bluuebunny/crossref_metadata_2025 huggingface dataset:
The Wounded Healer in Shared Traumatic Reality After the Seventh of October Attack: “That the Personal World and the Professional World are Shattered”
Authors: Cohen-Biton Liraz
Published: October 2024

In Shared Traumatic Reality (STR), therapists and patients face similar threats, leading to increased stress and blurred personal-professional boundaries for healthcare providers. It impacts everyone in the community, as witnessed in the southern region of Israel. The challenge for caregivers aiding displaced individuals was unique—providing therapy while caring for their children. STR poses challenges but also growth opportunities. Experiencing trauma firsthand offers insights, fostering professional and personal development. Despite the difficulties of handling loss and traumatic stories, this reality demands new coping mechanisms for healthcare providers to grow through adversity. Community involvement aids professional empowerment amidst STR, reinforcing therapists’ identification with patients. This new reality reveals remarkable resilience among those who endured tragedies, offering lessons in vicarious resilience. The concept of the wounded healer (WH) reflects how personal trauma can enhance therapeutic abilities by profoundly empathizing with patients’ pain. Navigating personal hardships is crucial to avoid projecting onto patients during therapy. The WH's identification with patient trauma strengthens the therapeutic bond, leading to better outcomes.
Voices of Thai Patients With Non-Communicable Diseases Towards Healthy and Ready Meal Products: A Mixed-Methods Research
Authors: Sooampon Sireerat , Sooampon Sutti
Published: October 2024

Introduction

Healthy diets reduce the risk of several non-communicable diseases (NCDs) from diabetes to heart disease and hypertension to cancer. Given their busy lifestyles, it is difficult for individuals to routinely prepare healthy food. Therefore, healthy and ready meal products have been developed and commercially launched in Thailand.

Objectives

Considering ready and healthy meals as an innovative product line in the Thai market, the aim of this study was to identify the factors that influence NCD patients to adopt this product innovation.

Methods

This study used a mixed-methods approach based on Roger's model of innovation adoption. Two hundred and twenty NCD patients completed a questionnaire regarding their expectations towards healthy meal products. In-depth interviews were conducted with 20 respondents to explore the underlying reasons behind their scoring decisions in the questionnaires.

Results

The findings revealed that the highest rated items were the expectation that healthy meals reduce the severity of disease, help avoid high-cholesterol food, and comprise a variety of meal choices. Instead of celebrity marketing and corporate branding, the patients preferred healthy meals that are recommended by health professionals and produced by university research teams. The qualitative findings also demonstrated that most patients welcomed healthy menus as a preventive treatment, but still have concerns regarding the availability and quality of the products.

Conclusion

This study reveals the expectations of prospective consumers, specifically NCD patients, towards healthy and ready meal products. It adds key information for food producers, health professionals, and policymakers to foster healthy food innovation, especially in the context of emerging economies like Thailand where healthy food choices are limited.
Seismic mitigation of porcelain cylindrical electrical equipment using synergistic concept with base isolation and tuned mass damper
Authors: Bai Wen , Zhu Wang , Moustafa Mohamed A. , Dai Junwu
Published: October 2024

Porcelain cylindrical electrical equipment (PCEEs), such as potential and current transformers, are critical components of electrical substations and essential to power supply networks. Nevertheless, previous strong earthquakes have rendered high vulnerability and poor performance of PCEE during seismic occurrences. To improve seismic performance of PCEE and alleviate adverse seismic impacts, an innovative synergistic mitigation method based on base isolation (BI) and tuned mass damper (TMD) was proposed and subsequently employed to PCEE. Combining BI with TMD allows for a greater utilization of each technology’s capabilities while also circumventing some of the limits of each. While TMD effectiveness is sensitive to input ground motion frequencies, BI could act as a filter to tune input frequency and help TMD fulfill better damping effectiveness. TMD could in return help BI achieve better stability under long-period dominant or pulse-like ground motions. The BI-TMD effectiveness and robustness were investigated using finite element modeling and nonlinear time history analysis. A comprehensive parametric study that considers variable PCEE frequencies, BI periods, TMD mass ratios, and TMD control frequencies was conducted. Results show that the proposed BI-TMD method can significantly enhance the effectiveness and robustness beyond BI single control in mitigating seismic responses of PCEE.
Epigenetic features support the diagnosis of B-cell prolymphocytic leukemia and identify 2 clinicobiological subtypes
Authors: Charalampopoulou Stella , Chapiro Elise , Nadeu Ferran , Zenz Thorsten , Beà Sílvia , Martínez-Farran Ares , Aymerich Marta , Rozman Maria , Roos-Weil Damien , Bernard Olivier , Susin Santos A. , Parker Helen , Walewska Renata , Oakes Christopher C. , Strefford Jonathan C. , Campo Elías , Matutes Estela , Duran-Ferrer Martí , Nguyen-Khac Florence , Martín-Subero José I.
Published: October 2024

