bluuebunny/crossref_metadata_2025 huggingface dataset:
How I use next-generation sequencing–MRD to plan approach and prevent relapse after HCT for children and adults with ALL
Authors: Muffly Lori , Liang Emily C. , Dolan J. Gregory , Pulsipher Michael A.
Published: May 2024

Measurable residual disease (MRD) evaluation by multiparameter flow cytometry (MFC) or quantitative polymerase chain reaction methods is an established standard of care for assessing risk of relapse before or after hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL). Next-generation sequencing (NGS)–MRD has emerged as a highly effective approach that allows for the detection of lymphoblasts at a level of <1 in 106 nucleated cells, increasing sensitivity of ALL detection by 2 to 3 logs. Early studies have shown superior results compared with MFC and suggest that NGS-MRD may allow for the determination of patients in whom reduced toxicity transplant preparative approaches could be deployed without sacrificing outcomes. Many centers/study groups have implemented immune modulation approaches based on MRD measurements that have resulted in improved outcomes. Challenges remain with NGS-MRD, because it is not commercially available in many countries, and interpretation of results can be complex. Through patient case review, discussion of relevant studies, and detailed expert opinion, we share our approach to NGS-MRD testing before and after HCT in pediatric and adult ALL. Improved pre-HCT risk classification and post-HCT monitoring for relapse in bone marrow and less invasive peripheral blood monitoring by NGS-MRD may lead to alternative approaches to prevent relapse in patients undergoing this challenging procedure.
Real-Time Intelligent Diagnosis of Co-frequency Vibration Faults in Rotating Machinery Based on Lightweight-Convolutional Neural Networks
Authors: Pan Xin , Zhang Xiancheng , Jiang Zhinong , Bin Guangfu
Published: May 2024

The co-frequency vibration fault is one of the common faults in the operation of rotating equipment, and realizing the real-time diagnosis of the co-frequency vibration fault is of great significance for monitoring the health state and carrying out vibration suppression of the equipment. In engineering scenarios, co-frequency vibration faults are highlighted by rotational frequency and are difficult to identify, and existing intelligent methods require more hardware conditions and are exclusively time-consuming. Therefore, Lightweight-convolutional neural networks (LW-CNN) algorithm is proposed in this paper to achieve real-time fault diagnosis. The critical parameters are discussed and verified by simulated and experimental signals for the sliding window data augmentation method. Based on LW-CNN and data augmentation, the real-time intelligent diagnosis of co-frequency is realized. Moreover, a real-time detection method of fault diagnosis algorithm is proposed for data acquisition to fault diagnosis. It is verified by experiments that the LW-CNN and sliding window methods are used with high accuracy and real-time performance.
Accuracy of cup placement compared with preoperative surgeon targets in primary total hip arthroplasty using standard instrumentation and techniques: a global, multicenter study
Authors: Meermans Geert , Fawley David , Zagra Luigi , ten Broeke René H. M. , Johnson Kory , Bernard Thierry , Thomason Henry Clayton
Published: May 2024

Background

Acetabular cup positioning in total hip arthroplasty (THA) is closely related to outcomes. The literature has suggested cup parameters defined by the Lewinnek safe zone; however, the validity of such measures is in question. Several studies have raised concerns about the benefits of using the Lewinnek safe zone as a predictor of success. In this study we elected to use prospective surgeon targets as the basis for comparison to see how successful surgeons are positioning their cup using standard instruments and techniques.

Methods

A prospective, global, multicenter study was conducted. Cup positioning success was defined as a composite endpoint. Both cup inclination and version needed to be within 10° of the surgeon target to be considered a success. Radiographic analysis was conducted by a third-party reviewer.

Results

In 170 subjects, inclination, target versus actual, was 44.8° [standard deviation (SD 0.9°)] and 43.1° (SD 7.6°), respectively (p = 0.0029). Inclination was considered successful in 84.1% of cases. Mean version, target versus actual, was 19.4° (SD 3.9°) and 27.2° (SD 5.6°), respectively (p < 0.0001). Version was considered successful in 63.4% of cases, and combined position (inclination and version) was considered successful in 53.1%.

