bluuebunny/crossref_metadata_2025 huggingface dataset:
PHBS ANAK USIA DINI DALAM MENCEGAH PENULARAN PENYAKIT MELALUI CUCI TANGAN
Authors: Agustiani Sirli , Nurvinanda Rezka
Published: March 2024

Mencuci tangan merupakan hal yang sangat penting untuk anak. Mencuci tangan bukan hanya mencegah diri dari tertularnya virus COVID-19 namun juga dapat mengurangi berbagai penyakit yang dapat menular di masa yang akan datang. Kuman penyakit mudah ditularkan melalui tangan. Pentingnya peningkatan kesadaran akan pentingnya melakukan kebiasaan mencuci tangan pada anak mampu meningkatkan kesehatan anak. Anak-anak harus tahu kapan mereka mencuci tangan. Sasaran yaitu anak-anak usia dini yang bersekolah di TK/PAUD Jasmine Tuatunu. Pemberian pendidikan kesehatan dilakukan dengan menggunakan leaflet, pemutaran video sambil bernyanyi serta demonstrasi secara langsung terkait cara mencuci tangan dengan baik dan benar. Anak usia dini harus dibiasakan untuk mandiri membiasakan perilaku hidup bersih dan sehat walaupun proses pemahaman mereka secara tidak langsung dipahami namun proses dalam memahami dan mengimplementasikan terkait perilaku hidup bersih dan sehat salah satunya dengan menerapkan perilaku mencuci tangan tetap harus didampingi dan diberikan oleh orang tua maupun guru di sekolah. pengetahuan dan keterampilan anak-anak dalam melakukan kegiatan cuci tangan menggunakan sabun dan air mengalir terlihat ada peningkatan, hal ini dilihat dari kelancaran dan antusiasme mereka saat melakukan praktik cuci tangan.
Tremor in cervical dystonia
Authors: Beylergil Sinem Balta , Mukunda Krishna Nikhil , Elkasaby Mohamed , Perlmutter Joel S. , Factor Stewart , Bäumer Tobias , Feurestein Jeanne , Shelton Erika , Bellows Steven , Jankovic Joseph , Mahajan Abhimanyu , Wamer-Rosen Tila , Reich Stephen G. , Wagle Shukla Aparna , Malaty Irene , Espay Alberto , Duque Kevin , LeDoux Mark S. , Saunders-Pullman Rachel , Leaver Katherine , Frank Samuel , Pantelyat Alexander , Fung Victor , Pirio Richardson Sarah , Berman Brian , Stover Natividad , Deik Andres , Ondo William , Groth Christopher , Jinnah Hyder A. , Shaikh Aasef G.
Published: March 2024

Background: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources.

Methods: We analyzed the largest cohort of CD patients (n = 3117) available to date, collected from 37 movement disorder centers in North America, Europe, and Asia. We used machine learning to determine what clinical features from clinician reports predicted the presence of tremor as well as its regular or irregular appearance.

Results: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was interpreted as irregular in 1,022, regular in 345, and mixed (both irregular and regular) in 442. A feature importance analysis determined that greater severity of CD, longer disease duration, and older age, in descending order, predicted the presence of neck tremor. The probability of neck tremor was reduced if the dystonia affected other body parts in addition to the neck. We also found a significantly heightened risk for developing neck tremor in women. An additional feature importance analysis indicated that increased severity of dystonia affecting other body parts, severity of CD, and prolonged disease duration was associated with a lower likelihood of regular neck tremor while increased age predicted a higher likelihood.

Conclusion: Machine learning recognized the most relevant clinical features that can predict concurrent neck tremor and its irregularity in a large multi-center dystonia cohort. These results may facilitate a more accurate description of neck tremor and improved care path in CD.
Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors
Authors: Wang Xuekun , Xu Jin , Guo Qingcheng , Li Zhenhua , Cao Jiawei , Fu Rongrong , Xu Mengjiao , Zhao Xiang , Wang Fugui , Zhang Xinmeng , Dong Taimin , Li Xu , Qian Weizhu , Hou Shen , Ji Lusha , Zhang Dapeng , Guo Huaizu
Published: March 2024

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%–22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.
Effect of E-waste copper alloy additions on the microstructure and organization of Cu90PSn brazing joints
Authors: Bao Li , Yang Jiao , Zhang Shannan , Ding Tianran
Published: March 2024

