bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective aneurysmal sac neck-targeted embolization during endovascular aneurysm repair of abdominal aortic aneurysm with hostile neck anatomy
Authors: Zhang Lifeng , Tang Yongjiang , Wang Jiantao , Liu Xianjun , Liu Yang , Zeng Wei , He Chunshui
Published: June 2023

Purpose: To evaluate the efficacy and safety of selective aneurysmal sac neck-targeted embolization in patients undergoing endovascular aneurysm repair (EVAR) with hostile neck anatomy.
Materials and Methods: We enrolled 28 patients with hostile neck anatomy who underwent EVAR with a low-profile stent graft between October 2020 and June 2022. Before excluding the entire aneurysm during the procedure, a buddy wire was loaded prophylactically into the sac through the contralateral limb side. When type Ia endoleak persist despite adjunctive treatment, this preloaded wire could be utilized as an access to enable a catheter to reach the space between the stent graft and sac neck to perform coil embolization. In the absence of type Ia endoleak, the wire was simply retracted. The primary outcome of this study was freedom from sac expansion and endoleak-related reinterventions during the follow-up period; secondary outcomes included technical success, intraoperative and in-hospital postoperative complications.
Results: Out of the 28 patients with hostile neck morphology, 11 of them (39.5%) who had type Ia endoleak received intra-procedure treatment with sac neck-targeted detachable coil embolization. The preloaded wire was removed from 17 patients (60.7%) who did not show type Ia endoleak. The coiling group had longer operating durations (81.27±11.61 vs. 70.71±7.17 minutes, P<0.01) and utilized more contrast than the non-coiling group (177.45±52.41 vs. 108.24±17.49 ml, p<0.01). In the entire cohort, technical success was 100% and there were no procedure-related complications. At a mean follow-up of 18.6±5.2 months (range 12-31), there was no sac expansion(19 sac regression, 67.86%; 9 stability, 32.14% ) and endoleak-related reintervention.
Conclusions: Selective aneurysmal sac neck-targeted embolization for the treatment of type Ia endoleak in patients with hostile neck anatomy undergoing EVAR is safe and could reduce type Ia endoleak and prevent related sac expansion after EVAR.
Prediction of Raw Mill Fan Vibrations Based on Machine Learning Models
Authors: ZAKI Smail , BENCHEKROUN MOHAMMED TOUM , ABOUSSALEH MOHAMMED , HEZZEM Brahim , LAACHA Hicham
Published: June 2023

In the cement manufacturing process, kiln process fans play a vital role. This article presents an extensive investigation into the prediction of Raw Mill Fan vibrations using machine learning models. The study evaluates multiple machine learning models, including k-nearest neighbors, linear regression, random forest, support vector machines (SVM), XGBoost, kernel ridge, support vector regression (SVR), recurrent neural networks (RNN), dense networks, and artificial neural networks (ANN). Performance evaluation metrics such as R2 and RMSE are employed to assess the accuracy of these models. The results demonstrate that both the Random Forest and XGBoost models exhibit remarkable predictive performance, with high R2 scores and low RMSE values. The conclusions drawn from these findings have important implications for the operation of the raw mill fan, as the adoption of predictive maintenance strategies can minimize downtime and enhance operational efficiency. Therefore, this study suggests that the incorporation of machine learning models into the monitoring and maintenance practices of kiln process fans has the potential to bring about a revolutionary improvement in the overall performance of the kiln process, yielding superior outcomes.
Experimental study of proppant based fracturing fluid flowing through regular Fracture geometry in different rock samples
Authors: Soomro Najeeb Anjum , Ansari Ubedullah , Memon Bilal Shams , Memon Muhammad Khan
Published: June 2023

The efficiency hydraulic fracturing procedure must be enhanced by introducing various types of proppants to extract maximum production from low permeability reservoirs. The problem with hydraulic fracturing procedure is the selection of appropriate proppant type for specific composition of reservoir rock. Therefore, this study provides an experimental investigation on flow behavior of proppant-based fracturing fluid through regular fracture geometries in different rock samples. The challenge for conducting such an investigation is to achieve detailed fracture response of fracture network while fracturing a rock at surface in laboratory. For this purpose, a specially designed assembly on laboratory scale was used to perform an experiment on fracturing. The assembly was designed to hold cylindrical core samples which are either outcropped from the original location or by forming limestone, sandstone molds. The results of this revealed that the permeabilities were altered from 2.3 to 3.3mD for limestone samples, 2.2 to 2.9mD for shale samples and 2.1 to 3.5mD for sandstone samples. Moreover, mechanical behavior was insightful for shale samples as their tensile strength ranged from 1080 to 130 psi with the average magnitudes of 700 to 720 psi. The bulk density of proppants was found to be 95.90 lbm/ft³ and the settling packed porosity of the proppants was calculated to be 0.420 with the specific gravity of 2.65. Further, the pattern of geometry observed in sandstone and shale formation was vertical linear while in limestone the shape of fracture was parabolic therefore such proppants are more fracture length yielding for sandstone and shale formations. The study concludes that limestone formation requires different configuration while fracturing through proppants and shale and limestone has similar fracture behavior while proppant based hydraulic fracturing. The outcomes of this study are very useful to design any fracture activity considering the fracture behavior of different formations to specific type of proppants.
Diversity-oriented synthesis of 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids as antimicrobial agents and DFT study
Authors: Chudasama Dipakkumar D. , Patel Manan S. , Parekh Jaydeepkumar N. , Patel Harsh C , Rajput Chetan V. , Chikhaliya Navin p , Ram Kesur R
Published: June 2023

