contrast showed an enlarged right paratracheal lymph node. Histopathological analysis from a transthoracic needle biopsy of the paratracheal lymph node revealed diffuse large B-cell lymphoma. The patient underwent aggressive R-CHOP chemotherapy, achieving a favorable complete response.

Conclusion

This is a particular case involving the occurrence of NBTE and Raynaud phenomenon as the initial paraneoplastic manifestations in a previously healthy young man. Reports of NBTE associated with lymphoproliferative conditions are quite rare, with fewer than ten cases described in the literature. To our knowledge, this is the first case of NBTE specifically associated with diffuse large B-cell lymphoma.
Patient-specific implants made of 3D printed bioresorbable polymers at the point-of-care: material, technology, and scope of surgical application
Authors: Maintz Michaela , Tourbier Céline , de Wild Michael , Cattin Philippe C. , Beyer Michel , Seiler Daniel , Honigmann Philipp , Sharma Neha , Thieringer Florian M.
Published: April 2024

Background

Bioresorbable patient-specific additive-manufactured bone grafts, meshes, and plates are emerging as a promising alternative that can overcome the challenges associated with conventional off-the-shelf implants. The fabrication of patient-specific implants (PSIs) directly at the point-of-care (POC), such as hospitals, clinics, and surgical centers, allows for more flexible, faster, and more efficient processes, reducing the need for outsourcing to external manufacturers. We want to emphasize the potential advantages of producing bioresorbable polymer implants for cranio-maxillofacial surgery at the POC by highlighting its surgical applications, benefits, and limitations.

Methods

This study describes the workflow of designing and fabricating degradable polymeric PSIs using three-dimensional (3D) printing technology. The cortical bone was segmented from the patient’s computed tomography data using Materialise Mimics software, and the PSIs were designed created using Geomagic Freeform and nTopology software. The implants were finally printed via Arburg Plastic Freeforming (APF) of medical-grade poly (L-lactide-co-D, L-lactide) with 30% β-tricalcium phosphate and evaluated for fit.

Results

3D printed implants using APF technology showed surfaces with highly uniform and well-connected droplets with minimal gap formation between the printed paths. For the plates and meshes, a wall thickness down to 0.8 mm could be achieved. In this study, we successfully printed plates for osteosynthesis, implants for orbital floor fractures, meshes for alveolar bone regeneration, and bone scaffolds with interconnected channels.

Conclusions

This study shows the feasibility of using 3D printing to create degradable polymeric PSIs seamlessly integrated into virtual surgical planning workflows. Implementing POC 3D printing of biodegradable PSI can potentially improve therapeutic outcomes, but regulatory compliance must be addressed.
Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments
Authors: Tabberer Maggie , Williamson Nicola , Tatlock Sophi , Gater Adam , Grimes Rebecca , Akinseye Chika , Neil David , Mahon-Smith Aoife , Nelsen Linda
Published: April 2024

Background

Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients’ health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient’s functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited.

Methods

This two-stage qualitative study used semi-structured interviews in patients aged 45–80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30–80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction.

Results

In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results.

Conclusion

The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies.

Trial number

GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473.
Type 1 diabetes mellitus: retrospect and prospect
Authors: Addissouky Tamer A. , Ali Majeed M. A. , El Sayed Ibrahim El Tantawy , Wang Yuliang
Published: April 2024

Background

Type 1 diabetes (T1D) is an autoimmune disease leading to destruction of insulin-producing pancreatic beta cells. Both genetic and environmental factors contribute to pathogenesis. The incidence of T1D is increasing worldwide, with significant geographic and ethnic variations. Patients present with symptoms of hyperglycemia and diabetes complications.

Main body

In T1D, autoreactive T cells and autoantibodies destroy beta cells, causing insulin deficiency. Exogenous insulin therapy is essential but cannot replicate normal physiology. Management requires intensive lifestyle education on diet, exercise, glucose monitoring and avoiding complications, in addition to insulin. Novel therapies like immunotherapy, cell transplantation, artificial pancreas devices and AI algorithms aim to improve care. Strategies for reversing T1D involve combination immunotherapies to block autoimmunity and regenerate beta cells via stem cells or xenotransplantation.