The effects of different contents of e-waste alloy on the microstructure and joint properties of Cu90PSn brazing filler metal was investigated during copper and copper brazing. Microstructure of base metal and brazing filler metal was studied with scanning electronic microscopy (SEM). The properties of brazing joint obtained by adding different electronic waste filler metal for smelting copper alloy were compared together. The results indicated that the fluidity of Cu90PSn brazing filler metal was weakened and the spreading property of Cu90PSn brazing filler metal was damaged after the addition of e-waste copper alloy. The structure of Cu90PSn brazing filler metal is mainly composed of (Cu), Cu3P and (Cu,Sn) compounds. When a small amount of electronic waste copper alloy is added, a trace amount of Fe in the brazing filler metal is distributed in the matrix structure of the filler metal in the form of solid solution. With the increase of copper alloys contents by smelting e-waste, Fe content in Cu90PSn brazing filler metal increases; the granular Fe3P phosphide changes into lamellar form. The Cu3P compound phase changes from continuous large orderly arrangement to discontinuous small block structure. Therefore, adding a trace amount of electronic waste copper alloy to the solder induction brazing copper/copper can obtain a uniform composition of the brazing structure. And the welding performance is not affected. However, As the content of e-waste smelted copper alloy continues to increase, the tensile strength shows a downward trend, which is attributed to the presence of brittle compound Fe3P in the joint.
Vaginal microbiota transplantation is a truly opulent and promising edge: fully grasp its potential
Authors: Meng Yiming , Sun Jing , Zhang Guirong
Published: March 2024

Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.
Dopamine promotes Klebsiella quasivariicola proliferation and inflammatory response in the presence of macrophages
Authors: Li Xiang , Cheng Lin , Liu Xueyang , Wang Xiaoli , Li Rui , Fan Shao , Yan Qiulong , Ma Tonghui , Ma Yufang , Kang Jian
Published: March 2024

Background

Dopamine, a frequently used therapeutic agent for critically ill patients, has been shown to be implicated in clinical infections recently, however, the precise mechanisms underlying this association remain elusive. Klebsiella quasivariicola, a novel strain belonging to the Klebsiella species, exhibits potential pathogenic attributes. The impact of dopamine on K. quasivariicola infection has aroused our interest.

Objective

Considering the contribution of host immune factors during infection, this study aimed to investigate the intricate interactions between K. quasivariicola, dopamine, and macrophages were explored.

Methods

RAW264.7 cells and C57/BL6 mice were infected with K. quasivariicola, and the bacterial growth within macrophage, the production of inflammatory cytokines and the pathological changes in mice lungs were detected, in the absence or presence of dopamine.

Results

Dopamine inhibited the growth of K. quasivariicola in the medium, but promoted bacterial growth when co-cultured with macrophages. The expression of proinflammatory cytokines increased in RAW 264.7 cells infected with K. quasivariicola, and a significant rise was observed upon the addition of dopamine. The infection of K. quasivariicola in mice induced an inflammatory response and lung injury, which were exacerbated by the administration of dopamine.

Conclusions

Our findings suggest that dopamine may be one of the potential risk factors associated with K. quasivariicola infection. This empirical insight provides solid references for clinical precision medicine. Furthermore, an in vitro model of microbes-drugs-host immune cells for inhibitor screening was proposed to more accurately replicate the complex in vivo environment. This fundamental work had contributed to the present understanding of the crosstalk between pathogen, dopamine and host immune cells.
The importance of quantifying fitness-determining traits throughout life to assess the application of reproductive technologies for amphibian species recovery
Authors: Silla Aimee J. , Byrne Phillip G.
Published: March 2024

The application of reproductive technologies to amphibian conservation breeding programs is gaining momentum and the field is poised to contribute significantly toward amphibian species recovery. We briefly discuss the opportunities for reproductive technologies to enhance conservation breeding outcomes, including their potential to enhance the genetic management, and in turn, the fitness of threatened species. Despite this potential, an important consideration that is not yet well understood is the degree to which specific reproductive technologies might influence (either enhance, or in some instances potentially decrease) individual fitness and lead to shifts in population viability. The development of a standardised approach to monitoring offspring throughout life-stages to detect changes to morphology, behaviour, physiology, survivorship, and developmental trajectories is essential. The primary focus of this review is to provide a ‘best-practise’ framework for quantifying key fitness determining traits expected to contribute to the fitness of individuals and long-term viability of populations, which will ultimately allow us to progress the field of amphibian reproductive technologies and assess the impact of protocol refinement.
Comparing the efficacy of glucocorticoids and anti-VEGF in treating diabetic macular edema: systematic review and comprehensive analysis
Authors: Cheng Zhi’ang , Liu Xiaoyong
Published: March 2024

Introduction

The aim of this study was to better understand the efficacy of various drugs, such as glucocorticoids and anti-vascular endothelial growth factors (VEGF), in the treatment of diabetic macular edema (DME), and to evaluate various clinical treatment regimens consisting of different therapeutic measures.

Methods

This study included randomized controlled trials up to February 2023 comparing the efficacy of corticosteroid-related therapy and anti-VEGF therapy. PubMed, the Cochrane Library, and Embase were searched, and the quality of the studies was carefully assessed. Finally, 39 studies were included.

Results

Results at 3-month followup showed that intravitreal injection of bevacizumab (IVB) + triamcinolone acetonide (TA) was the most beneficial in improving best-corrected visual acuity and reducing the thickness of macular edema in the center of the retina in patients with DME. Results at 6-month follow-up showed that intravitreal dexamethasone (DEX) was the most effective in improving patients’ bestcorrected visual acuity and reducing the thickness of central macular edema.