A straightforward and high yielding synthetic approach is employed to synthesize the novel 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids 7(a-t) as new antimicrobial agents with two pharmacophore in the effective two step synthesis. The first step is the four component one-pot synthesis of highly functionalized pyrazolo[5,1-b]quinazolines 5(a-j) catalysed by TBAB, with the advantages of an environmentally benign reaction, high yielding, quick reaction time, and operational simplicity. In the subsequent stage, CuSO4/NaAsc system was employed to synthesize the 1H-1,2,3-triazole tethered pyrazolo[1,5-b]quinazoline hybrids as 1H-1,2,3-triazoles are the structures of great diversity and importance in diverse therapeutics containing numerous biological activities. The geometry optimizations have been studied to support the possible mechanism through density functional theory (DFT) calculations using B3LYP/6–31 + G (d,p) basis set. The antimicrobial activity of all the synthesized hybrid compounds have been preliminary tested using the broth dilution technique against two gram-positive and two gram-negative bacterial strains as well as two fungal strains. In comparison to standard drugs, the majority of compounds exhibited good to moderate activity. Among the all the compounds, 7a (MIC 12.5 µg/mL) against Pseudomonas aeruginosa, 7j (MIC 50 µg/mL) against Bacillus subtilis and Rhizopus oryzae and 7t (MIC 50 µg/mL) against Aspergillus parasiticus have remarkable antimicrobial potency as compared to standard drug.
The Influence of Various Grease Compositions and Silver Nanoparticle Additives on Electrically Induced Rolling-element Bearing Damage
Authors: Bond Samuel , Jackson Robert L. , Mills German
Published: June 2023

Electrified mechanical contacts and electrical connectors are an integral part of electric vehicles, and their reliable performance is essential. This has become increasingly important for electric vehicles where leakage current could potentially load the motor bearings and many other contacts in the drive system. Such leakage current has been shown to rapidly accelerate surface degradation via small scale arcing across lubricating films. Recent work suggests that metallic nanoparticle additives in lubricants may be useful to improve the performance of these contacts. Presented in this report are results from a study on Ag nanoparticle enhanced polyurea greases under electro-tribological loads. Greases with mineral and synthetic base oils with and without additives were also tested for comparison purposes. The results indicate a reduction in pitting from arcing in the presence of nanoparticles, although oils with other additives also appear to exhibit an enhanced performance.
Self-perception of dual career barriers and athletic identity in student-athletes with disabilities according to socio-demographic, sport and academic variables
Authors: Maciá-Andreu María José , Vaquero-Cristóbal Raquel , Meroño Lourdes , Abenza-Cano Lucía , García-Roca Juan Alfonso , Cánovas-Álvarez Francisco José , Díaz-Aroca Álvaro , Capranica Laura , Stanescu Mónica , Pereira Antonino , Doupona Mojca , Mendes Francisco , Figueiredo Abel , Isidori Emanuele , Sánchez-Pato Antonio , Leiva Alejandro
Published: June 2023

The objective of this study was to analyse the perceived barriers to dual career success and athletic identity of student-athletes according to sociodemographic, sport, and academic variables. The final sample consisted of 203 student-athletes with disabilities from five European countries. The questionnaires used were ESTPORT, EBBS and AIMS. It was found that: a) women showed higher levels of tiredness (p=0.028); b) student-athletes with cerebral palsy and deafness showed higher barriers (p=0.023-0.001); c) semi-professional and professional student-athletes showed higher barriers (p=0.040-0.034) and identity as athletes (p=0.043-0.000); d) student-athletes who were at the end of their sports career showed significantly higher barriers (p=0.010) and lower athlete identity (p=0.022-0.000); and e) student-athletes in pre-university and university degree studies showed higher barriers (p=0.030-0.001). In conclusion, the self-perception of barriers is quite relevant, with differences arising from socio-demographic characteristics, type of disability, stage of sports career and type of education attended.
Integrating rare genetic variants into DPYD pharmacogenetic testing may help preventing fluoropyrimidine-induced toxicity
Authors: Fellah Sandy , Hennart Benjamin , Sabaouni Naoual , Boukrout Nihad , Hauwaert Cynthia Van der , Delage Clément , Cheok Meyling , perrais michael , cauffiez christelle , allorge delphine , pottier nicolas , LARRUE Romain
Published: June 2023

