bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of a three-component intervention supporting unemployed individuals with mental health issues in their job search and mental health recovery (3for1): study protocol of a non-randomized controlled study
Authors: Schlachter Svenja , Adam Sophia Helen , Baxendale Maximilian , Gantner Melanie , Gralla Maria , Junne Florian , Martus Peter , Mehler Miriam , Nischk Daniel , Pumptow Marina , Erschens Rebecca , Gündel Harald , Rüsch Nicolas , von Wietersheim Jörn
Published: November 2024

Background

There is a vicious cycle between unemployment and mental health issues. Unemployed individuals with mental health issues require individualized support at multiple levels in order to promote their mental health, and obtain and retain employment. The 3for1-intervention program aims to provide such support with three components (short-term psychotherapy, job coaching based on the Individual Placement and Support approach, and peer support). This study protocol outlines how the effectiveness of this three-component intervention program in terms of re-employment, mental health, and psychosocial outcomes will be evaluated.

Methods

The 3for1-intervention program will be evaluated with a non-randomized controlled trial design in a multi-center study. 500 eligible participants aged between 18 and 60 years from six job centers in Southern Germany will be allocated to a control group or an intervention group. Allocation is time-based, with the control group being recruited first, followed by recruitment of the intervention group. The control group will receive treatment as usual, whereas the intervention group will receive treatment as usual as well as access to the three intervention components over a period of 12 months. Assessment will be conducted at baseline (t0), and 12 (t1) and 18 (t3) months later. The primary outcome will be the proportion of participants who are in employment subject to social insurance contributions at t1. Differences between control and intervention group will be tested with logistic regression analysis, controlling for relevant covariates. Analyses of secondary outcomes will relate to group differences regarding re-employment, health and well-being, social integration, help-seeking, and self-stigma at t1 and t2, applying logistic regression analysis or analysis of covariance. Additionally, usage of health services will be measured to evaluate the intervention program’s cost effectiveness.

Discussion

The 3for1-intervention aims to improve employability and mental health outcomes of a vulnerable population with high need for assistance. Improvements for this population would benefit the German welfare state as well. This study could provide valuable insights into the feasibility, implementation, and sustainability of this individualized, multi-level support program within German job centers.

Trial registration

This trial is registered with the German Clinical Trials Register: DRKS00029002 (registered on 11 May 2022).
Chronic renal impairment predicts oncological outcomes in UTUC patients undergoing RNU
Authors: Wong Chris Ho-Ming , Liu Kang , Zhao Hongda , Sabuncu Kubilay , Horuz Rahim , Albayrak Selami , Pilar Maria del , Pes Laguna , Rosette Jean de la , Teoh Jeremy Yuen-Chun
Published: November 2024

Objective

This study aims to explore the relationship between pre-existing renal impairment and oncological outcomes in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU) using data from a multicentre international registry.

Patients and methods

Data on non-metastatic UTUC patients who underwent RNU were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry. Patients were categorised into normal pre-operative renal function and chronic renal impairment (CKD) groups, with CKD defined as an estimated glomerular filtration rate below 60 mL/kg/1.73 m². Kaplan–Meier survival analysis was employed to investigate disease-free survival (DFS) and overall survival (OS). Multivariable Cox regression analysis was conducted to identify confounding variables.

Results

A total of 1393 patients diagnosed with UTUC who underwent RNU between 2014 and 2019 were analysed. 875 patients (62.4%) had normal renal function, whilst 528 patients (37.6%) had CKD prior to RNU. The two groups had similar proportions of bladder cancer history, comparable cardiovascular comorbidity, similar tumour stage, and comparable proportions receiving laparoscopic or robotic-assisted RNU. In multivariable cox regression analysis, CKD was found to be associated with inferior DFS (HR = 1.419; 95%CI = 1.060–1.898; p = 0.019). Upon multivariable analysis, pre-existing renal impairment and higher T stage (HR = 4.613; 95%CI = 1.829–4.712; p < 0.001) and the use of adjuvant chemotherapy (HR = 1.858; 95%CI = 1.229–2.807; p = 0.003) were also found to associate with worse DFS. Significant cardiovascular disease and higher T stage were associated with worse OS. Existing renal impairment at baseline did not have any significant associated with OS.