The recognition of B-cell prolymphocytic leukemia (B-PLL) as a separate entity is controversial based on the current classification systems. Here, we analyzed the DNA methylome of a cohort of 20 B-PLL cases diagnosed according to the guidelines of the International Consensus Classification/Fourth revised edition of the World Health Organization Classification, and compared them with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and normal B-cell subpopulations. Unsupervised principal component analyses suggest that B-PLL is epigenetically distinct from CLL, MCL, and SMZL, which is further supported by robust differential methylation signatures in B-PLL. We also observe that B-PLL can be segregated into 2 epitypes with differential clinicobiological characteristics. B-PLL epitype 1 carries lower immunoglobulin heavy variable somatic hypermutation and a less profound germinal center–related DNA methylation imprint than epitype 2. Furthermore, epitype 1 is significantly enriched in mutations affecting MYC and SF3B1, and displays DNA hypomethylation and gene upregulation signatures enriched in MYC targets. Despite the low sample size, patients from epitype 1 have an inferior overall survival than those of epitype 2. This study provides relevant insights into the biology and differential diagnosis of B-PLL, and potentially identifies 2 subgroups with distinct biological and clinical features.
Detecting complex infections in trypanosomatids using whole genome sequencing
Authors: Reis-Cunha João Luís , Jeffares Daniel Charlton
Published: October 2024

Background

Trypanosomatid parasites are a group of protozoans that cause devastating diseases that disproportionately affect developing countries. These protozoans have developed several mechanisms for adaptation to survive in the mammalian host, such as extensive expansion of multigene families enrolled in host-parasite interaction, adaptation to invade and modulate host cells, and the presence of aneuploidy and polyploidy. Two mechanisms might result in “complex” isolates, with more than two haplotypes being present in a single sample: multiplicity of infections (MOI) and polyploidy. We have developed and validated a methodology to identify multiclonal infections and polyploidy using whole genome sequencing reads, based on fluctuations in allelic read depth in heterozygous positions, which can be easily implemented in experiments sequencing genomes from one sample to larger population surveys.

Results

The methodology estimates the complexity index (CI) of an isolate, and compares real samples with simulated clonal infections at individual and populational level, excluding regions with somy and gene copy number variation. It was primarily validated with simulated MOI and known polyploid isolates respectively from Leishmania and Trypanosoma cruzi. Then, the approach was used to assess the complexity of infection using genome wide SNP data from 497 trypanosomatid samples from four clades, L. donovani/L. infantum, L. braziliensis, T. cruzi and T. brucei providing an overview of multiclonal infection and polyploidy in these cultured parasites. We show that our method robustly detects complex infections in samples with at least 25x coverage, 100 heterozygous SNPs and where 5–10% of the reads correspond to the secondary clone. We find that relatively small proportions (≤ 7%) of cultured trypanosomatid isolates are complex.

Conclusions

The method can accurately identify polyploid isolates, and can identify multiclonal infections in scenarios with sufficient genome read coverage. We pack our method in a single R script that requires only a standard variant call format (VCF) file to run (https://github.com/jaumlrc/Complex-Infections). Our analyses indicate that multiclonality and polyploidy do occur in all clades, but not very frequently in cultured trypanosomatids. We caution that our estimates are lower bounds due to the limitations of current laboratory and bioinformatic methods.
HTS and scRNA-seq revealed that the location and RSS quality of the mammalian TRBV and TRBJ genes impact biased rearrangement
Authors: Wu Yingjie , Wu Fengli , Ma Qingqing , Li Jun , Ma Long , Zhou Hou , Gong Yadong , Yao Xinsheng
Published: October 2024

The quality of Recombination signal sequences (RSSs), location, and genetics of mammalian V, D, and J genes synergistically affect the recombination frequency of genes; however, the specific regulatory mechanism and efficiency have not been elucidated. By taking advantage of single-cell RNA-sequencing (scRNA-seq) and high-throughput sequencing (HTS) to investigate V(D)J rearrangement characteristics in the CDR3 repertoire, we found that the distal and proximal V genes (or J genes) “to D” gene were involved in rearrangement significantly more frequently than the middle V genes (or J genes) in the TRB locus among various species, including Primates (human and rhesus monkey), Rodentia (BALB/c, C57BL/6, and Kunming mice), Artiodactyla (buffalo), and Chiroptera (Rhinolophus affinis). The RSS quality of the V and J genes affected their frequency in rearrangement to varying degrees, especially when the V-RSSs with recombination signal information content (RIC) score < -45 significantly reduced the recombination frequency of the V gene. The V and J genes that were “away from D” had the dual advantages of recombinant structural accessibility and relatively high-quality RSSs, which promoted their preferential utilization in rearrangement. The quality of J-RSSs formed during mammalian evolution was apparently greater than that of V-RSSs, and the D-J distance was obviously shorter than that of V-D, which may be one of the reasons for guaranteeing that the “D-to-J preceding V-to-DJ rule” occurred when rearranged. This study provides a novel perspective on the mechanism and efficiency of V-D-J rearrangement in the mammalian TRB locus, as well as the biased utilization characteristics and application of V and J genes in the initial CDR3 repertoire.
Revisits and frailty in older patients in the emergency department - a prospective observational multicenter study
Authors: Johansson Helena , Fahlander Sara , Hörlin Erika , Henricson Joakim , Munir Ehrlington Samia , Wretborn Jens , Wilhelms Daniel
Published: October 2024

Background

An increased number of revisits may signal that the immediate medical needs of patients seeking care at Emergency Departments (EDs) are not being met. The prevalence and characteristics of revisits to the EDs in Sweden among older patients, and its association to frailty, are unknown. We aimed to investigate the prevalence of ED revisits among patients over 65 years of age, living with or without frailty, and its association with rate of admission, and mortality; in the Swedish ED setting.

