bluuebunny/crossref_metadata_2025 huggingface dataset:
Tai Chi exercise reduces circulating levels of inflammatory oxylipins in postmenopausal women with knee osteoarthritis: results from a pilot study
Authors: Shen Chwan-Li , Newman John W. , Elmassry Moamen M. , Borkowski Kamil , Chyu Ming-Chien , Kahathuduwa Chanaka , Neugebauer Volker , Watkins Bruce A.
Published: August 2023

Background

Tai Chi (TC) controls pain through mind–body exercise and appears to alter inflammatory mediators. TC actions on lipid biomarkers associated with inflammation and brain neural networks in women with knee osteoarthritic pain were investigated.

Methods

A single-center, pre- and post-TC group (baseline and 8 wk) exercise pilot study in postmenopausal women with knee osteoarthritic pain was performed. 12 eligible women participated in TC group exercise. The primary outcome was liquid chromatography tandem mass spectrometry determination of circulating endocannabinoids (eCB) and oxylipins (OxL). Secondary outcomes were correlations between eCB and OxL levels and clinical pain/limitation assessments, and brain resting-state function magnetic resonance imaging (rs-fMRI).

Results

Differences in circulating quantitative levels (nM) of pro-inflammatory OxL after TC were found in women. TC exercise resulted in lower OxL PGE1 and PGE2 and higher 12-HETE, LTB4, and 12-HEPE compared to baseline. Pain assessment and eCB and OxL levels suggest crucial relationships between TC exercise, inflammatory markers, and pain. Higher plasma levels of eCB AEA, and 1, 2-AG were found in subjects with increased pain. Several eCB and OxL levels were positively correlated with left and right brain amygdala-medial prefrontal cortex functional connectivity.

Conclusion

TC exercise lowers pro-inflammatory OxL in women with knee osteoarthritic pain. Correlations between subject pain, functional limitations, and brain connectivity with levels of OxL and eCB showed significance. Findings indicate potential mechanisms for OxL and eCB and their biosynthetic endogenous PUFA precursors that alter brain connectivity, neuroinflammation, and pain.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT04046003.
Salivary and fecal microbiota: potential new biomarkers for early screening of colorectal polyps
Authors: Zhang Limin , Feng Ziying , Li Yinghua , Lv Cuiting , Li Chunchun , Hu Yue , Fu Mingsheng , Song Liang
Published: August 2023

Objective

Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.

Methods

In this case–control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).

Results

In comparison to the HC group, the CP group’s microbial diversity increased in saliva and decreased in feces (p < 0.05), but there was no significantly difference in microbiota richness (p > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified Porphyromonas gingivalis, Fusobacterium nucleatum, Leptotrichia wadei, Prevotella intermedia, and Megasphaera micronuciformis as the major contributors to the salivary microbiota, and Ruminococcus gnavus, Bacteroides ovatus, Parabacteroides distasonis, Citrobacter freundii, and Clostridium symbiosum to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.

Conclusion

The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.
Carbapenem-resistant Citrobacter freundii harboring blaKPC−2 and blaNDM−1: a study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS6100
Authors: Zhang Feilong , Li Ziyao , Liu Xinmeng , Hu Yanning , Zhao Jiankang , Zhang Yulin , Fan Yanyan , Lei Zichen , Yang Xinrui , Li Zhihua , Li Chen , Wu Yongli , Lu Binghuai
Published: August 2023

Introduction

The increase in clinical Enterobacteriaceae with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential dissemination of blaKPC−2- and blaNDM−1-coharboring carbapenem-resistant Citrobacter freundii (CRCF).

Methods

Four blaKPC−2- and blaNDM−1-coharboring CRCF strains were collected from our surveillance of the prevalence of carbapenem-resistant Enterobacteriaceae. The isolates were assessed using species identification, antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, plasmid stability, and fitness costs. Clonality, genome, plasmidome, and phylogeny were analyzed to reveal potential dissemination.

Results

Three ST523 blaKPC−2- and blaNDM−1-coharboring CRCF strains, collected from the same hospital within 1 month, exhibited high homology (both identity and coverage >99%), implying clonal dissemination and a small-scale outbreak. Moreover, the blaKPC−2 and blaNDM−1 genes were coharbored on an IncR plasmid, probably generated by a blaKPC−2-harboring plasmid acquiring blaNDM−1, in these three strains. Importantly, the IncR plasmid may form a transferable hybrid plasmid, mediated by IS6100 via transposition, with another IncFII plasmid included in the same C. freundii strain. Furthermore, the blaKPC−2 and blaNDM−1 of the fourth CRCF strain are located on two different non-transferable plasmids lacking complete transfer elements. Additionally, throughout the course of the 10-day continuous passage, the genetic surroundings of blaNDM−1 in four CRCF strains were gradually excised from their plasmids after the 8th day, whereas they maintained 100% retention for blaKPC−2. Genome and plasmidome analyses revealed that blaKPC−2- or blaNDM−1-harboring C. freundii were divergent, and these plasmids have high homology to plasmids of other Enterobacteriaceae.

