bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare copy-number variants as modulators of common disease susceptibility
Authors: Auwerx Chiara , Jõeloo Maarja , Sadler Marie C. , Tesio Nicolò , Ojavee Sven , Clark Charlie J. , Mägi Reedik ,   Estonian Biobank Research Team, Esko Tõnu , Metspalu Andres , Milani Lili , Nelis Mari , Reymond Alexandre , Kutalik Zoltán
Published: January 2024

Background

Copy-number variations (CNVs) have been associated with rare and debilitating genomic disorders (GDs) but their impact on health later in life in the general population remains poorly described.

Methods

Assessing four modes of CNV action, we performed genome-wide association scans (GWASs) between the copy-number of CNV-proxy probes and 60 curated ICD-10 based clinical diagnoses in 331,522 unrelated white British UK Biobank (UKBB) participants with replication in the Estonian Biobank.

Results

We identified 73 signals involving 40 diseases, all of which indicating that CNVs increased disease risk and caused earlier onset. We estimated that 16% of these associations are indirect, acting by increasing body mass index (BMI). Signals mapped to 45 unique, non-overlapping regions, nine of which being linked to known GDs. Number and identity of genes affected by CNVs modulated their pathogenicity, with many associations being supported by colocalization with both common and rare single-nucleotide variant association signals. Dissection of association signals provided insights into the epidemiology of known gene-disease pairs (e.g., deletions in BRCA1 and LDLR increased risk for ovarian cancer and ischemic heart disease, respectively), clarified dosage mechanisms of action (e.g., both increased and decreased dosage of 17q12 impacted renal health), and identified putative causal genes (e.g., ABCC6 for kidney stones). Characterization of the pleiotropic pathological consequences of recurrent CNVs at 15q13, 16p13.11, 16p12.2, and 22q11.2 in adulthood indicated variable expressivity of these regions and the involvement of multiple genes. Finally, we show that while the total burden of rare CNVs—and especially deletions—strongly associated with disease risk, it only accounted for ~ 0.02% of the UKBB disease burden. These associations are mainly driven by CNVs at known GD CNV regions, whose pleiotropic effect on common diseases was broader than anticipated by our CNV-GWAS.

Conclusions

Our results shed light on the prominent role of rare CNVs in determining common disease susceptibility within the general population and provide actionable insights for anticipating later-onset comorbidities in carriers of recurrent CNVs.
An optimized capsule neural networks for tomato leaf disease classification
Authors: Abouelmagd Lobna M. , Shams Mahmoud Y. , Marie Hanaa Salem , Hassanien Aboul Ella
Published: January 2024

Plant diseases have a significant impact on leaves, with each disease exhibiting specific spots characterized by unique colors and locations. Therefore, it is crucial to develop a method for detecting these diseases based on spot shape, color, and location within the leaves. While Convolutional Neural Networks (CNNs) have been widely used in deep learning applications, they suffer from limitations in capturing relative spatial and orientation relationships. This paper presents a computer vision methodology that utilizes an optimized capsule neural network (CapsNet) to detect and classify ten tomato leaf diseases using standard dataset images. To mitigate overfitting, data augmentation, and preprocessing techniques were employed during the training phase. CapsNet was chosen over CNNs due to its superior ability to capture spatial positioning within the image. The proposed CapsNet approach achieved an accuracy of 96.39% with minimal loss, relying on a 0.00001 Adam optimizer. By comparing the results with existing state-of-the-art approaches, the study demonstrates the effectiveness of CapsNet in accurately identifying and classifying tomato leaf diseases based on spot shape, color, and location. The findings highlight the potential of CapsNet as an alternative to CNNs for improving disease detection and classification in plant pathology research.
Evidence-practice gap analysis in the role of tick in brucellosis transmission: a scoping review
Authors: Ma Rui , Li Chunfu , Gao Ai , Jiang Na , Feng Xinyu , Li Jian , Hu Wei
Published: January 2024

Background

Brucellosis is a zoonotic affliction instigated by bacteria belonging to the genus Brucella and is characterized by a diverse range of pervasiveness, multiple transmission routes, and serious hazards. It is imperative to amalgamate the current knowledge and identify gaps pertaining to the role of ticks in brucellosis transmission.

Methods

We systematically searched China National Knowledge Infrastructure (CNKI), WanFang, Google Scholar, and PubMed on the topic published until April 23, 2022. The procedure was performed in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The selected articles were categorized across three major topic areas, and the potential data was extracted to describe evidence-practice gaps by two reviewers.

Results

The search identified 83 eligible studies for the final analyses. The results highlighted the potential capacity of ticks in brucellosis transmission as evidenced by the detection of Brucella in 16 different tick species. The pooled overall prevalence of Brucella in ticks was 33.87% (range: 0.00–87.80%). The review also revealed the capability of Brucella to circulate in parasitic ticks' different developmental stages, thus posing a potential threat to animal and human health. Empirical evidence from in vitro rodent infection experiments has revealed that ticks possess the capability to transmit Brucella to uninfected animals (range: 45.00–80.00%). Moreover, significant epidemiological associations have been found between the occurrence of brucellosis in animals and tick control in rangelands, which further suggests that ticks may serve as potential vectors for brucellosis transmission in ruminants. Notably, a mere three cases of human brucellosis resulting from potential tick bites were identified in search of global clinical case reports from 1963 to 2019.

