bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis
Authors: WANG mengqi , yang naisu , Laterrière Mario , Gagné David , Omonijo Faith , Ibeagha-Awemu Eveline Mengwi
Published: October 2023

Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry. Multi-omics approaches enable the comprehensive investigation of the complex interactions between multiple layers of information to provide a more holistic view of disease pathogenesis. Therefore, this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data (mRNA and lncRNA), small RNA sequencing data (miRNA) and DNA methylation sequencing data of milk somatic cells from ten healthy cows and twenty cows with naturally occurring subclinical mastitis caused byStaphylococcus aureusorStaphylococcus chromogenes. Results Functional investigation of the data sets through gene sets analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, providing further insights into subclinical mastitis and revealing the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis. The abundant genomic and epigenomic signatures with significant alterations related to subclinical mastitis were observed, including 30,846, 2552, 1276 and 57 differential MHBs (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, five Factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factors 1 and Factor 2 in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. Also, networks of important functional gene sets with the involvement of multi-OMICs signatures were demonstrated, which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis. Furthermore, multi-omics integration enabled the association of the epigenomic regulatory factors of altered genes in important pathways, such as ‘Staphylococcus aureusinfection pathway’ and ‘natural killer cell mediated cytotoxicity pathway’, etc., which provides further insights into mastitis regulatory mechanisms. Moreover, few multi-omics signatures (14 dMHBs, 25 DEGs, 18 DELs and 5 DEMs) were identified as candidate discriminant signatures with capacity of distinguishing subclinical mastitis cows from healthy cows. Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis, which may ultimately lead to the development of more effective mastitis control and management strategies.
Exploring the connection between ethylene and somatic embryogenesis: an in silico analysis of gene pathways
Authors: Barros Artur Gomes , Neto Antonio Rodrigues da Cunha , Esteves Giovana , Resende Arlinda de Jesus Rodrigues , Pimenta Lidiane , Santos Breno Régis
Published: October 2023

Somatic embryogenesis is a plant cloning process that enables the development of embryos without meiosis or fertilization. It can occur naturally or be induced through laboratory-induced stress. The indirect method is preferred for industrial production. The excessive presence of ethylene in in vitro cultures can hinder plant development and shoot formation. However, the impact of ethylene on somatic embryogenesis is not well understood. In light of the foregoing, we assessed the correlation between ethylene and somatic embryogenesis through an in silico methodology for predicting gene pathways. Using the STRING platform, the genes AGL15 and ERF115 were selected. This allowed for enrichment analyses to comprehend the individual functions of these genes in the somatic embryogenesis process influenced by ethylene. The results indicate that plant stress induces ethylene production, activating genes such as ERF115 and HAD19. This results in cellular senescence in certain structures and cell proliferation in others. Furthermore, the transport of substances from areas of cell death to sites of proliferation is driven by the PLT3 gene. This region is crucial for somatic embryogenesis development, activating genes responsible for somatic embryogenesis.
Geographic Analysis of Emergency Newborn Referral Patterns in Southern Ghana and Implications for Neonatal Survival
Authors: Amponsah Edith , Twum-Danso Nana , Ansong David , Delamater Paul , Boadu Richard , Owen Medge , Chinbuah Margaret , Sagoe-Moses Isabella
Published: October 2023

Introduction: From 1990 to 2020, neonatal mortality declined by 52% globally and 45% in Ghana. Yet this fell short of the national goal. Critical contributors to this shortfall include limited and unreliable access to Emergency Obstetric and Newborn Care (EmONC). Effective and efficient health care referral networks are an integral but under-studied component of EmONC.
Objectives: This study aimed to assess the longitudinal and geographic patterns in newborn referral rates in Making Every Baby Count Initiative (MEBCI), a project that aimed to improve the quality of facility-based care for newborns in 4 administrative regions through clinical training, facility readiness, and advocacy.
Methods: 155 health facilities from the 4 targeted administrative regions were included in the sample. A multilevel Poisson growth curve model was used to examine changes in newborn referral rates over time, and correlation analysis was conducted to assess the association between travel time and referral rates. A geographic information system was used to estimate and visualize the average travel time with a 4-wheeled automobile.
Results: The overall rate of newborns referred out of MEBCI-participating facilities increased over time. Mean travel times from referring facilities to their respective regional hospitals varied across regions (lowest: 78mins, highest: 120mins). Overall, across the 4 MEBCI-participating regions, there was a negative correlation between referral rates and travel time (r = -0.37, p < .001).
Conclusion: The MEBCI-supported facilities experienced statistically significant overall increases in newborn referral rates over time. Facilities furthest from the regional hospitals experienced the lowest referral rates, suggesting that long distances and travel times may have influenced providers’ decisions to refer or patients’ acceptance of referral.
A bright radio burst from FRB 20200120E in a globular cluster of the nearby galaxy M81
Authors: Wu Xue-Feng , Zhang Songbo , Wang Jieshuang , Yang X , Li Ye , Geng Jin-Jun , Tang Zhenfan , Chang Chenming , Luo J.T. , Wang XingChuan , Dai Z. G. , Zhang Bing
Published: October 2023