Discussion

Overall, IVB+TA was beneficial in improving best-corrected visual acuity and reducing central macular edema thickness over a 3-month follow-up period, while DEX implants had a better therapeutic effect than anti-VEGF agents at 6 months, especially the patients with severe macular edema and visual acuity impaired.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=397100, identifier CRD42023397100.
Developing a hybrid data-driven and informed model for prediction and mitigation of agricultural nitrous oxide flux hotspots
Authors: Vemuri Nikhil
Published: March 2024

Nitrous oxide (N2O) is one of the most significant contributors to greenhouse forcing and is the biggest contributor to ozone depletion in the 21st century, and roughly 70% of anthropogenic nitrous oxide emissions are from agriculture and soil management. Agricultural nitrous oxide emissions are shown to spike during hotspot events, and according to the data used in this study, over 78% of nitrous oxide flux occurred during just 15% of the recorded data points. Due to the complex biogeochemical processes governing nitrous oxide formation, machine learning and process-based models often fail to predict agricultural nitrous oxide flux. A novel informed neural network was developed that combined the trainability of neural networks with the rigorous differential equation-based framework of process-based models. Differential equations that explained the variability of various nitrogen-containing compounds in soil were derived, and integrated into the network loss. The informed model explained ∼85% of variation in the data and had an F1 score of 0.75, a marked improvement over the classical model explaining ∼30% of variation and having a score of 0.53. The informed network was also able to perform exceptionally well with only small subsets of the training data, having an F1 score of 0.41 with only 25% of training data. The model not only shows great promise in the remarkably accurate prediction of these hotspots but also serves as a potential new paradigm for physics-informed machine learning techniques in environmental and agricultural sciences.
Systemic inflammatory regulators and preeclampsia: a two-sample bidirectional Mendelian randomization study
Authors: Li Chu , Tian Yishu , Dougarem Djouhayna , Sun Litao , Zhong Zixing
Published: March 2024

Background:

Systemic inflammatory regulators have been associated with preeclampsia (PE) during pregnancy; however, there is inconsistent evidence from animal models and observational results.

Methods:

Using summary data from genome-wide association studies (GWASs), we performed a bidirectional Mendelian randomization (MR) analysis of two samples of systemic inflammatory regulators (n = 8,186) and PE (n = 267,242) individuals of European ancestry. As our primary analysis, we used the random-effects inverse-variance weighted (IVW) approach. Sensitivity and pleiotropy analyses were conducted using the MR–Egger method, weighted median, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Cochran’s Q test.

Results:

The results indicate that there is a correlation between a higher circulating level of tumor necrosis factor alpha (TNF-α) and interleukin-9 (IL-9) and an increased risk of PE (odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.09–1.60, p = 0.004 and OR = 1.28, 95% CI: 1.02–1.62, p = 0.033, respectively). Conversely, lower levels of stem cell growth factor beta (SCGF-β) (OR = 0.89, 95% CI: 0.80–0.99, p = 0.027) and interleukin-5 (IL-5) (OR = 0.80, 95% CI: 0.65–0.98, p = 0.030) are linked to an increased risk of PE. The macrophage migration inhibitory factor (MIF) is the downstream inflammatory regulator of PE, according to reverse magnetic resonance imaging studies.

Conclusion:

Our study suggests that SCGF-β, IL-5, IL-9, and TNF-α causally affect the PE risk, while PE is causally associated with MIF. Further studies are needed to validate these biomarkers in managing PE.
The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study
Authors: Das Juhina , Bera Saurav , Ganguly Nilanjan , Guha Ipsita , Ghosh Halder Tithi , Bhuniya Avishek , Nandi Partha , Chakravarti Mohona , Dhar Sukanya , Sarkar Anirban , Das Tapasi , Banerjee Saptak , Ghose Sandip , Bose Anamika , Baral Rathindranath
Published: March 2024

Introduction

Murine tumor growth restriction by neem leaf glycoprotein (NLGP) was established in various transplanted models of murine sarcoma, melanoma and carcinoma. However, the role of NLGP in the sequential carcinogenic steps has not been explored. Thus, tongue carcinogenesis in Swiss mice was induced by 4-nitroquinoline-1-oxide (4NQO), which has close resemblance to human carcinogenesis process. Interventional role of NLGP in initiation-promotion protocol established during 4NQO mediated tongue carcinogenesis in relation to systemic immune alteration and epithelial-mesenchymal transition (EMT) is investigated.

Methods

4NQO was painted on tongue of Swiss mice every third day at a dose of 25µl of 5mg/ml stock solution. After three consecutive treatments with 4NQO (starting Day7), one group of mice was treated with NLGP (s.c. 25μg/mice/week), keeping a group as PBS control. Mice were sacrificed in different time-intervals to harvest tongues and studied using histology, immunohistochemistry, flow-cytometry and RT-PCR on different immune cells and EMT markers (e-cadherin, vimentin) to elucidate their phenotypic and secretory status.