Conclusion

This study shows that with traditional methods of placing the cup intraoperatively, surgeons are only accurate 53.1% of the time compared with a predicted preoperative plan. This study suggests that the inconsistency in cup positioning based on the surgeon’s planned target is potentially another important variable to consider while using a mechanical guide or in freehand techniques for cup placement in THA.

Trial Registration: This study is registered on ClinicalTrials.gov, NCT03189303.
Liver sinusoidal endothelial cells rely on oxidative phosphorylation but avoid processing long-chain fatty acids in their mitochondria
Authors: Kaczara Patrycja , Czyzynska-Cichon Izabela , Kus Edyta , Kurpinska Anna , Olkowicz Mariola , Wojnar-Lason Kamila , Pacia Marta Z. , Lytvynenko Olena , Baes Myriam , Chlopicki Stefan
Published: May 2024

Background

It is generally accepted that endothelial cells (ECs), primarily rely on glycolysis for ATP production, despite having functional mitochondria. However, it is also known that ECs are heterogeneous, and their phenotypic features depend on the vascular bed. Emerging evidence suggests that liver sinusoidal ECs (LSECs), located in the metabolically rich environment of the liver, show high metabolic plasticity. However, the substrate preference for energy metabolism in LSECs remains unclear.

Methods

Investigations were conducted in primary murine LSECs in vitro using the Seahorse XF technique for functional bioenergetic assays, untargeted mass spectrometry-based proteomics to analyse the LSEC proteome involved in energy metabolism pathways, liquid chromatography-tandem mass spectrometry-based analysis of acyl-carnitine species and Raman spectroscopy imaging to track intracellular palmitic acid.

Results

This study comprehensively characterized the energy metabolism of LSECs, which were found to depend on oxidative phosphorylation, efficiently fuelled by glucose-derived pyruvate, short- and medium-chain fatty acids and glutamine. Furthermore, despite its high availability, palmitic acid was not directly oxidized in LSEC mitochondria, as evidenced by the acylcarnitine profile and etomoxir’s lack of effect on oxygen consumption. However, together with l-carnitine, palmitic acid supported mitochondrial respiration, which is compatible with the chain-shortening role of peroxisomal β-oxidation of long-chain fatty acids before further degradation and energy generation in mitochondria.

Conclusions

LSECs show a unique bioenergetic profile of highly metabolically plastic ECs adapted to the liver environment. The functional reliance of LSECs on oxidative phosphorylation, which is not a typical feature of ECs, remains to be determined.
Eco-friendly bio-nanocomposites: pioneering sustainable biomedical advancements in engineering
Authors: Nandhini J. , Karthikeyan E. , Rajeshkumar S.
Published: May 2024

Biomedical nanocomposites, which are an upcoming breed of mischievous materials, have ushered in a new dimension in the healthcare sector. Incorporating these materials tends to boost features this component already possesses and give might to things these components could not withstand alone. The biopolymer, which carries the nanoparticles, can simultaneously improve the composite's stiffness and biological characteristics, and vice versa. This increases the options of the composite and the number of times it can be used. The bio-nanocomposites and nanoparticles enable the ecocompatibility of the medicine in their biodegradability, and they, in this way, have ecological sustainability. The outcome is the improved properties of medicine and its associated positive impact on the environment. They have broad applications in antimicrobial agents, drug carriers, tissue regeneration, wound care, dentistry, bioimaging, and bone filler, among others. The dissertation on the elements of bio-nanocomposites emphasizes production techniques, their diverse applications in medicine, match-up issues, and future-boasting prospects in the bio-nanocomposites field. Through the utilization of such materials, scientists can develop more suitable for the environment and healthy biomedical solutions, and world healthcare in this way improves as well.
Development of Novel KASP Markers for Improved Germination in Deep-Sown Direct Seeded Rice
Authors: Sandhu Nitika , Singh Jasneet , Ankush Ade Pooja , Augustine Gaurav , Raigar Om Prakash , Verma Vikas Kumar , Pruthi Gomsie , Kumar Arvind
Published: May 2024

Background

The lack of stable-high yielding and direct-seeded adapted varieties with better germination ability from deeper soil depth and availability of molecular markers are major limitation in achieving the maximum yield potential of rice under water and resource limited conditions. Development of high-throughput and trait-linked markers are of great interest in genomics-assisted breeding. The aim of present study was to develop and validate novel KASP (Kompetitive Allele-Specific PCR) markers associated with traits improving germination and seedling vigor of deep sown direct seeded rice (DSR).

