bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the value and knowledge gains from an online tick identification and tick-borne disease management course for the Southeastern United States
Authors: Lippi Catherine A. , Gaff Holly D. , White Alexis L. , Ryan Sadie J.
Published: July 2024

Background

Tick-borne diseases are a growing public health threat in the United States. Despite the prevalence and rising burden of tick-borne diseases, there are major gaps in baseline knowledge and surveillance efforts for tick vectors, even among vector control districts and public health agencies. To address this issue, an online tick training course (OTTC) was developed through the Southeastern Center of Excellence in Vector-Borne Diseases (SECOEVBD) to provide a comprehensive knowledge base on ticks, tick-borne diseases, and their management.

Methods

The OTTC consisted of training modules covering topics including tick biology, tick identification, tick-borne diseases, and public health, personal tick safety, and tick surveillance. The course was largely promoted to vector control specialists and public health employees throughout the Southeastern US. We collected assessment and survey data on participants to gauge learning outcomes, perceptions of the utility of knowledge gained, and barriers and facilitators to applying the knowledge in the field.

Results

The OTTC was successful in increasing participants’ baseline knowledge across all course subject areas, with the average score on assessment increasing from 62.6% (pre-course) to 86.7% (post-course). More than half of participants (63.6%) indicated that they would definitely use information from the course in their work. Barriers to using information identified in the delayed assessment included lack of opportunities to apply skills (18.5%) and the need for additional specialized training beyond what the OTTC currently offers (18.5%), while the main facilitator (70.4%) for applying knowledge was having opportunities at work, such as an existing tick surveillance program.

Conclusions

Overall, this OTTC demonstrated capacity to improve knowledge in a necessary and underserved public health field, and more than half of participants use or plan to use the information in their work. The geographic reach of this online resource was much larger than simply for the Southeastern region for which it was designed, suggesting a much broader need for this resource. Understanding the utility and penetrance of training programs such as these is important for refining materials and assessing optimal targets for training.
Associations of different combinations of moderate-vigorous physical activity and muscle-strengthening activity with mortality among US lung cancer survivors
Authors: Song Weiwei , Zou Menglin , Zheng Weishuai , Hu Xingxing , Gao Han , Cheng Zhenshun
Published: July 2024

Background

To investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors.

Methods

This nationwide prospective cohort study used data from the US National Health Interview Survey 2009–2018. A total of 785 lung cancer survivors were included in the study. Participants were linked to the National Death Index through December 31, 2019. Self-reported MVPA and MSA frequency data were used to obtain 4 mutually exclusive exposure categories. Multivariate Cox proportional hazard models were applied to explore the association between exposure categories and outcomes.

Results

The mean (standard deviation [SD]) age of the study population was 69.1 (11.3) years and 429 (54.6%) were female. Among them, 641 (81.7%) were White and 102 (13.0%) were Black. The median follow-up time was 3 years (2526 person-years), and 349 (44.5%) all-cause deaths and 232 (29.6%) cancer deaths occurred. Compared to the MVPA < 60 min/week and MSA < 2 sessions/week group, individuals in the MVPA ≥ 60 min/week and MSA < 2 sessions/week group showed hazard ratios (HRs) of 0.50 (95% CI, 0.36–0.69) for all-cause mortality and 0.37 (95% CI, 0.20–0.67) for cancer mortality after the adjustment of covariates. Those in the MVPA ≥ 60 min/week and MSA ≥ 2 sessions/week group exhibited HRs of 0.52 (95% CI, 0.35–0.77) for all-cause mortality and 0.27 (95% CI, 0.12–0.62) for cancer mortality when compared to the MVPA < 60 min/week and MSA < 2 sessions/week group. We also identified distinct non-linear relationships between MVPA and outcomes risk among two MSA frequency subgroups.