Methods

This was a prospective, multicentre study of patients over 65 years of age with an index visit to one of three Swedish EDs during May-Nov 2021. Frailty was assessed in conjunction with standard triage, using the 9-level Clinical Frailty Scale (CFS) with a CFS score of 5 to 8 as cut-off for identifying frailty. For all patients who made a revisit within 90 days of their index visit, we collected information about the revisit, admission, and mortality.

Results

A total of 1835 patients made an index visit which were included, and out of those, 595 patients made a revisit within 90 days of the index visit. Patients living with frailty (CFS 5 to 8) were more likely to make a revisit to the ED at 8 to 30 days (17% vs. 11%, diff 6%, 95% CI 2–10%, p < 0.001) and at 31 to 90 days (19% vs. 12%, diff 7%, 95% CI 3–10%, p < 0.001) and be admitted to in-hospital care during their revisit (57% vs. 47%, diff 10%, 95% CI, 1–18%, p < 0.05), compared to patients living without frailty. Results also show that patients living with frailty had a higher overall mortality rate (17% vs. 5%, diff 12%, 95% CI 7–18%, p < 0.001). However, among patients living without frailty, making a revisit slightly increased the mortality rate compared to those who did not (5% vs. 2%, diff 3%, 95% CI 1–10%, p < 0.05).

Conclusions

Patients living with frailty make more revisits, are more often admitted to in-hospital care, and have a higher overall mortality rate than patients not living with frailty. Frailty, assessed with the CFS may be a simple and useful indicator of increased risk of adverse events, including revisits, in the ED.
Health care utilization at the end of life in Parkinson’s disease: a population-based register study
Authors: Leavy Breiffni , Åkesson Elisabet , Lökk Johan , Schultz Torbjörn , Strang Peter , Franzén Erika
Published: October 2024

Background

Knowledge of health care utilization at the end of life in Parkinson’s disease (PD) is sparse. This study aims to investigate end of life health care utilization, characterized by emergency room (ER) visits, receipt of specialized palliative care (SPC), and acute hospital deaths in a Swedish population-based PD cohort.

Methods

We conducted a retrospective cohort study on deceased patients (≥ 18 years) with a PD diagnosis during their last year of life (n = 922), based on health care-provider data from Region Stockholm´s data warehouse, for the study period 2015–2021. Univariable and multivariable logistic regression analyses tested associations and adjusted Odds ratios (aORs) were calculated.

Results

During the last month of life, approx. half of the cohort had emergency room (ER) visits and risk of frailty (measured by Hospital Frailty Risk Score) significantly predicted these visits (aOR, 3.90 (2.75–5.55)). In total, 120 people (13%) received SPC during their last three months of life, which positively associated with risk for frailty, (aOR, 2.65 (1.43–4.94, p = 0.002). In total, 284 people (31%) died in acute hospital settings. Among community-dwellers, male gender and frailty were strongly associated with acute hospital deaths (aOR, 1.90 (1.15–3.13, p = 0.01) and 3.70 (1.96–6.98, p < 0.0001)).

Conclusions

Rates of ER visits at end of life and hospital deaths were relatively high in this population-based cohort. Considering a high disease burden, referral to SPC at end of life was relatively low. Sex-specific disparities in health care utilization are apparent. Identifying people with high risk for frailty could assist the planning of optimal end-of-life care for people with PD.
Predicting clinical events characterizing the progression of amyotrophic lateral sclerosis via machine learning approaches using routine visits data: a feasibility study
Authors: Guazzo Alessandro , Atzeni Michele , Idi Elena , Trescato Isotta , Tavazzi Erica , Longato Enrico , Manera Umberto , Chió Adriano , Gromicho Marta , Alves Inês , de Carvalho Mamede , Vettoretti Martina , Di Camillo Barbara
Published: October 2024

Background

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in death within a short time span (3-5 years). One of the major challenges in treating ALS is its highly heterogeneous disease progression and the lack of effective prognostic tools to forecast it. The main aim of this study was, then, to test the feasibility of predicting relevant clinical outcomes that characterize the progression of ALS with a two-year prediction horizon via artificial intelligence techniques using routine visits data.

Methods

Three classification problems were considered: predicting death (binary problem), predicting death or percutaneous endoscopic gastrostomy (PEG) (multiclass problem), and predicting death or non-invasive ventilation (NIV) (multiclass problem). Two supervised learning models, a logistic regression (LR) and a deep learning multilayer perceptron (MLP), were trained ensuring technical robustness and reproducibility. Moreover, to provide insights into model explainability and result interpretability, model coefficients for LR and Shapley values for both LR and MLP were considered to characterize the relationship between each variable and the outcome.

