bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural approach of using nisin and its nanoform as food bio-preservatives against methicillin resistant Staphylococcus aureus and E.coli O157:H7 in yoghurt
Authors: Elsherif Walaa M. , Hassanien Alshimaa A. , Zayed Gamal M. , Kamal Sahar M.
Published: May 2024

Background

Natural antimicrobial agents such as nisin were used to control the growth of foodborne pathogens in dairy products. The current study aimed to examine the inhibitory effect of pure nisin and nisin nanoparticles (nisin NPs) against methicillin resistant Staphylococcus aureus (MRSA) and E.coli O157:H7 during the manufacturing and storage of yoghurt. Nisin NPs were prepared using new, natural, and safe nano-precipitation method by acetic acid. The prepared NPs were characterized using zeta-sizer and transmission electron microscopy (TEM). In addition, the cytotoxicity of nisin NPs on vero cells was assessed using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The minimum inhibitory concentrations (MICs) of nisin and its nanoparticles were determined using agar well-diffusion method. Further, fresh buffalo’s milk was inoculated with MRSA or E.coli O157:H7 (1 × 106 CFU/ml) with the addition of either nisin or nisin NPs, and then the inoculated milk was used for yoghurt making. The organoleptic properties, pH and bacterial load of the obtained yoghurt were evaluated during storage in comparison to control group.

Results

The obtained results showed a strong antibacterial activity of nisin NPs (0.125 mg/mL) against MRSA and E.coli O157:H7 in comparison with control and pure nisin groups. Notably, complete eradication of MRSA and E.coli O157:H7 was observed in yoghurt formulated with nisin NPs after 24 h and 5th day of storage, respectively. The shelf life of yoghurt inoculated with nisin nanoparticles was extended than those manufactured without addition of such nanoparticles.

Conclusions

Overall, the present study indicated that the addition of nisin NPs during processing of yoghurt could be a useful tool for food preservation against MRSA and E.coli O157:H7 in dairy industry.
Nine-year seroepidemiological study of severe fever with thrombocytopenia syndrome virus infection in feral horses in Cape Toi, Japan
Authors: Mekata Hirohisa , Yamada Kentaro , Umeki Kazumi , Yamamoto Mari , Ochi Akihiro , Umekita Kunihiko , Kobayashi Ikuo , Hirai Takuya , Okabayashi Tamaki
Published: May 2024

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal zoonosis caused by ticks in East Asia. As SFTS virus (SFTSV) is maintained between wildlife and ticks, seroepidemiological studies in wildlife are important to understand the behavior of SFTSV in the environment. Miyazaki Prefecture, Japan, is an SFTS-endemic area, and approximately 100 feral horses, called Misaki horses (Equus caballus), inhabit Cape Toi in Miyazaki Prefecture. While these animals are managed in a wild-like manner, their ages are ascertainable due to individual identification. In the present study, we conducted a seroepidemiological survey of SFTSV in Misaki horses between 2015 and 2023. This study aimed to understand SFTSV infection in horses and its transmission to wildlife. A total of 707 samples from 180 feral horses were used to determine the seroprevalence of SFTSV using enzyme-linked immunosorbent assay (ELISA). Neutralization testing was performed on 118 samples. In addition, SFTS viral RNA was detected in ticks from Cape Toi and feral horses. The overall seroprevalence between 2015 and 2023 was 78.5% (555/707). The lowest seroprevalence was 55% (44/80) in 2016 and the highest was 92% (76/83) in 2018. Seroprevalence was significantly affected by age, with 11% (8/71) in those less than one year of age and 96.7% (435/450) in those four years of age and older (p < 0.0001). The concordance between ELISA and neutralization test results was 88.9% (105/118). SFTS viral RNA was not detected in ticks (n = 516) or feral horses. This study demonstrated that horses can be infected with SFTSV and that age is a significant factor in seroprevalence in wildlife. This study provides insights into SFTSV infection not only in horses but also in wildlife in SFTS-endemic areas.
Hydrops fetalis caused by a complex congenital heart defect with concurrent hypoplasia of pulmonary blood vessels and lungs visualized by micro-CT in a French Bulldog
Authors: Szaluś-Jordanow Olga , Barszcz Karolina , Mądry Wojciech , Buczyński Michał , Czopowicz Michał , Gierulski Adam , Moroz-Fik Agata , Mickiewicz Marcin , Grzegorczyk Michał , Jaroszewicz Jakub
Published: May 2024

Background

Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species, including dogs. Most of cases result from a heart defect. Exact nature of this defect is rarely clarified.