Conclusions

It is imperative to improve the techniques used to identify Brucella in ticks, particularly by developing a novel, efficient, precise approach that can be applied in a field setting. Furthermore, due to the lack of adequate evidence of tick-borne brucellosis, it is essential to integrate various disciplines, including experimental animal science, epidemiology, molecular genetics, and others, to better understand the efficacy of tick-borne brucellosis. By amalgamating multiple disciplines, we can enhance our comprehension and proficiency in tackling tick-borne brucellosis.
Lives ‘on hold’ in Europe: an explorative review of literature on youth aspirations and futures in situations of migration and mobility
Authors: Doumas Kyriaki , Avery Helen
Published: January 2024

This explorative literature review aims to examine the content and methodologies of recent empirical studies on the aspirations of youth in situations of migration in Europe. The search yielded 30 peer-reviewed social science publications in English for the period 2010–2022, including both intra-European migrants ages 10–24 and youth with backgrounds from outside Europe. Contextual analysis was used to analyse the content of the reviewed studies, while a typology developed by Beckert and Suckert was used to examine features of the future appearing in the studies’ research aims, methodology and findings. The analysis broadly situated the studies within constructivist traditions, occupying a mid-position between deterministic and agency-oriented epistemologies. All the features of the future listed by Beckert and Suckert were found in the material, but the categories 'Temporal configurations of the future' and 'Space of the future' showed greater complexities. Participants in the studies lived in different European countries and the study samples comprised a wide range of ages, socioeconomic backgrounds, and status of residence. Nevertheless, barriers linked to participants' position as migrants were tangible, while the ability these young people had to envisage the future was strongly affected by uncertainties linked to migration policy and administrative decisions on their status. A mismatch could notably be observed between youth aspirations and the opportunities offered by their life situation, which led to delays in life projects and the inability to plan ahead.

Critical relevance statement

By an analysis of social studies research on aspirations of youth in situations of migration in various European countries, this review highlights the need to consider implications for youth aspirations and life trajectories in both policy and practice

Key points

• Young people in situations of migration have high aspirations but confront substantial barriers

• Uncertainties prevent youth from long-term planning and realising life projects

• Current policies create conditions that are not consistent with European values and ambitions
Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study
Authors: Crombé Amandine , Bertolo Frédéric , Vanhersecke Lucile , Guegan Jean-Philippe , Bessede Alban , Perret Raul , Le Loarer François , Chaire Vanessa , Coindre Jean-Michel , Lucchesi Carlo , Italiano Antoine
Published: January 2024

Metabolic elevation in soft-tissue sarcomas (STS), as documented with 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) has been linked with cell proliferation, higher grade, and lower survivals. However, the recent diagnostic innovations (CINSARC gene-expression signature and tertiary lymphoid structure [TLS]) and therapeutic innovations (immune checkpoint inhibitors [ICIs]) for STS patients underscore the need to re-assess the role of 18F-FDG-PET/CT. Thus, in this correspondence, our objective was to investigate the correlations between STS metabolism as assessed by nuclear imaging, and the immune landscape as estimated by transcriptomics analysis, immunohistochemistry panels, and TLS assessment. Based on a prospective cohort of 85 adult patients with high-grade STS recruited in the NEOSARCOMICS trial (NCT02789384), we identified 3 metabolic groups according to 18F-FDG-PET/CT metrics (metabolic-low [60%], -intermediate [15.3%] and high [24.7%]). We found that T-cells CD8 pathway was significantly enriched in metabolic-high STS. Conversely, several pathways involved in antitumor immune response, cell differentiation and cell cycle, were downregulated in extreme metabolic-low STS. Next, multiplex immunofluorescence showed that densities of CD8+, CD14+, CD45+, CD68+, and c-MAF cells were significantly higher in the metabolic-high group compared to the metabolic-low group. Lastly, no association was found between metabolic group and TLS status. Overall, these results suggest that (i) rapidly proliferating and metabolically active STS can instigate a more robust immune response, thereby attracting immune cells such as T cells and macrophages, and (ii) metabolic activity and TLS could independently influence immune responses.
Rapid assays of SARS-CoV-2 virus and noble biosensors by nanomaterials
Authors: Liu Yang , Li Yilong , Hang Yuteng , Wang Lei , Wang Jinghan , Bao Ning , Kim Youngeun , Jang Ho Won
Published: January 2024

The COVID-19 outbreak caused by SARS-CoV-2 in late 2019 has spread rapidly across the world to form a global epidemic of respiratory infectious diseases. Increased investigations on diagnostic tools are currently implemented to assist rapid identification of the virus because mass and rapid diagnosis might be the best way to prevent the outbreak of the virus. This critical review discusses the detection principles, fabrication techniques, and applications on the rapid detection of SARS-CoV-2 with three categories: rapid nuclear acid augmentation test, rapid immunoassay test and biosensors. Special efforts were put on enhancement of nanomaterials on biosensors for rapid, sensitive, and low-cost diagnostics of SARS-CoV-2 virus. Future developments are suggested regarding potential candidates in hospitals, clinics and laboratories for control and prevention of large-scale epidemic.