Conclusion

While type 1 diabetes remains challenging, ongoing research provides hope. Elucidating individualized disease mechanisms and translating findings into precision prevention and treatment approaches are critical to improving long-term outcomes. Innovative and multi-targeted therapies may fundamentally change the trajectory of T1D.
New recommendations on cerebral venous and dural sinus thrombosis from the German consensus-based (S2k) guideline
Authors: Weimar C , Beyer-Westendorf J , Bohmann FO , Hahn G , Halimeh S , Holzhauer S , Kalka C , Knoflach M , Koennecke H-C , Masuhr F , Mono M-L , Nowak-Göttl U , Scherret E , Schlamann M , Linnemann B
Published: April 2024

Over the last years, new evidence has accumulated on multiple aspects of diagnosis and management of cerebral venous and dural sinus thrombosis (CVT) including identification of new risk factors, studies on interventional treatment as well as treatment with direct oral anticoagulants. Based on the GRADE questions of the European Stroke Organization guideline on this topic, the new German guideline on CVT is a consensus between expert representatives of Austria, Germany and Switzerland. New recommendations include:

• CVT occurring in the first weeks after SARS-CoV-2 vaccination with vector vaccines may be associated with severe thrombocytopenia, indicating the presence of a prothrombotic immunogenic cause (Vaccine-induced immune thrombotic thrombocytopenia; VITT).

• D-dimer testing to rule out CVT cannot be recommended and should therefore not be routinely performed.

• Thrombophilia screening is not generally recommended in patients with CVT. It should be considered in young patients, in spontaneous CVT, in recurrent thrombosis and/or in case of a positive family history of venous thromboembolism, and if a change in therapy results from a positive finding.

• Patients with CVT should preferably be treated with low molecular weight heparine (LMWH) instead of unfractionated heparine in the acute phase.

• On an individual basis, endovascular recanalization in a neurointerventional center may be considered for patients who deteriorate under adequate anticoagulation.

• Despite the overall low level of evidence, surgical decompression should be performed in patients with CVT, parenchymal lesions (congestive edema and/or hemorrhage) and impending incarceration to prevent death.

• Following the acute phase, oral anticoagulation with direct oral anticoagulants instead of vitamin K antagonists should be given for 3 to 12 months to enhance recanalization and prevent recurrent CVT as well as extracerebral venous thrombosis.

• Women with previous CVT in connection with the use of combined hormonal contraceptives or pregnancy shall refrain from continuing or restarting contraception with oestrogen–progestagen combinations due to an increased risk of recurrence if anticoagulation is no longer used.

• Women with previous CVT and without contraindications should receive LMWH prophylaxis during pregnancy and for at least 6 weeks post partum.

Although the level of evidence supporting these recommendations is mostly low, evidence from deep venous thrombosis as well as current clinical experience can justify the new recommendations.

This article is an abridged translation of the German guideline, which is available online.
Role of magnetic resonance imaging (MRI) in liver iron quantification in thalassemic (thalassemia major) patients
Authors: Seema Rohilla , Singh Chadha Kawaljeet , Anjali Verma , Singh Gill Paramjeet , Alka Yadav , Deepak Singla
Published: April 2024

Background

Iron overload is a major problem in beta thalassemia patients due to repeated blood transfusions. The liver is the first organ to be loaded with iron. An accurate assessment of iron overload is necessary for managing iron chelation therapy in such patients. Iron quantification by MRI scores over liver biopsy due to its non-invasive nature.