Conclusion

This cohort study demonstrated that higher levels of MVPA and MSA combined might be associated with optimal reductions of mortality risk in lung cancer survivors.
Comparison of the clinical efficacy and prognosis of the two techniques for treating partial articular-sided supraspinatus tendon tears under arthroscopy
Authors: Zhang Li , Fang Zhanglu , Zhang Yin , Wang Xun , Hong Zheping
Published: July 2024

Background

At present, shoulder arthroscopy is usually used for treatment of rotator cuff injuries. There is still debate over the precise technique of using shoulder arthroscopy to treat partial articular-sided supraspinatus tendon injuries.

Objective

To compare the clinical efficacy of the arthroscopic transtendon repair method and the arthroscopic full-thickness repair method in the treatment of patients with Ellman III partial articular-sided supraspinatus tendon tears and to analyze the influencing factors of postoperative efficacy.

Study design

Cohort study; level of evidence,4.

Methods

A total of 84 partial-thickness rotator cuff tear (PTRCT) patients with Ellman III injuries who underwent surgical treatment in our hospital between January 2017 and January 2020 were selected and divided into the arthroscopic trans-tenon repair group (32 cases) and the arthroscopic full-thickness repair group (52 cases). Shoulder joint pain and functional status were assessed by the Constant score, ASES score and VAS score; shoulder mobility was assessed by measuring shoulder ROM. The clinical outcomes of the two groups of patients were compared, and the factors affecting the postoperative efficacy of the patients were investigated.

Results

All patients were followed up for at least 2 years. The Constant score, ASES score, and VAS score of the two groups of patients were all improved compared with those before surgery, and the differences were statistically significant (P < 0.05). There were no significant differences in the Constant score, ASES score, or VAS score between the two groups (P > 0.05). The results of binary logistic regression analysis showed that the preoperative ASES score and whether biceps tenotomy was performed were independent risk factors for satisfactory postoperative efficacy (P < 0.05).

Conclusion

For patients with Ellman III partial articular-sided supraspinatus tendon tears, the arthroscopic transtendon repair method and the arthroscopic full-thickness repair method can both significantly improve the shoulder pain and function of the patient, but there is no significant difference between the efficacy of the two surgical methods. The preoperative ASES score and whether biceps tenotomy was performed were independent risk factors for satisfactory postoperative efficacy in PTRCT patients with Ellman III injury.
Evaluation of the accuracy of conventional and digital implant impression techniques in bilateral distal extension cases: a randomized clinical trial
Authors: Elashry Wafaa Youssef , Elsheikh Mohamed Maamoun , Elsheikh Ali Mohamed
Published: July 2024

Background

This clinical study aims to evaluate the accuracy of the conventional implant impression techniques compared to the digital impression ones in bilateral distal extension cases.

Methods

A total of 32 implants were placed in eight patients missing all mandibular posterior teeth except the first premolars. Each patient received a total of four implants, with two implants placed on each side, in order to provide support for three units of screw-retained zirconia restorations. Following osteointegration, the same patient underwent two implant-level impression techniques: Conventional open-tray impressions CII (splinted pick-up) and digital implant impressions DII with TRIOS 3 Shape intraoral scanner. The accuracy of impressions was evaluated utilizing a three-dimensional superimposition analysis of standard tessellation language (STL) files. Subsequently, the scan bodies were segmented using Gom inspect software to measure three-dimensional deviations in a color-coding map. Data were statistically analyzed using the Kruskal Wallis test and then a post-hoc test to determine the significance level (P < 0.05).

Results

The study revealed that higher angular and positional deviations were shown toward distal scan bodies compared to mesial ones for both impression techniques. However, this difference was not statistically significant (P > 0.05).

Conclusion

Splinted open-tray conventional impression and intraoral scanning implant impression techniques have demonstrated comparable accuracy.