Case presentation

A newborn, male French bulldog puppy with severe HF underwent a full anatomopathological examination to diagnose the primary cause of HF. Based on the anatomopathological examination, fetal ultrasound, and micro-computed tomography, transposition of the great arteries with hypoplasia of the ascending aorta, aortic arch interruption, ostium secundum atrial septal defect, severe tricuspid valve dysplasia, as well as hypoplasia of pulmonary vessels and lungs were diagnosed.

Conclusions

This is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.
Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism
Authors: Li Ming , Kang Shiyao , Deng Xuming , Li Huimin , Zhao Yuan , Tang Wenru , Sheng Miaomiao
Published: May 2024

Triple-negative breast cancer (TNBC) is highly malignant and lacks effective biotherapeutic targets. The development of efficient anticancer drugs with low toxicity and few side effects is a hotspot in TNBC treatment research. Although erianin is known to have potent antitumor activity, its regulatory mechanism and target in TNBC have not been fully elucidated, hampering further drug development. This study showed that erianin can significantly inhibit TNBC cell proliferation and migration, promote cell apoptosis, and inhibit the growth of transplanted tumors in mice. Mechanistically, through network pharmacology analysis, molecular docking and cellular thermal shift assays, we preliminarily identified SRC as the cellular target of erianin. Erianin potently inhibited the expression of SRC, which mediated the anticancer effect of erianin in TNBC. Moreover, erianin can downregulate the expression of genes related to cholesterol synthesis and uptake by targeting SRC, interfering with cholesterol levels in TNBC, thereby inhibiting the progression of TNBC in vivo and in vitro. Taken together, our results suggest that erianin may inhibit the progression of TNBC by suppressing SRC-mediated cholesterol metabolism, and erianin has the great potential to be an effective treatment for TNBC patients.
Phytochemical evaluation of Ziziphus mucronata and Xysmalobium undulutum towards the discovery and development of anti-malarial drugs
Authors: Buthelezi Muzi N. , Tshililo Vhahangwele G. , Kappo Abidemi P. , Simelane Mthokozisi B. C.
Published: May 2024

Background

The development of resistance by Plasmodium falciparum is a burdening hazard that continues to undermine the strides made to alleviate malaria. As such, there is an increasing need to find new alternative strategies. This study evaluated and validated 2 medicinal plants used in traditional medicine to treat malaria.

Methods

Inspired by their ethnobotanical reputation of being effective against malaria, Ziziphus mucronata and Xysmalobium undulutum were collected and sequentially extracted using hexane (HEX), ethyl acetate (ETA), Dichloromethane (DCM) and methanol (MTL). The resulting crude extracts were screened for their anti-malarial and cytotoxic potential using the parasite lactate dehydrogenase (pLDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, respectively. This was followed by isolating the active compounds from the DCM extract of Z. mucronata using silica gel chromatography and structural elucidation using spectroscopic techniques (NMR: 1H, 12C, and DEPT). The active compounds were then targeted against P. falciparum heat shock protein 70–1 (PfHsp70-1) using Autodock Vina, followed by in vitro validation assays using ultraviolet–visible (UV–VIS) spectroscopy and the malate dehydrogenase (MDH) chaperone activity assay.

Results

The extracts except those of methanol displayed anti-malarial potential with varying IC50 values, Z. mucronata HEX (11.69 ± 3.84 µg/mL), ETA (7.25 ± 1.41 µg/mL), DCM (5.49 ± 0.03 µg/mL), and X. undulutum HEX (4.9 ± 0.037 µg/mL), ETA (17.46 ± 0.024 µg/mL) and DCM (19.27 ± 0.492 µg/mL). The extracts exhibited minimal cytotoxicity except for the ETA and DCM of Z. mucronata with CC50 values of 10.96 and 10.01 µg/mL, respectively. Isolation and structural characterization of the active compounds from the DCM extracts revealed that betulinic acid (19.95 ± 1.53 µg/mL) and lupeol (7.56 ± 2.03 µg/mL) were responsible for the anti-malarial activity and had no considerable cytotoxicity (CC50 > µg/mL). Molecular docking suggested strong binding between PfHsp70-1, betulinic acid (− 6.8 kcal/mol), and lupeol (− 6.9 kcal/mol). Meanwhile, the in vitro validation assays revealed the disruption of the protein structural elements and chaperone function.

Conclusion

This study proves that X undulutum and Z. mucronata have anti-malarial potential and that betulinic acid and lupeol are responsible for the activity seen on Z. mucronata. They also make a case for guided purification of new phytochemicals in the other extracts and support the notion of considering medicinal plants to discover new anti-malarials.
Integrin-linked kinase mRNA expression in circulating mononuclear cells as a biomarker of kidney and vascular damage in experimental chronic kidney disease
Authors: Campillo Sofía , Gutiérrez-Calabrés Elena , García-Miranda Susana , Griera Mercedes , Fernández Rodríguez Loreto , de Frutos Sergio , Rodríguez-Puyol Diego , Calleros Laura
Published: May 2024

Background

Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated.