Conclusion

In this multicentre registry, preoperative chronic renal impairment was identified as an independent predictor of inferior DFS in patients undergoing RNU for non-metastatic UTUC. Preoperative CKD could serve as a clinical predictor of poorer oncological outcomes.
Extracts ofHylotelephiumerythrostictum (miq.) H. Ohba ameliorate intestinal injury by scavenging ROS and inhibiting multiple signaling pathways in Drosophila
Authors: Kim Hyonil , Yi Xinyu , Xue Hongmei , Yue Guanhua , Zhu Jiahua , Eh Tongju , Wang Sihong , Jin Li Hua
Published: November 2024

Background

The intestinal epithelial barrier is the first line of defense against pathogens and noxious substances entering the body from the outside world. Through proliferation and differentiation, intestinal stem cells play vital roles in tissue regeneration, repair, and the maintenance of intestinal homeostasis. Inflammatory bowel disease (IBD) is caused by the disruption of intestinal homeostasis through the invasion of toxic compounds and pathogenic microorganisms. Hylotelephium erythrostictum (Miq.) H. Ohba (H. erythrostictum) is a plant with diverse pharmacological properties, including antioxidant, anti-inflammatory, antidiabetic, and antirheumatic properties. However, the roles of H. erythrostictum and its bioactive compounds in the treatment of intestinal injury are unknown.

Methods

We examined the protective effects of H. erythrostictum water extract (HEWE) and H. erythrostictum butanol extract (HEBE) on Drosophila intestinal injury caused by dextran sodium sulfate (DSS) or Erwinia carotovoracarotovora 15 (Ecc15).

Results

Our findings demonstrated that both HEWE and HEBE significantly prolonged the lifespan of flies fed toxic compounds, reduced cell mortality, and maintained intestinal integrity and gut acid‒base homeostasis. Furthermore, both HEWE and HEBE eliminated DSS-induced ROS accumulation, alleviated the increases in antimicrobial peptides(AMPs) and intestinal lipid droplets caused by Ecc15 infection, and prevented excessive ISC proliferation and differentiation by inhibiting the JNK, EGFR, and JAK/STAT pathways. In addition, they reversed the significant changes in the proportions of the gut microbiota induced by DSS. The bioactive compounds contained in H. erythrostictum extracts have sufficient potential for use as natural therapeutic agents for the treatment of IBD in humans.

Conclusion

Our results suggest that HEWE and HEBE are highly effective in reducing intestinal inflammation and thus have the potential to be viable therapeutic agents for the treatment of gut inflammation.

Clinical trial number

Not applicable.
“How can we help you?”: results of a scoping review on the perceived needs of people living with chronic pain regarding physiotherapy
Authors: Gervais-Hupé Jonathan , Filleul Arthur , Perreault Kadija , Gaboury Isabelle , Wideman Timothy H. , Charbonneau Céline , Loukili Fatiha , Beauvais Romane , Campeau Marc-Antoine , Jacob Gevrey , Lasnier Noémie , Hudon Anne
Published: November 2024

Background

Physiotherapy is effective to reduce pain and improve the quality of life of people living with chronic pain. To offer high-quality physiotherapy services, these services must be patient-centred and respond to patients’ needs. However, few studies seem to target patients’ perceived needs, whereas more studies tend to focus on needs assessed by healthcare experts, which are not always in line with patients’ perceived needs. In addition, people living with chronic pain are often faced with several health inequities and may have varied perceived needs depending on their personal conditions. To offer services that truly meet patients’ needs, it is therefore crucial to understand these needs. This scoping review aims to identify and map the perceived needs of people living with chronic pain towards physiotherapy services.

Methods

To conduct this review, we followed the six stages framework proposed by Arksey and O’Malley. We searched four databases (Medline, Embase, CINHAL and APA PsycINFO) as well as the grey literature. We included all studies describing the needs, demands, preferences or expectations of adults living with chronic pain towards physiotherapy. We then performed an inductive thematic analysis of the results and discussion sections of these studies to identify the perceived needs. Once those needs were identified, we mapped them into the seven dimensions of the patient-centred healthcare delivery framework.

Results

Our review included 96 studies. Various perceived needs were identified through the thematic analysis, such as the needs for an empathetic relationship; for a clear, adapted and supervised exercise program; and for personalized treatment. Our mapping into the patient-centred healthcare delivery framework showed that most studies reported needs associated with the dimensions of interpersonal care, individualized healthcare and professional care. Needs associated with the other dimensions of the framework (access; coordination and continuity; services and facilities; data and information) were less frequently mentioned.

Conclusions

The results of this review have enabled us to identify and better understand multiple needs perceived by people living with chronic pain regarding physiotherapy services. The perceived needs identified through this scoping review were mapped within the seven dimensions of the Patient-centred healthcare delivery framework.
Beyond Lux: methods for species and photoreceptor-specific quantification of ambient light for mammals
Authors: McDowell Richard J. , Didikoglu Altug , Woelders Tom , Gatt Mazie J. , Moffatt Finn , Notash Saba , Hut Roelof A. , Brown Timothy M. , Lucas Robert J.
Published: November 2024

Background

Light is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. Light is commonly measured in lux. However, this employs a spectral weighting function for human luminance and is not suitable for ‘non-visual’ effects of light or use across species. In humans, a photoreceptor-specific (α-opic) metrology system has been proposed as a more appropriate way of measuring light.