Variability in genes involved in drug pharmacokinetics or drug response can be responsible for suboptimal treatment efficacy or predispose to adverse drug reactions. In addition to common genetic variations, large-scale sequencing studies have uncovered multiple rare genetic variants predicted to cause functional alterations in genes encoding proteins implicated in drug metabolism, transport, and response. To understand the functional importance of rare genetic variants in DPYD, a pharmacogene whose alterations can cause severe toxicity in patients exposed to fluoropyrimidine-based regimens, massively parallel sequencing of the exonic regions and flanking splice junctions of the DPYD gene was performed in a series of nearly 3 000 patients categorized according to pre-emptive DPD enzyme activity using the [UH2]/[U] plasma ratio as a surrogate marker of DPD activity. Our results underscore the importance of integrating next-generation sequencing-based pharmacogenomic interpretation into clinical decision making to minimize fluoropyrimidine-based chemotherapy toxicity without altering treatment efficacy.
Anticancer and apoptotic effects of orange peel extract and naringin on doxorubicin-induced apoptosis in human esophageal squamous carcinoma cell line
Authors: Tajodini Mahbube , Samadi Firooz , Asadi Jahanbakhsh , Khosravi Aoub , Samadi Faezeh
Published: June 2023

Orange peel contains bioactive compounds with high antioxidant properties that may exhibit pharmacological effects on cancer cells with low toxicity. This study sought to investigate the anticancer and apoptotic effects of orange peel extract (OPE) and its main flavonoid derivative, naringin (NR), on doxorubicin (Dox)-induced apoptosis in a human esophageal squamous carcinoma cell line (ESCC). The cytotoxicity and DNA fragmentation were evaluated using the methylthiazoletetrazolium (MTT) and fluorescent nuclear dye 4’,6-diamidino-2-phenylindole (DAPI) assays, respectively. The protein expression of Bax, Bcl-2, p21, p53, and caspases 8 and 9 were measured using ELISA. A dose-dependent decline was observed in the viability of YM-1 cells treated with OPE, NR, and Dox. The combination effects of Dox with OPE and NR indicated a protective effect against Dox-induced cytotoxicity. Similarly, apoptotic bodies decreased in the interaction between Dox with OPE and NR. Up-regulation of pro-apoptotic Bax gene was found in YM-1 cells subjected to treatments. Interaction between Dox+OPE and Dox+NR resulted in the down-regulation of Bax. Activation of the executioner 8 and 9 caspases was found in the YM-1 cell line exposed to Dox and its combination with OPE and NR. The overexpression of anti-tumor p21 and p53 genes were observed in the YM-1 cells subjected to the treatments. However, down-regulation of P21 and P53 anti-tumor genes were found by the interaction of Dox with OPE and NR. In conclusion, this study suggests that OPE and NR have a pro-apoptotic potential on ESCC through Bax-dependent pathways and are promising agents to attenuate the toxic effect of Dox on ESCC.
CST1 promotes the metastasis by mediating an oxidative phosphorylation/MEK/ERK axis in esophageal squamous carcinoma cancer
Authors: Zhang Liangming , Chen Xiongfeng , Wang Jianwei , Chen Meihong , Zhuang Wanzhen , Xia Yu , Huang Zhixin , Zheng Yue , Huang Yi
Published: June 2023

Cysteine Protease Inhibitor 1 (CST1), a cystatin superfamily protein with the effect on the inhibition of cysteine protease activity , is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role on regulating cancer cell growth. However, the relationship and role of CST1 and OXPHOS on esophageal squamous cell carcinoma (ESCC) remains unknown. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Especially mentioned, we found that CST1 is closely associated with OXPHOS by the analysis of transcriptome sequencing. And then, based on real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence (IF), co-immunoprecipitation (CO-IP), and additions of OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we defined the effect of CST1 on mitochondrial complex I enzyme activity by interacting with GRIM19 protein to elevate OXPHOS levels, and the reciprocal regulatory relationship existed between OXPHOS and MEK/ERK pathway in ESCC cells. Finally, a study in vivo well demonstrated the potential of CST1 on ESCC metastasis by the regulation of OXPHOS and MEK/ERK pathway. This study is the first to unveil the oncogenic role of CST1 on ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate an OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS might be a promising target for ESCC treatment.
A Novel Algorithm to Spatio-Temporal Data Clustering on Indian Earthquake Dataset
Authors: Meshram Swati , Wagh Kishor P.
Published: June 2023

The seismic map of India displays the Himalayas, the North-East and the Andaman-Nicobar Islands are highly seismically active regions. The characteristics of the seismicity of Indian sub-continent needs to analyzed. This paper presents a novel algorithm to analyse data through partitioning by forming clusters. The clusters of spatial and spatio-temporal data are generated by distributing the data in spatial buckets or bins, finding the neighbouring buckets, and reducing the computation of distance. Moreover, centroid selection method focuses on randomly selecting centroids, based on the density of data in the spatial region. The advantage of the algorithm is, it is simpler in design and one parameter settings required. The result indicates that the approach is effective in detecting spatio-temporal patterns as clusters on the earthquake catalogue dataset. The experiments demonstrate the regions with higher occurrence of earthquake events, have more clusters formed depicting the earthquake prone areas. The clustering quality measured by Silhouette index is in the range of 0.88 to 0.93, which reflects good clusters are formed.
Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC BeadChip microarrays for dementia research
Authors: Zhang Wei , Young Juan I. , Gomez Lissette , Schmidt Michael A. , Lukacsovich David , Varma Achintya , Chen X. Steven , Kunkle Brian , Martin Eden R. , Wang Lily
Published: June 2023