Methods

CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice.

Results

The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice.

Conclusions

ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.

Graphical Abstract

ILK content in circulating mononuclear cells reflects renal and vascular damage in a CKD experimental model.
Angiolipoma associated with antiretroviral switch therapy: a case report
Authors: Taylor Gregory H. , Pandit Neha Sheth
Published: May 2024

Background

Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse transcriptase inhibitor-based regimens. Resolution of symptoms have occurred with switches to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; however, little is known regarding the development of angiolipomas when switching from NNRTI- to modern, integrase strand transfer inhibitor-based regimens. We describe a patient who underwent switch therapy from tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) to tenofovir alafenamide/FTC/bictegravir (TAF/FTC/BIC) who later developed angiolipomas.

Case Presentation

A 55-year-old male had been on TDF/FTC/EFV for 8 years before switching to TAF/FTC/BIC. Nineteen months after antiretroviral switch, the patient presented with multiple lesions in the upper extremities and abdomen. Diagnostic biopsies revealed non-encapsulated angiolipomas and HHV-8 and non-alcoholic fatty liver disease was ruled out. New lesions continued to appear 29 months after ART switch, after which now lesions appeared and prior lesions remained stable with no increase in size noted. No surgical intervention or change in antiretroviral therapy was needed.

Conclusions

Angiogenesis may have been suppressed with TDF/FTC/EFV treatment, however when switched to TAF/FTC/BIC, promoted the growth of angiolipomas. Clinicians should be aware of the impact of switching to modern ART therapies resulting in possible adipogenesis.
Immersive VR for upper-extremity rehabilitation in patients with neurological disorders: a scoping review
Authors: Ceradini Matteo , Losanno Elena , Micera Silvestro , Bandini Andrea , Orlandi Silvia
Published: May 2024

Background

Neurological disorders, such as stroke and chronic pain syndromes, profoundly impact independence and quality of life, especially when affecting upper extremity (UE) function. While conventional physical therapy has shown effectiveness in providing some neural recovery in affected individuals, there remains a need for improved interventions. Virtual reality (VR) has emerged as a promising technology-based approach for neurorehabilitation to make the patient’s experience more enjoyable. Among VR-based rehabilitation paradigms, those based on fully immersive systems with headsets have gained significant attention due to their potential to enhance patient’s engagement.

Methods

This scoping review aims to investigate the current state of research on the use of immersive VR for UE rehabilitation in individuals with neurological diseases, highlighting benefits and limitations. We identified thirteen relevant studies through comprehensive searches in Scopus, PubMed, and IEEE Xplore databases. Eligible studies incorporated immersive VR for UE rehabilitation in patients with neurological disorders and evaluated participants’ neurological and motor functions before and after the intervention using clinical assessments.

Results

Most of the included studies reported improvements in the participants rehabilitation outcomes, suggesting that immersive VR represents a valuable tool for UE rehabilitation in individuals with neurological disorders. In addition, immersive VR-based interventions hold the potential for personalized and intensive training within a telerehabilitation framework. However, further studies with better design are needed for true comparison with traditional therapy. Also, the potential side effects associated with VR head-mounted displays, such as dizziness and nausea, warrant careful consideration in the development and implementation of VR-based rehabilitation programs.

Conclusion

This review provides valuable insights into the application of immersive VR in UE rehabilitation, offering the foundation for future research and clinical practice. By leveraging immersive VR’s potential, researchers and rehabilitation specialists can design more tailored and patient-centric rehabilitation strategies, ultimately improving the functional outcome and enhancing the quality of life of individuals with neurological diseases.
PPP2R2A inhibition contributes to preeclampsia by regulating the proliferation, apoptosis, and angiogenesis modulation potential of mesenchymal stem cells
Authors: Liu Yan , Gu Fangle , Gao Jun , Gu Yingyan , Li Zhiyue , Lu Dan , Zhang Yanxin
Published: May 2024

Background

The precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE.

Methods

Reverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay.

Results

PPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment.

Conclusion

PPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment.
Human T-cell lymphotropic virus type 1 (HTLV-1) grip on T-cells: investigating the viral tapestry of activation
Authors: Letafati Arash , Bahavar Atefeh , Tabarraei Alijan , Norouzi Mehdi , Amiri Abdollah , Mozhgani Sayed-Hamidreza
Published: May 2024

Introduction

Human T-cell Lymphotropic virus type 1 (HTLV-1) belongs to retroviridae which is connected to two major diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL). This study aims to investigate the mRNA expressions of key proteins correlated to T-cell activation in asymptomatic carriers (ACs) HTLV-1 infected patients, shedding light on early molecular events and T-cell activation following HTLV-1 infection.