Results

Here we establish technology to allow this α-opic measurement approach to be readily extended across mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. We develop a high-throughput method to derive spectral sensitivities for recombinantly expressed mammalian opsins and use it to establish the spectral sensitivity of melanopsin from 13 non-human mammals. We further address the need for simple measurement strategies for species-specific α-opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware multichannel light sensor for ‘point and click’ measurement. We finally demonstrate that species-specific α-opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species.

Conclusions

Our study presents methods for measuring light in species-specific α-opic units that are superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.
Euphorbium compositum SN improves the innate defenses of the airway mucosal barrier network during rhinovirus infection
Authors: Rajput Charu , Ganjian Haleh , Muruganandam Ganesh , Weyer Kathrin , Dannenmaier Julia , Seilheimer Bernd , Sajjan Umadevi
Published: November 2024

Background

Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection.

Methods

Mucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined.

Results

ECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance.

Conclusions

ECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections.
The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy
Authors: Boneva Stefaniya K. , Wolf Julian , Jung Malte , Prinz Gabriele , Chui Toco Y. P. , Jauch Jacqueline , Drougard Anne , Pospisilik J. Andrew , Schlecht Anja , Bucher Felicitas , Rosen Richard B. , Agostini Hansjürgen , Schlunck Günther , Lange Clemens A. K.
Published: November 2024

Background

Despite great advances in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. While resident vitreous macrophages called hyalocytes have been implicated in the pathophysiology of vitreoretinal proliferative disease previously, little is known about their exact role in PDR. In this study, we address molecular and cellular alterations in the vitreous of PDR patients as a means towards assessing the potential contribution of hyalocytes to disease pathogenesis.

Results

A total of 55 patients were included in this study encompassing RNA-Sequencing analysis of hyalocytes isolated from the vitreous of PDR and control patients, multiplex immunoassay and ELISA analyses of vitreous samples from PDR and control patients, as well as isolation and immunohistochemical staining of cultured porcine hyalocytes. Transcriptional analysis revealed an enhanced inflammatory response of hyalocytes contributing to the cytokine pool within the vitreous of PDR patients by expressing interleukin-6, among others. Further, increased angiopoietin-2 expression indicated that hyalocytes from PDR patients undergo a proangiogenic shift and may thus mediate the formation of retinal neovascularizations, the hallmark of PDR. Finally, RNA-Sequencing revealed an upregulation of factors known from hemoglobin catabolism in hyalocytes from PDR patients. By immunohistochemistry, cultured porcine hyalocytes exposed to red blood cells were shown to engulf and phagocytose these, which reveals hyalocytes’ potential to dispose of erythrocytes. Thus, our data suggest a potential role for vitreous macrophages in erythrophagocytosis and, thereby, clearance of vitreous hemorrhage, a severe complication of PDR.

Conclusion

Our results strongly indicate a critical role for vitreous hyalocytes in key pathophysiological processes of proliferative diabetic retinopathy: inflammation, angiomodulation and erythrophagocytosis. Immunomodulation of hyalocytes may thus prove an essential novel therapeutic approach in diabetic vitreoretinal disease.
A rotenone organotypic whole hemisphere slice model of mitochondrial abnormalities in the neonatal brain
Authors: Butler Brendan , Renney Malcolm , Bennett Kristin , Charpentier Gisele , Nance Elizabeth
Published: November 2024

Mitochondrial abnormalities underscore a variety of neurologic injuries and diseases and are well-studied in adult populations. Clinical studies identify critical roles of mitochondria in a wide range of developmental brain injuries, but models that capture mitochondrial abnormalities in systems representative of the neonatal brain environment are lacking. Here, we develop an organotypic whole-hemisphere (OWH) brain slice model of mitochondrial dysfunction in the neonatal brain. We extended the utility of complex I inhibitor rotenone (ROT), canonically used in models of adult neurodegenerative diseases, to inflict mitochondrial damage in OWH slices from term-equivalent rats. We quantified whole-slice health over 6 days of exposure for a range of doses represented in ROT literature. We identified 50 nM ROT as a suitable exposure level for OWH slices to inflict injury without compromising viability. At the selected exposure level, we confirmed exposure- and time-dependent mitochondrial responses showing differences in mitochondrial fluorescence and nuclear localization using MitoTracker imaging in live OWH slices and dysregulated mitochondrial markers via RT-qPCR screening. We leveraged the regional structures present in OWH slices to quantify cell density and cell death in the cortex and the midbrain regions, observing higher susceptibilities to damage in the midbrain as a function of exposure and culture time. We supplemented these findings with analysis of microglia and mature neurons showing time-, region-, and exposure-dependent differences in microglial responses. We demonstrated changes in tissue microstructure as a function of region, culture time, and exposure level using live-video epifluorescence microscopy of extracellularly diffusing nanoparticle probes in live OWH slices. Our results highlight severity-, time-, and region-dependent responses and establish a complimentary model system of mitochondrial abnormalities for high-throughput or live-tissue experimental needs.
Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates
Authors: Lalagkas Panagiotis N. , Melamed Rachel D.
Published: November 2024