Conclusion

Clonal dissemination of ST523 blaKPC−2- and blaNDM−1-coharboring CRCF strains was detected, and we first reported blaKPC−2 and blaNDM−1 concomitantly located on one plasmid, which could be transferred with mediation by IS6100 via transposition. Continued surveillance should urgently be implemented.
Mendelian randomization supports causality between gut microbiota and chronic hepatitis B
Authors: Zhang Quanzheng , Zhou Jinhua , Zhang Xiaoxiao , Mao Rui , Zhang Chuan
Published: August 2023

Background

Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation.

Methods

Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program.

Results

According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34–0.96; false discovery rate [FDR] = 0.046), genus Family XIII AD3011 group (OR = 0.60; 95% CI, 0.39–0.91; FDR = 0.026), genus Prevotella 7 (OR = 0.73; 95% CI, 0.56–0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03–3.12; FDR = 0.061), genus Eggerthella group (OR = 1.34; 95% CI, 1.04–1.74; FDR = 0.043), genus Eubacterium ventriosum group (OR = 1.59; 95% CI, 1.01–2.51; FDR = 0.056), genus Holdemania (OR = 1.35; 95% CI, 1.00–1.82; FDR = 0.049), and genus Ruminococcus gauvreauii group (OR = 1.69; 95% CI, 1.10–2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs).

Conclusion

In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.
Biosynthesis and characterization of silver nanoparticles generated from peels of Solanum tuberosum (potato) and their antibacterial and wastewater treatment potential
Authors: Deepa  , Dhanker Raunak , Kumar Ram , Kamble Shashank S. , Kamakshi  , Goyal Shubham
Published: August 2023

Global food production consumes a large fraction of energy budget, land area, and freshwater; however, a larger fraction of the produce is lost or unutilized, which has potential to produce useful products for human use. The biogenic synthesis of silver nanoparticles from such waste food appears to be a promising strategy. A conservative estimate of 70–140 thousand tons of potato peels is produced annually by food-chain companies globally; however, they are primarily utilized to produce substandard feed for livestock or manure. For the formation of highly profitable compounds, enhancement of value, and the process of extraction, such as nanocomposite, organic antioxidants, and organic meal inclusions, potato peels can be used as a cheap, productive, and readily available source of raw material. In the present research, silver nanoparticles (AgNPs) were extracted from the peels of potato (Solanum tuberosum). The fabrication of potato peel-derived AgNPs was established using UV-visible spectroscopy analysis. Approaches like X-ray diffraction (XRD), attenuated total reflection-infrared (ATR-IR) spectroscopy analysis, and field emission scanning electron microscopy (FESEM) were used to determine the characteristics of the AgNPs. Additionally, strains of Gram-positive bacteria such as Staphylococcus aureus (S. aureus) (ATCC 25923) and Gram-negative bacteria such as Escherichia coli (E. coli) (ATCC 25922) were used to determine the antibacterial activity of AgNPs via the disc diffusion technique. The antibacterial properties of AgNPs could help protect food from microbial contamination. Furthermore, AgNPs were tested for their potential application in purification of industrial wastewater. The results revealed that AgNPs derived from the potato peels could be used in industrial and biomedical applications and possess excellent antibacterial activity. Our research suggests that AgNPs can be extracted from a safe and ecofriendly fabrication technique from largely unused potato peels that have a great potential for inhibiting the bacterial growth and for the in situ purification of wastewater in the upcoming years. Therefore, besides value addition to the farm produce, such recycling of potato peels is likely to reduce the burden of the solid waste volumes in agro-centers, kitchen wastes, and food industries across the globe.
Embolization of unruptured wide-necked aneurysms at the MCA bifurcation using the Neuroform atlas stent-assisted coiling: a two-center retrospective study
Authors: Zhang Xuexian , Wang Ruidong , Ding Yuhan , Li Wei , Ren Hong , Zhang Jun
Published: August 2023

Background

The management of middle cerebral artery (MCA) aneurysms remains a controversial topic, and MCA aneurysms have traditionally been treated primarily by surgical clipping. The Neuroform Atlas Stent™ (NAS, available from Stryker Neurovascular, Fremont, California) represents the latest generation of intracranial stents with improved stent delivery system capabilities.

Objective

This study aims to investigate the safety, feasibility and efficacy exhibited by NAS in treating unruptured aneurysms at the MCA bifurcation.

Methods

This was a two-center retrospective study involving 42 patients with unruptured wide-necked aneurysms (WNAs) of the MCA treated with the NAS from October 2020 to July 2022.