Material and Methods

The study involved 40 participants, including 20 ACs and 20 healthy subjects. Blood samples were collected, ELISA assessment for screening and confirmation with PCR for Trans-activating transcriptional regulatory protein (Tax) and HTLV-1 basic leucine zipper factor (HBZ) of the HTLV-1 were done. mRNA expressions of C-terminal Src kinase (CSK), Glycogen Synthase Kinase-3 Beta (GSK3β), Mitogen-Activated Protein Kinase 14 (MAP3K14 or NIK), Phospholipase C Gamma-1 (PLCG1), Protein Tyrosine Phosphatase non-Receptor Type 6 (PTPN6) and Mitogen-Activated Protein Kinase Kinase Kinase-7 (SLP-76) and Mitogen-Activated Protein Kinase14 (MAP3K7 or TAK1) were assayed using RT-qPCR. Statistical analyses were performed using PRISM and SPSS software.

Results

While there were no significant upregulation in CSK and PTPN6 in ACs compared to healthy individuals, expression levels of GSK3β, MAP3K14, PLCG1, SLP-76, and TAK1 were significantly higher in ACs compared to healthy subjects which directly contributes to T-cell activation in the HTLV-1 ACs.

Conclusion

HTLV-1 infection induces differential mRNA expressions in key proteins associated with T-cell activation. mRNAs related to T-cell activation showed significant upregulation compared to PTPN6 and CSK which contributed to T-cell regulation. Understanding these early molecular events in ACs may provide potential markers for disease progression and identify therapeutic targets for controlling viral replication and mitigating associated diseases. The study contributes novel insights to the limited literature on T-cell activation and HTLV-1 pathogenesis.
Plasma biomarkers increase diagnostic confidence in patients with Alzheimer’s disease or frontotemporal lobar degeneration
Authors: Altomare Daniele , Libri Ilenia , Alberici Antonella , Rivolta Jasmine , Padovani Alessandro , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Borroni Barbara
Published: May 2024

Background

The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer’s disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center.

Methods

Anonymized clinical reports of patients diagnosed with AD or Frontotemporal Lobar Degeneration with available plasma biomarkers (Aβ42, Aβ42/Aβ40, p-tau181, p-tau231, NfL, GFAP) were independently assessed by two neurologists who expressed diagnosis and diagnostic confidence three times: (T0) at baseline based on the information collected during the first visit, (T1) after plasma biomarkers, and (T2) after traditional biomarkers (when available). Finally, we assessed whether clinicians’ interpretation of plasma biomarkers and the consequent clinical impact are consistent with the final diagnosis, determined after the conclusion of the diagnostic clinical and instrumental work-up by the actual managing physicians who had complete access to all available information.

Results

Clinicians assessed 122 reports, and their concordance ranged from 81 to 91% at the three time points. At T1, the presentation of plasma biomarkers resulted in a change of diagnosis in 2% (2/122, p = 1.00) of cases, and in increased diagnostic confidence in 76% (91/120, p < 0.001) of cases with confirmed diagnosis. The change in diagnosis and the increase in diagnostic confidence after plasma biomarkers were consistent with the final diagnosis in 100% (2/2) and 81% (74/91) of cases, respectively. At T2, the presentation of traditional biomarkers resulted in a further change of diagnosis in 13% (12/94, p = 0.149) of cases, and in increased diagnostic confidence in 88% (72/82, p < 0.001) of cases with confirmed diagnosis.

Conclusions

In an academic tertiary care center, plasma biomarkers supported clinicians by increasing their diagnostic confidence in most cases, despite a negligible impact on diagnosis. Future prospective studies are needed to assess the full potential of plasma biomarkers on clinical grounds.
Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank
Authors: Zhang Tingjing , An Yu , Shen Zhenfei , Yang Honghao , Jiang Jinguo , Chen Liangkai , Lu Yanhui , Xia Yang
Published: May 2024

Background

Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer’s disease and related dementias (ADRD), Parkinson’s disease (PD), and neurodegenerative deaths.

Methods

This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations.

Results

During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events.