Background
DNA methylation (DNAm) has been implicated in many diseases including dementia. Array-based technologies offer a cost-effective and comprehensive approach for measuring DNAm on a genome-wide scale. However, the accuracy of DNAm measurements obtained using Illumina arrays can vary across different probes. Previous research has focused primarily on assessing the reliability of DNAm in younger subjects, and have compared duplicate samples between the 450k-450k or 450k-EPIC platforms, with limited investigations on EPIC-EPIC comparisons.
Methods
We conducted a comprehensive assessment of probe reliability on the Illumina EPIC arrays using 138 duplicated blood DNAm samples from subjects older than 65 years in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. To assess the reliability of each probe, we computed intraclass correlations (ICCs) for each probe. Both the magnitude and patterns of reliability in the EPIC-EPIC comparison were assessed. Furthermore, we also investigated the impact of probe reliability on the analyses of epigenome-wide association studies (EWAS).
Results
Our findings revealed the reliability of probes on the EPIC arrays is higher than those of previous studies involving duplicate measurements on 450k-EPIC or 450k-450k arrays. Consistent with earlier research, we observed increased reliability in probes with substantial between-subject variances or average methylation beta values ranging from 0.2 to 0.8. Lower reliability was observed in type I probes or probes located within the promoter and CpG island regions. In addition, we found some probes can yield high ICC values despite significant disagreement in duplicate measurements, primarily due to their relatively high between-subject variance. To account for such discrepancies explicitly, we introduced a novel statistical measure called the modified ICC, which penalizes the ICC based on the half-width of the 95% confidence limits of agreement. Importantly, we found probe reliability has significant implications in various downstream analyses of EWAS, such as meta-analysis, differentially methylated regions analysis, and integrative analyses within the cross-tissue or multi-omics contexts.
Conclusion
We developed a valuable resource for dementia research, providing crucial reliability information for probes on the EPIC array. This resource can be utilized to identify and prioritize high-quality probes, thereby minimizing the potential for false discoveries and maximizing the potential of EWAS.
Enhancing Cardiovascular Disease Prediction: A Domain Knowledge-Based Feature Selection and Stacked Ensemble Machine Learning Approach
Authors: Rustamov Zahiriddin , Rustamov Jaloliddin , Zaki Nazar , Turaev Sherzod , Sultana Most Sarmin , Tan Jeanne Ywei , Balakrishnan Vimala
Published: June 2023

Cardiovascular diseases (CVDs) are prevalent disorders affecting the heart or blood arteries. Early disease detection significantly enhances survival prospects, thus emphasizing the necessity for accurate prediction methods. Emerging technologies, such as machine learning (ML), present promising avenues for more precise prediction of CVDs. However, a critical challenge lies in developing models that not only ensure optimal predictive performance but also conform to well-established domain knowledge, thereby enhancing their credibility. Single classifiers often fall short due to issues like overfitting and bias. In response, this study proposes a domain knowledge-based feature selection integrated with a stacking ensemble classifier. The Framingham Heart Study, UCI Heart Disease and UAE retrospective cohort study datasets were utilized for training and evaluation of the ML algorithms. The results indicate that the proposed domain knowledge-based feature selection performs on par with frequently adopted feature selection techniques. Moreover, the proposed stacked ensemble, in conjunction with domain knowledge-based feature selection, achieved the highest metrics with 89.66% accuracy, and 89.16% F1-score on the Framingham dataset. Similarly, the proposed method achieved an F1-score of 85.26% and 96.23% on the UCI Heart Disease and UAE datasets. Furthermore, this study employs explainable AI techniques to illuminate the decision-making process of the predictive models. Thus, the study establishes that domain knowledge-based feature selection promotes the credibility of ML models without compromising predictive performance.
Pro198Leu polymorphism in the GPX1 gene has no influence on selenium biomarkers after Brazil nut consumption in rheumatoid arthritis patients
Authors: Callou Kátia Rau de Almeida , Duarte Graziela Biude Silva , Reis Bruna Zavarize , Hoff Leonardo Santos , Pollak Daniel Feldman , Cozzolino Silvia Maria Franciscato
Published: June 2023

Background: Chronic inflammation and increased oxidative stress in rheumatoid arthritis (RA) patients can affect selenium (Se) nutritional status and the consumption of food sources such as Brazil nuts, can improve this condition. However, the presence of genetic polymorphisms in selenoproteins could influence Se biomarkers and their bioavailability. This study aimed to evaluate the effect of Brazil nut consumption on Se biomarkers in RA patients and the influence of Pro198Leu polymorphism in the GPX1 gene.
Methods: This study was conducted with 45 RA patients who consumed one unit of Brazil nut per day (300 μg/Se) for eight weeks. Blood and 24-hour urine collection were analyzed before and after the intervention to assess Se biomarkers and to obtain DNA and RNA samples. Gene expression of GPX1 and Pro198Leu (rs1050450) genotyping was determined by real-time PCR using TaqMan Assays.
Results: RA patients were Se deficiency and Brazil nut intake was efficient to improve all nutritional biomarkers related to this mineral. According to the genotypes, after Brazil nut intervention period both CC and CT+TT had a significant (P<0.05) change in Se biomarkers, except the CT+TT carriers for GPx1 concentration (P=0.136). The analysis considering the intervention time and genotype factors did not show significant variation for all Se biomarkers.
Conclusion: The consumption of Brazil nuts for eight weeks was efficient to improve Se biomarkers in RA patients independent of the genotypes of Pro198Leu SNP in the GPX1 gene.
Simulations of Fluid Dynamics (CFD), radiation distribution and chemical reaction in the photoreactor
Authors: Fedailaine M. , Lahmar H , Benamira M , Trari M.
Published: June 2023