Results

The stent was used to treat 42 cases of unruptured WNA at the MCA bifurcation. Endovascular treatment techniques had a 100% success rate. Immediate postoperative angiography found complete aneurysm occlusion in 34 patients (80.9%) (mRRC 1), neck remnant in 7 patients (16.7%) (mRRC 2), and residual aneurysm in 1 patient (2.4%) (mRRC 3). The thromboembolic complication rate was 2.4% (1/42). The follow-up period was 8.7 months on average (3–16 months). The last angiographic follow-up results revealed complete aneurysm occlusion in 39 patients (92.9%) (mRRC 1), neck remnant in 3 (7.1%) patients (mRRC 2), no aneurysm recanalization or recurrence, and no cases of stent intimal hyperplasia. During the latest clinical follow-up, all patients had an mRS score of 0.

Conclusion

Our study demonstrates that the NAS can be applied to treat unruptured WNAs at the MCA bifurcation with favorable safety, feasibility, and efficacy.
Postural orthostatic tachycardia syndrome and other related dysautonomic disorders after SARS-CoV-2 infection and after COVID-19 messenger RNA vaccination
Authors: Gómez-Moyano Elisabeth , Rodríguez-Capitán Jorge , Gaitán Román Daniel , Reyes Bueno José Antonio , Villalobos Sánchez Aurora , Espíldora Hernández Francisco , González Angulo Gracia Eugenia , Molina Mora María José , Thurnhofer-Hemsi Karl , Molina-Ramos Ana Isabel , Romero-Cuevas Miguel , Jiménez-Navarro Manuel , Pavón-Morón Francisco Javier
Published: August 2023

The COVID-19 pandemic has caused a challenge for our society due to the post-acute sequelae of the disease. Persistent symptoms and long-term multiorgan complications, known as post-acute COVID-19 syndrome, can occur beyond 4 weeks from the onset of the COVID-19 infection. Postural orthostatic tachycardia syndrome (POTS) is considered a variety of dysautonomia, which is characterized by chronic symptoms that occur with standing and a sustained increase in heart rate, without orthostatic hypotension. POTS can lead to debilitating symptoms, significant disability, and impaired quality of life. In this narrative review, the etiopathogenic basis, epidemiology, clinical manifestations, diagnosis, treatment, prognosis, and socioeconomic impact of POTS, as well as other related dysautonomic disorders, after COVID-19 infection and SARS-CoV-2 postvaccination, were discussed. After a search conducted in March 2023, a total of 89 relevant articles were selected from the PubMed, Google Scholar, and Web of Science databases. The review highlights the importance of recognizing and managing POTS after COVID-19 infection and vaccination, and the approach to autonomic disorders should be known by all specialists in different medical areas. The diagnosis of POTS requires a comprehensive clinical assessment, including a detailed medical history, physical examination, orthostatic vital signs, and autonomic function tests. The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. Further research is needed to understand the underlying mechanisms, risk factors, and optimal treatment strategies for this complication.
A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila
Authors: Kobayashi Riho , Nakane Shin , Tomita Jun , Funato Hiromasa , Yanagisawa Masashi , Kume Kazuhiko
Published: August 2023

Sleep behavior has been observed from non-vertebrates to humans. Sleepy mutation in mice resulted in a notable increase in sleep and was identified as an exon-skipping mutation of the salt-inducible kinase 3 (Sik3) gene, conserved among animals. The skipped exon includes a serine residue that is phosphorylated by protein kinase A. Overexpression of a mutant gene with the conversion of this serine into alanine (Sik3-SA) increased sleep in both mice and the fruit fly Drosophila melanogaster. However, the mechanism by which Sik3-SA increases sleep remains unclear. Here, we found that Sik3-SA overexpression in all neurons increased sleep under both light–dark (LD) conditions and constant dark (DD) conditions in Drosophila. Additionally, overexpression of Sik3-SA only in PDF neurons, which are a cluster of clock neurons regulating the circadian rhythm, increased sleep during subjective daytime while decreasing the amplitude of circadian rhythm. Furthermore, suppressing Sik3-SA overexpression specifically in PDF neurons in flies overexpressing Sik3-SA in all neurons reversed the sleep increase during subjective daytime. These results indicate that Sik3-SA alters the circadian function of PDF neurons and leads to an increase in sleep during subjective daytime under constant dark conditions.
Elevated first-trimester hepcidin level is associated with reduced risk of iron deficiency anemia in late pregnancy: a prospective cohort study
Authors: Sun Peng , Zhou Yueqin , Xu Suhua , Wang Xiaotong , Li Xiuxiu , Li Hailin , Lin Zongyu , Huang Fenglian , Zhu Lewei , Zhu Yanna
Published: August 2023

Background

Iron deficiency (ID) and iron deficiency anemia (IDA) during pregnancy are highly prevalent worldwide. Hepcidin is considered an important biomarker of iron status. Currently, few longitudinal cohort studies have assessed the potential causal relationship between hepcidin and ID/IDA. Therefore, we aimed to investigate the association of first-trimester maternal serum hepcidin with third-trimester ID/IDA risk in a prospective cohort.

