bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing the proportion of flower strips promotes natural enemies to enhance aphid biocontrol and wheat yields
Authors: Liang Xiaoyi , Ouyang Fang , Zhang Xingrui , Yuan Yiyang , Li Zhuo , Ge Feng
Published: October 2023

Sowing flower strips adjacent to cropsis an effective practice for promoting natural enemies, enhancing biological pest control servicesand conserving biodiversity. However, few studies have considered the relationships of the proportion of flower strips with pest control servicesand crop yield. We conducted a three-year field experiment (including a control: 0% and three treatments: 5%, 10% and 15%) to determine the biocontrol service potential of sowing strips of Cnidium monnieri (L.) Cuss flowers adjacent to wheat and to reveal the relationships of the proportion of flower strips with pests, natural enemies, biological pest control services and wheat yield. Compared with the control (0%), flower strips promoted suppression of wheat aphid abundance by ladybugs and parasitoids. With an increasing proportion of flower strips, the predatory ladybug abundance and parasitism rates increased, while aphid abundance decreased. The relative biocontrol services index (RBSI) in the control (0%) was significantly lower than those in the treatments (5%, 10% and 15%). The wheat yield in the control (0%) was significantly lower than those in the treatments (5%, 10% and 15%). With an increasing proportion of flower strips, the RBSI and yield increased. In conclusion, sowing strips of C. monnieri flowers adjacent to wheat is a promising measure for providing considerable biocontrol services and increasing wheat yields. Specifically, natural enemies, biocontrol service potential and wheat yield were enhanced with an increasing proportion of flower strips. A 10% or 15% installment of flower strips is suggested to provide substantial biocontrol services and sustain wheat yields.
Comparison of the response to neoadjuvant therapy between immunohistochemistry HER2 (3+) and HER2 (2+)/ISH-positive early- stage breast cancer: A retrospective multicenter cohort study
Authors: Jiao Dechuang , Li Guangyu , Dai Hao , Wang Jia , Zhang Jiao , Hou Yangyang , Guo Xuhui , Zhao Yajie , Gong Xilong , Liu Zhenzhen
Published: October 2023

Background According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2(3+) and HER2(2+)/in situ hybridization (ISH) amplified [HER2(2+)/ISH+] breast cancer(BC)s fall under the HER2-positive BC category.However,there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2(3+) and HER2(2+)/ISH+ early BC.We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2(3+) and HER2(2+)/ISH+ BC.
Methods We examined two distinct cohorts. Cohort one (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy(NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base (SJTU-BCDB). Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2(3+) early BC [HER2(3+) group], (2) patients with HER2(2+)/ISH+ early BC [HER2(2+)/ISH+ group]. Among those excluded from analysis were patients <18 years or >80 years of age. Clinicopathological parameters,long-term outcomes and intrinsic subtypes were analyzed.
Results In the C1 population, 83.7% had HER2(3+) BC, while 16.3% had HER2(2+)/ISH+ BC. HER2(3+) patients had a significantly higher PCR rate (38.9%) than HER2(2+)/ISH+ patients (18.1%) (P<0.001) ,but the DFS was comparable after a median follow-up of 29 months(P=0.556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2(3+) BC but not in HER2(2+)/ISH+ BC. In the C2 population, 97.75% HER2(3+) and 52.17% HER2(2+)/ISH+ were HER2 enriched(HER2E) subtype (P<0.001). HER2E showed increased PCR rates compared to non-HER2E (P=0.004).
Conclusions Compared to HER2(3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2(2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in HER2 (2+)/ISH+ BC patients is essential.
Spherical orbits around Kerr-Newman and regular black holes
Authors: Andaru Langga , Alam Agya , Jayawiguna Byon , Ramadhan Handhika
Published: October 2023

We conduct a complete study on spherical orbits around charged (Kerr-Newman) and nonsingular (Ghosh) black holes. Using the Mino formalism, the analytical solutions for the geodesics can be obtained. We found that the Kerr-Newman's charge tends to force the orbits to be more equatorial, both for photon as well as for massive particles. Specifically for spherical photon orbits, the black hole's charge enables some of the orbits to switch from retrograde to prograde. For both models, we found that the stable spherical photon orbits exist only inside the horizons, much like the case for Kerr. For the regular black hole, however, the naked condition can exist without any physical problem. Thus, this condition, we dubbed the naked regularity, enables the existence of stable spherical orbits. We investigate these orbits, both null and timelike, and analyze their behavior.
Evidence to practice – lessons learnt in developing an implementation strategy for an online digital health intervention (Eczema Care Online)
Authors: Howells Laura , Thomas Kim S , Santer Miriam , Muller Ingrid , Greenwell Kate , Roberts Amanda , Williams Hywel C , Harvey Jane , Lax Stephanie J , Rogers Natasha K , Sach Tracey H , Lawton Sandra , Steele Mary , Sivyer Katy , Hooper Julie , Ahmed Amina , Wilczynska Sylvia , Langan Sinead , Leighton Paul
Published: October 2023