Background

Current effective breast cancer treatment options have severe side effects, highlighting a need for new therapies. Drug repurposing can accelerate improvements to care, as FDA-approved drugs have known safety and pharmacological profiles. Some drugs for other conditions, such as metformin, an antidiabetic, have been tested in clinical trials for repurposing for breast cancer. Here, we exploit the genetics of breast cancer and linked predisposing diseases to propose novel drug repurposing opportunities. We hypothesize that if a predisposing disease contributes to breast cancer pathology, identifying the pleiotropic genes related to the risk of cancer could prioritize drugs, among all drugs treating a predisposing disease. We aim to develop a method to not only prioritize drugs for repurposing, but also to highlight shared etiology explaining repurposing.

Methods

We compile breast cancer’s predisposing diseases from literature. For each predisposing disease, we use GWAS summary statistics data to identify genes in loci showing genetic correlation with breast cancer. Then, we use a network approach to link these shared genes to canonical pathways. Similarly, for all drugs treating the predisposing disease, we link their targets to pathways. In this manner, we are able to prioritize a list of drugs based on each predisposing disease, with each drug linked to a set of implicating pathways. Finally, we evaluate our recommendations against drugs currently under investigation for breast cancer.

Results

We identify 84 loci harboring mutations with positively correlated effects between breast cancer and its predisposing diseases; these contain 194 identified shared genes. Out of the 112 drugs indicated for the predisposing diseases, 74 drugs can be linked to shared genes via pathways (candidate drugs for repurposing). Fifteen out of these candidate drugs are already in advanced clinical trial phases or approved for breast cancer (OR = 9.28, p = 7.99e-03, one-sided Fisher’s exact test), highlighting the ability of our approach to identify likely successful candidate drugs for repurposing.

Conclusions

Our novel approach accelerates drug repurposing for breast cancer by leveraging shared genetics with its known predisposing diseases. The result provides 59 novel candidate drugs alongside biological insights supporting each recommendation.
Physics-informed two-tier neural network for non-linear model order reduction
Authors: Hong Yankun , Bansal Harshit , Veroy Karen
Published: November 2024

In recent years, machine learning (ML) has had a great impact in the area of non-intrusive, non-linear model order reduction (MOR). However, the offline training phase often still entails high computational costs since it requires numerous, expensive, full-order solutions as the training data. Furthermore, in state-of-the-art methods, neural networks trained by a small amount of training data cannot be expected to generalize sufficiently well, and the training phase often ignores the underlying physical information when it is applied with MOR. Moreover, state-of-the-art MOR techniques that ensure an efficient online stage, such as hyper reduction techniques, are either intrusive or entail high offline computational costs. To resolve these challenges, inspired by recent developments in physics-informed and physics-reinforced neural networks, we propose a non-intrusive, physics-informed, two-tier deep network (TTDN) method. The proposed network, in which the first tier achieves the regression of the unknown quantity of interest and the second tier rebuilds the physical constitutive law between the unknown quantities of interest and derived quantities, is trained using pretraining and semi-supervised learning strategies. To illustrate the efficiency of the proposed approach, we perform numerical experiments on challenging non-linear and non-affine problems, including multi-scale mechanics problems.
Reduction of oxidative damage caused by Fusarium falciforme and Fusarium foetens in schefflera plants using chitosan nanoparticles loaded with l-proline or indole butyric acid
Authors: Imara Doaa A. , Ghebrial Eman W. R. , EL-Abeid Sozan E. , Hussein Eman M. A. , Elsayed Mona I. E. , Yousef Rania S.
Published: November 2024

Background

Root rot, wilt diseases, and rooting processes have been the major factors that constrain schefflera production. This study focuses on the impact of innovative applications of eco-friendly materials like chitosan nanoparticles loaded with l-proline or indole butyric acid to replace traditional chemical fungicides in controlling root rot and wilt diseases, as well as the vegetative propagation success of leafy stem schefflera cuttings.