Results

Local administration of 4NQO for consecutive 300 days promotes significant alteration in tongue mucosa including erosion in papillae and migration of malignant epithelial cells to the underlying connective tissue stroma with the formation of cell nests (exophytic-hyperkeratosis with mild dysplasia). Therapeutic NLGP treatment delayed pre-neoplastic changes promoting normalization of mucosa by maintaining normal structure. Flow-cytometric evidences suggest that NLGP treatment upregulated CD8+, IFNγ+, granzyme B+, CD11c+ cells in comparison to 4NQO treated mice with a decrease in Ki67+ and CD4+FoxP3+ cells in NLGP treated cohort. RT-PCR demonstrated a marked reduction of MMP9, IL-6, IL-2, CD31 and an upregulation in CCR5 in tongues from 4NQO+NLGP treated mice in comparison to 4NQO treated group. Moreover, 4NQO mediated changes were associated with reduction of e-cadherin and simultaneous up-regulation of vimentin expression in epithelium that was partially reversed by NLGP.

Discussion

Efficacy of NLGP was tested first time in sequential carcinogenesis model and proved effective in delaying the initial progression. NLGP normalizes type 1 immunity including activation of the CD8+T effector functions, reduction of regulatory T cell functions, along with changes in EMT to make the host systemically alert to combat the carcinogenic threat.
The clinical relevance of heme detoxification by the macrophage heme oxygenase system
Authors: Yeudall Scott , Upchurch Clint M. , Leitinger Norbert
Published: March 2024

Heme degradation by the heme oxygenase (HMOX) family of enzymes is critical for maintaining homeostasis and limiting heme-induced tissue damage. Macrophages express HMOX1 and 2 and are critical sites of heme degradation in healthy and diseased states. Here we review the functions of the macrophage heme oxygenase system and its clinical relevance in discrete groups of pathologies where heme has been demonstrated to play a driving role. HMOX1 function in macrophages is essential for limiting oxidative tissue damage in both acute and chronic hemolytic disorders. By degrading pro-inflammatory heme and releasing anti-inflammatory molecules such as carbon monoxide, HMOX1 fine-tunes the acute inflammatory response with consequences for disorders of hyperinflammation such as sepsis. We then discuss divergent beneficial and pathological roles for HMOX1 in disorders such as atherosclerosis and metabolic syndrome, where activation of the HMOX system sits at the crossroads of chronic low-grade inflammation and oxidative stress. Finally, we highlight the emerging role for HMOX1 in regulating macrophage cell death via the iron- and oxidation-dependent form of cell death, ferroptosis. In summary, the importance of heme clearance by macrophages is an active area of investigation with relevance for therapeutic intervention in a diverse array of human diseases.
Effects of typhoons on primary production and dissolved oxygen in the East China Sea
Authors: Yang Wen , Wu Haokun , Zhang Wenxia
Published: March 2024

Previous investigations confirm that typhoons deliver both dissolved oxygen and nutrient sources via promoting vertical/lateral exchanges between water masses. The former one replenishes oxygen for the bottom water and prevents persistent oxygen depletion, while the latter one facilitates primary production and subsequent subsurface oxygen consumption. However, it is left unknown if typhoons ultimately result in net gain or loss of dissolved oxygen during the passage. Tropical cyclone information, satellite observations, and numerical simulations were used to investigate the response of primary production and dissolved oxygen dynamics to typhoons. Results imply that both typhoon intensity, and distance between typhoon track and the Changjiang estuary control the magnitude of responses in primary production, air-sea oxygen flux, advection-induced oxygen variation, and oxygen consumption variation. The model-based oxygen budget analysis indicated that oxygen content increased after the passage of all typhoons occurred between 2011-2020. The findings in this study suggest that typhoons ultimately result in net gain of oxygen. The increased strength and frequency of typhoon in the warming future would play an important role in counteracting deoxygenation, which is likely to slow down the pace of deterioration of the seasonal hypoxia in this region.
Accuracy of an artificial intelligence as a medical device as part of a UK-based skin cancer teledermatology service
Authors: Marsden Helen , Kemos Polychronis , Venzi Marcello , Noy Mariana , Maheswaran Shameera , Francis Nicholas , Hyde Christopher , Mullarkey Daniel , Kalsi Dilraj , Thomas Lucy
Published: March 2024

Introduction

An artificial intelligence as a medical device (AIaMD), built on convolutional neural networks, has demonstrated high sensitivity for melanoma. To be of clinical value, it needs to safely reduce referral rates. The primary objective of this study was to demonstrate that the AIaMD had a higher rate of correctly classifying lesions that did not need to be referred for biopsy or urgent face-to-face dermatologist review, compared to teledermatology standard of care (SoC), while achieving the same sensitivity to detect malignancy. Secondary endpoints included the sensitivity, specificity, positive and negative predictive values, and number needed to biopsy to identify one case of melanoma or squamous cell carcinoma (SCC) by both the AIaMD and SoC.

Methods

This prospective, single-centre, single-arm, masked, non-inferiority, adaptive, group sequential design trial recruited patients referred to a teledermatology cancer pathway (clinicaltrials.gov NCT04123678). Additional dermoscopic images of each suspicious lesion were taken using a smartphone with a dermoscopic lens attachment. The images were assessed independently by a consultant dermatologist and the AIaMD. The outputs were compared with the final histological or clinical diagnosis.