Graphical Abstract
Value of high frame rate contrast enhanced ultrasound in gallbladder wall thickening in non-acute setting
Authors: Zhu Lianhua , Li Nan , Zhu Yaqiong , Han Peng , Jiang Bo , Li Miao , Luo Yukun , Clevert Dirk-André , Fei Xiang
Published: January 2024

Background

Ultrasound (US) has been widely used in screening and differential diagnosis of gallbladder wall thickening (GWT). However, the sensitivity and specificity for diagnosing wall-thickening type gallbladder cancer are limited, leading to delayed treatment or overtreatment. We aim to explore the value of high frame rate contrast enhanced ultrasound (H-CEUS) in distinguishing wall-thickening type gallbladder cancer (malignant) from GWT mimicking malignancy (benign).

Methods

This retrospective study enrolled consecutive patients with non-acute GWT who underwent US and H-CEUS examination before cholecystectomy. Clinical information, US image and H-CEUS image characteristics between malignant and benign GWT were compared. The independent risk factors for malignant GWT on H-CEUS images were selected by multivariate logistic regression analysis. The diagnostic performance of H-CEUS in determining malignant GWT was compared with that of the gallbladder reporting and data system (GB-RADS) score.

Results

Forty-six patients included 30 benign GWTs and 16 malignant GWTs. Only mural layering and interface with liver on US images were significantly different between malignant and benign GWT (P < 0.05). Differences in enhancement direction, vascular morphology, serous layer continuity, wash-out time and mural layering in the venous phase of GWT on H-CEUS images were significant between malignant and benign GWT (P < 0.05). The sensitivity, specificity and accuracy of H-CEUS based on enhancement direction, vascular morphology and wash-out time in the diagnosis of malignant GWT were 93.75%, 90.00%, and 91.30%, respectively. However, the sensitivity, specificity and accuracy of the GB-RADS score were only 68.75%, 73.33% and 71.74%, respectively. The area under ROC curve (AUC) of H-CEUS was significantly higher than that of the GB-RADS score (AUC = 0.965 vs. 0.756).

Conclusions

H-CEUS can accurately detect enhancement direction, vascular morphology and wash-out time of GWT, with a higher diagnostic performance than the GB-RADS score in determining wall-thickening type gallbladder cancer. This study provides a novel imaging means with high accuracy for the diagnosis of wall-thickening type gallbladder cancer, thus may be better avoiding delayed treatment or overtreatment.
Validation of an automated sample preparation module directly connected to LC-MS/MS (CLAM-LC-MS/MS system) and comparison with conventional immunoassays for quantitation of tacrolimus and cyclosporin A in a clinical setting
Authors: Shimada Tsutomu , Kawakami Daisuke , Fujita Arimi , Yamamoto Rintaro , Hara Satoshi , Ito Kiyoaki , Mizushima Ichiro , Kitajima Shinji , Iwata Yasunori , Sakai Norihiko , Kawano Mitsuhiro , Wada Takashi , Sai Yoshimichi
Published: January 2024

Background

Therapeutic drug monitoring (TDM) systems generally use either liquid chromatography/tandem mass spectrometry (LC-MS/MS) or immunoassay, though both methodologies have disadvantages. In this study, we aimed to evaluate whether a CLAM-LC-MS/MS system, which consists of a sample preparation module directly connected to LC-MS/MS, could be used for clinical TDM work for immunosuppressive drugs in whole blood, which requires a hemolytic process. For this purpose, we prospectively validated this system for clinical measurement of tacrolimus and cyclosporin A in patients’ whole blood. The results were also compared with those of commercial immunoassays.

Methods

Whole blood from patients treated with tacrolimus or cyclosporin A at the Department of Nephrology and Departments of Rheumatology, Kanazawa University Hospital, from May 2018 to July 2019 was collected with informed consent, and drug concentrations were measured by CLAM-LC-MS/MS and by chemiluminescence immunoassay (CLIA) for tacrolimus and affinity column-mediated immunoassay (ACMIA) for cyclosporin A. Correlations between the CLAM-LC-MS/MS and immunoassay results were analyzed.

Results

Two hundred and twenty-four blood samples from 80 patients were used for tacrolimus measurement, and 76 samples from 21 patients were used for cyclosporin A. Intra- and inter-assay precision values of quality controls were less than 7%. There were significant correlations between CLAM-LC-MS/MS and the immunoassays for tacrolimus and cyclosporin A (Spearman rank correlation coefficients: 0.861, 0.941, P < 0.00001 in each case). The drug concentrations measured by CLAM-LC-MS/MS were about 20% lower than those obtained using the immunoassays. CLAM-LC-MS/MS maintenance requirements did not interfere with clinical operations. Compared to manual pretreatment, automated pretreatment by CLAM showed lower inter-assay precision values and greatly reduced the pretreatment time.