Results

Fusarium foeten (strain 1) and Fusarium falciforme (strains 2 and 4) were first identified as root rot and wilt pathogens of schefflera in Egypt based on morphological features and confirmed with molecular analyses. Fusarium foetens (strain 1) and F. falciforme (strain 2) have the most aggressive action, as the infection percentages significantly increased in the pathogenicity test. The disease incidence reached 38.88 and 44.44%, respectively, whereas the disease severity was 18.51 and 26.84%, respectively. Chitosan nanoparticles at a concentration of 25 mg/L were the most effective dose, leading to a significant reduction in disease incidence to 25.00%, disease severity to 4.17%, and playing a vital role in activating plant defense, which correlates well with improved growth characteristics. The novel strategy of L-proline loaded on chitosan nanoparticles (LP-CSNPs) application occupied the first rank at protective influence against root rot and wilt disease-induced oxidative stress, signaling a defensive function that was freelance verified. L-proline loaded on chitosan nanoparticles (LP-CSNPs) at 0.125–0.25 g/L had a significant impact on reducing the incidence and severity of root rot and wilt diseases, as well as improving photosynthetic pigments and free radical scavenging activities, which included strengthening plant defense and further validating the findings from the biochemical trait analysis. The TT biplot graph was an influential statistical tool to study the impacts of treatments on schefflera production and its attributes and to discover the interrelationships among them.

Conclusions

Applying LP-CSNPs is one of the best techniques to manage schefflera root rot and wilt diseases, since it can be utilized as a growth stimulator and defense activator with sustainable increased efficiency.

Graphical Abstract
The development of a C5.0 machine learning model in a limited data set to predict early mortality in patients with ARDS undergoing an initial session of prone positioning
Authors: Hannon David M. , Syed Jaffar David Abbas , McNicholas Bairbre , Madden Michael , Laffey John G.
Published: November 2024

Background

Acute Respiratory Distress Syndrome (ARDS) has a high morbidity and mortality. One therapy that can decrease mortality is ventilation in the prone position (PP). Patients undergoing PP are amongst the sickest, and there is a need for early identification of patients at particularly high risk of death. These patients may benefit from an in-depth review of treatment or consideration of rescue therapies. We report the development of a machine learning model trained to predict early mortality in patients undergoing prone positioning as part of the management of their ARDS.

Methods

Prospectively collected clinical data were analysed retrospectively from a single tertiary ICU. The records of patients who underwent an initial session of prone positioning whilst receiving invasive mechanical ventilation were identified (n = 131). The decision to perform prone positioning was based on the criteria in the PROSEVA study. A C5.0 classifier algorithm with adaptive boosting was trained on data gathered before, during, and after initial proning. Data was split between training (85% of data) and testing (15% of data). Hyperparameter tuning was achieved through a grid-search using a maximal entropy configuration. Predictions for 7-day mortality after initial proning session were made on the training and testing data.

Results

The model demonstrated good performance in predicting 7-day mortality (AUROC: 0.89 training, 0.78 testing). Seven variables were used for prediction. Sensitivity was 0.80 and specificity was 0.67 on the testing data set. Patients predicted to survive had 13.3% mortality, while those predicted to die had 66.67% mortality. Among patients in whom the model predicted patient would survive to day 7 based on their response, mortality at day 7 was 13.3%. Conversely, if the model predicted the patient would not survive to day 7, mortality was 66.67%.

Conclusions

This proof-of-concept study shows that with a limited data set, a C5.0 classifier can predict 7-day mortality from a number of variables, including the response to initial proning, and identify a cohort at significantly higher risk of death. This can help identify patients failing conventional therapies who may benefit from a thorough review of their management, including consideration of rescue treatments, such as extracorporeal membrane oxygenation.

This study shows the potential of a machine learning model to identify ARDS patients at high risk of early mortality following PP. This information can guide clinicians in tailoring treatment strategies and considering rescue therapies. Further validation in larger cohorts is needed.
Effectiveness and safety of mineralocorticoid receptor antagonists in heart failure patients with and without diabetes: a systematic review and meta-analysis
Authors: Adji Arga Setyo , Widjaja Jordan Steven , de Liyis Bryan Gervais
Published: November 2024

Background

Mineralocorticoid receptor antagonists (MRAs) have been shown to improve outcomes in various populations of heart failure (HF) patients. However, the impact of concomitant diseases, such as diabetes mellitus (DM), on these outcomes remains unclear. This meta-analysis aimed to evaluate the efficacy and safety of MRAs in heart failure patients with and without diabetes mellitus.

Methods

A systematic search was conducted on PubMed, Scopus, and Google Scholar databases up to April 30, 2024. Data analysis was performed using a random-effects model to account for variability across studies, and statistical analysis was carried out using Review Manager 5.4. Efficacy and safety parameters were evaluated in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.