Results

A total of 700 patients with 867 lesions were recruited, of which 622 participants with 789 lesions were included in the per-protocol (PP) population. In total, 63.3% of PP participants were female; 89.0% identified as white, and the median age was 51 (range 18–95); and all Fitzpatrick skin types were represented including 25/622 (4.0%) type IV-VI skin. A total of 67 malignant lesions were identified, including 8 diagnosed as melanoma. The AIaMD sensitivity was set at 91 and 92.5%, to match the literature-defined clinician sensitivity (91.46%) as closely as possible. In both settings, the AIaMD identified had a significantly higher rate of identifying lesions that did not need a biopsy or urgent referral compared to SoC (p-value = 0.001) with comparable sensitivity for skin cancer.

Discussion

The AIaMD identified significantly more lesions that did not need to be referred for biopsy or urgent face-to-face dermatologist review, compared to teledermatologists. This has the potential to reduce the burden of unnecessary referrals when used as part of a teledermatology service.
A low-cost and eco-friendly recombinant protein expression system using copper-containing industrial wastewater
Authors: Zhou Xiaofeng , Xiang Qiyu , Wu Yubei , Li Yongjuan , Peng Tiantian , Xu Xianxian , Zhou Yongguang , Zhang Lihe , Li Jianghui , Du Linyong , Tan Guoqiang , Wang Wu
Published: March 2024

The development of innovative methods for highly efficient production of recombinant proteins remains a prominent focus of research in the biotechnology field, primarily due to the fact that current commercial protein expression systems rely on expensive chemical inducers, such as isopropyl β-D-thiogalactoside (IPTG). In our study, we designed a novel approach for protein expression by creating a plasmid that responds to copper. This specialized plasmid was engineered through the fusion of a copper-sensing element with an optimized multiple cloning site (MCS) sequence. This MCS sequence can be easily customized by inserting the coding sequences of target recombinant proteins. Once the plasmid was generated, it was introduced into an engineered Escherichia coli strain lacking copA and cueO. With this modified E. coli strain, we demonstrated that the presence of copper ions can efficiently trigger the induction of recombinant protein expression, resulting in the production of active proteins. Most importantly, this expression system can directly utilize copper-containing industrial wastewater as an inducer for protein expression while simultaneously removing copper from the wastewater. Thus, this study provides a low-cost and eco-friendly strategy for the large-scale recombinant protein production. To the best of our knowledge, this is the first report on the induction of recombinant proteins using industrial wastewater.
Low-contrast visual acuity test is associated with central inflammation and predicts disability development in newly diagnosed multiple sclerosis patients
Authors: Dolcetti Ettore , Buttari Fabio , Bruno Antonio , Azzolini Federica , Gilio Luana , Di Caprio Veronica , Lauritano Gianluca , Borrelli Angela , Galifi Giovanni , Furlan Roberto , Finardi Annamaria , Musella Alessandra , Guadalupi Livia , Mandolesi Georgia , Rovella Valentina , Centonze Diego , Stampanoni Bassi Mario
Published: March 2024

Introduction

The visual system is a prominent site of damage in MS since the earliest phases of the disease. Altered low-contrast visual acuity (LCVA) test has been associated with visual impairment and retinal degeneration, predicting medium- and long-term disability. However, it is unclear whether LCVA may also represent a reliable measure of neuroinflammation and a predictor of disease evolution in the very early stages of MS.

Methods

We explored in a group of 76 consecutive newly diagnosed relapsing–remitting MS (RR-MS) patients without visual impairment or altered visual evoked potentials, the association between LCVA scores at 2.5% and 1.25% and clinical characteristics, including prospective disability evaluated after 1- and 2 years of follow-up. Associations between LCVA and the CSF levels of IL-10 at diagnosis were also analyzed.

Results

A negative correlation was found between LCVA at 2.5% and Expanded Disability Status Scale (EDSS) evaluated at first (Spearman’s Rho = −0.349, p = 0.005, n = 62) and second year (Spearman’s Rho = −0.418, p < 0.001, n = 62) of follow-up, and negative correlations were found with Multiple Sclerosis Severity Score (MSSS) at first (Spearman’s Rho = −0.359, p = 0.004, n = 62) and second year (Spearman’s Rho = −0.472, p < 0.001, n = 62). All the data were confirmed by a mixed effect model, considering other clinical variables. A positive correlation was found between the CSF concentrations of IL-10 and LCVA at 2.5% (Spearman’s Rho = 0.272, p = 0.020, n = 76), and 1.25% (Spearman’s Rho, = 0.276, p = 0.018, n = 76), also evidenced in a linear regression.

Discussion

In MS patients at diagnosis, altered LCVA may be associated with CSF inflammation and represent a useful parameter to identify patients with worse disease course.
Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis
Authors: Ma Mian , Cheng Ying , Hou Xiaoxia , Li Zhisen , Wang Meixia , Ma Bodun , Cheng Qingzhang , Ding Zhiliang , Feng Hongxuan
Published: March 2024

Objective

To investigate the serum biomarkers in patients with drug-resistant epilepsy (DRE).