Trial registration

Clinical Trials.gov Registration ID NCT05912725. Registered 22/06/ 2023- Retrospectively registered, https://register.clinicaltrials.gov.
A biobehavioral observational study to understand the multilevel determinants of cardiovascular health in Black women: the BLOOM Study protocol
Authors: Liao Yue , Brothers R. Matthew , Brown Kyrah K. , Lee Rebecca E.
Published: July 2024

Background

The racial/ethnic and gender disparities in cardiovascular disease (CVD) morbidity and mortality in the United States are evident. Across nearly every metric, non-Hispanic Black women have poorer overall cardiovascular health. Emerging evidence shows a disproportionately high burden of increased CVD risk factors in Black women of childbearing age, which has a far-reaching impact on both maternal and child outcomes, resulting in premature onset of CVD and further widens the racial disparities in CVD. There is growing recognition that the fundamental driver of persistent racial/ethnic disparities in CVD, as well as disparities in behavioral risk factors such as physical activity and sleep, is structural racism. Further, the lived personal experience of racial discrimination not only has a negative impact on health behaviors, but also links to various physiological pathways to CVD risks, such as internalized stress resulting in a pro-inflammatory state. Limited research, however, has examined the interaction between daily experience and health behaviors, which are influenced by upstream social determinants of health, and the downstream effect on biological/physiological indicators of cardiovascular health in non-pregnant Black women of childbearing age.

Methods/Design

The BLOOM Study is an observational study that combines real-time ambulatory assessments over a 10-day monitoring period with in-depth cross-sectional lab-based physiological and biological assessments. We will use a wrist-worn actigraphy device to capture 24-h movement behaviors and electronic ecological momentary assessment to capture perceived discrimination, microaggression, and stress. Blood pressure will be captured continuously through a wristband. Saliva samples will be self-collected to assess cortisol level as a biomarker of psychological stress. Lab assessments include a fasting venous blood sample, and assessment of various indices of peripheral and cerebral vascular function/health. Participants’ address or primary residence will be used to obtain neighborhood-level built environmental and social environmental characteristics. We plan to enroll 80 healthy Black women who are between 18 and 49 years old for this study.

Discussion

Results from this study will inform the development of multilevel (i.e., individual, interpersonal, and social-environmental levels) lifestyle interventions tailored to Black women based on their lived experiences with the goal of reducing CVD risk.

ClinicalTrials.gov Identifier

NCT06150989.
CALU promotes lung adenocarcinoma progression by enhancing cell proliferation, migration and invasion
Authors: Li Yan , Sun Shengnan , Zhang Hui , Jing Yongjian , Ji Xingzhao , Wan Qiang , Liu Yi
Published: July 2024

Background

Lung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms.

Methods

5-ethynyl-2’-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells.

Results

The mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells.

Conclusions

The anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.
Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients
Authors: Hovorkova Lenka , Winkowska Lucie , Skorepova Justina , Krumbholz Manuela , Benesova Adela , Polivkova Vaclava , Alten Julia , Bardini Michela , Meyer Claus , Kim Rathana , Trahair Toby N. , Clappier Emmanuelle , Chiaretti Sabina , Henderson Michelle , Sutton Rosemary , Sramkova Lucie , Stary Jan , Polakova Katerina Machova , Marschalek Rolf , Metzler Markus , Cazzaniga Giovanni , Cario Gunnar , Trka Jan , Zaliova Marketa , Zuna Jan
Published: July 2024

Background

The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively.

Methods

By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed “Break-App” web tool to allow visualization and various analyses of the breakpoints. Pearson’s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses.

Results

Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications.

Conclusions

Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.
Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway
Authors: Zhou Chunhao , Cai Zhihai , Guo Jialiang , Li Chengfu , Qin Chenghe , Yan Juanwen , Yang Dehong
Published: July 2024

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1–34), we previously designed a novel PTH analog, PTH(3–34)(29–34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA–MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.
Population-Specific gene expression profiles in prostate cancer: insights from Weighted Gene Co-expression Network Analysis (WGCNA)
Authors: Manouchehri Laleh , Zinati Zahra , Nazari Leyla
Published: July 2024