Results

The meta-analysis included a total of 21,832 subjects from ten studies. The pooled results demonstrated that MRAs, compared to placebo, significantly reduced all-cause mortality in HF patients with and without DM (RR: 0.85; 95%CI 0.75–0.96; p = 0.009). A similar effect was observed in HF patients without DM (RR: 0.83; 95%CI 0.71–0.97; p = 0.02), while no significant effect was detected in the DM subgroup (RR: 0.87; 95%CI 0.69–1.11; p = 0.27). Both treatments had comparable effects on cardiovascular mortality in HF patients with and without DM (RR: 0.88; 95%CI 0.82–0.94; p = 0.0002), in HF patients with DM (RR: 0.90; 95%CI 0.81–1.01; p = 0.08), and in the non-DM subgroup (RR: 0.86; 95%CI 0.79–0.94; p = 0.0009). MRAs significantly reduced the risk of cardiovascular mortality in HF patients with and without DM (RR: 0.82; 95%CI 0.72–0.94; p = 0.005) and in HF patients with DM (RR: 0.79; 95%CI 0.63–0.98; p = 0.03), but no significant effect was observed in the non-DM subgroup (RR: 0.85; 95%CI 0.69–1.05; p = 0.13). Furthermore, compared to placebo, MRAs were associated with an increased risk of hyperkalemia (> 5.5 mEq/L) in HF patients with and without DM (RR: 1.63; 95%CI 1.18–2.24; p = 0.003), particularly in HF patients with DM (RR: 1.44; 95%CI 0.97–2.13; p = 0.07) and in the non-DM subgroup (RR: 1.87; 95%CI 1.34–2.61; p = 0.0002).

Conclusion

MRAs are effective in reducing all-cause mortality, cardiovascular death, and cardiovascular mortality in heart failure patients. However, the use of MRAs is associated with an increased risk of hyperkalemia, necessitating careful monitoring, particularly in patients with diabetes mellitus.
Application of electromagnetic method to seaward slope: Case study from Saemangeum Seawall in South Korea
Authors: Kang Hyeonwoo , Bang Minkyu , Seol Soon Jee , Lim Kyounghak , Yong Hwan-Ho
Published: November 2024

As the world’s dams and seawalls age, there has been increasing attention toward the safety of these structures and monitoring of their condition using various geophysical methods. However, assessing seaward slopes, which are directly impacted by waves and tides and a seawater-filled riprap stone deposit structure, has been challenging due to the highly conductive environment and the difficulty in installing contact equipment. This study examines the feasibility of using electromagnetic (EM) surveys to monitor seawall slopes by analyzing and interpreting multifrequency EM data measured across a two-year period along the seawall slope of the Saemangeum Seawall in South Korea, which is recognized as the world’s longest seawall. The repeatability of data measured at the same survey line across the two years substantiates the reliability of EM survey data. The field data are inverted using a 2.5D regularized Gauss-Newton method. The EM responses calculated from the inverted resistivity model closely mirror the field data. The inversion results consistently indicate the presence of an isolated conductive anomaly with seawater resistivity below the survey line on the seaward slope. This suggests scouring erosion by seawater and affirms the applicability of the EM surveys to seaward slope monitoring. In addition, the EM responses are affected significantly by sea level changes during the survey; these variations are quantified in this study. Thus, our results indicate the effectiveness of the EM method in monitoring the seaward slope to assess the safety of seawalls and provide a comprehensive overview of the entire data analysis and inversion processes, as a valuable reference for those using EM technology in their work.
Usage of the National Cancer Institute Cancer Research Data Commons by Researchers: A Scoping Review of the Literature
Authors: Chen Zhaoyi , Kim Erika , Davidsen Tanja , Barnholtz-Sloan Jill S.
Published: November 2024

PURPOSE

Over the past decade, significant surges in cancer data of all types have happened. To promote sharing and use of these rich data, the National Cancer Institute's Cancer Research Data Commons (CRDC) was developed as a cloud-based infrastructure that provides a large, comprehensive, and expanding collection of cancer data with tools for analysis. We conducted this scoping review of articles to provide an overview of how CRDC resources are being used by cancer researchers.

METHODS

A thorough literature search was conducted to identify all relevant publications. We included publications that directly cited CRDC resources to specifically examine the impact and contributions of CRDC by itself. We summarized the distributions and trends of how CRDC components were used by the research community and discussed current research gaps and future opportunities.

RESULTS

In terms of CRDC resources used by the research community, encouraging trends in utilization were observed, suggesting that CRDC has become an important building block for fostering a wide range of cancer research. We also noted a few areas where current applications are rather lacking and provided insights on how improvements can be made by CRDC and research community.

