bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfluorooctane sulfonic acid exposure and diabetes: a cross-sectional analysis of American adults and in vitro experiments
Authors: Liu Keliang , Sun Linqing , Xu Haiming , Li Sirui , Sun Lei , Tian Yuhui , Liu Zhihong
Published: October 2023

Background

Perfluorooctane sulfonic acid (PFOS) exposure has a negative impact on the environment and biological health. However, the relationship between PFOS exposure and diabetes in adults is not clear.

Objective

In this study, we included two distinct components: (1) in the cross-sectional analysis, we used data from the National Health and Nutrition Inspection Survey (NHANES) from 2015 to 2018 and eventually included 2539 subjects. The association between PFOS exposure and the risk of diabetes in adults was assessed by a logistic regression model, and further subgroup analysis was carried out according to sex, hypertension status and high cholesterol status. We adjusted for all covariates and found that the positive association between higher PFOS exposure and diabetes remained stable. (2) In vitro experiments were conducted as follows, rat insulinoma β cells (INS-1) were used as experimental materials; cell proliferation activity was detected using the MTT assay; quantitative real-time PCR was used to detect the mRNA expression of insulin; and Western blotting was used to detect insulin protein expression levels.

Results

Compared with Q1, the OR of the highest exposure level group (Q4) of PFOS was 1.342(95% CI 0.940, 1.916). We conducted a logistic regression analysis based on sex, hypertension, and high cholesterol stratification. Stratified by sex, we found that the exposure level of PFOS was significantly positively associated with diabetes (P for trend < 0.05). Subgroup analysis showed that the positive association between PFOS exposure and diabetes was more significant in nonhypertensive individuals (P for trend < 0.01) and those with normal cholesterol levels (P for trend < 0.001). To further determine the causal relationship between PFOS exposure and diabetes, we used rat insulinoma β cells (INS-1) as experimental materials to study the effect of PFOS exposure on insulin secretion. We found that PFOS exposure significantly affected insulin secretion and insulin mRNA and protein expression.

Conclusions

In summary, PFOS exposure is positively associated with the risk of diabetes. However, further studies are needed to confirm our results.
Composition of pathogenic microorganism in chronic osteomyelitis based on metagenomic sequencing and its application value in etiological diagnosis
Authors: Zhang Kang , Bai Yu-zhe , Liu Chang , Liu Shan-shan , Lu Xin-xin , Yang Run-gong
Published: October 2023

Background

Traditionally, conventional microbiological culture methods have been used to detect pathogenic microorganisms in chronic osteomyelitis. However, these methods have been found to have a low detection rate, complicating the precise guidance of infection treatment. This study employed metagenomic next-generation sequencing (mNGS) to detect these microorganisms in chronic osteomyelitis with three main objectives: 1). Gain a deeper understanding of the composition of pathogenic microorganisms in chronic osteomyelitis. 2). Compare the microbial detection rates between mNGS and the standard culture methods used in laboratories to enhance the effectiveness of the traditional culture methods. 3). Explore the potential of mNGS in etiological diagnosis.

Methods

Fifty clinically confirmed intraoperative bone tissue samples of chronic osteomyelitis from January 2021 to December 2021 were collected and subjected to mNGS and microbiological testing, respectively. The orthopaedic surgeon combined clinical manifestations and related examinations to determine the causative pathogens.

Results

The culture method obtained 29 aerobic and parthenogenic anaerobic bacteria, 3 specific anaerobic bacteria, and 1 yeast-like fungus. Thirty-six aerobic and parthenogenic anaerobic bacteria, 11 specific anaerobic bacteria, and 1 yeast-like fungus were obtained by mNGS, and 2 Mycobacterium tuberculosis(MTB) strains were detected. However, there was no significant difference in the overall positive detection rate between mNGS and the culture method (P = 0.07), and the two were not statistically significant in detecting aerobic and partly anaerobic bacteria (P = 0.625). But, mNGS was significantly superior to culture in detecting anaerobic bacteria and Mycobacterium tuberculosis (P<0.05).

Conclusions

The mNGS method has enhanced our understanding of the distribution of pathogenic microorganisms in chronic osteomyelitis. Traditional culture methods help isolate and cultivate aerobic and facultative anaerobic bacteria, and fungi, and are also utilized for antibacterial drug sensitivity tests. However, mNGS has shown superior capabilities in detecting anaerobic bacteria, MTB, and mixed infection bacteria. This finding offers invaluable guidance for improving laboratory microbial culture and detection conditions. Hence, mNGS should be judiciously used for chronic osteomyelitis, and PCR can be implemented for certain difficult-to-culture microorganisms, such as MTB.
Antiemetic prophylaxis with droperidol in morphine-based intravenous patient-controlled analgesia: a propensity score matched cohort study
Authors: Tan Jia Qi , Wu Hsiang-Ling , Wang Yi-Chien , Cata Juan P. , Chen Jui-Tai , Cherng Yih-Giun , Tai Ying-Hsuan
Published: October 2023

Background

There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA.

Methods

Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).

Results

After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35–0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41–0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups.