Fast radio bursts (FRBs) are immensely energetic millisecond-duration radio pulses . Observations indicate that nearby FRBs can be produced by both young stellar populations, as suggested by the detection of FRB 20200428 from a Galactic magnetar SGR 1935+2154, and old stellar populations, as suggested by the localization of the repeating source FRB 20200120E in a globular cluster of M81 . Nevertheless, the burst energies of FRB 20200120E are significantly smaller than those of other cosmological FRBs, even falling below the energy of the Galactic event FRB 20200428. Additionally, its burst energy distribution displays a steep power law tail at high fluences. It is unclear whether this type of source can contribute to the cosmological FRB population. Here we report the detection of a burst from FRB 20200120E in 1.1-1.7 GHz, with a fluence of approximately 31.4 Jy ms, which is more than 44 times larger than the previous detected bursts ∼ 1.4 GHz frequencies and five times more energetic than FRB 20200428 . It reaches one-third of the energy of the weakest burst from FRB 20121102A detected so far and is detectable at a distance exceeding 200Mpc. This suggests that globular clusters can host cosmological FRBs, and the currently localized FRB sample could contain FRBs from globular clusters. Together with SGR 1935+2154, these two most nearby sources support multiple progenitor sources for FRBs.
Prognostic factors for premature cardiovascular disease mortality in Malaysia: A modelling approach using semi-parametric and parametric survival analysis with National Health and Morbidity Survey linked mortality data
Authors: Hasani Wan Shakira Rodzlan , Musa Kamarul Imran , Omar Mohd Azahadi , Hanis Tengku Muhammad , Kueh Yee Cheng , Ganapathy Shubash Shander , Yusoff Muhammad Fadhli Mohd , Ahmad Noor Ani
Published: October 2023

Background
Cardiovascular disease (CVD) is the leading cause of premature mortality worldwide, with a pronounced impact in low- and middle-income countries. Despite existing research on CVD risk factors, the study of premature CVD mortality in Malaysia remains limited. This study employs survival analysis to model modifiable risk factors associated with premature CVD mortality among Malaysian adults.
Method
We utilised data from Malaysia's National Health and Morbidity Survey (NHMS) conducted in 2006, 2011, and 2015, linked with mortality records. The cohort comprised individuals aged 18 to 70 during the NHMS interview. Follow-up extended to 2021, with the primary event of interest being CVD-related premature mortality between ages 30 and 70. This study employed six survival models: a semi-parametric Cox proportional hazard (PH) and five parametric survival models, which were Exponential, Weibull, Gompertz, log-normal and log-logistic distributions using R software. The age standardized incidence rate (ASIR) of premature CVD mortality was calculated per 1000 person-years.
Results
Among 63,722 participants, 886 (1.4%) experienced premature CVD mortality, with an ASIR of 1.80 per 1000 person-years. The best-fit models (based on AIC value) were the stratified Cox model by age (semi-parametric) and the log-normal accelerated failure time (AFT) model (parametric). Males had higher risk (Hazard Ratio, HR = 2.68) and experienced 49% shorter survival time (Event Time Ratio, ETR = 0.51) compared to females. When compared to Chinese ethnicity, Indians, Malays, and other Bumiputera had higher HR and lower survival times. Rural residents and those with lower education also faced increased HRs and reduced survival times. Diabetes, both diagnosed (HR = 3.26, ETR = 0.37) and undiagnosed (HR = 1.63, ETR = 0.63), increased mortality risk and decreased survival time by 63% and 37%, respectively. Diagnosed and undiagnosed hypertension elevated risk (HR = 1.84, 1.46) and reduced survival time by 47% and 32% (ETR = 0.53, 0.68) respectively. Undiagnosed hypercholesterolemia increased risk (HR = 1.31) and lowered survival time by 20% (ETR = 0.80), with no significant association for diagnosed hypercholesterolemia. Additionally, current smoking and abdominal obesity elevated risk (HR = 1.38, 1.60) and shortened survival (ETR = 0.81, 0.71).
Conclusion
The semi-parametric and parametric survival models both highlight the considerable impact of socioeconomic status and modifiable risk factors on premature CVD mortality, underscoring the imperative for targeted interventions to effectively mitigate these effects.
Clinical Prediction Models for Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma
Authors: Luo Shuli , Lai Fenghua , Liang Ruiming , Li Bin , He Yufei , Chen Wenke , Zhang Jiayuan , Li Xuyang , Xu Tianyi , Hou Yingtong , Liu Yihao , Long Jianyan , Yang Zheng , Chen Xinwen
Published: October 2023