This study investigates the genetic factors contributing to the disparity in prostate cancer incidence and progression among African American men (AAM) compared to European American men (EAM). The research focuses on employing Weighted Gene Co-expression Network Analysis (WGCNA) on public microarray data obtained from prostate cancer patients. The study employed WGCNA to identify clusters of genes with correlated expression patterns, which were then analyzed for their connection to population backgrounds. Additionally, pathway enrichment analysis was conducted to understand the significance of the identified gene modules in prostate cancer pathways. The Least Absolute Shrinkage and Selection Operator (LASSO) and Correlation-based Feature Selection (CFS) methods were utilized for selection of biomarker genes. The results revealed 353 differentially expressed genes (DEGs) between AAM and EAM. Six significant gene expression modules were identified through WGCNA, showing varying degrees of correlation with prostate cancer. LASSO and CFS methods pinpointed critical genes, as well as six common genes between both approaches, which are indicative of their vital role in the disease. The XGBoost classifier validated these findings, achieving satisfactory prediction accuracy. Genes such as APRT, CCL2, BEX2, MGC26963, and PLAU were identified as key genes significantly associated with cancer progression. In conclusion, the research underlines the importance of incorporating AAM and EAM population diversity in genomic studies, particularly in cancer research. In addition, the study highlights the effectiveness of integrating machine learning techniques with gene expression analysis as a robust methodology for identifying critical genes in cancer research.
Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer
Authors: Li Xiaoxi , Su Nan , Yu Haining , Li Xiaoyan , Sun Shu-lan
Published: July 2024

Background

In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism.

Methods

We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1.

Results

HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions.

Conclusions

Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.
Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study
Authors: Yu Jing , Liu Jian-Ming , Chen Hui-Yi , Xiong Wei-Ming
Published: July 2024

Oseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van’t Hoff equation were − 77.49 kJ/mol, -176.54 J/(mol∙K), and − 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.
Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid
Authors: Cornelli Lotte , Van Paemel Ruben , Ferro dos Santos Maísa R. , Roelandt Sofie , Willems Leen , Vandersteene Jelle , Baert Edward , Mus Liselot M. , Van Roy Nadine , De Wilde Bram , De Preter Katleen
Published: July 2024

Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.
Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer’s disease: a nationwide nested case-control study
Authors: Damsgaard Line , Janbek Janet , Laursen Thomas Munk , Vestergaard Karsten , Gottrup Hanne , Jensen-Dahm Christina , Waldemar Gunhild
Published: July 2024

Background

Patients with young onset Alzheimer’s disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis.

Methods

In a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016–2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals.

Results

The study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05–1.31), increasing to 1.57 (95% CI 1.39–1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users.

Conclusions

In this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD.
Advancements in hand-drawn chemical structure recognition through an enhanced DECIMER architecture
Authors: Rajan Kohulan , Brinkhaus Henning Otto , Zielesny Achim , Steinbeck Christoph
Published: July 2024

Accurate recognition of hand-drawn chemical structures is crucial for digitising hand-written chemical information in traditional laboratory notebooks or facilitating stylus-based structure entry on tablets or smartphones. However, the inherent variability in hand-drawn structures poses challenges for existing Optical Chemical Structure Recognition (OCSR) software. To address this, we present an enhanced Deep lEarning for Chemical ImagE Recognition (DECIMER) architecture that leverages a combination of Convolutional Neural Networks (CNNs) and Transformers to improve the recognition of hand-drawn chemical structures. The model incorporates an EfficientNetV2 CNN encoder that extracts features from hand-drawn images, followed by a Transformer decoder that converts the extracted features into Simplified Molecular Input Line Entry System (SMILES) strings. Our models were trained using synthetic hand-drawn images generated by RanDepict, a tool for depicting chemical structures with different style elements. A benchmark was performed using a real-world dataset of hand-drawn chemical structures to evaluate the model's performance. The results indicate that our improved DECIMER architecture exhibits a significantly enhanced recognition accuracy compared to other approaches.

Scientific contribution

The new DECIMER model presented here refines our previous research efforts and is currently the only open-source model tailored specifically for the recognition of hand-drawn chemical structures. The enhanced model performs better in handling variations in handwriting styles, line thicknesses, and background noise, making it suitable for real-world applications. The DECIMER hand-drawn structure recognition model and its source code have been made available as an open-source package under a permissive license.

Graphical Abstract
Ultrasensitive detection of uveal melanoma using [18F]AlF-NOTA-PRGD2 PET imaging
Authors: Wang Ling , Zhu Xue , Xue Yan , Huang Zhihong , Zou Wenjun , Zhang Zhengwei , Yu Mengxi , Pan Donghui , Wang Ke
Published: July 2024

Background

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted.