Results

Out of 58 designed KASP assays, four KASP assays did not show any polymorphism in any of the eleven genetic backgrounds considered in the present study. The 54 polymorphic KASP assays were then validated for their robustness and reliability on the F1s plants developed from eight different crosses considered in the present study. The third next validation was carried out on 256 F3:F4 and 713 BC3F2:3 progenies. Finally, the reliability of the KASP assays was accessed on a set of random 50 samples from F3:F4 and 80–100 samples from BC3F2:3 progenies using the 10 random markers. From the 54 polymorphic KASP, based on the false positive rate, false negative rate, KASP utility in different genetic backgrounds and significant differences in the phenotypic values of the positive (desirable) and negative (undesirable) traits, a total of 12 KASP assays have been selected. These 12 KASP include 5 KASP on chromosome 3, 1 on chromosome 4, 3 on chromosome 7 and 3 on chromosome 8. The two SNPs lying in the exon regions of LOC_Os04g34290 and LOC_Os08g32100 led to non-synonymous mutations indicating a possible deleterious effect of the SNP variants on the protein structure.

Conclusion

The present research work will provide trait-linked KASP assays, improved breeding material possessing favourable alleles and breeding material in form of expected pre-direct-seeded adapted rice varieties. The marker can be utilized in introgression program during pyramiding of valuable QTLs/genes providing adaptation to rice under DSR. The functional studies of the genes LOC_Os04g34290 and LOC_Os08g32100 possessing two validated SNPs may provide valuable information about these genes.
Machine learning based DNA melt curve profiling enables automated novel genotype detection
Authors: Boussina Aaron , Langouche Lennart , Obirieze Augustine C. , Sinha Mridu , Mack Hannah , Leineweber William , Aralar April , Pride David T. , Coleman Todd P. , Fraley Stephanie I.
Published: May 2024

Surveillance for genetic variation of microbial pathogens, both within and among species, plays an important role in informing research, diagnostic, prevention, and treatment activities for disease control. However, large-scale systematic screening for novel genotypes remains challenging in part due to technological limitations. Towards addressing this challenge, we present an advancement in universal microbial high resolution melting (HRM) analysis that is capable of accomplishing both known genotype identification and novel genotype detection. Specifically, this novel surveillance functionality is achieved through time-series modeling of sequence-defined HRM curves, which is uniquely enabled by the large-scale melt curve datasets generated using our high-throughput digital HRM platform. Taking the detection of bacterial genotypes as a model application, we demonstrate that our algorithms accomplish an overall classification accuracy over 99.7% and perform novelty detection with a sensitivity of 0.96, specificity of 0.96 and Youden index of 0.92. Since HRM-based DNA profiling is an inexpensive and rapid technique, our results add support for the feasibility of its use in surveillance applications.
CAREx: context-aware read extension of paired-end sequencing data
Authors: Kallenborn Felix , Schmidt Bertil
Published: May 2024

Background

Commonly used next generation sequencing machines typically produce large amounts of short reads of a few hundred base-pairs in length. However, many downstream applications would generally benefit from longer reads.

Results

We present CAREx—an algorithm for the generation of pseudo-long reads from paired-end short-read Illumina data based on the concept of repeatedly computing multiple-sequence-alignments to extend a read until its partner is found. Our performance evaluation on both simulated data and real data shows that CAREx is able to connect significantly more read pairs (up to $$99\%$$

99
%

for simulated data) and to produce more error-free pseudo-long reads than previous approaches. When used prior to assembly it can achieve superior de novo assembly results. Furthermore, the GPU-accelerated version of CAREx exhibits the fastest execution times among all tested tools.