Purpose: Accurate preoperative diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains an unsolved problem. This study aimed to construct a nomogram and scoring system for predicting LNM based on the clinical characteristics of patients with PTC.
Methods: 1400 patients with PTC who underwent thyroidectomy and lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled and randomly divided into training and internal testing sets. Furthermore, 692 patients with PTC from three other medical centers were collected as external testing sets. Least absolute shrinkage and selection operator (LASSO) was used to screen the predictors, and a nomogram was constructed. In addition, a scoring system was constructed using 10-fold cross-validation. The performances of the two models were verified among datasets and compared with preoperative ultrasound (US).
Results: Six independent predictors were included in the multivariate logistic model: age, sex, US diagnosis of LNM, tumor diameter, location, and thyroid peroxidase antibody level. The areas under the receiver operating characteristic curve (AUROC) (95% confidence interval) of this nomogram in the training, internal testing, and three external testing sets were 0.816 (0.791-0.840), 0.782 (0.727-0.837), 0.759 (0.699-0.819), 0.749 (0.667-0.831), and 0.777 (0.726-0.828), respectively. The AUROC of the scoring system were 0.810 (0.785-0.835), 0.772 (0.718-0.826), 0.736 (0.675-0.798), 0.717 (0.635-0.799) and 0.756 (0.704-0.808), respectively. The prediction performances were both significantly superior to those of preoperative US (P<0.001).
Conclusion: The nomogram and scoring system performed well in different datasets and significantly improved the preoperative prediction of LNM than US alone.
Prognostic implication of ITGB8 and its relationship with immune response
Authors: Jin Zhao , Jiao Zonglin , Song Lei , Zhang Yu , Zhang Minghui , Zhao Yanbin
Published: October 2023

Background
Integrin β8 (ITGβ8) belongs to the β subunit family of integrin. It plays a role in cells and extracellular matrix participating in the proliferation and metastasis of tumours. It is upregulated in various cancers, including non-small-cell lung cancer (NSCLC). Researches show that ITGβ8 may be involved in regulating immunity escape in some tumors. However, it is still unclear whether ITGβ8 is involved in the immune regulation of NSCLC. Here, bioinformatics analysis and basic experiments were used to investigated the expression of ITGβ8 and its potential association with immune in NSCLC.
Methods
We used bioinformatics technology to analyze not only the expression of ITGβ8 in NSCLC tissues in database, but also the correlation between ITGβ8 expression and immune cell infiltration, TMB, immune checkpoint genes, signaling pathways and patient survival. The expression of ITGβ8 in NSCLC cells was verified by WB and RT-qPCR. Kaplan-Meier survival curves were used to analyze the relationship between ITGβ8 expression and prognosis. Log-rank test and Cox proportional-hazards model were used to identify risk factors.
Results
The TCGA and HPA database as well as our NSCLC tissue specimens showed high expression of ITGβ8 in NSCLC. Its expression was positively correlated with lymph node metastasis and TNM stage. ITGβ8 expression was downregulated in type C3 (inflammatory) and upregulated in C6 (TGF-β dominant) immune subtypes in LUAD and LUSC. In LUAD, the expression of ITGβ8 was significantly positively correlated with macrophages and NK cells. It is negative related to CD8 T cells and Th17 cells in both LUAD and LUSC. KEGG analysis revealed that ITGβ8 was significantly involved in activation of MAPK signaling pathway, TNF signaling pathway and Hippo signaling pathways, et. Highly expressed ITGβ8 has a shorter survival in NSCLC. Patients with high ITGβ8 expression were significantly shorter survival compared with low ITGβ8 expression who receiving immunotherapy. The objective response rate was 66.7% for high ITGβ8 expression compared with 52.4% for low ITGβ8 expression.
Conclusions
ITGβ8 is highly expressed in NSCLC and is involved in regulating the immune process of NSCLC. It may be an important immune predictive biomarker that provides a new idea for the treatment of NSCLC.
Pilot Trial of an Electronic Patient-Reported Outcome Monitoring System in Patients with Metastatic Breast Cancer Undergoing Chemotherapy
Authors: Taira Naruto , Yuichiro Kikawa , Takayuki Iwamoto , Yuichiro Miyoshi , Kyoko Hara , Seiji Yoshitomi , Hajime Hikino , Hirotoshi Takahashi , Daisuke Takabatake , Shinichiro Kubo , Masahiko Ikeda , Hiroyoshi Doihara , Tadahiko Shien , Hiromi Okuyama , Yuko Tanabe , Fumikata Hara , Kosho Yamanouchi , Yasuhiro Hagiwara , Masataka Sawaki
Published: October 2023

Background
Electronic patient-reported outcomes monitoring (ePROM) is a useful communication tool for patients and healthcare providers in cancer chemotherapy. In this study, we examined the feasibility of our newly developed ePROM system, which we refer to as “Hibilog”.
Methods
An ePROM app was developed by extracting 18 items from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE). Symptom monitoring was conducted every two weeks for patients with metastatic breast cancer undergoing chemotherapy. The primary outcome was the response rate to the ePROM system. The secondary outcomes were response time, item missing rate, and distribution of responses for each symptom.
Results
A total of 71 cases (mean age 52.6 years) were analyzed. Performance status was 0 in 76% of the cases and 1 or higher in 24%. First-line treatment was being administered in 30% of cases, second-line treatment in 17%, and third-line or higher treatment in 53%. The response rate to the ePROM system from registration to week 40 remained high at around 80%, indicating good compliance. The average response time was 5.5 min and the missing rate for each item was below 0.3%. Among 1,093 responses, the top 3 symptoms causing interference with daily life were Fatigue (63%), Numbness & tingling (48%), and General pain (46%).
Conclusion
Our developed ePROM system was able to capture symptoms accurately in patients with metastatic breast cancer undergoing chemotherapy while maintaining a high response compliance.
Pollution characteristics and source analysis of heavy metals in surface sediments obtained from Shishi Wetland Park, Fujian,China
Authors: Zhang Wenting , Sun Jingwei , Han Chenlu , Sun Jingwei , Yunfeng Yunfeng , Huang Yaoyi
Published: October 2023