Results

The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer.

Conclusion

[18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis.

Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972.
ASOD: an adaptive stream outlier detection method using online strategy
Authors: Hu Zhichao , Yu Xiangzhan , Liu Likun , Zhang Yu , Yu Haining
Published: July 2024

In the current era of information technology, blockchain is widely used in various fields, and the monitoring of the security and status of the blockchain system is of great concern. Online anomaly detection for the real-time stream data plays vital role in monitoring strategy to find abnormal events and status of blockchain system. However, as the high requirements of real-time and online scenario, online anomaly detection faces many problems such as limited training data, distribution drift, and limited update frequency. In this paper, we propose an adaptive stream outlier detection method (ASOD) to overcome the limitations. It first designs a K-nearest neighbor Gaussian mixture model (KNN-GMM) and utilizes online learning strategy. So, it is suitable for online scenarios and does not rely on large training data. The K-nearest neighbor optimization limits the influence of new data locally rather than globally, thus improving the stability. Then, ASOD applies the mechanism of dynamic maintenance of Gaussian components and the strategy of dynamic context control to achieve self-adaptation to the distribution drift. And finally, ASOD adopts a dimensionless distance metric based on Mahalanobis distance and proposes an automatic threshold method to accomplish anomaly detection. In addition, the KNN-GMM provides the life cycle and the anomaly index for continuous tracking and analysis, which facilities the cause analysis and further interpretation and traceability. From the experimental results, it can be seen that ASOD achieves near-optimal F1 and recall on the NAB dataset with an improvement of 6% and 20.3% over the average, compared to baselines with sufficient training data. ASOD has the lowest F1 variance among the five best methods, indicating that it is effective and stable for online anomaly detection on stream data.
Alopecia areata following COVID-19 vaccine: a systematic review
Authors: Zhu Yunxia , Ouyang Xiaoliang , Zhang Deng , Wang Xiuping , Wu Liang , Yu Simin , Tan Yanping , Li Wei , Li Chunming
Published: July 2024

Background

To date, multiple cases of adverse reactions to COVID-19 vaccines have been reported worldwide. Alopecia areata (AA) is an uncommon type of adverse reaction reported in some articles and has a significant social and psychological impact on patients. Our study aimed to review the AA and COVID-19 vaccine literature.

Methods

This systematic review was conducted by searching for articles on AA following COVID-19 vaccines in international databases such as Embase, MEDLINE, PubMed, Web of Knowledge, and Ovid from December 2019 to December 30, 2023. We included studies that provided data for AA patients following COVID-19 vaccination with at least one dose. Data on sex, age, country/region of origin, vaccine type, days between vaccination and symptom presentation, manifestations of AA, trichoscopy and histopathological findings, treatment, and outcomes were included.

Results

In total, 579 explored studies were identified and assessed, and 25 articles with a total of 51 patients were included in the review. Twenty-seven (52.9%) patients developed new-onset AA following receiving the COVID-19 vaccine, and AA recurrence or exacerbation occurred after receiving the COVID-19 vaccine in 24 (47.1%) patients with preexisting disease. Five vaccines were reported to cause AA in all cases. The Pfizer vaccine (45.1%) was the most frequently reported, followed by the ChAdOx1 nCoV-19 vaccine (27.5%), Moderna mRNA-1273 (19.6%), Sinopharm (3.9%) and SinoVac (3.9%). AA occurred most frequently within one month after the 1st dose, and then, the incidence decreased gradually with time. Topical or systemic corticosteroids were used in 38 patients. Eleven patients were treated with a Janus Kinase inhibitor (jakinib) inhibitor, eight with tofacitinib, and three with an unspecified jakinib. However, 3 of the 11 patients experienced exacerbations after treatment.