Results

On the one hand, predicting death was successful as both models yielded F1 scores and accuracy well above 0.7. The model explainability analysis performed for this outcome allowed for the understanding of how different methodological approaches consider the input variables when performing the prediction. On the other hand, predicting death alongside PEG or NIV proved to be much more challenging (F1 scores and accuracy in the 0.4-0.6 interval).

Conclusions

In conclusion, predicting death due to ALS proved to be feasible. However, predicting PEG or NIV in a multiclass fashion proved to be unfeasible with these data, regardless of the complexity of the methodological approach. The observed results suggest a potential ceiling on the amount of information extractable from the database, e.g., due to the intrinsic difficulty of the prediction tasks at hand, or to the absence of crucial predictors that are, however, not currently collected during routine practice.
Co-designing a blueprint for spreading person-centered, Whole Health care to HIV specialty care settings: a mixed methods protocol
Authors: Rupcic Sonia , Tam Ming Z. , DeLaughter Kathryn L. , Gifford Allen L. , Barker Anna M. , Bokhour Barbara G. , Xu Chris , Dryden Eileen , Anderson Ekaterina , Jasuja Guneet K. , Boudreau Jacqueline , Douglas Jamie H. , Hyde Justeen , Mozer Reagan , Zeliadt Steven B. , Fix Gemmae M.
Published: October 2024

Background

Since 2013, the Veterans Health Administration (VHA) has advanced a person-centered, Whole Health (WH) System of Care, a shift from a disease-oriented system to one that prioritizes “what matters most” to patients in their lives. Whole Health is predicated on patient-provider interactions marked by a multi-level understanding of health and trusted relationships that promote well-being. Presently, WH implementation has been focused largely in primary care settings, yet the goal is to effect a system-wide transformation of care so that Veterans receive WH across VHA clinical settings, including specialty care. This sort of system-wide cultural transformation is difficult to implement.

Methods

This three-aim mixed methods study will result in a co-designed implementation blueprint for spreading WH from primary to specialty care settings. Taking HIV specialty care as an illustrative case- because of its diverse models of relationships to primary care - to explore how to spread WH through specialty care settings. We will use the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to organize quantitative and qualitative data and identify key determinants of WH receipt among Veterans living with HIV. Through a co-design process, we develop an adaptable implementation blueprint that identifies and matches implementation strategies to different HIV specialty care configurations.

Discussion

This study will co-design a flexible implementation blueprint for spreading WH from VHA primary care throughout HIV specialty care settings. This protocol contributes to the science of end-user engagement while also answering calls for greater transparency in how implementation strategies are identified, tailored, and spread.
The use of outcome data from quality registries to learn and improve; a Dutch nationwide quantitative analysis in five disease areas
Authors: Slingerland Stacey R. , Moers Lise A. M. , Medendorp Niki M. , van der Nat Paul B. , Derks Lineke , Timmermans Marijke J. C. , de Keizer Nicolette , ten Dam Marc , Denissen Geke , van Veghel Dennis
Published: October 2024

Background

Clinical quality registries (CQR) aid in measuring, collecting and monitoring outcome data but it is still unknown how these data are used by hospitals to improve the quality of care. This study assessed the current state of outcome-based quality improvement in the Netherlands in 2022 based on data from multiple disease areas and CQRs; cardiothoracic surgery (Netherlands Heart Registration [NHR]), cardiology (NHR), nephrology, (Nefrovision), intensive care (National Intensive Care Evaluation [NICE]), and orthopaedic surgery (Dutch Arthroplasty Register [LROI]).

Methods & results

The Health Outcomes Management Evaluation (HOME) model was used to assess the current state of outcome-based quality improvement. A questionnaire with 36 questions was sent to healthcare departments of the six disease areas in participating hospitals within five quality registrations in the Netherlands. In total, 124 responses were received; 20 within cardiology, 12 within cardiothoracic surgery, 30 within nephrology, 35 within intensive care and 27 within orthopaedic surgery. Results showed outcome measures were actively used to improve the quality of care, several improvement initiatives were implemented, but outcomes were not always monitored regularly. Results differed between hospitals, but differences were limited between disease areas.

Conclusion

The current state of outcome-based quality improvement in all five disease areas is that outcome measures were consequently employed and used on a frequent basis aiming to achieve quality improvement in healthcare. Results can be improved by structurally embedding the entire improvement cycle into the organisation.
Future health technology trends, policy, and governance perspective: the Turkish case
Authors: Kambur Elif Sena , Yıldırım Hasan Hüseyin
Published: October 2024

Background

Advanced health technologies that emerge with the development of technology have an impact on health systems. This study aimed to determine the effects of these technologies on Türkiye’s health system and present policy recommendations to reshape Türkiye’s health system and policies accordingly.

Methods

Interviews were conducted with senior managers, bureaucrats, policy-makers and decision-makers from seven different institutions on the subject. Content analysis was performed on the data obtained and evaluative categories were established.

Results

It was concluded that these technologies would not have a positive impact on two identified themes, a negative impact on seven themes and a predominant impact on five themes in Türkiye.