Thirteen surface sediment samples were collected to study the metal content and pollution sources in the sediment of Shishi Wetland Park. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyse the contents of seven metals (Cr, Ni, Zn, Cu, Cd, Tl, and Pb) in the samples. The metal content was evaluated using contamination factor (CF), geological accumulation index (Igeo), and pollution load index (PLI). The pollution sources were qualitatively analysed using principal component analysis (PCA) and cluster analysis (CA), and the contribution rate of potential sources was quantitatively calculated using an absolute principal component score multiple linear regression model (APCS-MLR). The CF of Cd is greater than 3, indicating heavy pollution; Ni also causes heavy pollution, and the other metals evaluated showed lower values of pollution. The minimum degree of the coefficient of variation of Tl indicates contribution primarily from natural sources. The results of the geological accumulation index indicated that Cd was the most heavy pollutant. The pollution load indices of sampling points 7, 11, and 13 on the western side of the region were all greater than two, indicating severe pollution. The results of source analysis using multivariate statistical analysis showed that Cr, Ni, Cu, and Zn mainly originated from industrial and agricultural production activities, with an average contribution rate of 47.7%. Cd and Pb mainly originated from transportation sources, with an average contribution rate of 47.0%. Tl originated mainly from the parent material, with a contribution rate of approximately 33.4%.
A nosocomial outbreak of Mycobacterium Abscessus infection in a private hospital of Shanghai, China, 2021
Authors: Liu Yan , Jiang Yuan , Shi Qing-Feng , He Chen-Yu , Shan Ling-Ying , Zheng Yi-Hui , Zhang Yu-Yan , Sha Wei , Wu Zhe-Yuan , Chen Jing , Zhang Yang-Yi , Bao Rong , Gao Xiao-Dong , Zhang Huan-Sheng , Shen Xin
Published: October 2023

Background:
Mycobacterium abscessus is a rapid-growing mycobacterium, and it is often present in the water supply of hospital. Here we describe an outbreak of M. Abscessus infection in a private hospital in Shanghai, the epidemiological investigation and control measures were also conducted.
Methods:
From September 27th to October 1st, 2021, four consecutive AFB-positive patients from same ward in a private hospital who were first suspected of MTB infection were reported to Putuo district Center for Disease Control. Bronchial lavage fluids were sampled from all inpatients for both Mycobacterium culture and metagenome sequencing analysis (mNGS). Epidemiological investigation and environmental examination were conducted during this outbreak.
Findings:
Three of the four index patients had positive culture result for M. abscessus, while mNGS showed positive sequencing results in all 4 patients. However, 32 environmental samples from different sources were negative for M. abscessus. A series of infection control measures were strictly performed, and no further cases were reported in one year follow up.
Conclusions:
This nosocomial outbreak was caused by M. abscessus but the accurate source remains uncertain. The unique pathogen was captured by mNGS, and this sequencing technique can play an important role in identifying nosocomial outbreak.
Establishment and application of multiplex PCR scheme for simultaneously distinguishing muscle tissues of mink, fox and raccoon dog from conventional livestock and poultry
Authors: Pan Yao , Wang Xuemin , Ma Wenjie , Li Hongmei , Sun Yuxin , Qiu Jianhua , Guo Huijun
Published: October 2023

It is possible and risky for fur animal carcasses to be mixed into meat products, which is a potential danger for meat quality safety and human health. Therefore, meat validation of quality and constituents is crucial. A variety of methods have been developed to identify muscle tissues of different species. However, these methods have the disadvantages of poor repeatability, complex operation and low efficiency, and can not simultaneously detect multiple species of muscle tissue. The purpose of this study was to construct a multiplex PCR protocol to detect the samples of mink, fox and raccoon dog. In this study, the specific primers of mink, fox and raccoon dog were designed according to the variable region sequence of mitochondrial cytochrome b (Cytb) gene. The primers showed good specificity and 50 ℃ was determined as the optimal annealing temperature. The lowest concentration of DNA template of mink, fox or raccoon dog that could be determined simultaneously by a single tube was 1 pg/µL. Clinical tissue samples detect analysis test results showed that this method could identify whether the tissue samples of three fur animals were mixed from the muscles of chickens, ducks, dogs, cattle, sheep, pigs and rabbits in one PCR reaction simultaneously. In conclusion, the scheme exhibited the advantages of convenient operation, low cost, strong species specificity, high sensitivity, good stability and repeatability. The systematic optimized inspection process can be applied to meat detection to ensure veterinary public health safety, which has important scientific significance, production, public health and safety significance.
A Scoping Review on the Nature and Impact of Gender Based Violence on Women Primary Producers.
Authors: O'Mullan Cathy , Sinai Saba , Kaphle Sabitra
Published: October 2023