Conclusion

CAREx is a new MSA-based algorithm and software for producing pseudo-long reads from paired-end short read data. It outperforms other state-of-the-art programs in terms of (i) percentage of connected read pairs, (ii) reduction of error rates of filled gaps, (iii) runtime, and (iv) downstream analysis using de novo assembly. CAREx is open-source software written in C++ (CPU version) and in CUDA/C++ (GPU version). It is licensed under GPLv3 and can be downloaded at (https://github.com/fkallen/CAREx).
Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data
Authors: Ren Yongcheng , Wang Wenwen , Zou Haiyin , Lei Yicun , Li Yiduo , Li Zheng , Zhang Xiaofang , Kong Lingzhen , Yang Lei , Cao Fuqun , Yan Wei , Wang Pengfei
Published: May 2024

Background

Limited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people.

Methods

In this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study.

Results

The prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65–0.92) and 0.80(0.71–0.90), respectively (P-trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84–0.91).

Conclusions

Each increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.
Clinical distinctions in symptomatology and psychiatric comorbidities between misdiagnosed bipolar I and bipolar II disorder versus major depressive disorder
Authors: Wu Zhiguo , Wang Jun , Zhang Chen , Peng Daihui , Mellor David , Luo Yanli , Fang Yiru
Published: May 2024

Background

To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD .

Methods

The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses.

Results

A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD .

Conclusion

The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.
Evaluation of osteomeatal complex by cone-beam computed tomography in patients with maxillary sinus pathology and nasal septum deviation
Authors: İncebeyaz Burak , Öztaş Bengi
Published: May 2024

Background

This study aimed to determine if there is a relationship between the presence of maxillary sinus pathology, nasal septum deviation and various lengths of the osteomeatal complex.

Methods

A total of 223 CBCT images were included in the study. The lengths of the osteomeatal complex (maxillary sinus ostium width, infundibulum length, maxillary sinus ostium height) were analyzed. The presence of maxillary sinus pathology, nasal septum deviation, age, sex, right-left, septum deviation level, and the relationship between pathology level and all variables were evaluated.

Results

The average maxillary sinus ostium width, ostium height and infundibulum length were 3.06 ± 0.70 mm, 30.10 ± 5.43 mm and 8.82 ± 1.86 mm, respectively. Ostium width was significantly higher in the healthy group than in the groups evaluated in the presence of deviation and pathology. A significant difference was found in infundibulum length only between the healthy condition and the condition evaluated in the presence of deviation. No significant difference was observed between the groups in terms of ostium height. In all groups, ostium height and infundibulum length were significantly higher in men than in women. The age group with the highest average ostium height was found in the 35–44 age group (p < 0.001).

Conclusion

Identifying normal and abnormal conditions in the osteomeatal complex area is important for diagnosing the cause of a patient's complaint, guiding the surgical procedures to be performed, and preventing possible complications that may arise during surgical procedures.
The effect of antiresorptive therapy on the prevalence and severity of oral lichen planus: a retrospective study
Authors: Parvini Puria , Obreja Karina , Cafferata Emilio A. , Aini Tuba , Lermen Yanislava , Begic Amira , Sader Robert , Schwarz Frank
Published: May 2024

Background

Antiresorptive therapy (AR) disrupts osseous homeostasis and can induce direct irritation over the gastrointestinal mucosa; however, its possible erosive effects on the oral epithelium have not been totally described. Among the most frequent oral erosive lesions, oral lichen planus (OLP) frequently presents as painful mucosal ulcerations, arising from basal membrane inflammatory damage. Thus, the aim of this retrospective study was to describe the association between AR and the incidence of OLP.

Methods

This case-control study included data from 148 patients (17 patients undergoing AR therapy (AR group) / 131 without AR therapy (Control group)). Each patient record was systematically processed and the association between AR drugs and OLP clinical characteristics within both groups was assessed.

Results

The erosive form of OLP was significantly more frequent in the AR group than in the Control group (p = 0.029). Indeed, the AR treatment using alendronic acid (41.2%) was the most frequently reported. Additionally, the erosive form of OLP showed the strongest association with pain and burning sensation among the OLP types (p < 0.050). However, disease worsening and AR consumption were not significantly associated (p = 0.150).