Background – Research is not often readily taken up in healthcare, which results in research waste. Eczema Care Online (www.EczemaCareOnline.org.uk/) has been shown in randomised controlled trials to be an effective online self-management intervention to improve eczema outcomes. Implementation requires adoption at patient/family, clinician and organisational levels. This paper aims to describe the lessons learnt from developing and delivering an implementation strategy for an online digital health intervention for eczema self-management.
Methods – Data from systematic reviews, stakeholder consultation meetings, interviews with trial participants, intervention usage data during the trial, and existing eczema information websites informed our implementation plan. Using Normalisation Process Theory, an implementation plan combined these findings with practical, context-specific actions to encourage wider adoption of the intervention.
Results – Barriers and facilitators to implementation were identified. Key lessons learnt include 1) start implementation work early 2) maintain flexibility to explore multiple routes to implementation 3) use secondary data sources 4) balance theory with practicalities 5) consider longer-term maintenance beyond the life of the research project.
Conclusion – Implementation planning is a key stage of the research process that is often not adequately resourced. Implementation planning ensures effective interventions developed and evaluated in research studies are utilised in everyday practice.
WITHDRAWN: Exploring Pathogenesis and Biomarkers Through Establishment of a Rat Model of Male Infertility with Liver Depression and Kidney Deficiency
Authors: Shen Ying , Fan Jian , Liu Shaobo , Tao Ling , Yang Qingbo , Shen Xiangchun
Published: October 2023

Objectives
To establish a rat model that accurately replicates the clinical characteristics of Liver Depression and Kidney Deficiency (LD & KD) in male infertility (MI) and investigate the pathogenesis.
Methods
After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites.
Results
Compared to the control, the model exhibited significant manifestations of LD & KD in MI, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed.
Conclusion
The study successfully established a clinically relevant animal model of LD & KD in MI. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of LD & KD in MI.
Analysis of Psychiatric Adverse Events for Semaglutide, Liraglutide, and Tirzepatide Reported to the EudraVigilance Database
Authors: Tobaiqy Mansour , Elkout Hajer
Published: October 2023

Background
Weight reduction is essential for improving health in people with obesity and type 2 diabetes mellitus. Semaglutide, liraglutide, and tirzepatide are glucagon-like peptide-1 receptor agonists that are effective for weight management in conjunction with behavioral changes.
Aim
To identify and analyse the occurrence and the outcome of psychiatric adverse events associated with semaglutide, liraglutide, and tirzepatide.
Methods
All individual case safety reports (ICSR) for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 5/30/2023 were analysed. Descriptive statistics were used to describe the study population characteristics. Differences in proportions between the groups were compared using the chi-square test.
Results
During the study period, 31,444 adverse events reports were identified: semaglutide (n = 13,956, 44.4%), liraglutide (n = 16,748, 53.2%), and tirzepatide (n = 740, 2.3%). There were 372 reports with psychiatric adverse events reports (n = 372, 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187, 50.3%), followed by anxiety (n = 144, 38.7%) and suicide ideation (n = 73, 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide), and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9), resulting from completed suicidal attempts and depression.
Conclusion
Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide; however, the severity and fatal outcomes of some of these reports warrant further study.
The effects of higher or lower protein delivery on outcomes for mechanically ventilated critically ill patients:a systematic review and meta-analysis of randomized controlled trials
Authors: Zhang Ying , Yang Penglei , Yu Lina , Yuan Jun , Gu Xue , Yuan Zhou , Chen Lianxin , Zhang Xiaoli , Chen Qihong
Published: October 2023

Background
Pronounced variations in protein dosing recommendations are evident across sets of international guidelines for critically ill patients. To survey extant randomized controlled trial (RCT) data, the present article was formulated as a systematic review and meta-analysis aimed at comparing the effects of lower and higher levels of protein delivery on outcomes for mechanically ventilated critically ill patients.
Methods
The PubMed, Embase, Web of SCI, and Cochrane Library databases were searched for all relevant RCTs published as of May 16, 2023. Eligible RCTs were those that (1) enrolled critically ill individuals ≥ 18 years of age that were mechanically ventilated; (2) enrolled patients with an intensive care unit (ICU) length of stay ≥ 3 days; (3) included comparisons of protein doses; (4) reported similar energy intake levels among groups; and (5) included a discussion of clinical and/or patient-centered outcomes. Screening and quality analyses were independently performed by two investigators. Pooled risk ratios and mean difference values were then estimated for categorical and continuous variables random-effects meta-analyses.
Results
In total, 12 RCTs enrolled 2286 patients were included in these analyses. All 12 studies reported on mechanical ventilation duration and mortality. Overall mortality (RR 0.90, 95% CI 0.72–1.12, P = 0.33; I2 = 26%), the duration of mechanical ventilation (MD 0, 95%CI -0.58-0.58, P = 0.99; I2 = 0%), and other patient-centered outcomes were unaffected by the level of protein delivery. Subgroup analyses, however, suggested that higher levels of protein delivery with early exercise were associated with a reduced risk of in-ICU mortality (RR 0.63, 95% CI 0.42–0.94, P = 0.02; I2 = 0%).
Conclusion
These results suggest that higher levels of protein delivery have no significant impact on the clinical or patient-centered outcomes for mechanically ventilated critically ill patients. However, combining higher levels of protein delivery and early exercise may contribute to better patient outcomes, although additional RCTs will be necessary to confirm this possibility.
PROSPERO registration:CRD42023423246(16/05/2023)
Can sarcopenia predict poor prognosis of sepsis due to biliary sepsis?
Authors: Chun Soh Yeon , Cho Young Soon , Kim Han Bit
Published: October 2023