Methods

Total of 353 non-ID/IDA pregnant women at 11–13 weeks’ gestation were enrolled in Southern China and followed up to 38 weeks of gestation. Data on demography and anthropometry were obtained from a structured questionnaire at enrollment. Iron biomarkers including hepcidin were measured at enrollment and follow-up. Regression models were used to evaluate the association of first-trimester hepcidin with third-trimester ID/IDA risk.

Results

Serum hepcidin levels substantially decreased from 19.39 ng/mL in the first trimester to 1.32 ng/mL in the third trimester. Incidences of third-trimester ID and IDA were 46.2 and 11.4%, respectively. Moreover, moderate and high levels of first-trimester hepcidin were positively related to third-trimester hepcidin (log-transformed β = 0.51; 95% CI = 0.01, 1.00 and log-transformed β = 0.66; 95% CI = 0.15, 1.17). Importantly, elevated first-trimester hepcidin was significantly associated with reduced risk of third-trimester IDA (OR = 0.38; 95% CI = 0.15, 0.99), but not with ID after adjustment with potential confounders.

Conclusion

First-trimester hepcidin was negatively associated with IDA risk in late pregnancy, indicating higher first-trimester hepcidin level may predict reduced risk for developing IDA. Nonetheless, given the limited sample size, larger studies are still needed.
Applying the theoretical domains framework and behavior change wheel to inform interventions for food and food-related waste audits in hospital foodservices
Authors: Cook Nathan , Collins Jorja , Porter Judi , Goodwin Denise
Published: August 2023

Background

Completing aggregate food and food-related waste audits in hospital foodservices is an intense practice, however they can demonstrate problem areas that require attention to reduce waste. Identifying interventions to facilitate and improve the implementation of these audits can be guided by behavior change science. The aims of this study were to use behavior change theories and frameworks to (1) describe the drivers of behavior to complete food and food-related waste audits and (2) identify possible interventions that support the implementation and uptake of these audits.

Methods

Purposive sampling was used to recruit participants from hospitals in Victoria, Australia who worked in their foodservice system. Semi-structured interviews sought knowledge of participant’s perceived barriers and enablers to completing food and food-related waste audits. Deductive analysis using the Theoretical Domains Framework (TDF) and Capability Opportunity Motivation Behavior theory (COM-B) identified dominant drivers of behavior. TDF domains were then matched to their corresponding intervention functions according to the Behavior Change Wheel framework (BCW) to identify relevant strategies that may support audit implementation.

Results

Data from 20 interviews found the dominant COM-B constructs (TDF domains) were psychological capability (knowledge, skills), physical opportunity (environmental context and resources), and reflective motivation (social/professional role and identity, beliefs about capabilities). These dominant domains come from narratives that participants shared about foodservice staffs’ lack of knowledge, labor, time, and the hospital avoiding responsibility for audit completion. Corresponding intervention functions that could have the most potential for implementing waste audits were education, training, environmental restructuring, modeling, and enablement. Participants’ shared perspectives of audit enablers resembled these: for example, obtaining staff buy-in, reinforcing behavior through incentives and installing an audit champion.

Conclusion

To transition toward regular food and food-related waste auditing practices in hospital foodservices these findings may help identify practice and policy change that delivers standardized auditing activities to encourage long term behavior change. Interventions to support audit completion should address each behavioral construct and relevant domain, as individual hospital sites will experience unique contextual factors and expectations influencing audit outcomes. A co-design process that includes staff and stakeholders of hospital foodservices is recommended to enable engagement and practical solutions to audit implementation.
Physicochemical properties of superfine grinding-microwave modified artichoke soluble dietary fiber and their alleviation of alcoholic fatty liver in mice
Authors: Wang Yayi , He Bian , Zhang Linwei , Zhu Renwei , Huang Liang
Published: August 2023