Conclusions

Patients under AR therapy show more clinical symptoms associated to the erosive type of OLP. Regardless of the AR therapy, the erosive type of OLP is associated with more severe symptoms.
Exploring clinical specialists’ perspectives on the future role of AI: evaluating replacement perceptions, benefits, and drawbacks
Authors: Daniyal Muhammad , Qureshi Moiz , Marzo Roy Rillera , Aljuaid Mohammed , Shahid Duaa
Published: May 2024

Background of study

Over the past few decades, the utilization of Artificial Intelligence (AI) has surged in popularity, and its application in the medical field is witnessing a global increase. Nevertheless, the implementation of AI-based healthcare solutions has been slow in developing nations like Pakistan. This unique study aims to assess the opinion of clinical specialists on the future replacement of AI, its associated benefits, and its drawbacks in form southern region of Pakistan.

Material and methods

A cross-sectional selective study was conducted from 140 clinical specialists (Surgery = 24, Pathology = 31, Radiology = 35, Gynecology = 35, Pediatric = 17) from the neglected southern Punjab region of Pakistan. The study was analyzed using χ2 - the test of association and the nexus between different factors was examined by multinomial logistic regression.

Results

Out of 140 respondents, 34 (24.3%) believed hospitals were ready for AI, while 81 (57.9%) disagreed. Additionally, 42(30.0%) were concerned about privacy violations, and 70(50%) feared AI could lead to unemployment. Specialists with less than 6 years of experience are more likely to embrace AI (p = 0.0327, OR = 3.184, 95% C.I; 0.262, 3.556) and those who firmly believe that AI knowledge will not replace their future tasks exhibit a lower likelihood of accepting AI (p = 0.015, OR = 0.235, 95% C.I: (0.073, 0.758). Clinical specialists who perceive AI as a technology that encompasses both drawbacks and benefits demonstrated a higher likelihood of accepting its adoption (p = 0.084, OR = 2.969, 95% C.I; 0.865, 5.187).

Conclusion

Clinical specialists have embraced AI as the future of the medical field while acknowledging concerns about privacy and unemployment.
Characterization and pharmacokinetics of cinnamon and star anise compound essential oil pellets prepared via centrifugal granulation technology
Authors: Yi Dandan , Xu Wei , Qin Lanqian , Xiang Yifei , MO Yihao , Liu Xia , Liu Yu , Peng Jianbo , Liang Zhengmin , He Jiakang
Published: May 2024

Cinnamon and star anise essential oils are extracted from natural plants and provide a theoretical basis for the development and clinical application of compound essential oil pellets. However, cinnamon oil and star anise oil have the characteristics of a pungent taste, extreme volatility, poor palatability, and unstable physical and chemical properties, which limit their clinical use in veterinary medicine. In this study, the inhibitory effects of cinnamon oil and star anise oil on Escherichia coli and Salmonella were measured. Compound essential oil pellets were successfully prepared by centrifugal granulation technology. Subsequently, the in vitro dissolution of the pellets and their pharmacokinetics in pigs were investigated. The results showd that, cinnamon and star anise oils showed synergistic or additive inhibitiory effects on Escherichia coli and Salmonella. The oil pellets had enteric characteristics in vitro and high dissolution in vitro. The pharmacokinetic results showed that the pharmacokinetic parameters Cmax and AUC were directly correlated with the dosage and showed linear pharmacokinetic characteristics, which provided a theoretical basis for the development and clinical application of compound essential oil pellets.
Acod1/itaconate activates Nrf2 in pulmonary microvascular endothelial cells to protect against the obesity-induced pulmonary microvascular endotheliopathy
Authors: Zhu Li , Wu Zhuhua , Liu Yingli , Ming Yue , Xie Pei , Jiang Miao , Qi Yong
Published: May 2024

Background

Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear.

Methods

mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs.

Results

Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate.

Conclusion

Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.
Screening and genetic engineering of marine-derived Aspergillus terreus for high-efficient production of lovastatin
Authors: Na Han , Zheng Yao-yao , Jia Yaoning , Feng Jingzhao , Huang Jizi , Huang Jihao , Wang Chang-Yun , Yao Guangshan
Published: May 2024

Background

Lovastatin has widespread applications thanks to its multiple pharmacological effects. Fermentation by filamentous fungi represents the major way of lovastatin production. However, the current lovastatin productivity by fungal fermentation is limited and needs to be improved.