Conclusion

AA after COVID-19 vaccination is rare, and physicians should be aware of this phenomenon to improve early diagnosis and appropriate treatment.
Heat stress affects mammary metabolism by influencing the plasma flow to the glands
Authors: Zeng Jia , Wang Diming , Sun Huizeng , Liu Hongyun , Zhao Feng-Qi , Liu Jianxin
Published: July 2024

Background

Environmental heat stress (HS) can have detrimental effects on milk production by compromising the mammary function. Mammary plasma flow (MPF) plays a crucial role in nutrient supply and uptake in the mammary gland. In this experiment, we investigated the physiological and metabolic changes in high-yielding cows exposed to different degrees of HS: no HS with thermal-humidity index (THI) below 68 (No-HS), mild HS (Mild-HS, 68 ≤ THI ≤ 79), and moderate HS (Mod-HS, 79 < THI ≤ 88) in their natural environment. Our study focused on the changes in blood oxygen supply and mammary glucose uptake and utilization.

Results

Compared with No-HS, the MPF of dairy cows was greater (P < 0.01) under Mild-HS, but was lower (P < 0.01) in cows under Mod-HS. Oxygen supply and consumption exhibited similar changes to the MPF under different HS, with no difference in ratio of oxygen consumption to supply (P = 0.46). The mammary arterio-vein differences in glucose concentration were lower (P < 0.05) under Mild- and Mod-HS than under no HS. Glucose supply and flow were significantly increased (P < 0.01) under Mild-HS but significantly decreased (P < 0.01) under Mod-HS compared to No-HS. Glucose uptake (P < 0.01) and clearance rates (P < 0.01) were significantly reduced under Mod-HS compared to those under No-HS and Mild-HS. Under Mild-HS, there was a significant decrease (P < 0.01) in the ratio of lactose yield to mammary glucose supply compared to that under No-HS and Mod-HS, with no difference (P = 0.53) in the ratio of lactose yield to uptaken glucose among different HS situations.

Conclusions

Degrees of HS exert different influences on mammary metabolism, mainly by altering MPF in dairy cows. The output from this study may help us to develop strategies to mitigate the impact of different degrees of HS on milk production.
Exogenous ethephon treatment on the biosynthesis and accumulation of astragaloside IV in Astragalus membranaceus Bge. Var. Mongholicus (Bge.) Hsiao
Authors: Wu Haonan , Cui Hang , Tian Yu , Wu Jiawen , Bai Zhenqing , Zhang Xiujuan
Published: July 2024

Background

Astragaloside IV is a main medicinal active ingredient in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao, which is also the key biomarker of A. membranaceus quality. Ethylene has been well-documented to involve in secondary metabolites biosynthesis in plants. Nevertheless, how ethylene regulates astragaloside IV biosynthesis in A. membranaceus is still unclear. Therefore, in the present study different dosages and time-dependent exogenous application of ethephon (Eth) were employed to analyze astragaloside IV accumulation and its biosynthesis genes expression level in hydroponically A. membranaceus.

Results

Exogenous 200 µmol·L− 1Eth supply is most significantly increased astragaloside IV contents in A. membranaceus when compared with non-Eth supply. After 12 h 200 µmol·L− 1 Eth treatment, the astragaloside IV contents reaching the highest content at 3 d Eth treatment(P ≤ 0.05). Moreover, After Eth treatment, all detected key genes involved in astragaloside IV synthesis were significant decrease at 3rd day(P ≤ 0.05). However, SE displayed a significant increase at the 3rd day under Eth treatment(P ≤ 0.05). Under Eth treatment, the expression level of FPS, HMGR, IDI, SS, and CYP93E3 exhibited significant negative correlations with astragaloside IV content, while expression level of SE displayed a significant positive correlation.