Background
Women in low- and middle-income countries (LMICs) are primary producers of subsistence food and significant contributors to the agricultural economy. Gender Based Violence (GBV) adversely impacts their capacity to contribute and sustain their families and undermines social, economic, and human capital. Addressing GBV, therefore, is critical to creating safe and inclusive environments for women as primary producers to participate fully in rural communities. The aim of this scoping review is to explore the existing evidence on GBV in the context of women primary producers in LMICs to inform research gaps and priorities.
Methods
A scoping review was conducted using PubMed, Web of Science, Ebscohost and Google Scholar using keywords related to GBV and women producers in LMICs. Peer-reviewed journal articles published between January 2012 and June 2022 were included in the review. Duplicates were removed, titles and abstracts were screened, and characteristics and main results of included studies were recorded in a data charting form. A total of 579 records were identified, of which 49 studies were eligible for inclusion in this study.
Results
Five major themes were identified from our analysis: (1) extent and nature of GBV, (2) the impact of GBV on agricultural/primary production livelihood activities, (3) sociocultural beliefs, practices, and attitudes, (4) aggravating or protective factors, and (5) GBV interventions. Addressing GBV in agriculture requires inclusive research approaches and targeted interventions to empower women producers, promote gender equality, enhance agricultural productivity, and contribute to broader societal development. Despite attempts by researchers to delve into this issue, the pervasive under-reporting of GBV remains a challenge. The true extent and nature of GBV perpetrated against women is far from fully understood in this context.
Conclusion
Despite the significant challenges posed by GBV to the health, economy and livelihoods of women primary producers in LMICs, there is a paucity in the current state of knowledge. To make meaningful progress, more research is required to understand the relationship between GBV and agricultural settings, and to gain nuanced insight into the nature and impact of GBV on women primary producers in different regions and contexts.
Application of an inline synthetic high b-value reduced filed-of-view diffusion weighted imaging on differentiation prostate cancer from benign prostatic hyperplasia
Authors: Zhou Qiqi , Tang Qian , Sang Ling , Liu Chao , Xu Lin , Liu Weiyin , Chen Wen
Published: October 2023

Background:
This study aimed to evaluate the feasibility of reduced full-of-view synthetic high-b-value diffusion weighted images (rFOV-syDWIs) in the clinical application of prostate cancer based on image quality and diagnostic efficacy.
Methods:
We retrospectively evaluated the data of 52 patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) who visited our hospital from July to December 2021. All patients underwent rFOV-DWI scans, including a 13b-protocol: b =0, 25, 50, 75, 100, 150, 200, 400, 600, 1000, 1000, 1200 and 1500 s/mm2 and a 5b-protocol: b =0, 100, 400, 800,1500 s/mm2. rFOV-syDWIs with b values of 1000 (rFOV-syDWIb=1000) and 1500 (rFOV-syDWIb=1500) were generated from two different multiple-b-value image data sets using a mono-exponential fitting algorithm. According to homoscedasticity and normality assessed by Levene test and Shapiro–Wilk test, the inter-modality differences of quantitative measurements were respectively examined by Wilcoxon signed rank test or paired t test and the inter-group differences of ADC values were examined by independent t test or Mann-Whitney U test. In addition, comparisons of the performance efficacy of ADCs in differentiation of patients with PCa from BPH were examined using ROC curves.
Results:
Higher inter-reader agreement, CRs was found higher in 13b-protocol and 5b-protocol rFOV-syDWIb=1000/1500 compared to 13b-protocol rFOV-sDWIb=1000/1500 (P<0.05). AUCs of mean and median obtained from 5b-protocol syADCb=1000/1500 were equal or higher than those from13b-protocol syADCb=1000/1500.
Conclusions:
rFOV-syDWIs provided better lesion clarity and higher image quality than rFOV-sDWIs. 5b-protocol rFOV-syDWIs shortened scan time and synthetic ADCs offered reliable diagnosis value as scanned 13b-protocol DWIs.
WITHDRAWN: Development and Validation of an HPLC Method for the Determination of Dasatinib from Self-micro Emulsifying Drug Delivery System
Authors: Kokare Nitin , Shah Rohit
Published: October 2023