Aim of the study:
Sepsis is a life-threatening disease, contributing to significant morbidity and mortality. This study aimed to investigate the association between sarcopenia and the prognosis of patients with biliary sepsis, focusing on outcomes such as length of hospital stay (LOS), intensive care unit (ICU) admission, and in-hospital mortality.
Methods
This retrospective, single-center, observational study included adult patients with biliary sepsis who visited the emergency department between January 2016 and December 2021. Sarcopenia was assessed using the psoas muscle index (PMI). Using computed tomography imaging, the area of both sides of the psoas muscle at the L3 level was measured, and the PMI, corrected by the patient’s height was calculated. The primary outcome was in-hospital mortality, and the secondary outcomes were intensive care unit (ICU) admission, LOS, and 14-day mortality.
Results
A total of 745 patients were included in this study. Sarcopenia was defined as a PMI < 421 mm2/m2 for males and < 268 mm2/m2 for females with the lower quartile of PMI according to sex. The cohort was classified into sarcopenic (n = 189) and non-sarcopenic (n = 556) groups. There was a significant association between sarcopenia and in-hospital mortality (odds ratio, 3.81; 95% confidence interval, 1.08–13.47), while there was no significant association between sarcopenia and ICU admission. In addition, the median LOS in the sarcopenic group (10 [7–14] days) was significantly longer than the median (8 [6–11] days) in the non-sarcopenic group.
Conclusions
Sarcopenia was significantly associated with clinical outcomes, particularly in-hospital mortality and LOS, in patients with biliary sepsis.
Risk factor analysis for early development of calf muscular vein thrombosis after thoracic surgery:a prospective observational study
Authors: Xu Haitao , Miao Jing , She Tianyu , Liu Shuai , Jia Teng , Liu Jianwei , Ren Shuai , Zhang Qingguang
Published: October 2023

Background: Venous thromboembolism is a common complication after thoracic surgery. The early development of calf muscular vein thrombosis (CMVT) after thoracic surgery is not well understood. The purpose of our study was to find the incidence and risk factors of early CMVT after thoracic surgery.
Methods: We performed a prospective observational study in patients who received thoracic surgery from December 2021 to January 2023. The patients were assigned to either the CMVT or non-CMVT group based on their early postoperative lower extremity venous Doppler ultrasound results. The clinical characteristics of CMVT patients and non-CMVT patients would be compared and analyzed.Multivariate logistic regression analysis was conducted to identify independent risk factors associated with CMVT development. The area under the receiver operating characteristic curve was also calculated.
Results: A total of 745 patients were included in the final analysis, with 185 (24.8%) and 560 (75.2%) patients in the CMVT and non-CMVT groups, respectively. In the CMVT group, 7 (3.8%) and 87 (47.1%) patients had concurrent proximal deep vein thrombosis and bilateral lower extremity thrombosis, respectively.Multivariate logistic regression analysis showed that age (OR = 1.092, 95% CI = 1.064–1.120, P = 0.000), Caprini score (moderate and high risks) (OR = 2.029, 95% CI = 1.276–3.227, P= 0.003), non-anticoagulation (OR = 1.859, 95% CI = 1.147–3.013, P = 0.012), operative duration >135 minutes (OR = 1.697, 95% CI = 1.135–2.538, P= 0.010), and postoperative day 1 D-dimer level (OR = 1.342, 95% CI = 1.232–1.462, P = 0.000) were independent risk factors for early postoperative CMVT. The receiver operating characteristic curve analysis showed that the areas under the curve for age and postoperative day 1 D-dimer were 0.715 (cut off value of 58.5) and 0.781 (cut off value of 1.445), respectively.
Conclusions: The incidence of early CMVT after thoracic surgery was 24.8%. Nearly half of the CMVT patients had bilateral involvement. The risk of early CMVT was reduced after perioperative anticoagulation prophylaxis. In addition, older age, moderate and high Caprini risk score, operative time >135 minutes, and high postoperative day 1 D-dimer level were independent risk factors for the early development of CMVT after thoracic surgery.
Correlation analysis of clinical, pathological, imaging and genetic features of ground-glass nodule featured lung adenocarcinomas between high-risk and non-high-risk individuals
Authors: Ren Jing , Wang Yuan , Liu Chunrong , Yang Lan , Men Xinlu , Qiu Zhixin
Published: October 2023