Methods

Fifty-one patients with thalassemia major were subjected to 3.0-T MRI. Multiecho T2* sequence was used to cover the entire liver. Region of interest (ROI) was placed in three areas with maximum signal change, and an average T2* value was obtained. Similarly, a single ROI was placed at the mid-interventricular septum in the heart, and T2* value was obtained. T2* values so obtained were converted to iron concentration with the help of a T2* iron concentration calculator. The liver iron values were correlated with serum ferritin value.

Results

There was a significant negative correlation between liver iron concentration (LIC) and T2* value of the liver (r =  − 0.895, p < 0.01) and between cardiac iron concentration (CIC) and T2* value of the heart (r =  − 0.959, p < 0.01). There was a slight positive correlation between LIC and serum ferritin (r = 0.642, p < 0.01) and no correlation between CIC and serum ferritin (r =  − 0.137, p = 0.354).

Conclusions

MRI is a useful tool to titrate the doses of chelating agents as it is accurate and non-invasive, does not involve radiation hazards and hence can be repeated as and when needed. Simultaneous assessment of cardiac iron overload is an added advantage of MRI.
Clinical Knowledge and Reasoning Abilities of AI Large Language Models in Anesthesiology: A Comparative Study on the American Board of Anesthesiology Examination
Authors: Angel Mirana C. , Rinehart Joseph B. , Cannesson Maxime P. , Baldi Pierre
Published: April 2024

BACKGROUND:

Over the past decade, artificial intelligence (AI) has expanded significantly with increased adoption across various industries, including medicine. Recently, AI-based large language models such as Generative Pretrained Transformer-3 (GPT-3), Bard, and Generative Pretrained Transformer-3 (GPT-4) have demonstrated remarkable language capabilities. While previous studies have explored their potential in general medical knowledge tasks, here we assess their clinical knowledge and reasoning abilities in a specialized medical context.

METHODS:

We studied and compared the performance of all 3 models on both the written and oral portions of the comprehensive and challenging American Board of Anesthesiology (ABA) examination, which evaluates candidates’ knowledge and competence in anesthesia practice.

RESULTS:

Our results reveal that only GPT-4 successfully passed the written examination, achieving an accuracy of 78% on the basic section and 80% on the advanced section. In comparison, the less recent or smaller GPT-3 and Bard models scored 58% and 47% on the basic examination, and 50% and 46% on the advanced examination, respectively. Consequently, only GPT-4 was evaluated in the oral examination, with examiners concluding that it had a reasonable possibility of passing the structured oral examination. Additionally, we observe that these models exhibit varying degrees of proficiency across distinct topics, which could serve as an indicator of the relative quality of information contained in the corresponding training datasets. This may also act as a predictor for determining which anesthesiology subspecialty is most likely to witness the earliest integration with AI.

CONCLUSIONS:

GPT-4 outperformed GPT-3 and Bard on both basic and advanced sections of the written ABA examination, and actual board examiners considered GPT-4 to have a reasonable possibility of passing the real oral examination; these models also exhibit varying degrees of proficiency across distinct topics.
Parent-Child Incest and the Culture of Marriage in Colonial Guatemala
Authors: Saffa Sarah N.
Published: April 2024

Utilizing criminal records from the secular courts, this article examines incidents of sexual relations between parents and their biological children or stepchildren—both of which were considered incestuous under Spanish law—to explore how marriage and the marital relationship could motivate or rationalize episodes of parent-child incest in colonial Guatemala. Examination of parent-child incest through this lens shows how sons and daughters could become entangled in the sexual and emotional lives of their parents, providing a more nuanced view of the lived experience of kinship in colonial Latin America. It also demonstrates how incestuous offenders and their peers could allude to the culture of marriage and the state of the conjugal bond to both subtly and explicitly diminish the incestuous aspects of a sexual encounter, rendering it more culturally intelligible in the process.
Stereoelectroencephalography Electrode Implantation for Inpatient Workup of Treatment-Resistant Depression
Authors: Starkweather Clara Kwon , Sugrue Leo P. , Cajigas Iahn , Speidel Benjamin , Krystal Andrew D. , Scangos Katherine , Chang Edward F.
Published: April 2024

BACKGROUND AND OBJECTIVES:

Treatment-resistant depression is a leading cause of disability. Our center's trial for neurosurgical intervention for treatment-resistant depression involves a staged workup for implantation of a personalized, closed-loop neuromodulation device for refractory depression. The first stage (“stage 1”) of workup involves implantation of 10 stereoelectroencephalography (SEEG) electrodes bilaterally into 5 anatomically defined brain regions and involves a specialized preoperative imaging and planning workup and a frame-based operating protocol.