Conclusions

The results obtained by CLAM-LC-MS/MS were highly correlated with those of commercial immunoassay methods. CLAM-LC-MS/MS offers advantages in clinical TDM practice, including simple, automatic pretreatment, low maintenance requirement, and avoidance of interference.
Neural Correlates of Balance Skill Learning in Young and Older Individuals: A Systematic Review and Meta-analysis
Authors: Bakker Lisanne B. M. , Lamoth Claudine J. C. , Vetrovsky Tomas , Gruber Markus , Caljouw Simone R. , Nieboer Ward , Taube Wolfgang , van Dieën Jaap H. , Granacher Urs , Hortobágyi Tibor
Published: January 2024

Background

Despite the increasing number of research studies examining the effects of age on the control of posture, the number of annual fall-related injuries and deaths continues to increase. A better understanding of how old age affects the neural mechanisms of postural control and how countermeasures such as balance training could improve the neural control of posture to reduce falls in older individuals is therefore necessary. The aim of this review is to determine the effects of age on the neural correlates of balance skill learning measured during static (standing) and dynamic (walking) balance tasks in healthy individuals.

Methods

We determined the effects of acute (1–3 sessions) and chronic (> 3 sessions) balance skill training on balance in the trained and in untrained, transfer balance tasks through a systematic review and quantified these effects by robust variance estimation meta-analysis in combination with meta-regression. We systematically searched PubMed, Web of Science, and Cochrane databases. Balance performance and neural plasticity outcomes were extracted and included in the systematic synthesis and meta-analysis.

Results

Forty-two studies (n = 622 young, n = 699 older individuals) were included in the systematic synthesis. Seventeen studies with 508 in-analysis participants were eligible for a meta-analysis. The overall analysis revealed that acute and chronic balance training had a large effect on the neural correlates of balance skill learning in the two age groups combined (g = 0.79, p < 0.01). Both age groups similarly improved balance skill performance in 1–3 training sessions and showed little further improvements with additional sessions. Improvements in balance performance mainly occurred in the trained and less so in the non-trained (i.e., transfer) balance tasks. The systematic synthesis and meta-analysis suggested little correspondence between improved balance skills and changes in spinal, cortical, and corticospinal excitability measures in the two age groups and between the time courses of changes in balance skills and neural correlates.

Conclusions

Balance skill learning and the accompanying neural adaptations occur rapidly and independently of age with little to no training dose-dependence or correspondence between behavioral and neural adaptations. Of the five types of neural correlates examined, changes in only spinal excitability seemed to differ between age groups. However, age or training dose in terms of duration did not moderate the effects of balance training on the changes in any of the neural correlates. The behavioral and neural mechanisms of strong task-specificity and the time course of skill retention remain unclear and require further studies in young and older individuals.

Registration: PROSPERO registration number: CRD42022349573.
Effect of anti-epileptic drugs usage on thyroid profile in Egyptian epileptic children
Authors: Rafik Amira , El-Din Nahed Salah , El Khayat Naglaa Mohamed , Nada Maha , Abushady Eman Mones
Published: January 2024

Background

The long-term use of anti-seizure medications (ASMs) adversely affects thyroid, lipid profile and other metabolic functions. Subclinical hypothyroidism and alterations in thyroid hormone serum levels are reported with older ASMs in adults with limited and conflicting data of the influence of ASMs especially newer one on thyroid function in children. This study aimed to investigate the effects of conventional and newer ASMs whether mono or polytherapy on thyroid profile in children with epilepsy and its impact on lipid profile and metabolic functions.

Results

This study included 155 children with epilepsy (76 on monotherapy and 79 on polytherapy) with mean age of 9.677 ± 3.981 years (54.84% euthyroid, 31.61% hypothyroid, 9.68% subclinical hyperthyroid and 3.87% subclinical hypothyroid) and 78 healthy controls. Children with epilepsy whether on monotherapy or on polytherapy had a statistically significant thyroid profile abnormalities (hypothyroidism, sub-clinical hypothyroidism or sub-clinical hyperthyroidism), dyslipidemia, delayed growth and increase in DBP compared to control group. There was a statistically significant positive correlation between hypothyroidism and dyslipidemia as well as between hypothyroidism and delayed growth and increase in DBP. There was no statistically significant difference between polytherapy and monotherapy regarding thyroid and lipid parameters but children with epilepsy on polytherapy were associated with more statistically significant delay in growth and increase in DBP compared to monotherapy group. Carbamazepine had a statistically significant association with hypothyroidism, increase in DBP and higher total and LDL-cholesterol. Valproic acid had a statistically significant association with sub-clinical hypothyroidism with a positive dose correlation. Levetiracetam (LEV) was associated with a statistically significant lower HDL-cholesterol. All echocardiography data showed no abnormality.

Conclusion

ASMs whether older or newer generations can affect thyroid and lipid profile differently through different mechanisms that are dose and duration dependent regardless of the seizure type and age of the patient. ASMs mainly conventional ones are associated with hypothyroidism, sub-clinical hypothyroidism, sub-clinical hyperthyroidism, dyslipidemia and consequently delayed growth and diastolic blood pressure abnormalities.
Antioxidant and acetylcholinesterase inhibitory activities, in silico analyses, and anti-Alzheimer’s disease potential of leaf extracts of three Nigerian endemic medicinal plants (Spondias mombin, Carica papaya and Kalanchoe crenata)
Authors: Adetuyi Aanuoluwapo Ruth , Ayenero Michael E. , Olaleye Mary T. , Akindahunsi Afolabi A. , Akinmoladun Afolabi C.
Published: January 2024

Background

The evaluation of the correlations between antioxidant and anti-acetylcholinesterase activities of methanol leaf extracts of three Nigerian endemic plants, Spondias mombin, Carica papaya and Kalanchoe crenata, was carried out. Their constituent phytochemicals were identified by HPLC–DAD fingerprinting. The antioxidant activity as typified by 2,2-diphenyl-1-picrylhydrazyl (DPPH·), 2,2′-azino-bis-(3-ethylbenthiazoline-6-sulfonic acid (ABTS·+) and nitric oxide (NO) scavenging activities were evaluated. The acetylcholinesterase (AChE) inhibitory activity of the extracts was also determined.