The effects of superfine grinding (SG) and microwave treatment (MT) on the structure and physicochemical properties of artichoke soluble dietary fiber (ASDF) and its protective effects on mice with alcoholic fatty liver (AFL) were studied. We compared the changes in structural characteristics and physicochemical properties of ASDF, SG-ASDF (ASDF treated by SG), MT-ASDF (ASDF treated by MT), and CM-ASDF (ASDF treated by SG and MT). Moreover, we evaluated the effects of the obtained ASDF on the growth characteristics, blood lipid levels, and liver of mice with AFL. Our results of the study showed that CM-ASDF had a more concentrated and uniform particle size, a higher extraction rate of ASDF and significantly improved water-holding capacity (WHC), oil-holding capacity (OHC) and water swelling capacity (WSC) of ASDF (p < 0.05). After the ASDF intervention, mice with AFL exhibited a significant improvement in body lipid levels and reduce liver inflammation. Specifically, aspartate aminotransferase (AST), alanine aminotransferase (ALT), malonaldehyde (MDA), Tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were significantly increased (p < 0.05). And the hematoxylin–eosin (HE) staining results showed significant improvement of hepatic steatosis in mice with AFL. In summary, our study found that both SG and MT could improve the structure and physicochemical properties of ASDF, with CM-ASDF being the most effective. Additionally, CM-ASDF was selected to continue the investigation and demonstrated an excellent protective effect on mice with AFL, with the high dose group (H-ASDF) showing the greatest benefit. These findings provided some new insights for future comprehensive utilization of ASDF and drug development for the treatment of AFL.
Expression of p53 as a biomarker in determining response to apatinib for advanced gastric cancer
Authors: Qiu Zhiyuan , Qin Rong , Zhang Ziyi , Zhang Ting , Zhang Zhao , Qiao Chunyue , Xi Yan , Tian Guangyu , Wang Yan
Published: August 2023

Background

Apatinib has shown outstanding value in the treatment of advanced gastric cancer (AGC). However, no biomarkers are available to select AGC patients who will benefit from apatinib. The aim of the present study was to investigate the association between p53 and Ki67 expression of and the outcome in AGC patients treated with apatinib.

Methods

From December 2015 to December 2020, 92 AGC patients were enrolled and was retrospectively evaluated. They were given apatinib at a daily dose of 500 or 250 mg every 4 weeks to monitor clinical efficacy and adverse events (AEs). Kaplan-Meier method was used for survival analysis. Expression of p53 and Ki67 was detected by immunohistochemistry (IHC) and correlated with survival.

Results

Among 92 evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 17.4% and 79.3%, respectively, and none of them achieved a CR, 16 achieved a PR (17.4%) (95% CI 9.8%-26.1%). Stable disease (SD) was observed in 57.6% of patients (95% CI 49.2%-69.9%) and PD in 21.7% of patients (95% CI 13.6%-31.3%). The median progression free survival (mPFS) was 122.7 ± 8.2 days, and the median overall survival (mOS) was 203.4 ± 11.9 days. P53 expression was observed in 35 patients (38.0%) and high expression of Ki67 was detected in 34 patients (37.0%). There was a statistically significant inverse relationship between p53 and Ki67 expression (P=0.014). Moreover, p53 was significantly correlated with the OS (P=0.018), but Ki67 had no significant influence on OS.

Conclusions

Apatinib showed promising efficiency and was well tolerated as a second-line treatment for AGC patients. AGC patients with p53-negative were likely to benefit from apatinib treatment; however, the expression of Ki67 proteins has no significant impact on the outcome of AGC patients.
Laparoscopic aspirator bracket: a new instrument facilitating the aspiration and exposure of operative field simultaneously in laparoscopic nephron-sparing surgery
Authors: Yan Fengqi , Dou Xiaoliang , Zhu Guangfeng , Tang Qisheng , Zhang Bo , Zhao Bo , Yu Lei , Wang He , Wang Yong
Published: August 2023

Background

This study aims to describe a novel laparoscopic aspirator bracket (LAB) and its use in laparoscopic nephron-sparing surgery (NSS) by a simple enucleation (SE) technique.

Methods

A total of 123 renal tumor cases who underwent laparoscopic NSS via LAB or laparoscopic aspirator between July 2017 and April 2021 were retrospectively analyzed. General characteristics, perioperative data and postoperative follow-up data of patients were compared.

Results

The application of LAB in laparoscopic renal tumor SE surgery shortened the operation time (88.58 ± 38.25 vs. 102.25 ± 35.84 min, p < 0.05) and improved the zero ischemia rate (18.75% vs. 3.39%, p < 0.05), shortened warm ischemia time (16.17 ± 5.16 vs. 19.39 ± 5.62 min, p < 0.05) and decreased intraoperative blood loss (166.19 ± 111.60 vs. 209.15 ± 127.10 ml, p < 0.05). In addition, the serum creatinine and eGFR values in the LAB group also showed faster and better renal function recovery.