Results

In this study, the lovastatin-producing strains of Aspergillus terreus from marine environment were screened, and their lovastatin productions were further improved by genetic engineering. Five strains of A. terreus were isolated from various marine environments. Their secondary metabolites were profiled by metabolomics analysis using Ultra Performance Liquid Chromatography–Mass spectrometry (UPLC–MS) with Global Natural Products Social Molecular Networking (GNPS), revealing that the production of secondary metabolites was variable among different strains. Remarkably, the strain of A. terreus MJ106 could principally biosynthesize the target drug lovastatin, which was confirmed by High Performance Liquid Chromatography (HPLC) and gene expression analysis. By one-factor experiment, lactose was found to be the best carbon source for A. terreus MJ106 to produce lovastatin. To improve the lovastatin titer in A. terreus MJ106, genetic engineering was applied to this strain. Firstly, a series of strong promoters was identified by transcriptomic and green fluorescent protein reporter analysis. Then, three selected strong promoters were used to overexpress the transcription factor gene lovE encoding the major transactivator for lov gene cluster expression. The results revealed that compared to A. terreus MJ106, all lovE over-expression mutants exhibited significantly more production of lovastatin and higher gene expression. One of them, LovE-b19, showed the highest lovastatin productivity at a titer of 1512 mg/L, which represents the highest production level reported in A. terreus.

Conclusion

Our data suggested that combination of strain screen and genetic engineering represents a powerful tool for improving the productivity of fungal secondary metabolites, which could be adopted for large-scale production of lovastatin in marine-derived A. terreus.
Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma
Authors: Wang Qingshui , Liu Jiamin , Li Ruiqiong , Wang Simeng , Xu Yining , Wang Yawen , Zhang Hao , Zhou Yingying , Zhang Xiuli , Chen Xuequn , Zhuang Wei , Lin Yao
Published: May 2024

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.
Causal relationship between serum metabolites and juvenile idiopathic arthritis: a mendelian randomization study
Authors: Zhang Han , Ma Xiao , Liu Wanlu , Wang Ze , Zhang Zian , Chen GuanHong , Zhang Yingze , Wang Tianrui , Yu Tengbo , Zhang Yongtao
Published: May 2024

Background

Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies.

Methods

In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes.

Results

Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors—kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10− 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)—and three protective factors—3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14–0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20–0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51–0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA.

Conclusion

Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
Distinct clinical features of transplanted children with Parvovirus B19 infection
Authors: Jia Ran , Cao Lingfeng , Lu Lijuan , Zhong Huaqing , Xu Menghua , Liu Pengcheng , Zhu Xunhua , Su Liyun , Xu Jin
Published: May 2024

Background

The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven’t been comprehensively described.

Methods

We searched the medical records of all the transplant recipients who attended the Children’s Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children.

Results

A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system.

Conclusions

Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.
Measurement of perceived pressures in psychiatry: paper-and-pencil and computerized adaptive version of the P-PSY35 scale
Authors: Golay Philippe , Martinez Debora , Bachelard Mizué , Silva Benedetta , Brodard Alexandra , Perrin Jonathan , Pedro Fernando Nolan , Renaud Lou-Ann , Bonsack Charles , Morandi Stéphane
Published: May 2024

Purpose

Formal coercion in psychiatry is widely studied yet much less is known about pressures patients may experience, partly because of the very few measures available. The goal of this study was to validate the P-PSY35 (Pressures in Psychiatry Scale) and provide a paper-and-pencil and a computerised adaptive test (CAT) to measure pressures experienced by patients in psychiatry.

Methods

The P-PSY35 items were developed with users. Patients were evaluated during psychiatric hospitalisation or through an online survey. Mokken scale analysis and Item response theory (IRT) were used to select and estimate the items parameters. A Monte-Carlo simulation was performed to evaluate the number of items needed to transform the paper-and-pencil test into a reliable psychometric CAT.