Background
Early-stage lung adenocarcinomas manifested as ground-glass nodules (GGNs) are increasingly being detected, but screening and diagnosis for GGN-featured lung adenocarcinomas in different risk populations reach no agreement.
Objective
To analyze the clinical, pathological, imaging and genetic features of GGN-featured lung adenocarcinomas on high-resolution computed tomography (HRCT) in different risk groups.
Methods
Include patients with GGNs on HRCT surgically diagnosed as lung adenocarcinoma in the West China Hospital, Sichuan University from 2009 to 2021, and their clinical, pathological, imaging and gene sequencing data.
Results
According to Chinese Expert Consensus on Screening and Management of Lung Cancer, 1,800 patients with GGN-featured lung adenocarcinoma, 545 males (incl. 269 smokers) and 1,255 females (incl. 16 smokers), were divided into high-risk (509) and non-high-risk (1,291) groups. Among them, 1,095 were detected via physical examination. The mean age at diagnosis was 54.78 (23–84) and the mean time from detection to diagnosis was 9.59 months. There were more males than females in the high-risk group [288 (56.58%) vs 221 (43.42%)], just the opposite in the non-high-risk group [1,034 (80.09%) vs 257 (19.91%)] (both P < 0.001). No statistical difference was found in GGN detection way (P > 0.05). The frequency of invasive adenocarcinoma was higher in the high-risk group, while those of precursor lesions and minimally invasive adenocarcinoma were higher in the non-high-risk group (all P < 0.001). The preoperative follow-up time in the non-high-risk group was shorter (P < 0.05). A total of 711 gene mutations were observed in 473 patients with a ratio of non-high-risk to high-risk of 494:217. The incidence of EGFR mutation was not statistically significant (P = 0.824); while those of TP53 and KRAS mutations were higher in the high-risk group (P < 0.05).
Conclusions
GGN-featured lung adenocarcinoma is dominated by non-high-risk female patients. Shorter preoperative follow-up in the non-high-risk group and no statistical difference in GGN detection way suggests the existing screening criteria for high-risk population may not suit GGN-featured lung cancer. Additionally, the incidences of KRAS and TP53 mutations are higher in the high-risk group.
Effect of CoSn3 nanocrystals on Sn3Ag plating for electronic packaging
Authors: Wang Jintao , Zhang Luobin , Lv ZiWen , Wang Jianqiang , Zhang Weiwei , Wang Xinjie , Chen Hongtao , Li Mingyu
Published: October 2023

Plating Sn3Ag on copper substrates represents a crucial electronic packaging technique. In this study, we propose a novel composite plating approach, wherein CoSn3 nanocrystals (NS) are deposited within the Sn3Ag coating. The resulting reflowed Sn3Ag joints exhibit a range of distinctive properties. Notably, CoSn3 nanocrystals dissolve in Sn during the reflow process, thereby lowering the supercooling required for Sn nucleation. Consequently, Sn crystals grow in six-fold cyclic twins. Additionally, the dissolution of Co atoms in Sn leads to a reduced solubility of Cu atoms in Sn, consequently lowering the supercooling required for the nucleation of Cu6Sn5. Simultaneously, this phenomenon promotes the nucleation of Cu6Sn5, resulting in a considerable precipitation of CuSn5 nanoparticles within the joints. Therefore, the mechanical properties of the joints are significantly enhanced, leading to a notable 20% increase in shear strength. Furthermore, the presence and distribution of Co elements within Sn induce changes in the growth pattern of interfacial Cu6Sn5. The growth process of Cu6Sn5 is dominated by the interfacial reaction, leading to its growth in a faceted shape. During the aging process, the dissolution of Co elements in Sn impedes the continuous growth of Cu6Sn5 at the interface, causing Cu6Sn5 to be distributed in the form of islands inside the joint. Remarkably, elemental Co acts as an inhibitor for the development of Cu3Sn and reduces the occurrence of Kirkendall voids.
Microfluidics-free single-cell genomics reveals complex central-peripheral immune crosstalk in the mouse brain during peripheral inflammation
Authors: Tansey Malú , Boles Jake , Huarte Oihane Uriarte
Published: October 2023

Inflammation is a realized detriment to brain health in a growing number of neurological diseases, but querying neuroinflammation in its cellular complexity remains a challenge. This manuscript aims to provide a reliable and accessible strategy for examining the brain’s immune system. We compare the efficacy of cell isolation methods in producing ample and pure immune samples from mouse brains. Then, with the high-input single-cell genomics platform PIPseq, we generate a rich neuroimmune dataset containing microglia and many peripheral immune populations. To demonstrate this strategy’s utility, we interrogate the well-established model of LPS-induced neuroinflammation with single-cell resolution. We demonstrate the activation of crosstalk between microglia and peripheral phagocytes and highlight the unique contributions of microglia and peripheral immune cells to neuroinflammation. Our approach enables the high-depth evaluation of inflammation in longstanding rodent models of neurological disease to reveal novel insight into the contributions of the immune system to brain health.
NPM1-fusion proteins promote myeloid leukemogenesis
through XPO1-dependent HOX activation
Authors: Goyama Susumu , Shimosato Yuko , Yamamoto Keita , Jia Yuhan , Shiba Norio , Hayashi Yasuhide , Ito Shuichi , Kitamura Toshio
Published: October 2023