The development of a novel reverse-phase high-performance liquid chromatographic method for the detection of dasatinib, an anticancer drug, in bulk and a self-micro emulsifying drug delivery system has been according to the guidelines provided by the International Council for Harmonization Q2 (R1). However, researchers developed a method to quantify API dasatinib and dasatinib from many formulations like tablets, and small-volume parenterals but in this proposed work dasatinib is quantified from the self-micro emulsifying drug delivery system by novel method. This method is characterized by its simplicity, precision, and cost-effectiveness. The maximum wavelength (λ max) of Dasatinib was determined to be 324 nm. The mobile phase consisted of a mixture of Methanol and 0.1% Tri-Fluro acetic acid in a volumetric ratio of 55:45. The flow rate was set at 1.0 mL/min. The method was developed using a C18 column, namely the Agilent Zorbax SB-Aq with dimensions of 250 x 4.6 mm and a particle size of 5µ. The RP-HPLC method exhibited linearity, as evidenced by a high correlation coefficient of 0.9993. The accuracy evaluations of the reversed-phase high-performance liquid chromatography (RP-HPLC) method were conducted at three distinct levels, namely 80%, 100%, and 120%. The recovery of Dasatinib within these levels ranged from 98% to 101%, with a relative standard deviation (% RSD) of 0.73%. The method employed in this study demonstrated stability and robustness under various testing parameters. The Limit of Detection (LOD) and Limit of Quantification (LOQ) were determined to be 0.17 ug/ml and 0.50 ug/ml, respectively, for the RP-HPLC method. Forced degradation is employed to assess the stability-indicating properties of an assay through the use of specificity. The results of the validation parameters were found to be within the range recommended by the International Council for Harmonization (ICH). The methodology employed in this study demonstrated a high level of accuracy, precision, and cost-effectiveness, making it a viable approach for future research endeavors. This technique is employed for the quantification of bulk medicines and the determination of dose forms containing self-micro emulsifying drug delivery systems.
How many digits are needed?
Authors: Herbst Ira , Møller Jesper , Svane Anne Marie
Published: October 2023

Let $X_1,X_2,...$ be the digits in the base-$q$ expansion of a random variable $X$ defined on $[0,1)$ where $q\ge2$ is an integer. For $n=1,2,...$, we study the probability distribution $P_n$ of the (scaled) remainder $T^n(X)=\sum_{k=n+1}^\infty X_k q^{n-k}$: If $X$ has an absolutely continuous CDF then $P_n$ converges in the total variation metric to Lebesgue measure $\mu$ on the unit interval. Under weak smoothness conditions we establish first a coupling between $X$ and a non-negative integer valued random variable $N$ so that $T^N(X)$ follows $\mu$ and is independent of $(X_1,...,X_N)$, and second exponentially fast convergence of $P_n$ and its PDF $f_n$. We discuss how many digits are needed and show examples of our results.
MSC Classification: 60F25 , 62E17 , 37A50
Unraveling the immunophenotypic landscape in acute myeloid leukemia: genotype-phenotype associations and predictive modeling of outcome
Authors: Bonte Sarah , Couckuyt Artuur , Gassen Sofie Van , Janda Vince , Buysse Malicorne , Moors Ine , Philippé Jan , Hofmans Mattias , Kerre Tessa , Saeys Yvan
Published: October 2023

Acute myeloid leukemia (AML) comprises 32% of adult leukemia cases with a five-year survival rate of only 20–30%. Here, the immunophenotypic landscape of this heterogeneous malignancy is explored in a single-center cohort using a novel quantitative computational pipeline. For 122 patients who underwent induction treatment with intensive chemotherapy, leukemic cells were identified at diagnosis, computationally preprocessed and quantitatively subtyped. Computational analysis provided a broad characterization of inter- and intra-patient heterogeneity, unachievable with manual bivariate gating. Statistical testing discovered associations between CD34, CD117 and HLA-DR expression patterns and genetic abnormalities. We found presence of CD34 + cell populations at diagnosis to be associated with a shorter time-to-relapse. Moreover, CD34- CD117 + cell populations were associated with a longer time to AML-related mortality. Machine learning (ML) models were developed to predict two-year survival, European LeukemiaNet (ELN) risk category and inv(16) orNPM1mut, based on computationally quantified leukemic cell populations and limited clinical data, both readily available at diagnosis. We used explainable artificial intelligence (AI) to identify the key clinical characteristics and leukemic cell populations important for our ML models when making these predictions. Our findings highlight the importance of developing objective computational pipelines integrating immunophenotypic and genetic information in the risk stratification of AML.
Preclinical assessment of nirmatrelvir penetration into cerebrospinal fluid and central nervous system cells and tissues
Authors: Avedissian Sean , Malik Johid , Podany Anthony , Neely Michael , Rhodes Nathaniel , Scarsi Kimberly , Scheetz Marc , Duryee Michael , Modebelu Ukamaka , Mykris Timothy , Winchester Lee , Byrareddy Siddappa , Fletcher Courtney
Published: October 2023

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration for SARS-CoV-2, concentrations in the CSF and brain may be inadequate to achieve exposure similar to that of plasma, which may have implications for viral persistence and neurologic post-acute sequelae of COVID-19.
Multi-Modal Potential Based Non-linear PDE Model for Grayscale Image Inpainting
Authors: Kumar B.V. Rathish , Vijayakrishna Rowthu , Halim Abdul
Published: October 2023