CONCLUSION

CRDC, as the foundation of a National Cancer Data Ecosystem, will continue empowering the research community to effectively leverage cancer-related data, uncover novel strategies, and address the needs of patients with cancer, ultimately combatting this disease more effectively.
Uncovering Hypercalcemia of Malignancy Following Parathyroidectomy for Hyperparathyroidism
Authors: Nessa Lutfor , Enabi Joud , Gonuguntla Samhitha , Modi Bosky , Faheem Maida , Reddy Anand
Published: November 2024

Hypercalcemia is a common complication of malignancy, often attributed to elevated PTH-related protein levels mimicking the effects of PTH and promoting bone resorption. We present the case of a 67-year-old Hispanic female with a history of hypertension, type 2 diabetes mellitus, hyperlipidemia, and chronic kidney disease, who initially underwent parathyroidectomy for suspected primary hyperparathyroidism resulting from persistent hypercalcemia. Despite surgery, the patient continued to experience hypercalcemia and was subsequently diagnosed with diffuse large B-cell lymphoma with hypercalcemia as a rare but life-threatening complication. This case highlights the importance of considering malignancy as a potential cause of hypercalcemia, particularly in the context of hematologic malignancies such as diffuse large B-cell lymphoma. Prompt recognition and management are crucial to prevent severe complications associated with hypercalcemia. A multidisciplinary approach involving oncologists, endocrinologists, and supportive care teams is essential for effective management in such cases.
Calcitriol-Mediated Hypercalcemia Due to Liver Metastases in a Patient With Primary Pancreatic Neuroendocrine Tumor
Authors: Wolf Katherine I , Crysler Oxana V , Fontana Robert , Saberi Sima
Published: November 2024

Hypercalcemia is most commonly associated with primary hyperparathyroidism or malignancy in the setting of elevated parathyroid hormone-related protein or bone metastases. Calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcemia is rare and typically associated with granulomatous conditions; however, other solid-organ etiologies have been reported. Here, we detail the case of a 62-year-old man with metastatic pancreatic neuroendocrine tumor (pNET) with hypercalcemia refractory to traditional bisphosphonate therapy in the setting of vastly elevated 1,25-dihydroxyvitamin D. Only after initiation of chemotherapy with capecitabine and temozolomide did his serum calcium consistently improve and 1,25-dihydroxyvitamin D begin to decrease. There are fewer than 5 reported cases of a pNET resulting in calcitriol-mediated hypercalcemia. Prompt initiation of treatment for the underlying condition can result in a significant improvement in serum calcium or 1,25-dihydroxyvitamin D. Multiple reports have also demonstrated success with high-dose steroid administration in patients with other solid-organ etiologies of calcitriol-mediated hypercalcemia, but this has not yet been reviewed in the pNET population.
Pro-Con Debate: Air or Saline for Loss-of-Resistance Technique of Interlaminar Epidural Access with Fluoroscopy-Guided Pain Medicine Procedures
Authors: Hao David , Bonner Kirk , Burnham Taylor , Stojanovic Milan P.
Published: November 2024

In this Pro-Con commentary article, the Pro side advocates that using the loss of resistance (LOR) to air technique for interlaminar epidural access is safe as the risk of pneumocephalus is exceptionally low. They note that case reports detailing complications typically utilize at least 1 mL of air, frequently exceeding this amount. Even a 1-mL dosage surpasses the requirement, particularly when fluoroscopy is applied in the context of chronic pain management. The proponents also suggest a modified technique, where a syringe containing a drop of saline or contrast acts as a visual cue, minimizing air injection into the epidural space to a negligible quantity. Moreover, they emphasize that air facilitates the identification of any fluid as an indicator of unintended intrathecal access.

The Con perspective argues against the utilization of air for epidural access and advocates for the use of LOR with saline instead. This stance is supported by evidence pointing to a greater occurrence of adverse events, such as postdural puncture headache (PDPH) and pneumocephalus, associated with LOR to air compared to LOR with saline. They also argue that saline’s physical properties enhance tactile feedback, potentially contributing to its increased safety.

Both saline and air have been used for many years for epidural access via the interlaminar approach. Although both are generally accepted in practice, neither has been formally established as the standard of care. It would benefit the medical community to further delineate the pros and cons of each medium, enabling practitioners to make more informed decisions. This Pro-Con debate will provide 2 perspectives (Table) on the evidence and rationales for the use of air or saline for the LOR technique in interlaminar epidural access with fluoroscopy.
The “Canopy Approach”: Case Series Using Immersive Virtual Reality for Bottom-Up Target-Based Preoperative Planning in Pediatric Neurosurgery
Authors: Lai Grace Y. , Phelps Ryan R.L. , Singhal Nilika S. , Sullivan Joseph E. , Numis Adam L. , Auguste Kurtis I.
Published: November 2024

BACKGROUND:

Virtual reality (VR) is increasingly used for trajectory planning in neurosurgery.

OBJECTIVE:

To describe a case series showing the application of immersive VR involving both “top-down” from skull to lesion and “bottom-up” from lesion to skull approaches for trajectory planning in pediatric neurosurgical patients.

METHODS:

We detail the preoperative and intraoperative application of VR and clinical courses of 5 children (aged 7-14 years) with anatomically challenging intraparenchymal lesions that posed operative risks to nearby vascular anatomy and fiber tracts. Preoperative planning consisted of standard presurgical evaluation with computed tomography and magnetic resonance imaging used to render 3-dimensional models that could be viewed and manipulated using desktop software and immersive VR headsets and hand controllers by the surgeon and family. Patient satisfaction was evaluated by survey. Surgical outcomes were degree of seizure control or extent of resection.