Conclusion

Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.
Unusual phenotype in 35delG mutation: a case report
Authors: Yeral Cem , Seneldir Lutfu , Karakoc Arzu Hediye , Sap Aleyna , Yilmaz Oguz
Published: May 2024

Background

Mutations in the GJB2 gene, which encodes the protein connexin 26 and is involved in inner ear homeostasis, are identified in approximately 50% of patients with autosomal recessive nonsyndromic hearing loss, making it one of the primary causes of prelingual nonsyndromic hearing loss in various populations. The 35delG mutation, one of the most common mutations of the GJB2 gene, usually causes prelingual, bilateral mild to profound, nonprogressive sensorineural hearing loss.

Case presentation

We present an unusual case of an 18-year-old Turkish female with heterozygous 35delG mutation and postlingual, profound-sloping, progressive and fluctuating unilateral sensorineural hearing loss. The phenotype is different from the usual findings.

Conclusions

The 35delG mutation causing hearing loss may not always be reflected in the phenotype as expected and therefore may have different audiologic manifestations.
Resilient data-driven non-intrusive load monitoring for efficient energy management using machine learning techniques
Authors: Nutakki Mounica , Mandava Srihari
Published: May 2024

The integration of smart homes into smart grids presents numerous challenges, particularly in managing energy consumption efficiently. Non-intrusive load management (NILM) has emerged as a viable solution for optimizing energy usage. However, as smart grids incorporate more distributed energy resources, the complexity of demand-side management and energy optimization escalates. Various techniques have been proposed to address these challenges, but the evolving grid necessitates intelligent optimization strategies. This article explores the potential of data-driven NILM (DNILM) by leveraging multiple machine learning algorithms and neural network architectures for appliance state monitoring and predicting future energy consumption. It underscores the significance of intelligent optimization techniques in enhancing prediction accuracy. The article compares several data-driven mechanisms, including decision trees, sequence-to-point models, denoising autoencoders, recurrent neural networks, long short-term memory, and gated recurrent unit models. Furthermore, the article categorizes different forms of NILM and discusses the impact of calibration and load division. A detailed comparative analysis is conducted using evaluation metrics such as root-mean-square error, mean absolute error, and accuracy for each method. The proposed DNILM approach is implemented using Python 3.10.5 on the REDD dataset, demonstrating its effectiveness in addressing the complexities of energy optimization in smart grid environments.
Stable carbon isotope composition and intrinsic water use efficiency in plants along an altitudinal gradient on the eastern slope of Yulong Snow Mountain, China
Authors: Jiang Feng , Pu Tao , Xue Zi-Jing , Ma Yan-Wei , Shi Xiao-Yi , Shi Fu-Xi
Published: May 2024

Background

Stable carbon isotope composition (δ13Cp) can be used to estimate the changes in intrinsic water use efficiency (iWUE) in plants, which helps us to better understand plants’ response strategies to climate change. This study focused on the variations in δ13Cp and iWUE for the different life-form plants (i.e., herbs, shrubs, and trees) along an altitudinal gradient (3300, 3600, 3900, 4100, 4300, and 4500 m) on the eastern slope of Yulong Snow Mountain, southeastern margin of the Qinghai-Tibet Plateau. The response mechanisms of δ13Cp and iWUE for different life-form plants to altitude were thoroughly analyzed in this mountain ecosystem.

Results

The δ13Cp values of plants on the eastern slopes of Yulong Snow Mountain ranged from − 30.4‰ to − 26.55‰, with a mean of − 28.02‰, indicating a dominance of C3 plants. The δ13Cp and iWUE values varied among different life-form plants in the order of herbs > shrubs > trees, particularly in 3600, 3900, and 4300 m. The δ13Cp and iWUE values for herbs and shrubs increased with altitude and were mainly controlled by air temperature. The two parameters for trees exhibited a trend of initial decrease followed by an increase with altitude. Below 3900 m, the δ13Cp and iWUE values decreased with altitude, influenced by soil moisture. However, above 3900 m, the two parameters increased with altitude, mainly regulated by air temperature. In addition, iWUE was positively correlated with leaf P content but negatively correlated with leaf N:P ratio, especially for herbs and trees, suggesting that P plays a key role in modulating iWUE in this region.

Conclusions

The differentiated responses of water availability for different life-form plants to a higher altitudinal gradient are regulated by air temperature, soil moisture, and leaf P content in the Yulong Snow Mountain. These results provide valuable insights into understanding the water–carbon relationships in high-altitude ecosystems.
Teaching prudent antibiotic use on the go: a descriptive report on development, utilization and listener satisfaction of an educational podcast format for medical students and young professionals
Authors: Schneider Sandra , Bergmann Clara , Becker Felicia , Risse Lukas , Isner Caroline , Stocker Hartmut , Feufel Markus A. , Röhrig Alina , Kurzai Oliver , Lâm Thiên-Trí , Hagel Stefan , Pletz Mathias W. , Gastmeier Petra , Wiese-Posselt Miriam
Published: May 2024

Background

An important component in fostering the responsible use of antibiotics is training of new and future prescribers in this interdisciplinary topic. Because podcasts are playing an increasing role in medical education, we aimed to develop and evaluate a podcast format with practice and guideline-oriented learning content on antibiotic therapy for medical students and young medical professionals.