Nucleophosmin (NPM1) is a nucleolar protein and one of the most frequently mutated genes in acute myeloid leukemia (AML). In addition to the commonly detected frameshift mutations in exon12 (NPM1c), previous studies have identified NPM1 gene rearrangements leading to the expression of NPM1-fusion proteins in pediatric AML. However, whether the NPM1-fusions are indeed oncogenic and how the NPM1-fusions cause AML have been largely unknown. In this study, we investigated the subcellular localization and leukemogenic potential of two rare NPM1-fusion proteins, NPM1-MLF1 and NPM1-CCDC28A. NPM1-MLF1 is present in both the nucleus and cytoplasm and occasionally induces AML in the mouse transplantation assay. NPM1-CCDC28A localizes predominantly to the cytoplasm, immortalizes mouse bone marrow cells in vitro and efficiently induces AML in vivo. Mechanistically, both NPM1-fusions bind to the HOX gene cluster and, like NPM1c, cause aberrant upregulation of HOX genes in cooperation with XPO1. The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions. Thus, our study provides experimental evidence that both NPM1-MLF1 and NPM1-CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 may be a promising strategy for the NPM1-rearranged AML.
Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice
Authors: Zhang Chenyang , Peng Xin-Xin , Wu Yi , Peng Mai-Jiao , Liu Tian-Hao , Tan Zhou-Jin
Published: October 2023

Growing evidence has demonstrated that cold and humid environmental stress triggers gastrointestinal (GI) disorders. In this study, we explored the effects of intestinal microbiota homeostasis on the intestinal mucus barrier and GI disorders by cold and humid environmental stress. Moreover, the inner link between the intestinal mucosal microbiota and metabolites in mice with cold and humid environmental stress was interpreted by integrative analysis of PacBio HiFi sequencing microbial genomics and targeted metabolomics. In the current study, we found (1) after the cold and wet cold and humid environmental stress intervened in the intestinal microbiota disorder and homeostasis mice respectively, the bacterial culturing and fluorescein diacetate (FDA) microbial activity detection of intestinal microbiota including feces, intestinal contents, and intestinal mucosa suggested that the cold and humid environmental stress decreased the colony of culturable bacteria and microbial activity, in which intestinal microbiota disorder aggravated the injury of the intestinal mucus barrier and the GI symptoms related to cold and humid environmental stress; (2) the serum amino acid transferases such as glutamate pyruvic transa (GPT), and glutamic oxaloacetic transaminase (GOT) in cold and humid environmental stressed mice increased significantly, indicating that the intestinal microbiota adapted to cold and humid environmental stress by regulating the host's amino acid metabolism; (3) the integrative analysis of multi-omics illustrated a prediction model based on the microbiota Lactobacillus reuteri abundance and host amino acid level that can predict intestinal mucoprotein Muc2 with an adjusted R2 of 75.0%. In conclusion, the cold and humid environmental stress regulates the neurotransmitter amino acids metabolic function both in intestinal mucosal microbiota and host serum by adjusting the composition of the dominant bacterial population Lactobacillus reuteri, which contributes to the intestinal mucus barrier injury and GI disorders caused by cold and humid environmental stress.
Systematic Mendelian randomization study of the effect of gut microbiome and plasma metabolome on venous thromboembolism
Authors: Cheng Pengfei , He Yuan , hu junjie , Ye Da-Wei , Wang Wei-Ci , Wang Jin-Xi
Published: October 2023

Background Although there is considerable evidence suggesting a link between gut microbiota (GM) composition and venous thromboembolism (VTE)/deep vein thrombosis (DVT)/pulmonary embolism (PE), population-level studies that can establish a causal relationship are currently lacking. Methods Using two-sample Mendelian randomization (MR) approach was used to examine the causal effects of 211 GM and 489 plasma metabolites on VTE/PE/DVT. We employed instrumental variables comprised of single nucleotide polymorphisms (SNPs) strongly associated with GM composition and plasma metabolite levels to determine whether these factors play a causal role in the development of VTE/DVT/PE. Additionally, we conducted mediation analysis to explore the potential associations between specific taxonomic groups and metabolites. Results The MR analysis revealed significant associations between 16 taxonomic units and 40 metabolites with VTE/DVT/PE as the causative factors. Among these,Firmicutes,Clostridia,Roseburia,Ruminococcaceae NK4A214, andIntestinimonaswere found to have a protective effect against VTE/DVT/PE. In contrast,Bacteroidetes,Anaerotruncus,Victivallales,Desulfovibrionaceae,Clostridium innocuum,Eubacterium oxidoreducens, andLachnoclostridiumhave been identified as risk factors for VTE/DVT/PE. Reverse MR analysis revealed 11 associations between VTE/DVT/PE and GM. Furthermore, no significant heterogeneity or horizontal pleiotropy was observed in any of the instrumental variables. Mediation analysis revealed 10 intermediate relationships, and metabolic pathway analysis identified 6 significant pathways. Conclusions Our study emphasizes the significant causal associations between the gut microbiota (GM), plasma metabolome, and VTE/DVT/PE. These interconnections have the potential to be used as clinical biomarkers for risk stratification and prognosis assessment in patients with VTE/DVT/PE.
Prediction models for postoperative recurrence of non-lactating mastitis based on machine learning
Authors: Sun Jiaye , Shao Shijun , Wan Hua , Wu Xueqing , Feng Jiamei , Gao Qingqian , Qu Wenchao , Xie Lu
Published: October 2023