In this paper, we propose a multi-well potential based modified Cahn-Hilliardmodel for gray-scale image inpainting. An image specific multi-well potentialfunction is constructed from the histogram information of the given image. Existence,uniqueness and the continuous dependency of the solution on the initialdata, of the newly proposed modified Cahn-Hilliard equation has been establishedusing Faedo-Galerkin approach. Also the complete discretization error forthe numerical scheme based on convexity splitting in time and Fourier spectralmethod in space has been derived. Numerical simulations have been carried outon some standard gray-scale test images and the metrics PSNR, SNR, SSIMcorresponding to the obtained results are compared with those in the literature.
RETRACTED: Dealing with environmental stress: why to move towards a new approach to depression?
Authors: Russo Claudio
Published: October 2023

The authors have requested the removal of their preprint from Research Square. The author's request does not imply errors or misconduct.
Concentration detection algorithm of embedded gas detection system based on deep learning
Authors: Sun Shuyong
Published: October 2023

In daily life, whether it is the house where people live or the car they drive, air pollution can be seen almost everywhere, and human life and health are seriously threatened. There is an urgent need for a detection system for fast and accurate detection and assessment of ambient air quality. On the other hand, in the medical field, the detection of human exhaled gas can realize non-invasive and rapid early disease screening, but to achieve this purpose, a fast, accurate, highly sensitive and selective gas detection system is also required. At present, the research and development of gas detection system has attracted more and more attention of scholars, and the gas detection technology using porphyrin sensor array (PSA) chip is a hot topic in this research direction in recent years. Compared with traditional methods, this method has many obvious advantages and can meet the needs of fast, accurate and sensitive detection. In this paper, a PSA chip is used as a gas sensor, a set of PSA image acquisition and processing software is designed and developed on the Linux platform, and successfully transplanted to the ARM platform to build a complete gas detection system. Next, the data was collected and processed with ammonia gas as the detection object, and the quantitative analysis model of gas concentration was studied.
Efficacy of Intramedullary Bridge Fixation for Midshaft Clavicle Fractures: A Retrospective Analysis of a Novel Technique
Authors: Ma Tianyong , Su Huan , Lu Yihong , Chen Junping , Tan Weiyuan , Lei Fang , Wang Dewei
Published: October 2023

Objective: This study aimed to explore the efficacy of a novel intramedullary fixation technique using the ortho-bridge system (OBS) in midshaft clavicle fractures.
Methods: A total of 63 patients were included in this study, of which 35 were treated with plate internal fixation (LP group) and 28 with OBS intramedullary fixation (OBS group). Surgical time, intraoperative blood loss, incision length, fracture healing time, removal of internal fixation, visual analog scale (VAS) for shoulder pain, Constant Shoulder Score and complication occurrence were compared between the two groups.
Results: In preoperative general data, such as sex, age and fracture types were not significantly different between the two groups (P > 0.05). However, the OBSgroup showed better outcomes than the LP group in terms of surgical time, intraoperative blood loss and total incision length (P< 0.05). Additionally, the OBS group exhibited significantly shorter fracture healing time and internal fixation removal time than the LPgroup (P < 0.05). VAS scores at postoperative day 1, week 1, month 1 and month 3 were lower in the OBS group than in the LPgroup (P < 0.05).Furthermore, the OBS group had higher Constant Shoulder Scores at 1, 3, and 6 months than the LPgroup (P < 0.05), with no significant difference at 1 year postoperatively (P > 0.05). There was no scarring in the surgical incision in the OBS group, while 6 cases of scarring in the surgical incision occurred in the LP group. Lastly, complication incidence in the OBS group was lower than that in the LPgroup.
Conclusion: The study revealed that compared to locking plate internal fixation for midshaft clavicle fractures, OBS intramedullary fixation presents the advantages of less trauma, faster recovery, better efficacy and better aesthetic outcomes and comfort. Therefore, this technique may have potential clinical application as a novel treatment for midshaft clavicle fractures.
Pan-cancer Analysis of a Cytoskeleton Mobility related ARHGAP44 gene with Potential Implications in Cancer Prognosis Risk Prediction and Immune Landscape Modulation
Authors: Shen Ningning , Yang Huijun , Wang Xuzhi , Du Juan , Yang Zhiqing , Miao Lei , Liu Siying , Gao Lifang , Ma Wenxia , Wang Chen
Published: October 2023