Methods

We developed the concept for the podcast with the direct involvement of medical students and medical experts with teaching experience. We used video conferencing when recording the episodes in order to have quick, easy, and nationwide access to the experts involved. We released an episode every 2 to 4 weeks on the popular podcast platforms. The podcast was promoted through mailing lists, social and print media, and at conferences. The evaluation of episodes was based on user data provided by the platforms and an anonymous feedback questionnaire linked to each episode in the podcast notes.

Results

Between December 2021 and December 2022 19 episodes of InfectEd: der Antibiotika-Podcast were released. The mean duration of an episode was 91 min. By March 9, 2023, a total of 38,829 downloads and streams had been recorded. The majority of users listened to the podcast on a mobile device. The average playing time per episode was 65%. The feedback questionnaire was completed 135 times. 60.7% of respondents were female, 38.5% male. The majority of respondents were in their twenties and thirties (66.7%). 31.1% were medical students, 25.9% were residents, and 25.2% were specialists. Listeners were asked to rate episodes on a scale from 1 to 6, where 1 was “very good” and 6 was “insufficient.” Ratings did not differ significantly between female and male respondents or between medical students and others. 118 respondents (87.4%) reported an increase in knowledge. Free-text feedback frequently emphasized clinical and also exam relevance.

Conclusion

Our podcast format, developed with a user-centered approach, was broadly distributed and has been well accepted by both medical students and physicians alike. It provides a large number of learners with low-threshold access to current, guideline-orientated content and could be a useful supplement to conventional teaching formats.
Highly immunosuppressive myeloid cells correlate with early relapse after allogeneic stem cell transplantation
Authors: Notarantonio Anne-Béatrice , Bertrand Allan , Piucco Romain , Fievet Ghislain , Sartelet Hervé , Boulangé Laura , de Isla Natalia , De Carvalho Bittencourt Marcelo , Hergalant Sébastien , Rubio Marie-Thérèse , D’Aveni Maud
Published: May 2024

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for myeloid malignancies such as some acute myeloid leukemias (AML) and high-risk myelodysplastic syndromes (MDS). It aims to eradicate the malignant clone using immunocompetent donor cells (graft-versus-leukemia effect, GVL). Unfortunately, relapse is the primary cause of transplant failure mainly related on HLA loss or downregulation and upregulation of inhibitory ligands on blasts which result in donor immune effector dysfunctions.

Methods

Between 2018 and 2021, we conducted a monocentric prospective study including 61 consecutive patients transplanted for AML or high-risk MDS. We longitudinally investigated immune cells at days + 30, + 90 and + 180 post-transplant from bone marrow and peripheral blood. We assessed the dynamics between myeloid derived suppressor cells (MDSCs) and T-cells.

Results

Among the 61 patients, 45 did not relapse over the first 12 months while 16 relapsed during the first year post-transplant. Through months 1 to 6, comparison with healthy donors revealed an heterogenous increase in MDSC frequency. In all recipients, the predominant MDSC subset was granulocytic with no specific phenotypic relapse signature. However, in relapsed patients, in vitro and in vivo functional analyses revealed that MDSCs from peripheral blood were highly immunosuppressive from day + 30 onwards, with an activated NLRP3 inflammasome signature. Only circulating immunosuppressive MDSCs were statistically correlated to circulating double-positive Tim3+LAG3+ exhausted T cells.

Conclusion

Our simple in vitro functional assay defining MDSC immunosuppressive properties might serve as an early biomarker of relapse and raise the question of new preventive treatments targeting MDSCs in the future.

Trial registrationNCT03357172
Deciphering metabolic heterogeneity in retinoblastoma unravels the role of monocarboxylate transporter 1 in tumor progression
Authors: Tang Junjie , Liu Yaoming , Wang Yinghao , Zhang Zhihui , Nie Jiahe , Wang Xinyue , Ai Siming , Li Jinmiao , Gao Yang , Li Cheng , Cheng Chao , Su Shicai , Chen Shuxia , Zhang Ping , Lu Rong
Published: May 2024

Background

Tumors exhibit metabolic heterogeneity, influencing cancer progression. However, understanding metabolic diversity in retinoblastoma (RB), the primary intraocular malignancy in children, remains limited.