Conclusions

To adapt to the new health ecosystem in Türkiye, it is recommended to increase digital literacy, conduct economic evaluations of technologies, promote domestic production, ensure up-to-date follow-up, collaborate with the engineering field, enhance health technology evaluation practices, improve access to technologies and ensure that the infrastructures of health institutions are compatible with technologies. Various policy suggestions have been presented for the development of Türkiye’s health system.
Retraction Note: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments
Authors: Cake Caroline , Ogburn Emma , Pinches Heather , Coleman Garry , Seymour David , Woodard Fran , Manohar Sinduja , Monsur Marjia , Landray Martin , Dalton Gaynor , Morris Andrew D. , Chinnery Patrick F. ,   UK COVID-19 National Core Studies Consortium, Hobbs F. D. Richard , Butler Christopher
Published: October 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13063-021-05965-4.
Successful control of an environmental reservoir of NDM-producing Klebsiella pneumoniae associated with nosocomial transmissions in a low-incidence setting
Authors: Moulin Estelle , Filippidis Paraskevas , Paire-Ficout Corinne Aymon , Blanc Dominique S. , Grandbastien Bruno , Senn Laurence
Published: October 2024

Background

The hospital wastewater system has been reported as a source of nosocomial acquisition of carbapenemase producing Enterobacteriaceae (CPE) in various settings. Cleaning and disinfection protocols or replacement of contaminated equipment often fail to eradicate these environmental reservoirs, which can lead to long-term transmission of CPE. We report a successful multimodal approach to control a New Delhi metallo-beta-lactamase positive Klebsiella pneumoniae (NDM-KP) nosocomial outbreak implicating contamination of sink traps in a low-incidence setting.

Methods

Following the incidental identification of NDM-KP in a urine culture of an inpatient, we performed an epidemiological investigation, including patient and environmental CPE screening, and whole genome sequencing (WGS) of strains. We also implemented multimodal infection prevention and control (IPC) measures, namely the isolation of cases, waterless patient care, replacement of contaminated P-traps and connecting pieces, and bleach and steam disinfection of sinks for 6 months, followed by patient and environmental screenings for eradication.

Results

Between February and May 2022, five NDM-KP cases were identified in an eight-bed neurosurgical intermediate care unit. Among the eight sink traps of the unit, three were positive for NDM-KP. Patient and environmental isolates belonged to multilocus sequence typing ST-268. All isolate genomes were genetically very similar suggesting cross-transmission and a potential role of the environment as the source of transmissions. Following the introduction of combined IPC measures, no new case was subsequently detected and sink traps remained negative for NDM-KP within 6 months after the intervention.

Conclusion

The implementation of multimodal IPC measures, including waterless patient care combined with the replacement and disinfection of P-traps and connecting pieces, was successful in the control of NDM-KP after eight months. In a low-incidence setting, this approach has made it possible to pursue the objective of zero transmission of carbapenemase-producing Enterobacteriaceae (CPE).
A tumorigenicity evaluation platform for cell therapies based on brain organoids
Authors: Xue Jun , Chu Youjun , Huang Yanwang , Chen Ming , Sun Meng , Fan Zhiqin , Wu Yonghe , Chen Liang
Published: October 2024

Background

Tumorigenicity represents a critical challenge in stem cell-based therapies requiring rigorous monitoring. Conventional approaches for tumorigenicity evaluation are based on animal models and have numerous limitations. Brain organoids, which recapitulate the structural and functional complexity of the human brain, have been widely used in neuroscience research. However, the capacity of brain organoids for tumorigenicity evaluation needs to be further elucidated.

Methods

A cerebral organoid model produced from human pluripotent stem cells (hPSCs) was employed. Meanwhile, to enhance the detection sensitivity for potential tumorigenic cells, we created a glioblastoma-like organoid (GBM organoid) model from TP53−/−/PTEN−/− hPSCs to provide a tumor microenvironment for injected cells. Midbrain dopamine (mDA) cells from human embryonic stem cells were utilized as a cell therapy product. mDA cells, hPSCs, mDA cells spiked with hPSCs, and immature mDA cells were then injected into the brain organoids and NOD SCID mice. The injected cells within the brain organoids were characterized, and compared with those injected in vivo to evaluate the capability of the brain organoids for tumorigenicity evaluation. Single-cell RNA sequencing was performed to identify the differential gene expression between the cerebral organoids and the GBM organoids.

Results

Both cerebral organoids and GBM organoids supported maturation of the injected mDA cells. The hPSCs and immature mDA cells injected in the GBM organoids showed a significantly higher proliferative capacity than those injected in the cerebral organoids and in NOD SCID mice. Furthermore, the spiked hPSCs were detectable in both the cerebral organoids and the GBM organoids. Notably, the GBM organoids demonstrated a superior capacity to enhance proliferation and pluripotency of spiked hPSCs compared to the cerebral organoids and the mouse model. Kyoto Encyclopedia of Genes and Genomes analysis revealed upregulation of tumor-related metabolic pathways and cytokines in the GBM organoids, suggesting that these factors underlie the high detection sensitivity for tumorigenicity evaluation.