Objectives
The aim of this study is to build a machine learning (ML) model to predict the recurrence probability for postoperative non-lactating mastitis (NLM) by Random Forest (RF) and XGBoost algorithms. It can provide ability for identifying the risk of NLM recurrence and guidance of clinical treatment plan.
Methods
This study was conducted on inpatients who were admitted to the Mammary Department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine between July 2019 to December 2021. Inpatients data following up has been completed until December 2022. We used two ML approaches (RF and XGBoost) to build models and predict the NLM recurrence risk of female patients. Totally 258 patients have been randomly divided into a training set and a test set according to 75%-25% proportion. The model performance was evaluated based on Accuracy, Precision, Recall, F1-score, AUC. The Shapley Additive Explanations (SHAP) method was used to interpret the model.
Results
There were 48 (18.6%) NLM patients who experienced recurrence during the follow-up period. Ten features were selected in this study to build the ML model. For the RF model, BMI is the most important influence factor and for the XGBoost model is intraoperative discharge. The results of tenfold cross-validation suggest that both RF model and XGBoost model have good predictive performance, but XGBoost model has a better performance than RF model in our study. The trends of SHAP values of all features in our models are consistent with the trends of these features’ clinical presentation. The inclusion of these ten features in the model is necessary to build practical prediction models for recurrence.
Conclusions
The results of tenfold cross-validation and SHAP values suggest that the models have predictive ability. The trend of SHAP value provides auxiliary validation in our models and makes it has more clinical significance.
Complex alterations in inflammatory pain and analgesic sensitivity in young and ageing female rats: involvement of ASIC3 and Nav1.8 in primary sensory neurons
Authors: Messina Diego N. , Peralta Emanuel D. , Acosta Cristian G.
Published: October 2023

Background
The therapeutic failure in the management of chronic inflammatory pain in geriatric populations arises from drug-associated toxicity and lack of specific regulation of nociceptor excitability.
Methods
We compared 6 and 24 months-old female Wistar rats that underwent cutaneous inflammation to examine the role of Nav1.8 and ASIC3 in dorsal root ganglion (DRG) neurons in long-term inflammatory pain. We carried out this using a combination of behavioral pain assessments, qPCR, quantitative immunohistochemistry, selective pharmacological manipulation, ELISA, and the in vitroevaluation of cytokine effects.
Results
Older rats exhibited delayed recovery from mechanical allodynia and earlier onset of spontaneous pain than younger rats after inflammation. Moreover, the expression patterns of Nav1.8 and ASIC3 were time and age-dependent and ASIC3 levels remained elevated only in aged rats. In vivo, selective blockade of Nav1.8 with A803467 or of ASIC3 with APETx2 alleviated mechanical and cold allodynia and also spontaneous pain in both age groups with slightly different potency. Furthermore, in vitro IL-1β up-regulated Nav1.8 expression in DRG neurons cultured from young but not old rats. We also found that while TNF-α up-regulated ASIC3 expression in both age groups, IL-6 and IL-1β had this effect only on young and aged neurons, respectively.
Conclusion
Our findings demonstrate that inflammation-associated mechanical allodynia and spontaneous pain in the elderly can be more effectively treated by inhibiting ASIC3 than Nav1.8.
The Bioadhesive-Thermoresponsive Ophthalmic Gel Loaded Solid Dispersion of Triamcinolone Acetonide For Improvement of Ocular Inflammation Therapy
Authors: Stevani Hendra , Rachmawaty Dwi , Dewi Ratanasari , Arisanty Arisanty , Sinala Santi , Sukmawaty Muli
Published: October 2023

Background: In developed countries, 10% of blindness cases are caused by uveitis (UV). Triamcinolone acetonide (TA) is a corticosteroid that has been widely used for the treatment of ocular inflammation both in intravitreal injection preparations or as an eye drop. The solubility of TA which is practically insoluble in water is an obstacle to its development.
Objectives: This study aims to improve the therapeutic effectiveness of ocular inflammation by increasing the solubility of Triamcinolone acetonide (TA) as a hydrophobic drug. The enhancement of solubility allows for better bioavailability so it can optimize the therapy of UV.
Methods: The solid dispersion method was selected to enhance the solubility of TA by comparing solvent-evaporation and freeze-drying methods. The solid dispersion method (SD-TA) was made with PEG 6000 and PVP-K30 as surfactants and then characterized by FTIR, XR diffraction, and SEM. Furthermore, SD-TA was mixed into the gel base and an ex vivo study was for ensure the local therapy.
Result: The solvent-evaporation method produced more soluble TA than the freeze-drying method. F9 dissolved TA was ten times higher than pure TA (p<0.05). The G4c gel formula showed the ability to retain TA 3.15±0.15 mg at 24 h. Neither the G4c gel formula nor the SD-TA formula (F9) showed hemolysis activity. The gel also exhibits isotonic characteristics and did not cause any structural destruction of the RBCs.
Conclusion: This study successfully demonstrated the morphological and structural changes of TA in SD-TA which proved to increase TA solubility and potentially provide local therapeutic effects by bioadhesive-thermoresponsive gel for better treatment of inflammation in the eye such as uveitis.
Investigating the Association Between Rheumatoid Arthritis and Membranous Nephropathy: Mendelian Randomization and Bioinformatic Analysis
Authors: He Chuan , An PhD，Mingxin , Li Yuxuan
Published: October 2023