The fluid dynamic mechanics, Computational Fluid Dynamics (CFD), has become a valuable engineering tool for predicting the fluid flow, the quantity of movement transfer, the matter transfer as well as chemical reaction kinetics, by solving the numerical program using the Fluent software. In this study, CFD was used for the fluid dynamics analysis and simulation with a laminar flow regime on the chemical reactions, which excite the catalyst by a light source. The mineral pollutant (Ni2+) is reduced to elemental state in the photoreactor to different designs and models by photocatalysis leading to nickel in the form of a changeless cluster (Nio) and hydrogen in the form of gas (H2).
Thermo-responsive tri-modal antimicrobial platform for precise biofilm removal and enhanced wound healing
Authors: Du Ting , Cao Jiangli , Huang Yachen , Li XingXing , Wei Lifei , Xiao Zehui , Jiao Jingbo , Song Zhiyong , Liu Jifeng , Du Xinjun , Wang Shuo
Published: June 2023

A bacterial-specific therapeutic nanosystem (HMAPH) is developed based on biodegradable hollow mesoporous Prussian blue encapsulating photosensitizer methylene blue (MB), followed by modification with gold nanoparticles, polymyxin B (PMB), and hyaluronic acid (HA) to improve near-infrared (NIR) response release characteristics, specificity, and hydrophilicity. In this system, hyaluronic acid is decomposed under the action of hyaluronidase, and the exposed nanomaterials specifically bind the outer membrane of Pseudomonas aeruginosa (P. aeruginosa) through PMB to increase the membrane sensitivity to photodynamic treatment. Under dual light irradiation, a large amount of iron ions released by HMAPH can undergo Fenton reaction with H2O2 in bacteria to generate hydroxyl radicals (▪OH), enabling photothermal properties to directly kill cells by hyperthermia. Additionally, the photodynamic activity of MB released by photoinduced activation can generate reactive oxygen species, achieving synergistic and effective inhibition of P. aeruginosa. HMAPH can also inhibit and disrupt biofilm formation and down-regulate the expression of virulence factors. In vivo experiments revealed that HMAPH can accelerate P. aeruginosa-infected wound healing by promoting angiogenesis and skin regeneration, inhibiting inflammatory response, and promoting M1 to M2 polarization. Our work proposes a strategy against bacteria and biofilms through a synergistic photothermal-photodynamic-Fenton reaction, opening up new prospects for combating biofilm-associated infections.
In situ HER2 RNA expression as a predictor of pathologic complete response of HER2- positive breast cancer patients receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment
Authors: Lien Huang-Chun , Lo Chiao , Lee Yi-Hsuang , Lin Po-Hang , Wang Ming-Yang , Kuo Wen-Hung , Tsai Li-Wei , Lu Yen-Shen , Hu Hsiang-Wei , Li Yu-Chia , Huang Chiun-Sheng
Published: June 2023

Background
Immunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response.
Methods
We aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT).
Results
We validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1–4 BCs (66.7% vs. 15.9%, p < 0.0001). There were higher RNAscope scores and pCR rates in patients with HER2 IHC 3 + versus IHC 2+/FISH + BCs and HER2 RNAscope scores and pCR rates showed similar non-linear positive correlations with HER2 copy numbers and HER2/centromere 17 ratios. Moreover, in each HER2-positive IHC/FISH category, higher pCR rates were observed in patients with RNAscope scores of 5 versus 1–4 BC. Patients achieving pCR had BCs with notably higher HER2 RNAscope scores. Multivariate analysis identified HER2 RNAscope 5 as a strong pCR predictor [odds ratio = 10.865, p < 0.001]. The combined impact of multivariate analysis-defined pCR predictors demonstrated that a higher pCR rate was observed in patients with a score of 5 versus a score of 1–4 BCs regardless of the status of hormone receptor and mono-or dual anti-HER2 blockade.
Concusions:
Our results demonstrated that high isHRE (RNAscope score 5) is a strong pCR predictor in patients with HER2-positive BCs receiving NCTT, highlighting the complementary role of isHRE in stratifying HER2 status in tissue. Such stratification is relevant to anti-HER2 therapeutic efficacy, particularly using the cutoff of score 1–4 versus 5.
Linear growth of children with X-linked hypophosphatemia treated with Burosumab: a real-life observational study
Authors: Levy-Shraga Yael , Levi Shelly , Regev Ravit , Gal Shoshana , Brener Avivit , Lebenthal Yael , Gillis David , Strich David , Zung Amnon , Cleper Roxana , Borovitz Yael , Bello Rachel , Tenenbaum Ariel , Zadik Zvi , Davidovits Miriam , Zeitlin Leonid , Tiosano Dov
Published: June 2023