Conclusions

Our findings suggest that brain organoids could represent a novel and effective platform for evaluating the tumorigenic risk in stem cell-based therapies. Notably, the GBM organoids offer a superior platform that could complement or potentially replace traditional animal-based models for tumorigenicity evaluation.
NF1 expression profiling in IDH-wildtype glioblastoma: genomic associations and survival outcomes
Authors: Chang Michael , Sherief Mohamed , Ioannou Maria , Chinnasamy Viveka , Chen Lucy , Frost Michael , Mattson-Hoss Michelle , Sarnoff Herb , Kamson David O. , Holdhoff Matthias , Mukherjee Debraj , Bettegowda Chetan , Rincon-Torroella Jordina , Croog Victoria , Huang Peng , Rodriguez Fausto J. , Lucas Calixto-Hope G. , Schreck Karisa C.
Published: October 2024

Background

NF1 inactivation is associated with sensitivity to MEK inhibitor targeted therapy in low-grade and some high-grade gliomas. NF1 loss may also be a harbinger of exploitable vulnerabilities in IDH-wildtype glioblastoma (GBM). Accurate and consistent detection of NF1 loss, however, is fraught given the large gene size, challenges with complete coverage and variant calling upon sequencing, and mechanisms of mRNA and protein regulation that result in early degradation in the absence of genomic alterations. Here, we seek to perform a composite analysis for NF1 loss accounting for genomic alterations and protein expression via immunohistochemistry. We also characterize the landscape of NF1 alterations in GBM.

Methods

We assembled a single-institution, retrospective cohort of 542 IDH-wildtype GBM with somatic next generation sequencing to investigate the frequency and nature of detected NF1 alterations. We selected 69 GBMs from which to build a tissue microarray (TMA) of 44 NF1-wildtype and 25 NF1-mutant cases. We performed NF1 immunohistochemistry using two different NF1 antibodies (NFC, Sigma-Aldrich; and iNF-07E, iNFixion Bioscience) and correlated results with clinical, genomic, and other immunohistochemical features.

Results

In our retrospective cohort, we identified 88 IDH-wildtype GBM with NF1 alterations (16%). NF1 alterations were mutually exclusive with EGFR and MDM2 alterations (p-adj < 0.001, 0.05, respectively), but co-occurred with PIK3R1 alterations (Log2(OR) = − 1.6, p-adj = 0.03). Of the 63 scorable sporadic GBMs in the TMA, 14 harbored NF1 inactivating alterations and of those, 12 (86%) demonstrated minimal NF1 immunoreactivity by NFC antibody, compared to 8 (57%) by iNF-07E antibody. Among the 42 scorable NF1-wildtype GBM in the TMA, NF1 immunostaining was minimal in 18 (43%) by NFC antibody compared to 4 (10%) by iNF-07E antibody, potentially reflecting false positives or differential protein regulation. Minimal immunoreactivity by NFC antibody was associated with decreased median overall survival (8.5 vs. 16.4 months, p = 0.011). Cox proportional hazards model correcting for prognostic variables in this subset revealed HR 3.23 (95% CI 1.29–8.06, p = 0.01) associated with decreased NF1 expression by IHC.

Conclusion

NF1 immunostaining may serve as a sensitive surrogate marker of NF1 genomic inactivation and a valuable extension to next-generation sequencing for defining NF1 status. Minimal NF1 immunoreactivity is a poor prognostic marker, even in IDH-wildtype glioblastoma without apparent NF1 genomic alterations, but the underlying molecular mechanism requires further investigation.
Effects of climate change on open air heritage: a review and the situation in the region of Mediterranean
Authors: Nastou Marina Panagiota P. , Zerefos Stelios C.
Published: October 2024

This paper collects research information and registered data regarding the relationship between climate change and heritage, aiming to present a comprehensive state of studies and research on the subject. This relationship between these two cores is basically the main subject of this research, as well as the discovery of the areas with little information. Nowadays, there is a remarkable increase in the concern of the damage of cultural heritage and the research of methods and means of protection and of interpretation of its value. In the meanwhile, climate change is the other pillar of this paper, with evident damage, eminent jeopardy and accumulative downgrade of heritage assets. The aforementioned facts create a threatening background for the safeguarding of cultural and natural heritage and the transmission to the next generations. In general, stakeholders should focus on the mitigation of the human causes of climate change and the necessary adaptation to the climatic conditions for heritage protection. Through the collection of data, this paper presents the region of Mediterranean, as it has a strategic geographic location and the climatic conditions have already shown notable deviations. The presented information relates to the indices and measurements of the effects of climate change and the overall assessment of the risks of heritage, the irreversible impairment, the most common cultural aspects of the studies and the urgent need of protection. The scope of these data is the design of the appropriate management plan, taking into account the unique identity of each piece of heritage and its environment. To sum up, the kinds of heritage incorporated into the environment structuring a completed landscape with immediate exposure to the conditions, seem to lack the essential research for their preservation. For this reason, the adequate management of cultural and natural heritage in jeopardy, such as the cases in the Mediterranean region, require multidisciplinary assessment for heritage management.
Spatiotemporal distribution of toponymic cultural heritage in Jiangsu Province and its historical and geographical influencing factors
Authors: Jiao Min , Lu Lu
Published: October 2024