Results

A total of 274 patients were assessed. The P-PSY35 demonstrated good internal validity, internal consistency, convergent and divergent validity. The P-PSY35 could be substantially shortened while maintaining excellent reliability using the CAT procedure.

Conclusion

The P-PSY35 was developed in collaboration with users. It is a psychometrically rigorous tool designed to measure experienced pressures in French-language. The development and successful validation of the P-PSY35 represent a welcome step towards implementing and evaluating programs aimed at reducing negative consequences of coercion.
Translating global evidence into local implementation through technical assistance: a realist evaluation of the Bloomberg philanthropies initiative for global Road safety
Authors: Neill Rachel , Hernández Angélica López , Koon Adam D. , Bachani Abdulgafoor M.
Published: May 2024

Background

Traffic-related crashes are a leading cause of premature death and disability. The safe systems approach is an evidence-informed set of innovations to reduce traffic-related injuries and deaths. First developed in Sweden, global health actors are adapting the model to improve road safety in low- and middle-income countries via technical assistance (TA) programs; however, there is little evidence on road safety TA across contexts. This study investigated how, why, and under what conditions technical assistance influenced evidence-informed road safety in Accra (Ghana), Bogotá (Colombia), and Mumbai (India), using a case study of the Bloomberg Philanthropies Initiative for Global Road Safety (BIGRS).

Methods

We conducted a realist evaluation with a multiple case study design to construct a program theory. Key informant interviews were conducted with 68 government officials, program staff, and other stakeholders. Documents were utilized to trace the evolution of the program. We used a retroductive analysis approach, drawing on the diffusion of innovation theory and guided by the context-mechanism-outcome approach to realist evaluation.

Results

TA can improve road safety capabilities and increase the uptake of evidence-informed interventions. Hands-on capacity building tailored to specific implementation needs improved implementers’ understanding of new approaches. BIGRS generated novel, city-specific analytics that shifted the focus toward vulnerable road users. BIGRS and city officials launched pilots that brought evidence-informed approaches. This built confidence by demonstrating successful implementation and allowing government officials to gauge public perception. But pilots had to scale within existing city and national contexts. City champions, governance structures, existing political prioritization, and socio-cultural norms influenced scale-up.

Conclusion

The program theory emphasizes the interaction of trust, credibility, champions and their authority, governance structures, political prioritization, and the implement-ability of international evidence in creating the conditions for road safety change. BIGRS continues to be a vehicle for improving road safety at scale and developing coalitions that assist governments in fulfilling their role as stewards of population well-being. Our findings improve understanding of the complex role of TA in translating evidence-informed interventions to country-level implementation and emphasize the importance of context-sensitive TA to increase impact.
A protoplast-based transient gene expression assay for the identification of heat and oxidative stress-regulatory genes in perennial ryegrass
Authors: Lei Shanshan , Zhu Yaolong , Jia Weiyu , Zhang Jing , Chi Yingjun , Xu Bin
Published: May 2024

Background

With the accumulating omics data, an efficient and time-saving transient assay to express target genes is desired. Mesophyll protoplasts, maintaining most stress-physiological responses and cellular activities as intact plants, offer an alternative transient assay to study target genes’ effects on heat and oxidative stress responses.

Results

In this study, a perennial ryegrass (Loliumperenne L.) mesophyll protoplast-based assay was established to effectively over- or down-regulate target genes. The relative expression levels of the target genes could be quantified using RT-qPCR, and the effects of heat and H2O2-induced oxidative stress on protoplasts’ viability could be quantitatively measured. The practicality of the assay was demonstrated by identifying the potential thermos-sensor genes LpTT3.1/LpTT3.2 in ryegrass that over-expressing these genes significantly altered protoplasts’ viability rates after heat stress.