Methods

The metabolic landscape of RB was constructed based on single-cell transcriptomic sequencing from 11 RB and 5 retina samples. Various analyses were conducted, including assessing overall metabolic activity, metabolic heterogeneity, and the correlation between hypoxia and metabolic pathways. Additionally, the expression pattern of the monocarboxylate transporter (MCT) family in different cell clusters was examined. Validation assays of MCT1 expression and function in RB cell lines were performed. The therapeutic potential of targeting MCT1 was evaluated using an orthotopic xenograft model. A cohort of 47 RB patients was analyzed to evaluate the relationship between MCT1 expression and tumor invasion.

Results

Distinct metabolic patterns in RB cells, notably increased glycolysis, were identified. This metabolic heterogeneity correlated closely with hypoxia. MCT1 emerged as the primary monocarboxylate transporter in RB cells. Disrupting MCT1 altered cell viability and energy metabolism. In vivo studies using the MCT1 inhibitor AZD3965 effectively suppressed RB tumor growth. Additionally, a correlation between MCT1 expression and optic nerve invasion in RB samples suggested prognostic implications.

Conclusions

This study enhances our understanding of RB metabolic characteristics at the single-cell level, highlighting the significance of MCT1 in RB pathogenesis. Targeting MCT1 holds promise as a therapeutic strategy for combating RB, with potential prognostic implications.
Mechanisms maintaining right ventricular contractility-to-pulmonary arterial elastance ratio in VA ECMO: a retrospective animal data analysis of RV–PA coupling
Authors: Bachmann Kaspar F. , Moller Per Werner , Hunziker Lukas , Maggiorini Marco , Berger David
Published: May 2024

Background

To optimize right ventricular–pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV–PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV–PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV–PA coupling resulting from changing pre- and afterload conditions in VA ECMO.

Methods

In 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance.

Results

At no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; − 0.1 [− 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; − 0.2 [− 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p > 0.05). Extracorporeal flow did not change coupling (0.0 [− 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p < 0.001).

Conclusions

The right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular–arterial coupling during VA extracorporeal membrane oxygenation.
Secondary ileal lymph node metastases from rectal cancer: a case report
Authors: Ando Makoto , Takemura Nobuyuki , Oikawa Ryo , Yoshizaki Yuhi , Inagaki Fuyuki , Mihara Fuminori , Kiyomatsu Tomomichi , Yamada Kazuhiko , Kokudo Norihiro
Published: May 2024

Background

Colorectal cancer can invade adjacent organs, but rarely metastasizes to the regional lymph nodes (LNs) of the invaded organ. Herein, we report a case of rectal cancer invading the ileum and metastasized to the regional ileal LNs.

Case presentation

A 77-year-old male presented abdominal pain and anorexia, diagnosed with rectal cancer invading the small intestine and concurrently metastasized to the regional LN of the intestine and liver. High anterior resection and partial resection of the small intestine was performed, then, the patient was referred to our hospital for chemotherapy. We performed 17 cycles of systemic chemotherapy that achieved a partial reduction in size of the LN, followed by an ileocecal resection with ileal mesentery resection for regional LNs removal. Histopathological analysis of the resected ileal LNs and six liver lesions revealed a moderately differentiated tubular adenocarcinoma. The patient was discharged on postoperative day 18. Cancer recurrences developed in the lungs 5 months after the surgery, then to the liver and peritoneum, and further surgery and chemotherapy were performed. Despite the challenging presentation, the patient survived for 40 months after the first surgery.

Conclusions

We report a rare case of a surgical resection of a secondary ileal LN metastasis from rectal cancer. The patient survives for a relatively long time after surgical resection. When colorectal cancer invades the small intestine, clinicians should consider the possibility of secondary LN metastasis in the invaded site.
HIF-1α facilitates glioma proliferation and invasion by activating pyroptosis signaling axis
Authors: Wang Xin-Wei , Fu Hao , Zhang Ya-Min
Published: May 2024

Background

HIF-1α is thought to be a novel regulator which contributes to carcinogenesis. However, the mechanism underlying the effect of HIF-1α in gliomas remains largely unknown.

Methods

In the research, we demonstrate that HIF-lα mRNA and protein levels are elevated in glioma cells. The colony formation assays, transwell assays, and wound-healing assays showed that overexpression of HIF-1α promoted proliferation and invasion of glioma cells.

Results

Overexpression of HIF-lα also increased the expression of inflammatory factors related to pyrolysis (TNF-α, IL-10, and IL-1β) and protein related to pyrolysis signal pathway (NLRP3, ASC, caspase-1, GSDMD, and GSDME).