Results

The extracts contained appreciable amounts of the flavonoids, quercetin and kaempferol. The extracts of Spondias mombin, Carica papaya and Kalanchoe crenata showed concentration-dependent inhibitory activities against DPPH· and ABTS·+ with IC50 of 43.29 ± 0.443 µg/mL, 59.27 ± 0.644 µg/mL and 80.20 ± 0.414 µg/mL; 25.43 ± 0.325 (µg/mL), 39.84 ± 0.163 µg/mL and 59.02 ± 0.376 (µg/mL), respectively. The IC50 for the NO scavenging activities of the Spondias mombin, Carica papaya and Kalanchoe crenata extracts were 41.99 ± 0.217 µg/mL, 50.44 ± 0.281 µg/mL and 60.12 ± 0.512 µg/mL, respectively. The IC50 for the inhibitory effects on AChE was 53.24 ± 0.327 µg/mL, 60.95 ± 0.290 µg/m and 70.5 ± 0.426 µg/mL, respectively. The effectiveness of the plant in all the experimental tests was in the following order: S. mombin > C. papaya > K. crenata. The total flavonoid and total phenolic contents have extremely significant positive correlations with the antioxidant activities and AChE inhibitory activity. The correlation coefficients (r2) of DPPH scavenging activity and NO scavenging activity with the AChE inhibitory activity were 0.8295 µg/mL and 0.7337 µg/mL, respectively (P < 0.0001). The molecular docking and pharmacokinetic analyses on some constituent phytochemicals showed that quercetin, kaempferol, ferulic acid, leucocyanidin, gallic acid and isorhamnetin fulfilled the requirements for an anti-Alzheimer drug.

Conclusions

The results suggest that the plant species provide a significant source of secondary metabolites that can act as natural antioxidants and acetylcholinesterase inhibitors, which will be helpful in the treatment of Alzheimer’s disease.
Detection of Helicobacter pylori using Giemsa staining in chronic tonsillitis patients: cross-sectional study
Authors: Mahmoud Elawamry Mahmoud Ibrahim , El-Desouky Mohamed Ibrahim , Mohammed Tarek Gamal , Hussien Mohamed Ahmed , Mohamed Mohamed Nasr
Published: January 2024

Background

Helicobacter pylori (H. pylori) is a well-known bacteria that is recognized as the most prevalent infection in humans and is present in the majority of people in the world.

Aim

To investigate the presence of an extragastric reservoir of Helicobacter pylori in tonsillectomy specimens to ascertain whether it is an etiologic factor in the development of chronic tonsillitis.

Subjects and methods

The study included 100 patients of both sexes with chronic tonsillitis who visited the ENT (ear, nose, and throat) outpatient department and tested positive for H. pylori antigen in stool and tonsillectomy materials. Giemsa stain was used. The population was patients with chronic tonsillitis who had been diagnosed based on physical examination and history-taking at the (Oto-Rhino-Laryngology) outpatient clinic.

Results

It is shown that patients with positive H. pylori had considerably more acute tonsillitis attacks per year than those with negative H. pylori. Examining the patients with Giemsa modification staining revealed 40% of them to be positive.

Conclusion

H. pylori was found in the tonsil tissue of 40% of the patients with chronic tonsillitis using the Giemsa modification staining method, suggesting that H. pylori may be contributing etiologic factors in the development of chronic tonsillitis.
Prevalence, Dynamics, and Prognostic Role of Clonal Hematopoiesis of Indeterminate Potential in Patients With Breast Cancer
Authors: Morganti Stefania , Gibson Christopher J. , Jin Qingchun , Santos Katheryn , Patel Ashka , Wilson Alex , Merrill Margaret , Vincuilla Julie , Stokes Samantha , Lipsyc-Sharf Marla , Parker Tonia , King Tari A. , Mittendorf Elizabeth A. , Curigliano Giuseppe , Hughes Melissa E. , Stover Daniel G. , Tolaney Sara M. , Weeks Lachelle D. , Tayob Nabihah , Lin Nancy U. , Garber Judy E. , Miller Peter G. , Parsons Heather A.
Published: January 2024

PURPOSE

Clonal hematopoiesis of indeterminate potential (CHIP) is frequent in patients with solid tumors. Prospective data about CHIP prevalence at breast cancer diagnosis and its dynamic evolution under treatment selective pressure are limited.