RESULTS:

Three patients underwent lesion resection and 2 laser ablation. Modifications to 2-dimensional and “top-down” VR trajectory plans were made after “bottom-up” navigation in all cases. All families reported that the VR enhanced their understanding of the procedure. There were no complications, and no patients suffered permanent neurological deficits postoperatively. Gross total resection was achieved in all lesional cases, and patients with epilepsy achieved seizure freedom at 2 years postoperatively.

CONCLUSION:

Immersive VR allows operative corridors to be virtually traveled and viewed from a “top-down” and “bottom-up” perspective, as if looking up from under a forest canopy of overlying anatomy, for optimal trajectory planning and improvement of family understanding in pediatric neurosurgery.
Time-Dosed Stereotactic Radiosurgery for the Treatment of Cerebral Arteriovenous Malformations: An Early Institution Experience and Case Series
Authors: Sethi Akal , Chee Keanu , Chatain Gregoire P. , Wittenberg Blake , Seinfeld Joshua , Milgrom Sarah , Kavanagh Brian , Breeze Robert
Published: November 2024

BACKGROUND AND OBJECTIVES:

Stereotactic radiosurgery (SRS) is an effective treatment modality used by neurosurgeons to treat cerebral arteriovenous malformations (AVMs), particularly for treating AVMs <10 cm3. Current strategies include single-staged, dose-staged, and volume-staged SRS, all of which demonstrate varying effectiveness for treating large-volume AVMs (>10 cm3). We introduce a novel refinement called time-dosed SRS for the treatment of large-volume AVMs or AVMs located in eloquent areas. This study aims to detail treatment parameters, outcomes, and complications associated with time-dosed SRS in our early experience study.

METHODS:

We retrospectively reviewed all patients treated using time-dosed SRS at our institution. Data, including AVM location, history of hemorrhage, history of intervention, AVM volume, Spetzler-Martin grade, presence of residual disease, and occurrence of postprocedural complications, were collected.

RESULTS:

Sixteen patients were included. The median total AVM volumes treated were 9.64 cm3 (0.92-46.2 cm3) and 13.2 cm3 (3.0-42.2 cm3) in adults and children, respectively. The median margin doses for adults and children at each of the 3 stages were 10 Gy, 10 Gy (8-10 Gy) and 9 Gy (8-10 Gy), and 10 Gy, 10 Gy (9-10 Gy), and 10 Gy (8-10 Gy), respectively. The median total dose delivered was 29 Gy (27-30 Gy) in adults and 30 Gy (28-30 Gy) in children. The median radiological follow-up length was 35 months (9-62 months) in adults and 31 months (4-72 months) in pediatric patients. Complete obliteration was confirmed by cerebral angiogram in 6 adult patients and 1 pediatric patient. One adult patient and 2 pediatric patients suffered radiation-related toxicity. No patients suffered postprocedural hemorrhage.

CONCLUSION:

Time-dosed SRS seems to be effective for treating large AVMs or those in highly eloquent areas, with a low rate of complications.
Psychological Characteristics of Patients Undergoing Awake Craniotomy With Dexmedetomidine: A Retrospective Analysis
Authors: Cassa Maddalena Irma , Orena Eleonora Francesca , Seveso Mirella , Acerbi Francesco , Izzo Mikael Gian Andrea , Gemma Marco
Published: November 2024

BACKGROUND AND OBJECTIVES:

Only few studies have investigated the psychological profile of patient candidates for awake craniotomy (AC). The aim of this study was to describe the multidisciplinary clinical protocol adopted in our hospital and to retrospectively explore differences in psychological characteristic of 51 patients, analyzing association with the tolerability of the procedure.

METHODS:

During the preoperative neuropsychological assessment, the Pain Anxiety Symptoms Scale was administered to assess pain-related anxiety. Clinical characteristics and anesthesiological management were retrospectively recollected. The AC procedure was classified as “optimal” or “suboptimal” based on administration of rescue sedative midazolam doses because of psychomotor agitation or emotional distress in excess with respect to our anesthesiological protocol.

RESULTS:

The awake procedure was considered optimal in 33 cases (64.7% of total sample). General anesthesia was never required in our patients. No significant differences between optimal and suboptimal groups were found. No single variable was significant as a predictor of outcome on the univariate analysis, and no multivariate predictive model was possible.

CONCLUSION:

Although in our experience the Pain Anxiety Symptoms Scale score was not useful in identifying candidates for AC procedures, our multidisciplinary approach provided good results with respect to the tolerability of AC surgery. However, more studies are required to identify psychological profiles and preoperative possible warning signs to find the best course of surgery for each patient.