Conclusion

The new LAB could aspirate and expose the operative field with a single instrument. In operations that need to expose and aspirate simultaneously, such as in renal tumor simple enucleation, it could shorten operation time, reduce intraoperative blood loss and improve the postoperative renal function recovery.
Case Report: Unresectable pulmonary metastases of a giant cell tumor of bone treated with denosumab: a case report and review of literature
Authors: Miwa Shinji , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Igarashi Kentaro , Taniguchi Yuta , Morinaga Sei , Asano Yohei , Nojima Takayuki , Tsuchiya Hiroyuki
Published: August 2023

Giant cell tumors of bone (GCTB) sometimes metastasize to distant organs. In this case report, we present pulmonary metastases of GCTB mimicking malignancies. A 49-year-old man underwent two surgical treatments for a GCTB of the right proximal radius. At the time of the second surgery, no lesions were observed on chest radiography. Three years after surgery, the patient presented with cough and dyspnea, and chest radiography and computed tomography (CT) revealed multiple lung nodules. Positron emission tomography/CT revealed a high accumulation of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in multiple lesions. Based on the rapid growth and accumulation of 18F-FDG, a metastatic malignant tumor was suspected. CT-guided needle biopsy was performed, and the histology showed proliferation of spindle cells and multinuclear giant cells without malignant changes. Denosumab was administered because multiple lung lesions were unresectable. One month after denosumab treatment, CT showed marked shrinkage of the lesions, and the symptoms significantly improved. Eighteen months after the initial treatment with denosumab, the patient had no symptoms or tumor growth. Although its long-term efficacy and safety remain unclear, denosumab may be a treatment option for patients with unresectable pulmonary GCTB.
Dorsal subthalamic deep brain stimulation improves pain in Parkinson's disease
Authors: Askari Asra , Lam Jordan L. W. , Zhu Brandon J. , Lu Charles W. , Chou Kelvin L. , Wyant Kara J. , Patil Parag G.
Published: August 2023

Introduction

Inconsistent effects of subthalamic deep brain stimulation (STN DBS) on pain, a common non-motor symptom of Parkinson's disease (PD), may be due to variations in active contact location relative to some pain-reducing locus of stimulation. This study models and compares the loci of maximal effect for pain reduction and motor improvement in STN DBS.

Methods

We measured Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part I pain score (item-9), and MDS-UPDRS Part III motor score, preoperatively and 6–12 months after STN DBS. An ordinary least-squares regression model was used to examine active contact location as a predictor of follow-up pain score while controlling for baseline pain, age, dopaminergic medication, and motor improvement. An atlas-independent isotropic electric field model was applied to distinguish sites of maximally effective stimulation for pain and motor improvement.

Results

In 74 PD patients, mean pain score significantly improved after STN DBS (p = 0.01). In a regression model, more dorsal active contact location was the only significant predictor of pain improvement (R2 = 0.17, p = 0.03). The stimulation locus for maximal pain improvement was lateral, anterior, and dorsal to that for maximal motor improvement.

Conclusion

STN stimulation, dorsal to the site of optimal motor improvement, improves pain. This region contains the zona incerta, which is known to modulate pain in humans, and may explain this observation.
Establishment of a prediction model for histological chorioamnionitis and its association with outcomes of premature infants
Authors: Zhang Li , Fang Xin , Li Zhankui , Han Xiang , Du Hongyan , Qu Pengfei , Xu Feifei , Wu Lizhi , Li Yajun
Published: August 2023

Aim

This study aims to construct a prediction model for histological chorioamnionitis (HCA) and analyze the associations between the predicted risk of HCA and adverse outcomes in preterm infants.

Methods

In total, 673 subjects were included in this cohort study and divided into HCA group (n = 195) and non-HCA group (n = 478). A stepwise method was used to screen the predictors for HCA, binary logistic regression was used to construct the prediction model, and the associations between the predicted risk of HCA and adverse outcomes were analyzed.

Results

HCA occurred in 195 patients, accounting for 29.0%. The sensitivity of the prediction model was 0.821 [95% confidence interval (CI): 0.767–0.874)], the specificity was 0.684 (95% CI: 0.642–0.726), the positive predictive value was 0.514 (0.459–0.570), the negative predictive value was 0.903 (95% CI: 0.873–0.934), the area under the curve was 0.821 (95% CI: 0.786–0.855), and the accuracy was 0.724 (95% CI: 0.690–0.757). The predicted risk of HCA was associated with a higher risk of bronchopulmonary dysplasia (BPD) [odds ratio (OR) = 3.48, 95% CI: 1.10–10.95)], sepsis (OR = 6.66, 95% CI: 2.17–20.43), and neonatal infections (OR = 9.85, 95% CI: 3.59–26.98), but not necrotizing enterocolitis (OR = 0.67, 95% CI: 0.24–1.88), retinopathy of prematurity (OR = 1.59, 95% CI: 0.37–6.85), and brain damage (OR = 1.77, 95% CI: 0.82–3.83). After adjusting for confounders including gestational week at birth and birth weight, the risk of neonatal infections (OR = 5.03, 95% CI: 2.69–9.41) was increased in preterm infants’ exposure to HCA.