PATIENTS AND METHODS

We performed targeted error-corrected sequencing on 614 samples from 380 patients with breast cancer. We investigated the dynamics of CHIP on prospectively collected paired samples from patients with early breast cancer (eBC) receiving chemotherapy (CT) or endocrine therapy (ET). We assessed the correlation of CHIP with survival in patients with metastatic triple-negative breast cancer (mTNBC). We estimated the risk of progression to treatment-related myeloid neoplasms (t-MN) according to the clonal hematopoiesis risk score (CHRS). In exploratory analyses, we considered clonal hematopoiesis (CH) with variant allele fraction (VAF) ≥0.005.

RESULTS

CHIP was identified in 15% of patients before treatment. Few CHIP emerged after treatment, and the risk of developing new mutations was similar for patients receiving CT versus ET (odds ratio [OR], 1.16;
P
= .820). However, CT increased the risk of developing new CH with VAF ≥0.005 (OR, 3.45;
P
= .002). Five
TP53-
mutant CH with VAF ≥0.005 emerged among patients receiving CT. Most patients had low risk of t-MN according to the CHRS score. CHIP did not correlate with survival in mTNBC.

CONCLUSION

CHIP is frequent in patients with breast cancer. In this study, CT did not lead to emergence of new CHIP, and most patients had low risk of developing t-MN. This finding is reassuring, given long life expectancy of patients with eBC and the association of CHIP with morbidity and mortality. However,
TP53
-mutant CH with VAF ≥0.005 emerged with CT, which carries high risk of t-MN. Evolution of these small clones and their clinical significance warrant further investigation.
Epidemiology, Genetics, and DNA Methylation Grouping of Hyperostotic Meningiomas
Authors: Umbach Gray , Tran Edwina B. , Eaton Charlotte D. , Choudhury Abrar , Morshed Ramin , Villanueva-Meyer Javier E. , Theodosopoulos Philip V. , Magill Stephen T. , McDermott Michael W. , Raleigh David R. , Goldschmidt Ezequiel
Published: January 2024

BACKGROUND AND OBJECTIVES:

Meningiomas are the most common primary intracranial tumors and are among the only tumors that can form lamellar, hyperostotic bone in the tumor microenvironment. Little is known about the epidemiology or molecular features of hyperostotic meningiomas.

METHODS:

Using a retrospective database of 342 meningiomas treated with surgery at a single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), and surgical variables with the presence of MIH using generalized linear models. Meningioma DNA methylation grouping was analyzed on a separate population of patients from the same institution with preoperative imaging studies sufficient for identification of MIH (n = 200).

RESULTS:

MIH was significantly correlated with anterior fossa (44.3% of MIH vs 17.5% of non-MIH were in the anterior fossa P < .001, c2) or skull base location (62.5% vs 38.3%, P < .001, c2) and lower MIB-1 labeling index. Gross total resection was accomplished in 27.3% of tumors with MIH and 45.5% of nonhyperostotic meningiomas (P < .05, t test). There was no association between MIH and histological World Health Organization grade (P = .32, c2). MIH was significantly more frequent in meningiomas from the Merlin-intact DNA methylation group (P < .05). Somatic missense mutations in the WD-repeat–containing domain of the TRAF7 gene were the most common genetic alteration associated with MIH (n = 12 of 15, 80%, P < .01, c2).

CONCLUSION:

In this article, we show that MIH has a predilection for the anterior skull base and affected tumors are less amenable to gross total resection. We find no association between MIH and histological World Health Organization grade, but show that MIH is more common in the Merlin-intact DNA methylation group and is significantly associated with TRAF7 somatic missense mutations. These data provide a framework for future investigation of biological mechanisms underlying MIH.
Primary health care as the main guarantor of a healthy population in the country and a global challenge in the world: a systematic review
Authors: Abashidze-Gabaidze Gulnara , Khurtsia Lali , Gabaidze Mishiko , Loria Lasha
Published: January 2024

Background Primary health care (PHC) is a fundamental aspect of healthcare systems globally, playing a crucial role in maintaining the health of the population. Despite its importance, there are still gaps in the delivery of PHC services. This study aims to analyze the healthcare system and the existing gaps to develop strategies for improving PHC services. Methods This study is a meta-analysis of the last ten years of written research on PHC services. The data sources include peer-reviewed articles and other relevant literature on PHC services. The study explores PHC services in different countries, assesses existing research, and creates and implements new strategies for improving medical services in practice Studies focused explicitly on primary health care systems, policies, or interventions were included in the study. Eligibiloty criteria included research conducted within the past ten years to present contemporary insights, studies available in peer-reviewed journals and reputable databases and literature examining the influence of PHC on population health outcomes. This meta-analysis incorporates 38 studies within the last decade. Results The study identifies gaps in PHC services, including issues with access to care, affordability, and quality of care. It provides insights into the challenges faced by PHC systems worldwide, highlighting the need for strategies to address these issues. Conclusions The study contributes to a better understanding of the challenges faced by PHC systems worldwide and provides insights for policymakers and healthcare providers to improve healthcare services. The study’s findings underscore the importance of addressing the gaps in PHC services to improve health outcomes and ensure the provision of equitable and accessible healthcare services.
Decoding the mask: Identity in undergraduate medical education
Authors: Higgins Ryan , Stuckey Heather , Snyder Bethany , Costigan Heather , Pomerantz Lauren , Peyrot Mark , Stephens Mark
Published: January 2024

Abstract

Introduction: Developing a healthy sense of professional identity among medical students is an integral aspect of medical education. Despite its importance, addressing professional identity formation (PIF) in medical school has typically been limited to narrative methods. Mask-making represents a complementary visual modality to examine PIF in undergraduate medical education.