Methods

A total of 9 DRE patients and 9 controls were enrolled. Serum from DRE patients was prospectively collected and analyzed for potential serum biomarkers using TMT18-labeled proteomics. After fine quality control, bioinformatics analysis was conducted to find differentially expressed proteins. Pathway enrichment analysis identified some biological features shared by differential proteins. Protein–protein interaction (PPI) network analysis was further performed to discover the core proteins.

Results

A total of 117 serum differential proteins were found in our study, of which 44 were revised upwards and 73 downwards. The up-regulated proteins mainly include UGGT2, PDIA4, SEMG1, KIAA1191, CCT7 etc. and the down-regulated proteins mainly include ROR1, NIF3L1, ITIH4, CFP, COL11A2 etc. Pathway enrichment analysis identified that the upregulated proteins were mainly enriched in processes such as immune response, extracellular exosome, serine-type endopeptidase activity and complement and coagulation cascades, and the down-regulated proteins were enriched in signal transduction, extracellular exosome, zinc/calcium ion binding and metabolic pathways. PPI network analysis revealed that the core proteins nodes include PRDX6, CAT, PRDX2, SOD1, PARK7, GSR, TXN, ANXA1, HINT1, and S100A8 etc.

Conclusion

The discovery of these differential proteins enriched our understanding of serum biomarkers in patients with DRE and potentially provides guidance for future targeted therapy.
Large-scale real-world data on a multidisciplinary approach to spinal cord stimulation for persistent spinal pain syndromes: first evaluation of the Neuro-Pain® nationwide screening and follow-up interactive register
Authors: Bernaerts Lisa , Roelant Ella , Lecomte Frederic , Moens Maarten , Van Buyten Jean-Pierre , Billet Bart , Bryon Bart , Puylaert Martine , Turgay Tuna , Malone Maureen , Theys Tom , Van Zundert Jan , Berquin Anne , Crombez Erwin , De Coster Olivier , Vangeneugden Johan , Ly Huynh Giao , Louagie Marleen , Hans Guy Henri
Published: March 2024

Introduction

Spinal cord stimulation is a common treatment option for neuropathic pain conditions. Despite its extensive use and multiple technological evolutions, long term efficacy of spinal cord stimulation is debated. Most studies on spinal cord stimulation include a rather limited number of patients and/or follow-ups over a limited period. Therefore, there is an urgent need for real-world, long-term data.

Methods

In 2018, the Belgian government initiated a nationwide secure platform for the follow-up of all new and existing spinal cord stimulation therapies. This is a unique approach used worldwide. Four years after the start of centralized recording, the first global extraction of data was performed.

Results

Herein, we present the findings, detailing the different steps in the centralized procedure, as well as the observed patient and treatment characteristics. Furthermore, we identified dropouts during the screening process, the reasons behind discontinuation, and the evolution of key indicators during the trial period. In addition, we obtained the first insights into the evolution of the clinical impact of permanent implants on the overall functioning and quality of life of patients in the long-term.

Discussion

Although these findings are the results of the first data extraction, some interesting conclusions can be drawn. The long-term outcomes of neuromodulation are complex and subject to many variables. Future data extraction will allow us to identify these confounding factors and the early predictors of success. In addition, we will propose further optimization of the current process.
Grain nutritional and antioxidant profiling of diverse lentil (Lens culinaris Medikus) genetic resources revealed genotypes with high nutritional value
Authors: Riaz Fareeha , Hameed Amjad , Asghar Muhammad Jawad
Published: March 2024

The lentil (Lens culinaris Medikus ssp. Culinaris) is a self-pollinating, diploid (2n = 2X = 14) crop with a genome size of 4 Gbp. The present study was conducted to provide a database for the evaluation of lentil antioxidant capacity, nutritional quality, and biochemical attributes. For these purposes, lentil germplasm, including 100 exotic and local genotypes from different agro-climatic zones of Pakistan, was collected. Significant variation (p < 0.05) was found among the genotypes under investigation using the Tukey HSD test. Ascorbate peroxidase was highest in ALTINOPARK (2,465 Units/g s. wt.), catalase in LPP 12110 (5,595 Units/g s. wt.), superoxide dismutase in LPP 12105 (296.75 Units/g s. wt.), and peroxidase in NIAB Masoor 2002 (3,170 Units/g s. wt.). Furthermore, NLM 15016 had a maximum total antioxidant capacity of 15.763 mg/g s. wt. The maximum values of total soluble sugars (83.93 mg/g. s. wt.) and non-reducing sugars (74.79 mg/g. s. wt.) were noticed in NLM 15015. The highest reducing sugars were detected in ILL 8006 (45.68 mg/g. s. wt.) ascorbic acid in LPP 12182 (706 μg/g s. wt.), total phenolic content in NLI 17003 (54,600 μM/g s. wt.), and tannins in NLI 17057 (24,563 μM/g s. wt.). The highest chlorophyll a (236.12 μg/g s. wt.), chlorophyll b (317 μg/g s. wt.), total chlorophyll (552.58 μg/g s. wt.), and lycopene (10.881 μg/g s. wt.) were found in NLH 12097. Maximum total carotenoids were revealed in the local approved variety Markaz 2009 (17.89 μg/g s. wt.). Principal component analysis (PCA), correlation analysis (Pearson’s test), and agglomerative hierarchical clustering (AHC) were performed to detect the extent of variation in genotypes. In cluster analysis, all genotypes were categorized into three clusters. Cluster II genotypes showed remarkable divergence with cluster III. According to PCA, the contribution of PC-I regarding tested nutritional parameters toward variability was the highest (39.75%) and indicated positive factor loading for the tested nutritional and biochemical parameters. In conclusion, genotype X 2011S 33–34-32 can be used by the food industry in making pasta, multigrain bread, and snacking foods due to its high protein content for meat alternative seekers. Identified genotypes with high nutritional attributes can be utilized to improve quality parameters in the respective lentil breeding lines.
Recent trends in extraction, purification, structural characterization, and biological activities evaluation of Perilla frutescens (L.) Britton polysaccharide
Authors: Zhu Ling , Guan Lijun , Wang Kunlun , Ren Chuanying , Gao Yang , Li Jialei , Yan Song , Zhang Xindi , Yao Xinmiao , Zhou Ye , Li Bo , Lu Shuwen
Published: March 2024