Conclusions

These findings suggest that exogenous Eth treatment can influence the synthesis of astragaloside IV by regulating the expression of FPS, HMGR, IDI, SS, CYP93E3 and SE. This study provides a theoretical basis for utilizing molecular strategies to enhance the quality of A. membranaceus.
Design of point-of-care electrochemical sensor for therapeutic drug monitoring of ofloxacin in biological fluids
Authors: Kelani Khadiga M. , Fayez Yasmin Mohammed , Gad Asmaa G. , Mahmoud Amr M.
Published: July 2024

A disposable screen-printed sensor has been crafted specifically for therapeutic drug monitoring purposes, particularly for detecting ofloxacin in biological fluids. To enhance selectivity toward ofloxacin, a supramolecular calix [6] arene serves as the ionophore of choice. The sensor incorporates a graphene nanocomposite as an ion-to-electron transducer layer, which not only boosts potential stability but also mitigates potential drift. The developed ofloxacin sensor underwent rigorous characterization following IUPAC guidelines. The linearity range spans from 1 × 10–6 to 1 × 10–2 M, with a measured slope of 59.0 mV/decade. Impressively, it boasts a percentage recovery of 100.18 ± 1.60 and a low detection limit (LOD) of 6 × 10–7 M. Stability assessments indicate reliable performance over an extended period of 8 weeks. The versatility of this sensor extends to various applications, including the determination of ofloxacin in pharmaceutical formulations, bulk powder, and biological fluids. Notably, it has demonstrated efficacy post-bioanalysis validation, adhering to Food and Drug Administration regulations. This advancement holds promise for personalized therapeutic drug monitoring in clinical pharmacy studies and quality control laboratories, thereby optimizing patient care at the point-of-care.

Graphical abstract
Saving behavior among immigrant and native youth
Authors: Lössbroek Jelle , Van Tubergen Frank
Published: July 2024

This study investigates the role of migration background in the saving behavior of youth, with a focus on immigrant generation, national origin, and the influence of cultural and socioeconomic factors. Drawing on a nationally representative dataset of over 28,000 secondary school students in the Netherlands, we employ binary logit models to analyze two dimensions of saving behavior: the likelihood of saving money and the propensity to use bank accounts for savings. Our findings reveal significant disparities in saving behavior among immigrant and non-immigrant youth. Migrant youth are less likely to save overall, and when they do, they exhibit a reduced inclination to use bank accounts for their savings. Furthermore, the study uncovers nuanced patterns within the immigrant youth population. First-generation immigrant youth display lower levels of saving and bank account usage compared to their second-generation counterparts, particularly to those with one foreign-born parent. Distinct national origin effects are observed, as Turkish and Moroccan youth exhibit reduced likelihoods of saving, particularly through bank accounts, compared to Surinamese and Dutch Antillean youth. The results also indicate that the disparities in saving behavior across migration background, immigrant generation, and national origin are partly explained by socioeconomic and cultural forces. Socio-economic status and parental education emerge as key determinants, with higher parental socio-economic resources and education levels positively associated with youth saving behavior and bank account usage. Additionally, religious affiliation, particularly among Muslim youth, contributes to variations in saving behavior due to the prohibition of interest-bearing transactions.
Dynamic resectorization to improve utility of healthcare systems
Authors: Teymourifar Aydin , Trindade Maria A. M.
Published: July 2024

Balancing is an essential challenge in healthcare systems that requires effective strategies. This study aims to address this crucial issue by suggesting a practical approach. We show the potential of balancing a regional healthcare system to improve its utility. We consider a regional healthcare system comprising multiple hospitals with different sizes, capacities, quality of service, and accessibility. We define a utility function for the system based on the sectorization concept, which endeavors to form a balance between hospitals in terms of essential outputs such as waiting times and demands. The dynamic nature of the system means that this balance degrades over time, necessitating periodic sectorization, which is called resectorization. Our methodology stands out for incorporating resectorization as a dynamic strategy, enabling more flexible and responsive adaptations to continuously changing healthcare needs. Unlike previous studies, based on a system-oriented approach, our resectorization scenarios include the periodic closure of some hospitals. This enables us to enhance both the capacity and quality of healthcare facilities. Furthermore, in contrast to other studies, we investigate the states of diminishing demand throughout the resectorization process. To provide empirical insights, we conduct a simulation using data from a real-world case study. Our analysis spans multiple time periods, enabling us to dynamically quantify the utility of the healthcare system. The numerical findings demonstrate that substantial utility improvements are attainable through the defined scenarios. The study suggests a practical solution to the critical challenge of balancing issues in regional healthcare systems.