Background: Rheumatoid arthritis (RA) and membranous nephropathy (MN) are two autoimmune diseases that may coexist in some patients. Investigating the relationship between these diseases and elucidating potential shared pathogenic mechanisms is critical to understanding their co-occurrence.
Methods: MR analysis was performed using two separate samples. Genetic variants were used as instrumental variables to estimate causality between diseases. Bioinformatic analysis was performed on publicly available gene expression datasets from GEO databases to identify common genes and molecular pathways in immune cells associated with RA and MN.
Results: MR analysis did not reveal a causal relationship between RA and MN. [IVW:(MN on RA and RA on MN) OR<1, P>0.05)]. However, the bioinformatic analysis identified correlations between several genes involved in immune regulation, suggesting potential common molecular pathways underlying the co-occurrence of RA and MN.
Conclusions: Our findings suggest that the coexistence of RA and MN may not be directly causally related. The identified shared genes and immune pathways provide valuable insights into the pathogenesis of the co-occurrence, which may guide future investigations and therapeutic strategies for patients with these coexisting autoimmune diseases.
The Influence of Toxic Trolling Comments on Anti-vaccine YouTube Videos
Authors: Miyazaki Kunihiro , Uchiba Takayuki , Kwak Haewoon , An Jisun , Sasahara Kazutoshi
Published: October 2023

Anti-vaccine trolling on video-hosting websites hinders efforts to increase vaccination rates by using toxic language and threatful claims to intimidate people and promote vaccine hesitancy. However, there is a shortage of research investigating the effects of toxic messages on these platforms. This study collected YouTube anti-vaccine videos and examined the relationship between toxicity and fear in the comment section of these videos. We discovered that highly liked toxic comments elicited a significant level of fear in subsequent comments of the same videos. Moreover, we found intricate contagions across toxicity and fear within the comments. These findings suggest that initial troll comments can evoke negative emotions, which may fuel vaccine hesitancy on social media. Our research bears essential implications for managing public health messaging and online communities, particularly in moderating fear-mongering messages about vaccines.
Degree of COVID-19 Severity and Mortality in Stroke: Correlation of Clinical and Laboratory Parameters
Authors: Gofir Abdul , Syamsah Yossy Catarina Budi Nur , Setyawan Tommy Rachmat , Mianoki Adika , Silalahi Raymond Aris Nimrod Alvonsius , Nugroho Dhite Bayu , Rochmah Mawaddah Ar , Satriotomo Irawan
Published: October 2023

Background
Stroke is one of the neurological manifestations of COVID-19. Acute stroke patients with COVID-19 had a significant morbidity and mortality. The clinical and laboratory data of these patients were investigated to determine the key factors in predicting mortality.
Method
This retrospective case-control study was conducted at Dr. Sardjito General Hospital Yogyakarta, Indonesia using data from July 2020 - August 2021. All acute stroke patients with confirmed COVID-19 were included. Patients’ medical records were used to collect the clinical and laboratory data. For baseline characteristics, univariate tests were used, followed by bivariate and multivariate analyses to determine significant predictors of mortality.
Result
We included a total of 72 subjects, consisting of 65 (90.28%) subjects with ischemic stroke and 7 (9.72%) with hemorrhagic stroke. The overall mortality rate was 58.3%, which consisted of 50% ischemic and 8.3% hemorrhagic stroke cases. Lowered Glasgow Coma Scale (GCS), loss of consciousness, generalized seizures, worsened modified Ranking Scale (mRS), history of dyslipidemia, worsened clinical severity of COVID-19 infection, respiratory distress, higher neutrophil count, C-Reactive Protein levels (> 41mg/dl), Blood Urea Nitrogen (> 29.05mg/dl), and Random Blood Glucose level (> 111.5mg/dl) at admission were all significantly associated with mortality (p < 0.05). Cox regression analysis revealed a 17.535 higher risk of mortality in individuals with severe COVID-19 (p = 0.032). Higher mRS scores more than doubled the probability of mortality (p = 0.001).
Conclusion
The poorer functional status assessed by mRS and the greater degree of COVID-19 on admission should be carefully identified since they may increase the risk of mortality in stroke patients with COVID-19.
WITHDRAWN: Phenotypic Diversity of Wild Astragalus polycladus Resources
Authors: Liu Qingqing , Cai Zongcheng , Lv Liangyu , Shi Jianjun , Tong Junwei
Published: October 2023