Methods: 140 students from the Penn State University College of Medicine Class of 2022 participated in a mask-making activity as they transitioned to clinical clerkships. Students expressed their ideal professional self on the outside of the masks and their current sense of self on the inside of the masks. Masks were coded into 31 PIF categories, and data were analyzed using chi-square to identify significant (P < 0.05) differences between self and ideal profiles.

Results: Overall, the subdomains Communication skills, Observational Skills, and Relationships had the greatest incongruence between what students perceived as “ideal” and how they saw themselves.

Discussion: Mask-making is a modality for self-exploration in the context of identity formation in medical education. Students were able to identify potential areas of growth in their developing professional identities. Our findings suggest arts integration can support holistic student growth and development.
Improving safety performance in the Nigerian oil and gas construction industry through human factor engineering
Authors: Thomas Daniel Obioma , Oluchi Nwaichi Eucharia , Chinemerem Patricks
Published: January 2024

Background The Nigerian Oil and Gas construction industry faces challenges in incident prevention due to conflicting factors, including inadequate resource allocation, prioritization of quality and production over safety, communication gaps, insufficient supervision, poor workplace design, low risk perception, limited management commitment, worker incompetence, deficient design systems, and planning deficiencies. This research aims to develop a human factor engineering (HFE) model that supports the prevention of losses in Oil and Gas construction activities in Nigeria by assessing the influence of human factors on workers' behavior and organizational safety culture. Methods The study involved skilled construction workers with a minimum of two years of experience in upstream, downstream, and midstream sectors. Data collection utilized a descriptive study design with self-administered, structured questionnaires. IBM SPSS AMOS Structural Equation Modeling software was used for data analysis. Results The results indicate statistically significant Pearson's correlation coefficients between human factors and organizational safety culture, with p-values of 0.003, 0.002, 0.004, 0.009, and 0.002 for workplace, task, personal, organizational, and design factors, respectively. The structural equation regression model reveals statistically significant human factors and organizational safety culture, with path coefficients of -0.888, 2.630, -1.59, 4.645, and 0.492 for personal, organizational, workplace, design, and task factors, respectively. Conclusions The research concludes that engineered human factors contribute to improved safety performance in the Oil and Gas construction industry. To enhance safety, the study recommends that the Nigerian government establishes a construction safety board, organizations implement integrated contractor construction health and safety management systems, and workers take personal responsibility for their safety.
Social theory and science diplomacy
Authors: BERTELSEN Rasmus Gjedssø
Published: January 2024

This essay discusses the relationship between social theory and science diplomacy for both academic and policy application. This discussion is based on workpackage 2 Power with Science Diplomacy of H2020 Inventing a shared Science Diplomacy for Europe (InsSciDE) and consortium-wide discussions.

The outcome of the discussions on theory of science diplomacy is that it is unfeasible to develop one theory of science diplomacy. Science diplomacy practice is rich and wide-ranging. Science diplomacy as a concept continues to be contested and there is no consensus on a definition, which makes for dynamic research and debate. The conceptual instability of science diplomacy complicates defining it. After defining science diplomacy, it remains unclear what about science diplomacy to theorize.

Ideal types of science diplomacy practices address the definitional challenge for the time being and allow theorizing which brings order to rich empirical material and links science diplomacy practices to diplomacy analytically rather than normatively. Looking at science diplomacy as an independent, intermediary, or dependent variable contributes to theorizing it.
A novel and advanced control method based on Fuzzy-PI for joint wear simulators
Authors: Iyer Kaushikk Ravender , Keeling David , Hall Richard M
Published: January 2024

Background This research presents a novel approach to improve the control performance of joint wear simulators that are used for testing prostheses. For this application, precise controller tuning and minimal tracking errors are essential to meet compliance standards like ISO 18192-1 or ISO 14242-3, and to test under realistic activities of daily living (ADL) scenarios. Methods To address these challenges, the authors propose employing a single-input-multiple-output (SIMO) fuzzy logic control system to augment the traditional proportional-integral (PI) tuning process for joint simulation. To facilitate the development and testing of potential controllers, we utilize a benchtop hardware-in-the-loop (HiL) simulation environment, which facilitated cost-effective rapid control prototyping (RCP). This HiL simulation mimicked joint motion and loading conditions akin to real spinal and hip wear simulators. The objectives of the study are to develop a robust controller for tribological applications and joint simulators and investigate the use of Fuzzy Logic as a possible enhancement of the control system. The Fuzzy-PI controller combines the conventional PI controller with Fuzzy Logic acting as a supervisor, enhancing overall control performance and robustness. The controller adapts to the system's operating range and performance characteristics through a combination of membership functions and control rules. Results Results indicate that for ISO profiles with a fixed 1Hz frequency, both the traditional PI controller and the Fuzzy-PI controller perform equally well. However, as the frequency of the ISO profile increases or when handling ADL profiles with multiple frequency components, the Fuzzy-PI controller outperforms the PI controller. This was attributed to Fuzzy-PI's real-time adaptive capability to tune PI gains as frequency demands changed through a profile, providing a more robust and superior performance, particularly in challenging scenarios. Conclusions In conclusion, the Fuzzy-PI controller represents a promising advancement for joint wear simulators, offering improved control capabilities and better simulation of real-world physiological conditions.
From Chinese food to Japan’s Hokkaido heritage: The transformation of the grilled mutton or lamb dish ‘Jingisukan’
Authors: Iwama Kazuhiro
Published: January 2024