Conclusion

The model showed good predictive performance for identifying pregnant women with a higher risk of HCA. In addition, HCA was associated with the risk of BPD, sepsis, and infections in neonates.
Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells
Authors: Lin Ting-Chun , Soorneedi Anand , Guan Yingxue , Tang Ying , Shi Eleanor , Moore Matthew D. , Liu Zhenhua
Published: August 2023

Introduction: Diet-induced obesity has been shown to decrease the abundance of Turicibacter, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of Turicibacter potentially influential in the protection of intestinal tumorigenesis. Recently, Antrodia camphorata (AC), a medicinal fungus native to Taiwan, has emerged as a promising candidate for complementary and alternative cancer therapy. Small molecules and polysaccharides derived from AC have been reported to possess health-promoting effects, including anti-cancer properties.

Methods: Bacterial culture followed with cell culture were used in this study to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation.

Results:Turicibacter fermentation and the addition of AC polysaccharide led to a significant increase in the production of nutrients and metabolites, including α-ketoglutaric acid and lactic acid (p < 0.05). Treatment of Turicibacter fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including Tph1, Htr1d, Htr2a, Htr2b, and Htr2c (p < 0.05), and Wnt-signaling related protein and downstream gene expressions, such as phospho-GSK-3β, active β-catenin, c-Myc, Ccnd1, and Axin2 (p < 0.05). Additionally, it triggered the highest generation of reactive oxygen species (ROS), which activated PI3K/Akt and MAPK/Erk signaling and resulted in cleaved caspase-3 expression. In comparison, the treatment of AC polysaccharide without Turicibacter fermentation displayed a lesser effect.

Discussion: Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation.
Which is the top player for the cardiovascular safety? ibrutinib vs. obinutuzumab in CLL
Authors: Mascolo Annamaria , Di Napoli Raffaella , Balzano Nunzia , D’Alessio Elena , Izzo Imma , Rossi Francesco , Paolisso Giuseppe , Capuano Annalisa , Sportiello Liberata
Published: August 2023

Introduction: Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, is authorized for the treatment of chronic lymphocytic leukemia (CLL). This study aims to explore the cardiac safety profile of ibrutinib in comparison with obinutuzumab.

Methods: A retrospective pharmacovigilance study was conducted on data retrieved from the European pharmacovigilance database (Eudravigilance) from 1 January 2014 to 30 September 2022. To compare the reporting frequency of cardiovascular events among ibrutinib, obinutuzumab, and the combination of both.

Results: A total of 2 291 CV cases were retrieved, of which 1965 were related to ibrutinib, 312 to obinutuzumab, and 14 to the combination. Most cases referred to patients aged ≥65 years (N = 1,454; 63.47%) and male (N = 1,497; 65.34%). Most cases were serious (N = 2,131; 93.02%). The most reported events were: atrial fibrillation (N = 913; 31.31%) and haemorrhage (N = 201; 6.89%). A higher reporting frequency of CV events was found when ibrutinib was compared to obinutuzumab (ROR, 3.22; 95% CI, 2.89-3.60) or combination (ROR, 1.77; 95% CI, 1.11-2.83). A lower reporting was observed when obinutuzumab was compared to combination (ROR, 0.55; 95% CI, 0.34-0.88).

Discussion: A higher reporting frequency of CV events in patients exposed to ibrutinib in comparison with obinutuzumab was found. Further studies are needed to better explore the safety of ibrutinib.
Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy
Authors: Kammala Ananth K. , Richardson Lauren S. , Radnaa Enkhtuya , Han Arum , Menon Ramkumar
Published: August 2023

Introduction: Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate into clinical trials, leading to pregnant women being excluded from drug development considerations and clinical studies. To address this limitation, we explored the utility of in silico simulation modeling and microfluidic-based organ-on-a-chip platforms to assess potential interventional agents.

Methods: We developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) utilizing microfluidic channels to maintain intercellular interactions among seven different cell types (fetal membrane-decidua-placenta). This platform enabled the investigation of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. The data obtained from FMi-PLA-OOC were compared with existing data from in vivo animal models and ex vivo placenta perfusion models. Additionally, we employed mechanistically based simulation software (Gastroplus®) to predict pravastatin pharmacokinetics in pregnant subjects based on validated nonpregnant drug data.

Results: Pravastatin transfer across the FMi-PLA-OOC and predicted pharmacokinetics in the in silico models were found to be similar, approximately 18%. In contrast, animal models showed supraphysiologic drug accumulation in the amniotic fluid, reaching approximately 33%.