As a typical intangible cultural heritage, Toponymic Cultural Heritage (TCH) is rich in geographic information and semantic and physical connotations. In the context of the heritage conservation era, it is highly important to study the spatiotemporal distribution characteristics of toponymic cultural heritage and explore its historical and geographic influencing factors on the sustainable conservation and development of toponymic cultural heritage. However, most existing studies focus on the toponym cultural landscape, and less attention has been given to TCH. Therefore, on the basis of the data of 357 provincial TCH items in Jiangsu Province, this study investigated the spatiotemporal distribution characteristics and historical–geographical influencing factors of the TCH by using geospatial analysis methods, such as the average nearest neighbor, tyson polygon, kernel density estimation, standard deviational ellipse, and superposition coupling analysis, and proposed several strategies for adaptive reuse of TCH. The results show that (1) the TCHs of Jiangsu Province have a spatial distribution characteristic of "sparse in the north, scattered in the middle and dense in the south" and form a high-density agglomeration around the southern part of Jiangsu Province. In the distribution of cultural districts, the Jinling cultural district, the Wu cultural district, and the Huaiyang cultural district have the largest number of TCHs. (2) From the Pre-Qin period to the Ming and Qing Dynasties, TCHs, such as Nanjing, Yangzhou, Zhenjiang, Changzhou, and Suzhou, tended to merge in the southern part of Jiangsu. (3) In terms of type, the roads, streets and alleys of TCHs are the richest, and all types of TCHs are spatially clustered in the southern part of Jiangsu Province, which has a high level of urbanization, industrialization, and a superior geographic environment. (4) TCHs have spatial tendencies toward low altitudes and hydrophilicity, and relatively favorable natural geographical conditions provide a high-quality environment for TCHs in southern Jiangsu Province. Influenced by historical, humanistic, and geographical factors, TCH is unevenly developed spatially. As a historical population concentration area, an important political, economic, and cultural core area, and a center of gravity for cultural development, more TCH resources have survived in the southern part of Jiangsu Province. This study provides a new perspective for interpreting and recognizing TCH as a special intangible cultural heritage and can provide a reference for the sustainable conservation and development of TCH.
Height status matters for risk of mortality in critically ill children
Authors: Nosaka Nobuyuki , Anzai Tatsuhiko , Wakabayashi Kenji
Published: October 2024

Background

Anthropometric measurements are crucial in pediatric critical care, but the impact of height on ICU outcomes is underexplored despite a substantial number of short-for-age children in ICUs. Previous studies suggest that short stature increases the risk of poor clinical outcomes. This study examines the relationship between short stature and ICU outcomes.

Methods

We conducted a retrospective cohort study using a Japanese nationwide database (the Japanese Intensive Care Patient Database; JIPAD), which included pediatric patients under 16 years admitted to ICUs from April 2015 to March 2020. Height standard deviation scores (SD scores) were calculated based on age and sex. Short-stature patients were defined as height SD score <  − 2. The primary outcome was all-cause ICU mortality, and the secondary outcome was the length of stay in ICU.

Results

Out of 6,377 pediatric patients, 27.2% were classified as having short stature. The ICU mortality rate was significantly higher in the short-stature group compared to the normal-height group (3.6% vs. 1.4%, p < 0.01). Multivariable logistic regression showed that short stature was independently associated with increased ICU mortality (OR = 2.73, 95% CI 1.81–4.11). Additionally, the Fine–Gray subdistribution hazards model indicated that short stature was associated with a lower chance of ICU discharge for each additional day (HR 0.85, 95% CI 0.81–0.90, p < 0.01).

Conclusions

Short stature is a significant risk factor for increased ICU mortality and prolonged ICU stay in critically ill children. Height should be considered in risk assessments and management strategies in pediatric intensive care to improve outcomes.
Science for tomorrow’s neurosurgery: insights on establishing a neurosurgery patient group focused on developing novel intra-operative imaging techniques
Authors: MacCormac Oscar , Elliot Matthew , Whittaker Lisa , Bahl Anisha , Ségaud Silvère , Plowright Andrew J. , Winslade Shannon , Taylor-Gee Alice , Spencer Bella , Vercauteren Tom , Shapey Jonathan
Published: October 2024

Background

Incorporating patient and public involvement (PPI) in research is crucial for ensuring the relevance and success of studies, yet it remains significantly underutilised in surgical research.

Main body

This commentary presents insights from our neurosurgical research team’s experience with establishing and working with a PPI group called “Science for Tomorrow’s Neurosurgery” on research regarding novel intra-operative optical imaging techniques. Through collaboration with patient-focused charities, we have successfully incorporated patient perspectives into our work at each stage of the research pipeline, whilst adhering to core PPI principles, such as reciprocal relationships, co-learning, partnerships, and transparency.