Jingisukan is a dish in which mutton or lamb and vegetables are grilled using a uniquely shaped pan with a convex center. It originated from the popular Chinese dish ‘Kao Yang Rou’ (grilled mutton), which was discovered by Japanese individuals in Beijing and underwent modifications, leading to the creation of the distinctive name ‘Jingisukan’. This dish was then introduced to the Japanese in Northeast China, specifically known as ‘Manchuria’, and gained fame as a specialty of ‘Manchukuo’, being highly valued even by the Japanese army. Following Japan’s defeat in World War II, Jingisukan became a local dish in Hokkaido and was recognized as a ‘Hokkaido Heritage’ in 2004. The widespread popularity of this dish in Japan can be attributed to its association with Genghis Khan. However, in Mongolia, Genghis Khan is a revered national hero, leading to opposition from some people regarding the use of his name for a dish. This paper provides a concise overview of the birth and spread of Jingisukan, followed by an examination of how the Japanese perceived the history of Jingisukan, which was intertwined with imperialism after World War II. It investigates the reasons for and processes behind the transformation of the dish into local cuisine in Hokkaido. Post-war Jingisukan no longer evokes the heroic imagery used to boost morale during the pre-war and wartime periods. Instead, it became a comfort food that acknowledged the reality of defeat and served as a means of healing. During that time, Jingisukan spread throughout Hokkaido and came to be recognized as the ‘flavor of the homeland’, while also being utilized as a tourism resource. Can we cherish and utilize this dish and its name, which has been beloved by the Japanese for over a century, as a cultural heritage that connects many people, ethnicities, and nations?
A protocol for a systematic review and meta-analysis of tuberculosis care around the time of pregnancy
Authors: Carlsson Camilla , Lönnermark Elisabet , Datta Sumona , Evans Carlton A.
Published: January 2024

Background Tuberculosis is estimated to cause 1.5 million deaths annually and is most common during the reproductive years. Despite that fact, we found that tuberculosis screening, prevention or care recommendations for people around the time of pregnancy were absent from some national policy recommendations and varied in others. Objectives To address the apparent gaps and inconsistencies in policy, we aim to design a systematic review and meta-analysis of the original research evidence informing tuberculosis care around the time of pregnancy. Methods With assistance from librarians at the Biomedical library of the University of Gothenburg, Pubmed, CINAHL and Scopus databases will be searched. Search terms will aim to identify studies generating original research evidence informing care for tuberculosis around the time of pregnancy. Evidence may include: the outcome of TB and/or of pregnancy; the cost-effectiveness or acceptability of any intervention; the sensitivity and specificity of any assessment, selection, diagnostic or test criterion. The output from these literature searches will be screened by two independent reviewers to select the eligible studies for inclusion. Discrepancies will be resolved with a third reviewer. Firstly, publications that provide contextual data will be tabulated, summarising their main contributions. Secondly, studies that provide evidence directly guiding patient care will be our focus and will be considered to be key. The key studies will be subject to quality assessment, data extraction and when possible, meta-analysis. Conclusions This systematic review and meta-analysis aims to guide policy, practice and future research priorities concerning tuberculosis care around the time of pregnancy.
The genome sequence of the Brown Oak Tortrix, Archips crataeganus (Hübner, 1796)
Authors: Boyes Douglas , Gibbs Melanie ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: January 2024

We present a genome assembly from an individual female Archips crataeganus (the Brown Oak Tortrix; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 626.9 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 16.64 kilobases in length. Gene annotation of this assembly on Ensembl identified 19,596 protein coding genes.
Exploring Contrasting Effects of Trust in Organizational Security Practices and Protective Structures on Employees’ Security-Related Precaution Taking
Authors: Greulich Malte , Lins Sebastian , Pienta Daniel , Thatcher Jason Bennett , Sunyaev Ali
Published: January 2024

Encouraging employees to take security precautions is a vital strategy that organizations can use to reduce their vulnerability to information security (ISec) threats. This study investigates how the bright- and dark-side effects of trust in organizational information security impact employees’ intention to take security precautions. Employees who trust organizational security practices are more committed to protecting the organization and are more willing to take security precautions. To foster trust in organizational security practices and security commitment, ISec managers should establish a trusting security climate to ensure that employees can speak freely about the security problems they face in their work and receive support to resolve those problems if needed. This study also alerts managers to the potential adverse consequences of employees’ trust in the organization’s protective structures. We find that employees’ trust in the organization’s protective structures can backfire, making employees complacent regarding security. Further analyses indicate that security mindfulness mediates the influence of security complacency and security commitment on precaution taking. This study contributes by exploring and verifying the bright- and dark-side effects of trust in organizational ISec.