Discussion: The results from this study suggest that the FMi-PLA-OOC and in silico models can serve as alternative methods for studying drug pharmacokinetics during pregnancy, providing valuable insights into drug transport and metabolism across the placenta and fetal membranes. These advanced platforms offer promising opportunities for safe, reliable, and faster testing of therapeutic compounds, potentially reducing the number of pregnant women referred to as “therapeutic orphans” due to the lack of consideration in drug development and clinical trials. By bridging the gap between preclinical studies and clinical trials, these approaches hold great promise in improving maternal and neonatal health outcomes.
Soluble interleukin-1 receptor type 2 plasma levels in Parkinson’s disease: relationship with cardiac autonomic profile before and after peripheral mechanical somatosensory stimulation
Authors: Shiffer Dana , Zamunér Antonio Roberto , Minonzio Maura , Bulgheroni Mara , Porta Alberto , Leone Roberto , Bottazzi Barbara , Garlanda Cecilia , Colotta Francesco , Barbic Franca , Mantovani Alberto , Furlan Raffaello
Published: August 2023

Introduction: Systemic inflammation promotes neurodegeneration in Parkinson’s disease (PD). Interleukin-1 receptor type 2 (sIL-1R2) plasma levels increase during inflammation. Data on sIL-1R2 in PD patients and its relationship with PD cardiac autonomic profile are limited, given the possible anti-inflammatory effect of vagal activation. Previously, automated mechanical peripheral somatosensory stimulation (AMPSS) enhanced cardiac vagal modulation. Objectives were to 1) evaluate sIL-1R2 plasma concentrations in PD patients and healthy controls and 2) investigate the correlations between sIL-1R2 and cardiac autonomic indices obtained by spectrum analysis of heart rate variability before and after AMPSS.

Methods: sIL-1R2 plasma levels were assessed in 48 PD patients and 50 healthy controls. Electrocardiogram and beat-by-beat arterial pressure were recorded at baseline and after 5 AMPSS sessions in 16 PD patients.

Results: PD patients had higher sIL-1R2 levels than controls. In the PD subgroup, an inverse correlation between sIL-1R2 and HFnu was found. There was a negative correlation between changes induced by AMPSS on HFnu and sIL-1R2.

Discussion: Higher sIL-1R2 levels in PD patients reflect the inflammatory dysregulation associated with the disease. In PD patients, higher sIL-1R2 was associated with reduced cardiovagal tone. Increased cardiovagal modulation following AMPSS was associated with lower sIL-1R2 levels in Parkinson’s disease patients, suggesting inflammatory state improvement.
Identification of CmACL genes in melon and analysis of their potential functions in fruit sugar and acid accumulation
Authors: Ren Kaili , Kong Weiping , Tang Taoxia , Cheng Hong
Published: August 2023

Citric acid is the most important organic acid in melon and has a great influence on fruit flavor quality. ATP-citrate (pro-S) lyase (ACL) is a key regulator in the acetyl-CoA pathway and plays an important role in citric acid metabolism. In this study we analyzed the structure and phylogenetics of CmACL genes and their functions in sugar and acid accumulation in melon. A total of four CmACL genes were identified in the melon genome, and phylogenetic analysis assigned these genes into the α subfamily (CmACLα1 and CmACLα2) and the β subfamily (CmACLβ1 and CmACLβ2). Conserved motif and gene structure analyses showed that members of the same subfamily shared identical conserved motifs and gene structures, and probably have similar biological functions. Analysis of cis-acting elements revealed that CmACL promoter sequences contained regulatory elements related to light, stress, phytohormones, and growth and development, indicating that CmACL genes may be involved in melon growth and stress responses. The prediction of protein interaction network showed that CmACL proteins were closely related to the proteins belonging to tricarboxylic acid cycle, glyoxylic acid cycle and glycolytic pathway, suggesting that CmACL proteins may play an important role in sugar and acid metabolism. The expression of CmACLβ1 was significantly and positively correlated with sucrose content, and CmACLβ2 expression was significantly positively correlated with citric acid content, suggesting that CmACLβ1 and CmACLβ2 have important roles in sugar and acid accumulation in melon. Our results offer novel insights and avenues for the regulation of sugar and acid levels in melon and provide a theoretical foundation for breeding high-quality melon cultivars.
Normative developmental vs. reverse developmental trends in memory distortion: a framework to investigate the impact of internal and external influences on memory and their relevance to legal decisions
Authors: Rosendaul Brittany J. , Su I-An , Ceci Stephen J.
Published: August 2023

There are two opposing positions regarding the development of memory: the normative developmental position, and the reverse developmental position. The normative position, which has long been the default presupposition, supports the notion that susceptibility to memory distortion, including false memories, decreases with age. In contrast, the concept of “developmental reversals” supports the notion that susceptibility to memory distortion and false memories increases with age. Each perspective finds support from existing theories as well as from research on endogenous and exogenous sources of influence. In a legal context, having an accurate understanding of the developmental course of false memory can contribute on the one hand to mitigating wrongful convictions and, on the other hand, to appreciating the accuracy of children’s statements when warranted. This review aims to integrate the existing literature regarding these seemingly opposite developmental courses and construct a framework outlining the conditions under which we may observe one age trend over the other. This entails an examination of the paradigms that have been invoked to support these competing positions, specifically developmental responses to internal vs. external sources of distortion.