Purpose
To assess the long-term efficacy of burosumab for paediatric patients with X-linked hypophosphatemia, focusing on linear growth.
Methods
This multi-center retrospective study included 35 paediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results and rickets severity score (RSS), from two years prior to treatment initiation and up to four years after.
Results
Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6–15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1–4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after three months, and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8% to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from − 2.07 ± 1.05 to -1.72 ± 1.04 (p < 0.001), and from − 0.51 ± 1.12 to -0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from − 2.33 ± 1.12 to -1.94 ± 1.24, p = 0.042) and among those who did not (from − 2.01 ± 1.01 to -1.66 ± 1.01, p = 0.001).
Conclusion
Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity, and enhanced linear growth.
An Effective, Mechanochemical One-Pot Multi Gram Scale Synthesis of N-Bridged Fused Heterocycles under Solvent- Free Conditions
Authors: Chauhan Swati , Verma Pratibha , Srivast Vandana
Published: June 2023

KI/TBHP mediated C–N and C–S bonds formation of ketones with 2-aminopyridines under grinding condition to give the imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazole under ecologically friendly conditions have been established. The reaction proceeds under solvent-free condition, without using any metal catalyst and displays high yields. This protocol has several notable features including mild reaction condition, base-free, broad functional group tolerance and good reaction yield, avoid the use of expensive and air-sensitive reagents and can be performed under ambient reaction conditions.
Plasmodium falciparum population structure inferred by msp1 amplicon sequencing of parasites collected from febrile patients in Kenya
Authors: Andika Brian , Mobegi Victor , Gathii Kimita , Nyataya Josphat , Maina Naomi , Awinda George , Mutai Beth , Waitumbi John
Published: June 2023

Background
Multiplicity of infection (MOI) is an important measure of Plasmodium falciparum diversity, usually derived from the highly polymorphic genes such as msp1, msp2 and glurp as well as microsatellites. Conventional methods of deriving MOI lack fine resolution needed to discriminate minor clones. This study used amplicon sequencing (AmpliSeq) of Pfmsp1 to measure spatial and temporal genetic diversity of P. falciparum.
Methods
264 P. falciparum positive blood samples collected from areas of differing malaria endemicities between 2010 to 2019 were used. Pfmsp1 gene was amplified and amplicon libraries sequenced on Illumina MiSeq. Sequences were aligned against a reference sequence (NC_004330.2) and clustered to detect fragment length polymorphism and amino acid variations.
Results
Children <5 years had higher parasitemia (median = 23.5+5 SD, p = 0.03) than the >5-14 (= 25.3+5 SD), and those >15 (=25.1+6 SD). Of the alleles detected, 553 (54.5%) were K1, 250 (24.7%) MAD20 and 211 (20.8%) RO33 that grouped into 19 K1 allelic families (108-270 bp), 14 MAD20 (108-216 bp) and one RO33 (153 bp). AmpliSeq revealed nucleotide polymorphisms in alleles that had similar sizes, thus increasing the K1 to 104, 58 for MAD20 and 14 for RO33. By AmpliSeq, the mean MOI was 2.9 (+0.73, 95% CI) for the malaria endemic Lake Victoria region, 2.7 (+ 0.97, 95% CI) for the epidemic prone Kisii Highland and 1.4 (+ 0.19, 95% CI) for the seasonal malaria Semi-Arid region. MOI decreased with age: 2.5 (+ 0.68, 95% CI) for children <5 years, compared to 2.3 (+ 0.65, 95% CI) for ages 5 to 14 and 1.8 (+ 0.71, 95% CI) for those >15. Females had a higher MOI of 2.5 (+ 0.61, 95% CI), compared to males (1.9 (+ 0.49, 95% CI), though not statistically significant. In all regions, the number of alleles increased from the 2014-2015 period, more so in the Lake Victoria and the seasonal transmission arid regions.
Conclusion
Our findings highlight the added advantages of AmpliSeq in allele discrimination. MOI was influenced by age, gender and transmission settings, highlighting an additional level of complexity of P. falciparum population structure.
Gastrointestinal parasites of the wild ungulates (Mammalia: Cetartiodactyla) in the Hemis National Park, Ladakh, India
Authors: Zazay Jigmet , Bhat Bilal A. , Tak Hidayatullah , Lone Arif Nabi
Published: June 2023

Gastrointestinal parasitic infection is known to affect the health and population dynamics of wild ungulates. We evaluated the gastrointestinal parasitic prevalence and intensity of wild ungulates in the Hemis National Park of Ladakh by examining their fresh faecal samples. A total of 327 fresh faecal samples from three wild ungulates, blue sheep Pseudois nayaur (n = 127), Ladakh urial Ovis vignei vignei (n = 110) and Himalayan ibex Ibex siberica (n = 90) were collected between June 2021 and May 2022. The floatation and sedimentation techniques were employed for detection of parasitic eggs/oocysts. Out of 327 samples examined, 165 samples were infected with gastrointestinal parasites making an overall prevalence of (50.45%). During the present study seven parasitic genera were reported. Blue sheep was infected with Eimeria spp. (20.47%), Nematodirus spp. (8.66%), Strongyloides spp. (7.87%) and Moniezia spp. (6.29%). Ladakh urial was infected with Eimeria spp. (17.27%), Trichuris sp. (10.90%), Haemonchus sp. (5.45%) and Moniezia spp. (6.36%). Himalayan ibex was infected with Eimeria spp. (18.88%), Nematodirus spp. (8.88%) and Trichostrongylus spp. (5.55%). Out of 327 faecal samples examined, 36 samples (11%) were infected with mixed parasites. The highest prevalence was recorded in summer (64.42%) and the lowest in winter (33.82%). A significant difference in the parasitic prevalence was observed across seasons in each of the three wild ungulate hosts. However, there was no significant difference in the prevalence of parasites across these hosts.
Microbiome variations among age classes and diets of captive Asian elephants (Elephas maximus) in Thailand using full-length 16S rRNA nanopore sequencing
Authors: Klinsawat Worata , Uthaipaisanwong Pichahpuk , Jenjaroenpun Piroon , Sripib Supaphen , Wongsurawat Thidathip , Kusonmano Kanthida
Published: June 2023