Background Rho GTPases has been a well known family of small G proteins that regulate cellular cytoskeleton dynamics and involve in multiple critical steps of cancer progression. However, ARHGAP44 gene which is a member of GAP proteins that regulates the Rho GTPases cycling between their active GTP-bound and inactive GDP-bound state, its role in cancer development is still lack of understanding. The study is to analyze the function of ARHGAP44 gene in broad spectrum human cancers, thus aiding better understanding of the collaborative network of cytoskeleton related genes in cancers. Methods In the study, we started with the analysis of the genetic characteristics of ARHGAP44 gene, followed by its expression patterns, frequent alterations as well as survival prediction value in broad spectrum human cancers. Further, the probable reasons for the aberrant changed expression of ARHGAP44 in cancers comparing to corresponding normal control samples were investigated. Moreover, the correlation of ARHGAP44 with multiple critical clinical cancer parameters were in succession performed. Results Firstly, basic genetic physicochemical properties of ARHGAP44 were investigated including its aminoacid composition, estimated molecular weight and protein half life. Then, genetic alteration analysis revealed that ARHGAP44 expression various in human cancers, which was partly due to the modulation by DNA methylation and phosphorylation. Further, ARHGAP44 gene was indicated to be associated with multiple critical cancer traits including cancer stemness, cytoskeleton dynamics as well as immune infiltration in different human cancer types. Moreover, ARHGAP44 gene was also supported to be associated with the sensitivity of several chemotherapy related drugs. Conclusions Based on multiple bioinformatic analysis and TCGA pan-cancer data as well as certain local hospital samples, we revealed some valuable strategies to guide the therapeutic orientation concerning the role of ARHGAP44 gene in human cancers, although more detailed experiments and clinical trials are obligatory to support further clinical medical application of the gene, especially in each type of independent cancer.
Crystal growth, Structural, Optical, Thermal, DFT and Z-scan analyses of Imidazolium Hydrogen Oxalate Crystal for Nonlinear Optical applications
Authors: Chinnakannu Elavarasi , Sankar Mugundan , Chandran Senthilkumar , Thamotharan Keerthivasan , Manickam Srinivasan
Published: October 2023

Imidazolium Hydrogen Oxalate (IHO) single crystals were grown by the slow evaporation method. The title crystal crystallized in a monoclinic crystal structure with a centrosymmetric space group of P21/n. The 13C and 1H NMR spectra were obtained to understand the molecular structure of the IHO crystal. The 1H NMR contains a peak at 4.90 ppm, which is due to the presence of proton in oxalic acid. The O-H stretching vibration is noted at 3162 cm− 1 in FT-IR and in FT-Raman at 3172 cm− 1. The optical transparency and band gap were evaluated from the UV-Vis-NIR spectrum. The PL spectrum has a high violet emission band at 361nm. TG/DTG study was used to find the thermal stability of the IHO crystal. Hirshfeld surface (HS) analysis revealed the molecular intermolecular interactions in the IHO molecule. The molecular chemical stability of the IHO molecule is determined from the HOMO-LUMO energy gap. The DOS spectrum gives information about the bonding, antibonding, and zero bonding nature present in orbitals, atoms, and molecules. The dipole moment (µ) and total polarizability (α) of the IHO molecule are 13.0268 Debye and 8.2652 x 10− 24 esu, respectively. According to the Mulliken charge distribution, the C11 atom has the highest value, while the O16 atom has the lowest value. The IHO molecule's natural bond orbital (NBO) analysis was performed to ascertain the electron delocalization and conjugative interactions. The third-order nonlinear susceptibility (χ(3)) of the IHO crystal is determined to be 1.1916 x 10− 8 esu.
Identification of Ferroptosis-related Genes and Their CeRNA Network in Hypertrophic Cardiomyopathy Based on Bioinformatic Analysis
Authors: shen ming , Yu Chen , Yang Cui , Yan-Kun Shi
Published: October 2023

Background:
Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiomyopathy highly linked with the risk of sudden death and heart insufficiency in young people. The mechanics behind this condition are not comprehensively understood. However, emerging proof denotes the substantial involvement of ferroptosis in the onset and progression of cardiovascular illnesses. This study examines the connection between ferroptosis and hypertrophic cardiomyopathy, as well as the lncRNA-associated competing endogenous RNA (ceRNA) network of ferroptosis-related genes, using a bioinformatics approach.
Methods：
Four datasets (GSE180313, GSE36961, GSE188324, GSE197218) about HCM were retrieved from the GEO database. HCM-related module genes were identified by weighted gene co-expression network analysis (WGCNA) using the R WGCNA package. Ferroptosis-related genes were downloaded from the ferroptosis-related database FerrDb V2. Overlapping was performed to obtain the module genes associated with ferroptosis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R clusterprofiler package. The Protein–Protein Interaction (PPI) network was constructed using the STRING online analysis tool. The hub genes were identified using CytoHubba in Cytoscape. The expression of hub genes in cardiac tissues was examined using SPSS 27.0 statistic program. Then the lncRNA-associated ceRNA network was constructed using database prediction and Cytoscape software.
Results:
Sixty-four ferroptosis-related genes associated with HCM were identified through the use of WGCNA and FerrDB V2. Enrichment analysis showed that the pathways most highly enriched were related to lipid metabolism and iron ion homeostasis. From the PPI network construction and CytoHubba plug-in of Cytoscape, seven hub genes were obtained including PPARG, CD44, ACO1, SIRT1, CDKN2A, ADIPOQ, and TFRC. After validating in other gene expression datasets, we identified five hub-genes. These were then screened through ceRNA network construction, resulting in the identification of two key regulatory lncRNAs: NUTM2B-AS1 and XIST, along with two hub-genes, PPARG and CD.
Conclusions:
The hub genes (PPARG and CD44) may be regulated by the ceRNA regulatory network involving LncRNA XIST and NUTM2B-AS1, possibly influencing the pathogenesis of HCM in a ferroptosis regulatory manner.