Conclusion

We highlight the specific value added to our work in terms of participant recruitment, research ethics and results dissemination.
Jack of all trades, master of one: domain-specific and domain-general contributions to perceptual expertise in visual comparison
Authors: Growns Bethany , Dunn James D. , Helm Rebecca K. , Towler Alice , Mattijssen Erwin J. A. T. , Martire Kristy A.
Published: October 2024

Perceptual expertise is typically domain-specific and rarely generalises beyond an expert’s domain of experience. Forensic feature-comparison examiners outperform the norm in domain-specific visual comparison, but emerging research suggests that they show advantages on other similar tasks outside their domain of expertise. For example, fingerprint examiners not only outperform novices in fingerprint comparison, but also in face comparison. Yet, the extent to which their skills generalise is poorly understood. In this study, we investigated the generalisability of perceptual expertise amongst forensic examiners by comparing their performance to novices and other examiners within and outside their area of expertise. We recruited 85 experts from three forensic disciplines (face, fingerprint, and firearms) and asked them to complete four different visual comparison tasks: faces, fingerprints, firearms, and novel-objects. Examiners displayed domain-specific expertise: they outperformed novices and other examiners within their domain of visual comparison expertise. Yet, some of their skill also generalised: examiners also outperformed novices outside their area of expertise. However, while individual differences in examiners’ performance within their domain of experience were associated with their performance in a novel comparison task, they were not related to their performance on tasks outside their expert domain. These results provide key insight into the domain-specific and domain-general contributions of forensic examiners’ perceptual expertise. Forensic expertise lends some generalisable skill to other visual comparison tasks, but best performance is still seen within examiners’ domain of expertise.
Characterization and pathogenicity of newly recorded Clonostachys rogersoniana against woolly apple aphid (Eriosoma lanigerum Hausmann) from India
Authors: Kumar Dinesh , Kumari Neelam , Mhatre Priyank Hanuman , Pal Dharam , Naga Kailash Chandra , Watpade Santosh
Published: October 2024

Background

Woolly apple aphid (Eriosoma lanigerum Hausmann) (Homoptera: Aphididae) infests the aerial and edaphic portions of apple trees. It is responsible for the serious qualitative and quantitative reduction in apple fruits. This pest is mainly managed by chemical insecticides, so this present study was focused on the isolation of native entomopathogenic fungi (EPF), studying their growth characteristics and virulence against woolly apple aphids.

Results

Clonostachys rogersoniana, as an EPF from an insect cadaver, was isolated and characterized, using morphological, microscopic, and molecular techniques. To the best of our knowledge, this is the first report of the occurrence of this fungus from India and it is named “C. rogersoniana isolate PUSACR01”. The radial growth and conidial yield of this isolate were excellent on PDAY among ten different culture media, whereas the relative growth rate and conidial germination were good on PDA and CA. The isolated fungus showed 85 and 86.67% mortality rates in adult females of the woolly apple aphid on day 11 at a concentration of 1.0 × 107 and 1.0 × 108 conidia ml−1, respectively. The LC50 values determined by probit regression analysis for days 7, 9, and 11 were 1.12 × 107, 2.52 × 106, and 4.74 × 105 conidia ml−1, respectively, while LT50 for concentrations of 1.0 × 105, 1.0 × 106, 1.0 × 107, and 1.0 × 108 conidia ml−1 were 18.73, 9.39, 6.71, and 5.03 days, respectively.

Conclusion

Based on the present study, C. rogersoniana would be considered a good biological control agent against the woolly apple aphid in apple orchards.
Proteomic identification of apoplastic proteins from rice, wheat, and barley after Magnaporthe oryzae infection
Authors: Wang Jiyang , Diaz Josue , Hua Kangyu , Bellizzi Maria , Qi Linlu , Zhu Lin , Qu Menghan , Wang Guo-Liang
Published: October 2024

The fungal pathogen Magnaporthe oryzae causes devastating blast disease in various cereals, including rice (Oryza sativa), wheat (Triticum aestivum), maize (Zea mays), and barley (Hordeum vulgare). Despite previous reports on fungal host specificity, the mechanisms underlying differential host infection strategies remain unclear. This study aimed to identify differentially abundant proteins (DAPs) in the apoplast of rice, barley, and wheat following infection with two M. oryzae pathovars using liquid chromatography-tandem mass spectrometry (LC–MS/MS). LC–MS/MS analysis revealed an enrichment of both M. oryzae and host proteins in the apoplast during the compatible reaction compared to the incompatible reaction. DAPs from M. oryzae involved in the host interaction included secreted extracellular enzymes (e.g., hydrolases), which were significantly increased in the M. oryzae Oryzae (MoO)-infected rice apoplast. Among host proteins, the proportion of protein-modifying enzymes increased in the M. oryzae Triticum (MoT)-infected rice and MoO-infected wheat apoplastic fluids, particularly rice glycosidases, peroxidases, and serine proteases, as well as wheat serine proteases. Furthermore, DAPs from MoL-infected rice were enriched in carbohydrate metabolism, suggesting that carbohydrate metabolism-related proteins may play a vital role in rice resistance to MoL. Additionally, protein-modifying and cytoskeletal proteins, as well as stress-responsive proteins, were enriched in the MoO-infected wheat apoplastic fluid. Finally, DAPs from both MoO- and MoL-infected barley were enriched in hydrogen peroxide catabolism, suggesting that peroxidases may be vital for barley resistance to M. oryzae. The identification of DAPs from both M. oryzae strains and the three host plants offers valuable insights into the host specificity mechanisms of M. oryzae in cereal crops.