Conclusion

This protoplast-based rapid stress regulatory gene identification assay was briefed as ‘PRIDA’ that will complement the stable genetic transformation studies to rapidly identify candidate stress-regulatory genes in perennial ryegrass and other grass species.
Short developmental milestone risk assessment tool to identify Duchenne muscular dystrophy in primary care
Authors: van Dommelen Paula , van Dijk Oisín , de Wilde Jeroen A. , Verkerk Paul H.
Published: May 2024

Background

In patients without a family history, Duchenne muscular dystrophy (DMD) is typically diagnosed at around 4–5 years of age. It is important to diagnose DMD during infancy or toddler stage in order to have timely access to treatment, opportunities for reproductive options, prevention of potential fatal reactions to inhaled anesthetics, awareness of a child’s abilities needed for good parenting, and opportunities for enrolment in clinical trials.

Method

We aimed to develop a short risk assessment tool based on developmental milestones that may contribute to the early detection of boys with DMD in primary care. As part of the case-control 4D-DMD study (Detection by Developmental Delay in Dutch boys with DMD), data on developmental milestones, symptoms and therapies for 76 boys with DMD and 12,414 boys from a control group were extracted from the health records of youth health care services and questionnaires. Multiple imputation, diagnostic validity and pooled backward logistic regression analyses with DMD (yes/no) as the dependent variable and attainment of 26 milestones until 36 months of age (yes/no) as the independent variable were performed. Descriptive statistics on symptoms and therapies were provided.

Results

A tool with seven milestones assessed at specific ages between 12 and 36 months resulted in a sensitivity of 79% (95CI:67–88%), a specificity of 95.8% (95%CI:95.3–96.2), and a positive predictive value of 1:268 boys. Boys with DMD often had symptoms (e.g. 43% had calf muscle pseudohypertrophy) and were referred to therapy (e.g. 59% for physical therapy) before diagnosis.

Discussion

This tool followed by the examination of other DMD-related symptoms could be used by youth health care professionals during day-to-day health assessments in the general population to flag children who require further action.

Conclusions

The majority of boys (79%) with DMD can be identified between 12 and 36 months of age with this tool. It increases the initial a priori risk of DMD from 1 in 5,000 to approximately 1 in 268 boys. We expect that other neuromuscular disorders and disabilities can also be found with this tool.
Investigating the spatiotemporal patterns and clustering of attendances for mental health services to inform policy and resource allocation in Thailand
Authors: Rotejanaprasert Chawarat , Thanutchapat Papin , Phoncharoenwirot Chiraphat , Mekchaiporn Ornrakorn , Chienwichai Peerut , Maude Richard J
Published: May 2024

Background

Mental illness poses a substantial global public health challenge, including in Thailand, where exploration of access to mental health services is limited. The spatial and temporal dimensions of mental illness in the country are not extensively studied, despite the recognized association between poor mental health and socioeconomic inequalities. Gaining insights into these dimensions is crucial for effective public health interventions and resource allocation.

Methods

This retrospective study analyzed mental health service utilization data in Thailand from 2015 to 2023. Temporal trends in annual numbers of individuals visiting mental health services by diagnosis were examined, while spatial pattern analysis employed Moran’s I statistics to assess autocorrelation, identify small-area clustering, and hotspots. The implications of our findings for mental health resource allocation and policy were discussed.

Results

Between 2015 and 2023, mental health facilities documented a total of 13,793,884 visits. The study found anxiety, schizophrenia, and depression emerged as the top three illnesses for mental health visits, with an increase in patient attendance following the onset of the COVID-19 outbreak. Spatial analysis identified areas of significance for various disorders across different regions of Thailand. Positive correlations between certain disorder pairs were found in specific regions, suggesting shared risk factors or comorbidities.

Conclusions

This study highlights spatial and temporal variations in individuals visiting services for different mental disorders in Thailand, shedding light on service gaps and socioeconomic issues. Addressing these disparities requires increased attention to mental health, the development of appropriate interventions, and overcoming barriers to accessibility. The findings provide a baseline for policymakers and stakeholders to allocate resources and implement culturally responsive interventions to improve mental health outcomes.
An exploratory study on spatiotemporal clustering of suicide in Korean adolescents
Authors: Choi Won-Seok , Roh Beop-Rae , Jon Duk-In , Ryu Vin , Oh Yunhye , Hong Hyun Ju
Published: May 2024

Background

Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space–time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space–time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods.

Methods

From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9–18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides.

Results

We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7–59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups.

Conclusion

This study has defined the space–time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.