METHODS:

We rely on diffusion tractography when planning stereotactic targets for 3 of 5 anatomic areas. We outline the rationale and fiber tracts that we focus on for targeting amygdala, ventral striatum and ventral capsule, and subgenual cingulate. We also outline frame-based stereotactic considerations for implantation of SEEG electrodes.

EXPECTED OUTCOMES:

Our method has allowed us to safely target all 5 brain areas in 3 of 3 trial participants in this ongoing study, with adequate fiber bundle contact in each of the 3 areas targeted using tractography. Furthermore, we ultimately used tractography data from our stage 1 workup to guide targeting near relevant fiber bundles for stage 2 (implantation of a responsive neuromodulation device). On completion of our data set, we will determine the overlap between volume of tissue activated for all electrodes and areas of interest defined by anatomy and tractography.

DISCUSSION:

Our protocol outlined for SEEG electrode implantation incorporates tractography and frame-based stereotaxy.
Influence of Preoperative Motor Score and Patient Comorbidities on Transcranial Motor-Evoked Potential Acquisition in Intracranial Surgery: A Retrospective Cohort Study
Authors: Chen Adrian C. , Shah Harshal A. , Vilaysom Sabena , Ryan Casey , Kruse Aaron , D’Amico Randy S. , Silverstein Justin W.
Published: April 2024

BACKGROUND AND OBJECTIVES:

Intraoperative neurophysiological monitoring plays a pivotal role in modern neurosurgery, aiding in real-time assessment of eloquent neural structures to mitigate iatrogenic neural injury. This study represents the largest retrospective series to date in monitoring corticospinal tract integrity during intracranial surgery with transcranial motor-evoked potentials (TCMEPs), focusing on the influence of demographic factors, comorbidities, and preoperative motor deficits on the reliability of intraoperative neurophysiological monitoring. While the impact of patient-specific factors affecting TCMEP monitoring in spine surgery is well-documented, similar insights for intracranial surgery are lacking.

METHODS:

A total of 420 craniotomy patients were retrospectively analyzed from electronic medical records from December 2017 to February 2023, excluding patients without preoperative Medical Research Council scores or medical histories. Using intrinsic hand muscles as a robust data set, 840 hand TCMEPs acquired during intracranial surgery were assessed. Demographic and clinical factors, including preoperative motor scores, were analyzed to identify associations with TCMEP acquisition and amplitude. Nonparametric statistics and multivariate regression analysis were employed.

RESULTS:

TCMEPs were successfully acquired in 734 (87.7%) patient hands, even in the presence of preoperative motor deficits in 13.9% of total patient hands. Preoperative motor scores did not predict the ability to acquire baseline TCMEPs (P = .6). Notably, older age (P < .001) and hypertension (P = .01) were independent predictors of lower TCMEP acquisition rates. Preoperative motor scores significantly influenced TCMEP amplitudes, with higher scores correlating with higher amplitudes (1771 [SD = 1550] eve vs 882 [SD = 856] μV, P < .0001). Older age (P < .001) and chronic kidney disease (P = .04) were also associated with reduced TCMEP amplitudes.

CONCLUSION:

Our investigation into TCMEPs during intracranial surgery demonstrated a notably high acquisition rate in hand muscles, irrespective of preoperative motor deficits. Preoperative motor scores reliably correlated with TCMEP amplitudes in a linear fashion while advanced age and renal disease emerged as independent predictors of lower TCMEP amplitudes.