Conclusions

Therefore, we speculate that HIF-1α promotes the proliferation and invasion of glial cells by regulating pyrolysis pathway. These results might provide a novel strategy and target for treatment of glioma.
Common design and data elements on rectal artery embolization for treatment of symptomatic internal hemorrhoidal disease: an interactive systematic review of clinical trials
Authors: Morsi Samah , Linares Bolsegui Marisabel , Kobeissi Hassan , Ghozy Sherief , Kallmes David F. , Kelley Scott R. , Mathis Kellie L. , Dozois Eric J. , Loftus Conor G. , Bendel Emily C. , Vidal Vincent , Thompson Scott M.
Published: May 2024

Background

Internal hemorrhoids (IH) is a common medical condition that can result in morbidity secondary to bleeding and discomfort. Treatment for IH has traditionally consisted of dietary and conservative medical management, focal treatments including banding and sclerotherapy or hemorrhoidectomy. Recently, rectal artery embolization (RAE) has been studied as a potential treatment for bleeding predominant IH. We performed a common design and data element analysis of studies that report on RAE.

Materials and methods

We conducted a qualitative systematic literature review for rectal artery embolization (RAE) for symptomatic hemorrhoidal disease. The screening process involved five online databases (PubMed, Embase, Google Scholar, DOAJ, and Scopus). Additionally, ClinicalTrials.gov was examined for active, unpublished completed studies. The initial search yielded 2000 studies, with 15 studies meeting the inclusion criteria after screening and assessment. The included studies comprised one RCT, one case series, one pilot study and 12 cohort studies.

Results

The population analysis revealed a male predominance across all studies, with varying cohort sizes. The baseline Goligher hemorrhoid grade was utilized in 80% of studies. The majority (73.3%) employed a transfemoral approach, and coils were the primary embolic material in 60% of studies, 26.6% were combination of coils and particles, and 6.6% were particles only. Patient selection criteria highlighted RAE's applicability for high surgical risk patients and those with anemia, chronic hematochezia, or treatment-refractory cases. Exclusion criteria emphasized factors such as previous surgeries, colorectal cancer, rectal prolapse, acute hemorrhoidal complications, and contrast allergy.

Study designs varied, with cohort studies being the most common (12/15; 80%). Procedural details included the use of metallic coils and detachable micro-coils, with a high technical success rate reported in most studies ranging from 72 to 100%. The follow-up ranged from 1 to 18 months. The majority of studies reported no major immediate or post-procedural complications.

Conclusion

While all studies focused on RAE as a treatment for IH, there was a great degree of heterogeneity among included studies, particularly regarding inclusion criteria, exclusion criteria, outcomes measures and timeframe. Future literature should attempt to standardize these design elements to help facilitate secondary analyses and increase understanding of RAE as a treatment option.
Gravitating kinks with asymptotically flat metrics
Authors: Wang Ziqi , Zhong Yuan , Wang Hui
Published: May 2024

In this work, we consider a two-dimensional (2D) dilaton gravity model where the dilaton kinetic term

is modified by an additional derivative coupling term

. In the case with a canonical scalar matter field, the field equations of this model have a simple first-order formalism, from which exact static kink solutions can be constructed. The novelty of these solutions is that the corresponding metric can be asymptotically flat rather than asymptotically anti-de Sitter. The linear stability and the localization of scalar matter fields are also studied. It was found that the solutions are stable against small linear perturbations, and the localization of scalar matter fields can be realized by introducing scalar-kink interactions.
Thermodynamic properties of an interacting fermion-antifermion pair in a magnetized spacetime with a non-zero cosmological constant
Authors: Guvendi Abdullah , Boumali Abdelmalek
Published: May 2024

In a magnetized three-dimensional Bonnor-Melvin spacetime with a non-zero cosmological constant, we explore the dynamics of a fermion-antifermion pair interacting through an attractive Coulomb potential. To analyze the relativistic behavior, we seek an analytical solution for the fully covariant two-body Dirac equation derived from quantum electrodynamics. The resulting equation provides a second-order wave equation that governs the relative motion of the interacting pair. Obtaining an exact solution to this wave equation seems not possible; however, we notice solubility, especially when we consider particles to be closely spaced, meaning as the distance between them approaches zero. At that rate, we determine the energy eigenvalues and wave functions utilizing well-known special functions. By employing these solutions, we determine the thermal properties of this system. Despite the divergence observed in the partition function, we effectively tackle this issue by applying a regularization technique based on the mathematical zeta Hurwitz function. This method facilitates the computation of various thermal quantities, such as free energy, total energy, entropy function, and specific heat. Consequently, we provide an in-depth analysis of the thermodynamic characteristics of the system under consideration.