Perilla frutescens (L.) Britton is an annual herb plant of the Perilla genus in the Labiatae family, which is commonly utilized as an edible and medicinal resource. Polysaccharides are among the major components and essential bioactive compounds of P. frutescens, which exhibit a multitude of biological activities, including antioxidant, antitumor, anti-fatigue, immunoregulation, hepatoprotective, anti-inflammatory, and lipid-lowering effects. As a natural carbohydrate, P. frutescens polysaccharide has the potential to be utilized in the development of drugs and functional materials. In this paper, we provide an overview of progress made on the extraction, purification, structural characterization, and bioactivity of polysaccharides from different parts of P. frutescens. The challenges and opportunities for research are discussed, along with the potential development prospects and future areas of focus in the study of P. frutescens polysaccharides.
Dietary acid load and markers of malnutrition, inflammation, and oxidative stress in hemodialysis patients
Authors: Balali Arghavan , Nehls Marilyn S. , Tabibi Hadi , As’habi Atefeh , Arab Arman
Published: March 2024

Aims

The present study was conducted to examine the association between dietary acid load (DAL) and markers of inflammation, oxidative stress, and malnutrition in a group of Iranian hemodialysis (HD) patients.

Methods

This cross-sectional study was performed on individuals aged ≥18 years who were on HD at least 6 months before their enrollment in the study. A 4-day dietary recall was used for the evaluation of dietary intake. DAL was calculated using two methods including potential renal acid load (PRAL) and net endogenous acid production (NEAP). For assessing the malnutrition status, we used the subjective global assessment (SGA), dialysis malnutrition score (DMS), and malnutrition inflammation score (MIS). Fasting blood samples were collected from each participant to assess serum levels of high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), and endothelin-1.

Results

In total, 291 patients with a mean age of 57.73 ± 0.88 years and HD vintage of 4.27 ± 0.25 months were enrolled in the current study. Significant positive associations were observed between PRAL and hs-CRP (β = 1.77, 95% CI: 0.88, 2.65), sICAM-1 (β = 83.21, 95% CI: 10.39, 156.04), sVCAM-1 (β = 194.63, 95% CI: 74.68, 314.58), and sE-selectin (β = 6.66, 95% CI: 1.81, 11.50) among participants with the highest PRAL scores, compared to those with the lowest PRAL scores. NEAP was positively correlated with hs-CRP (β = 1.34, 95% CI: 0.46, 2.22), sICAM-1 (β = 88.83, 95% CI: 16.99, 160.67), and MDA (β = 0.35, 95% CI: 0.005, 0.71). Additionally, marginally significant higher odds of SGA (OR = 1.98, 95% CI: 0.95, 4.11) and DMS (OR = 1.94, 95% CI: 0.92, 4.05) were observed in individuals in the third tertile of PRAL vs. the first tertile of PRAL. NEAP had also a marginally significant positive correlation with DMS (OR = 2.01, 95% CI: 0.93, 4.31).

Conclusion

This study illustrates that higher consumption of acidic foods is correlated with markers of inflammation, oxidative stress, and malnutrition in HD patients.
Cost-effectiveness analysis of amivantamab plus chemotherapy versus chemotherapy alone in NSCLC with EGFR Exon 20 insertions
Authors: Yue Ping , Zhang Mengwei , Feng Yuanying , Gao Yuan , Sun Chao , Chen Peng
Published: March 2024

Objective

Amivantamab plus chemotherapy has been proved to be an efficient treatment strategy for non–small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions. The aim of this study was to conduct the cost-effectiveness analysis of amivantamab-chemotherapy compared with chemotherapy alone in NSCLC harboring EGFR exon 20 insertion mutations.

Methods

We constructed a Markov model based on the data derived from the PAPILLON trial. We evaluated the cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to evaluate the influence of different parameters on this model.