Asian elephants (Elephas maximus) have been known as a national symbol of Thailand and linked to Thai history and culture for centuries. The elephant welfare improvement is one of the major components to achieve sustainable captive management. Microbiome inhabiting digestive tracts have been shown with symbiotic relations to host health. This work provided high-resolution microbiome profiles of 32 captive elephants at a species level by utilizing full-length 16S rRNA gene nanopore sequencing. Eleven common uncultured bacterial species were found across elephants fed with solid food including uncultured bacterium Rikenellaceae RC9 gut group, Kiritimatiellae WCHB1-41, Phascolarctobacterium, Oscillospiraceae NK4A214 group, Christensenellaceae R-7 group, Oribacterium, Oscillospirales UCG-010, Lachnospiraceae, Bacteroidales F082, uncultured rumen Rikenellaceae RC9 gut group, and Lachnospiraceae AC2044 group. We observed microbiome shifts along the age classes of baby (0–2 years), juvenile (2–10 years), and adult (> 10 years). Interestingly, we found distinct microbiome profiles among adult elephants fed with a local palm, Caryota urens, as a supplement. Potential beneficial microbes have been revealed according to the age classes and feed diets. The retrieved microbiome data could be provided as good baseline microbial profiles for monitoring elephant health, and a guideline for dietary selection suitable for each age class.
Multicenter cohort study of the risk factors and mortality of Omicron variant SARS-CoV-2-infected patients with hematologic malignancies in hospitals
Authors: zong xiangping , Zhou Jin , Ma Xiao , Bai Lian , Yan Lingzhi , Geng Hongzhi , Zhang Ying , Li Jiaqi , Yang Qin , Zeng Liangyu , Lu Yutong , Liu Shuangzhu , Li Caixia , Wu Depei
Published: June 2023

Purpose
Evaluating risk factors of mortality and characters in patients with hematologic malignancy (HM) after anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination of China.
Methods
A total of 104 HMs were included with a median follow-up of 45 days.
Results
The overall mortality rate was 9.6%. In multivariable analyses, 1 or more comorbidities (P = 0.014), lactic dehydrogenase > 300 u/l (P = 0.014), albumin < 35 g/l (P = 0.017) and active malignancy (P = 0.009) were associated with severe and critical COVID-19. Conversely, patients who received 3 vaccinations had a lower possibility of severe infection (P = 0.022). Active malignancy and lactic dehydrogenase > 300 u/l were risk factors associated with higher mortality in multivariable analyses (P = 0.03; P = 0.038, respectively). We also found that the duration of a positive SARS-CoV-2 PCR test and the time to stable pneumonia by chest computed tomography scan in the severe and critical infection subgroups were significantly longer than those in the moderate infection group (P = 0.03 and P = 0.002, respectively).
Conclusions
These findings may contribute to guiding the management of HMs during the pandemic, and emphasizing the importance of starting treatment of aggressive HMs for earlier remission.
Bridging the Gap: A Comprehensive Evaluation of the Government of Tanzania Hospital Management Information System (GoTHOMIS) through Participatory Action Research
Authors: Mambile Cesilia , Mwogosi Augustino
Published: June 2023

This study addresses the implementation and impact of the Government of Tanzania’s Hospital Management Information System (GoTHOMIS) using a participatory action research (PAR) approach. Its purpose is to assess the implementation factors, strengths and weaknesses of GoTHOMIS on healthcare services in Tanzania. The research employs a PAR methodology involving stakeholders from healthcare facilities, administrators, and I.T. experts. Data collection methods include document evaluation and interviews with key informants. The findings highlight significant areas for improvement in the implementation process, characterized by a top-down approach and a lack of user participation, hindering the system’s successful adoption. Inadequate infrastructure, including network connectivity and outdated hardware, posed further challenges. Compatibility issues with peripheral devices and usability problems were also identified. Despite the challenges, GoTHOMIS demonstrated strengths such as improved accessibility, integration with the MTUHA reporting system, and automation of clinical tasks—weaknesses, including some system components, were only partially automated, which caused inefficiencies in the delivery of healthcare services and failure in integrating with other existing healthcare systems and data sources. Limitations of the study include a focus on selected healthcare facilities, limiting generalizability, and reliance on self-reported data, which may introduce biases. The study’s originality lies in applying a PAR approach to assess GoTHOMIS, providing valuable insights into implementation challenges and potential improvements.
Coping strategies mediate the relationship between fear of cancer recurrence and quality of life in postoperative patients with prostate cancer: a multicentre survey
Authors: Yu Chen , Jingzhen Zhu , Luqiang Zhou , Xiaojuan Yuan , Ji Zheng
Published: June 2023