To explore the phenotypic diversity of wild Astragalus polycladus resources, 150 wild Astragalus polycladus resources from 6 regions of Qinghai Province were used as materials, and 18 phenotypic traits were analyzed. The results showed that Astragalus polycladus had abundant phenotypic diversity in Qinghai Province, and the coefficient of variation of 18 phenotypic traits ranged from 1%-23%. Among them, the fertile tillers’ coarseness, fertile tillers’ length, and crown width are the most variable characteristics. Correlation analysis showed that there were significant or extremely significant correlations among other traits except for root number and stem length. At the same time, the phenotypic traits of Astragalus polycladus were related to latitude and longitude, altitude, and soil pH, and different traits were affected by different geographical factors, among which the corolla number was the most affected. Four principal components with eigenvalues greater than 1 were selected by principal component analysis, and the cumulative contribution rate was 77.151%, which contained most of the information about the phenotypic traits of Astragalus multicladus. Crown width and plant height had the greatest influence on the phenotypic traits diversity of Astragalus polycladus. These results indicate that the phenotypic traits of Astragalus polycladus resources in Qinghai Province are rich in diversity and have great potential for exploitation and utilization. This study provided a scientific basis for the breeding and preservation of superior germplasm resources of Astragalus polycladus.
Impact of difference in height of automated irrigation system and height of kidney on intrarenal pressure in an in vitro kidney model
Authors: Taguchi Makoto , Kinoshita Hidefumi
Published: October 2023

Purpose: To clarify the impact of the difference in height between an automated irrigation system and the renal pelvis using an artificial kidney model.
Methods: A flexible ureteroscope was placed into an artificial kidney model centrally through the ureteral access sheath, and the pressure in the model was measured as the intrarenal pressure (IRP). Three types of irrigation systems were used in this study: a pressure-controlled system, a gravity-based irrigation system, and an infusion pump. During measurements, either the working channel of the flexible ureteroscope was unoccupied or various instruments (200-μm laser fiber and 1.5-Fr retrieval basket) were inserted into the working channel. The three irrigation systems were evaluated under three conditions: at the same height as the artificial kidney model, 50 cm higher than the model, and 50 cm lower than the model. The maximum IRP was measured and compared.
Results: The IRP was affected by the height difference between the pressure-controlled system and the artificial kidney model in all conditions (p < 0.05). Additionally, the IRP was affected by the height difference between the gravity-based irrigation system and the artificial kidney model in all conditions (50 cm taller vs. same height, p < 0.05; 50 cm taller vs. 50 cm lower, p < 0.05). However, the IRP was not affected by the height difference between the infusion pump and the artificial kidney model in all conditions.
Conclusion: Clinicians should check whether there is a difference between the height of the kidney and the height of the pressure-controlled system.
Interferon-Induced Monocyte Immune Response Augments Immunotherapy and Correlates with Clinical Outcomes in Breast Cancer
Authors: Zhong Xugang , Liu Haitao , Gong Chuxiong , Yin Li , Fan Yong , He Zeju , Hong Zheping , Tong Yu , Meng Xiang , Li Yanlei , Li Yuewen , Kang Yao , Bi Qing
Published: October 2023

In this study, we established comprehensive single-cell transcriptomic profiles of myeloid cells and T cells in breast cancer and identified a group of monocytes that secrete various chemokines to promote anti-tumor immunity and respond to interferon-gamma (IFN-γ), as well as a group of T cells that self-secrete IFN-γ. Notably, these T cells not only serve as targets of IFN-γ but can also produce IFN-γ themselves. We observed a strong positive feedback loop between these unique monocytes and T cells. The monocytes secrete various chemokines to recruit T cells into the tumor microenvironment. Additionally, they produce SPP1, stimulating DC cells to produce IL-12, which further promotes the production of IFN-γ by T cells. On the other hand, the IFN-γ secreted by T cells further activates monocytes. Furthermore, after immunotherapy, there was a significant increase in these unique monocytes in the tumor microenvironment, indicating that they could serve as biomarkers of immunotherapeutic response and possess the potential to activate anti-tumor immunity. Finally, survival analysis and immune fluorescence staining of patient samples support the correlation between the density of these unique monocytes and patient prognosis. These findings underscore the importance of monocytes and their interactions with T cells in breast cancer, providing insights into potential targets for immunotherapy and prognosis assessment.
The response of the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1819) exposed to copper-doped zinc nanoparticles
Authors: BOUZIDI Imen , AYARI-KLITI Rakia , BEYREM Hamouda , MOUGIN Karine , SELLAMI Badreddine
Published: October 2023

The aim of this study is to evaluate the exposure effects to copper-doped zinc oxide nanoparticles (Cu-ZnO NPs) on bivalves through physiological and biochemical multi- markers. To achieve this objective, the selected biological material is the bioindicator mussel Mytilus galloprovincialis used as sentinel of marine pollution.
The evaluation of the physiological response has been established by the filtration and respiration capacity of the mussel. That of biochemical response has been studied through biomarkers such as superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and acetylcholinesterase (AChE).
The estimation of the toxicity of Cu-ZnO NPs through physiological parameters showed that the impact depends on the considered chemical compound and on its concentration. In addition to the contaminant concentration effect, the oxidative stress and neurotoxicity parameters depend on the organ involved.
Overall, the use of an integrative approach combining the physiological and biochemical responses represents a good way to understand the relational profile between contaminants and marine organisms that could be part of biomonitoring programs of coastal ecosystems.