Results

Compared with chemotherapy alone, amivantamab combined with chemotherapy treatment gained an incremental effectiveness of 0.473 QALYs and an incremental cost of $361,950.952, which resulted in an ICER of $765,224/QALY. The ICER was much higher than the willingness-to-pay threshold of 15,0000/QALY. One-way sensitivity analysis revealed that amivantamab cost was the leading influential factor in the model.

Conclusions

Compared with chemotherapy alone, amivantamab plus chemotherapy is not a cost-effective first-line treatment choice for NSCLC patients with EGFR exon 20 insertions. The costly price of amivantamab is one of the major reasons for the high cost of this combined treatment strategy. Therefore, it is imperative to take into account the high cost of amivantamab in the subsequent clinical application and strive to attain a relative equilibrium between its significant clinical benefit and economic encumbrance.
Defining reference values of arterioles in healthy individuals for studies with adaptive optics imaging
Authors: Kortuem Friederike C. , Merle David A. , Reith Milda , Kuehlewein Laura , Jung Ronja , Holocher Saskia , Stingl Krunoslav , Stingl Katarina , Kempf Melanie
Published: March 2024

Purpose

To investigate age-dependent wall to lumen ratio (WLR) reference values for healthy individuals in adaptive optics imaging (AO). WLR serves as an objective, dimensionless parameter for the evaluation of structural changes in vessels caused by conditions like arterial hypertension, diabetes or vascular stenosis.

Methods

50 right eyes of healthy individuals were examined by adaptive optics imaging. The central big arterioles and smaller arterial branches at least one disc diameter away from the optic disc, approximately above or below the macula were measured by the manufacturer’s software. The wall-lumen-ratio (WLR), the wall cross-sectional area (WCSA) and lumen diameter (LD) were assessed. Subsequent data analysis was performed with a focus on variables including age, gender and blood pressure.

Results

Normative values for WLR, WCSA and LD in 5 different age groups could be established. However, no significant differences between the age groups were found. Intra-subject comparisons revealed significantly higher WLRs on peripheral branches when compared to central arterioles. WLR showed in this normotensive cohort no relevant correlation with the systolic, diastolic and mean blood pressure. Gender and intraocular pressure had no influence on the vascular parameters.

Conclusion

AO is capable of examining vascular alterations in arterioles at an almost microscopic level. Age did not seem to alter WLR, normotensive blood pressure parameters showed also no significant impact. AO-based vessel analysis may provide clinically useful biomarkers for cardiovascular health and should be tested in future studies.
Efficacy and safety of PARP inhibitors combined with antiangiogenic agents in the maintenance treatment of ovarian cancer: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials
Authors: Wei Yan , He Li , Liu Tao , Guo Tao , Xie Cong , Jia Jigang , Lin Yonghong , Liu Jiang , Fan Jiayin
Published: March 2024

Background: Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer (OC). However, there is currently a lack of evidence-based study to directly compare the effects of combination therapy with these two drugs. Therefore, this study aimed to compare the efficacy and safety of combination therapy with PARP inhibitors and antiangiogenic agents in women with OC using a meta-analysis.

Methods: An exhaustive search of literature was undertaken using multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library to identify pertinent randomized controlled trials (RCTs) published up until 17 December 2023. The data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled. We computed the pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for PFS and OS, along with the relative risks (RRs) and 95% CIs for AEs. Trial sequential analysis, heterogeneity test, sensitivity analysis, and publication bias assessment were performed. Stata 12.0 and Software R 4.3.1 were utilized for all analyses.

Results: This meta-analysis included 7 RCTs with a total of 3,388 participants. The overall analysis revealed that combination therapy of PARP inhibitors and antiangiogenic agents significantly improved PFS (HR = 0.615, 95% CI = 0.517–0.731; 95% PI = 0.379–0.999), but also increased the risk of AEs, including urinary tract infection (RR = 1.500, 95% CI = 1.114–2.021; 95% PI = 0.218–10.346), fatigue (RR = 1.264, 95% CI = 1.141–1.400; 95% PI = 1.012–1.552), headache (RR = 1.868, 95% CI = 1.036–3.369; 95% PI = 0.154–22.642), anorexia (RR = 1.718, 95% CI = 1.320–2.235; 95% PI = 0.050–65.480), and hypertension (RR = 5.009, 95% CI = 1.103–22.744; 95% PI = 0.016–1580.021) compared with PARP inhibitor or antiangiogenic agent monotherapy. Our study has not yet confirmed the benefit of combination therapy on OS in OC patients (HR = 0.885, 95% CI = 0.737–1.063). Additionally, subgroup analyses further showed that combination therapy resulted in an increased risk of AEs, encompassing thrombocytopenia, vomiting, abdominal pain, proteinuria, fatigue, headache, anorexia, and hypertension (all p < 0.05).

Conclusion: Our study demonstrated the PFS benefit of combination therapy with PARP inhibitors and antiangiogenic agents in patients with OC. The OS result need to be updated after the original trial data is mature. Clinicians should be vigilant of AEs when administering the combination therapy in clinical practice.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023494482.