Purpose
The aim of the present study was to investigate the relationships between fear of cancer recurrence and quality of life in patients with prostate cancer. A model based on Lazarus’ and Folkman’s stress and coping theory tested the specific hypothesis: fear of cancer recurrence has a direct and indirect effect on quality of life mediated by coping strategies.
Methods
The study used a cross-sectional and correlational design. Patients (n = 305) with postoperative prostate cancer completed three questionnaires and provided background data in 2023, and a mediator model was tested using the PROCESS macro for SPSS.
Results
The test of the conceptual model confirmed the hypothesis. There was a significant direct and indirect effect of fear of cancer recurrence on quality of life through the mediators.
Conclusions
The coping strategies of face and yield are the most important mediating factors between fear of cancer recurrence and QoL in patients with chronic illness, which supports Lazarus’ and Folkman’s stress and coping theory.
Endogenous Market Coverage with Quality Dependent Production Costs
Authors: Pires Cesaltina Pacheco , Jorge Sílvia Ferreira , Catalão-Lopes Margarida , Pinho Joana , Garcês Pedro , Alventosa Adriana
Published: June 2023

This paper endogenizes market coverage in a vertically differentiated duopoly with quality dependent marginal production costs, where firms first choose qualities and then prices. When the lowest quality valuation is low, a partial coverage duopoly emerges. For slightly higher lowest quality valuation, a full coverage duopoly with a corner solution holds. For even higher lowest quality valuation, there are multiple equilibria. For highest lowest quality valuation, there is an interior full coverage duopoly. Interestingly, product differentiation increases with quality valuation heterogeneity, given a market configuration, but may decrease when accounting for an endogenous market coverage.
JEL classification: L13; L15; D43
Contact toxicity, antifeedant activity and oviposition preference of osthole against agricultural pests
Authors: Dong Fang , Chen Xin , Xingyuan Men , Li Zhuo , Kong Yujun , Yuan Yiyang , Ge Feng
Published: June 2023

Osthole, the dominant bioactive constituent in Cnidium monnieri, has been shown to exhibit acute insecticidal activities. However, its detailed toxicity, antifeedant and oviposition preference effects against agricultural pests has not been fully understood, which has greatly hindered its practical applications. This study is designed to investigate the contact toxicity, antifeedant activity and oviposition preference of osthole against three agricultural pests (Tetranychus urticae, Myzus persicae and Bactrocera dorsalis) to evaluate its potential agricultural applications. Our results showed that Cnidium monnieri (L.) Cusson (CMC) have a high osthole content of 11.4 mg/g. Osthole exhibited a comparable level of acute toxicity against T. urticae to four other coumarins found in CMC. Osthole demonstrated significant insecticidal activity against first instar nymphs and adults of T. urticae and M. persicae in a dose-dependent manner, but not against B. dorsalis adults. Osthole exposure reduced the fecundity and prolonged the developmental time of T. urticae and M. persicae. Leaf choice bioassays revealed potent antifeedant activity in T. urticae. Furthermore, female B. dorsalis showed a distinct preference for laying eggs in mango juice with 0.02 mg/mL osthole at 48 hours, a preference which persisted at 96 hours. These results provide valuable insights into the toxicity, repellent activity, and attractant activity of osthole, thereby contributing to its expanded use in pest control.
Integrating UAV Derived Vegetation and Texture Indices for Estimation of Leaf Nitrogen Concentration in Drip-Irrigated Cotton under Reduced Nitrogen Treatment and Different Plant Densities
Authors: Li Minghua , Liu Yang , Lu Xi , Jiang Jiale , Ma Xuehua , Wen Ming , Ma Fuyu
Published: June 2023

Background
Accurate assessment of nitrogen (N) status is important for N management and yield improvement. The N status in plant was affected by plant densities and N application rates, while the methods of assessing the N status in drip-irrigated cotton under reduced nitrogen treatment and different plant densities are lacking.
Methods
This study was conducted with four different N treatments (195.5, 299, 402.5, and 506 kg N ha− 1) and three sowing densities (6.9×104, 13.8×104, and 24×104 plants ha− 1) by using a low-cost Unmanned Aerial Vehicle (UAV) system to acquire RGB imagery at 10 m flight altitude at cotton main growth stages. We evaluated the performance of different ground resolutions (1.3-, 2.6-, 5.2-,10.4-, 20.8-, 41.6-, 83.2-, and 166.4-cm-ground-resolution) image textures, vegetation indices (VIs), and their combination for leaf N concentrations (LNC) estimation with four regression methods (stepwise multiple linear regression, SMLR; support vector regression, SVR; extreme learning machine, ELM; random forest, RF).
Results
The results showed that the combination of VIs and texture maintained higher estimation accuracy than using VIs or textures alone. Specifically, the RF regression models had the higher accuracy and stability than SMLR and other two machine learning algorithms. The best accuracy (R2 = 0.87, RMSE = 3.14g kg− 1, rRMSE = 7.00%) was obtained when RF was applied in combination with VIs and texture.
Conclusion
The combination of VIs and textures from UAV images using RF could improve the estimation accuracy of drip-irrigated cotton LNC and may have the potential contribution in rapid and non-destructive nutrition monitoring and diagnosis of other crops or other growth parameters.