Conclusions

The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.
Can peer effects explain prescribing appropriateness? a social network analysis
Authors: Wang Sophie Y. , Larrain Nicolas , Groene Oliver
Published: October 2023

Background

Optimizing prescribing practices is important due to the substantial clinical and financial costs of polypharmacy and an increasingly aging population. Prior research shows the importance of social relationships in driving prescribing behaviour. Using social network analysis, we examine the relationship between a physician practices’ connectedness to peers and their prescribing performance in two German regions.

Methods

We first mapped physician practice networks using links established between two practices that share 8 or more patients; we calculated network-level (density, average path length) and node-level measures (degree, betweenness, eigenvector). We defined prescribing performance as the total number of inappropriate medications prescribed or appropriate medications not prescribed (PIMs) to senior patients (over the age of 65) during the calendar year 2016. We used FORTA (Fit fOR The Aged) algorithm to classify medication appropriateness. Negative binomial regression models estimate the association between node-level measures and prescribing performance of physician practices controlling for patient comorbidity, provider specialization, percentage of seniors in practice, and region. We conducted two sensitivity analyses to test the robustness of our findings – i) limiting the network mapping to patients younger than 65; ii) limiting the network ties to practices that share more than 25 patients.

Results

We mapped two patient-sharing networks including 436 and 270 physician practices involving 28,508 and 20,935 patients and consisting of 217,126 and 154,274 claims in the two regions respectively. Regression analyses showed a practice’s network connectedness as represented by degree, betweenness, and eigenvector centrality, is significantly negatively associated with prescribing performance (degree—bottom vs. top quartile aRR = 0.04, 95%CI: 0.035,0.045; betweenness—bottom vs. top quartile aRR = 0.063 95%CI: 0.052,0.077; eigenvector—bottom vs. top quartile aRR = 0.039, 95%CI: 0.034,0.044).

Conclusions

Our study provides evidence that physician practice prescribing performance is associated with their peer connections and position within their network. We conclude that practices occupying strategic positions at the edge of networks with advantageous access to novel information are associated with better prescribing outcomes, whereas highly connected practices embedded in insulated information environments are associated with poor prescribing performance.
Activities of daily living limitations and family doctor contract services among overweight and obese older adults: is there a rural-urban difference?
Authors: Luo Jingjing , Zhao Dan , Gao Tingting , Sun Jingjie , Li Peilong , Wang Xuehong , Wang Xueqing , Chai Shujun , Li Jiayan , Zhou Chengchao
Published: October 2023

Background

The purpose of this study was to evaluate the relationship between activities of daily living (ADL) limitations and family doctor contract services among overweight and obese older adults, as well as to examine whether this association varies by urban-rural residence.

Methods

Data for the present study were obtained from the sixth Health Service of Shandong province, China. A total of 4,249 overweight and obese older adults were included in this study. Binary logistic regression models were used to evaluate the relationship between ADL limitations and family doctor contract services, to examine the potential differences between urban and rural areas.

Results

Of 4,249 overweight and obese older adults, the prevalence of limitations in ADL and family doctor service contracting rate in Shandong province were 12.47% and 66.46%, respectively. The results of the regression analyses revealed that overweight and obese older adults with ADL limitations were more likely to sign up for family doctor services than those without ADL limitations (OR = 1.27, 95%CI: 1.02–1.58, P = 0.033). Only among rural overweight and obese older adults, the relationship between ADL limitations and family doctor contract services was statistically significant (OR = 1.50, 95%CI: 1.13–1.99, P = 0.005).

Conclusions

Our study found a significant association between ADL limitations and family doctor contract services among overweight and obese older adults in Shandong, China. This relationship differed by urban-rural residence. To promote the positive development of the family doctor contract service system, the government should increase publicity, provide personalized contracted services, and prioritize the healthcare needs of overweight and obese older adults with ADL limitations, with special attention to rural areas.
Multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation: a randomized controlled pilot and feasibility study [ReFEx]
Authors: Wolf Florian , Nielsen Jörn , Saliger Jochen , Hennecken Eva , Kröber Philipp , Eschweiler Mareike , Folkerts Ann-Kristin , Karbe Hans , Zimmer Philipp
Published: October 2023

Background

Multimodal agility-based exercise training (MAT) is a group-based exercise training framework for persons with multiple sclerosis (pwMS) with a potential to impact fatigue and fatigability. In a mixed-methods design, this study evaluated the feasibility of implementing MAT in an inpatient rehabilitation setting and the feasibility of a randomized controlled trial (RCT) study protocol with ‘traditional’ strength and endurance training (SET) as an active control condition. Secondarily, preliminary outcome data was acquired.

Methods

PwMS with low to moderate disability and self-reported fatigue were randomly allocated to either MAT or SET when starting inpatient rehabilitation (4–6 weeks). The MAT-participants exercised in a group following a MAT-manual (sessions were gym- (5x/week) and pool-based (3x/week)). SET-participants exercised individually 5x/week on a cycle ergometer, and 3x/week on strength training machines. Feasibility assessments focused on processes, resources, management, time, and scientific domains. Assessed clinical outcomes at admission and discharge included perceived fatigue, motor and cognitive fatigability, cognitive performance, motor function, and balance confidence. Perceived fatigue was reassessed 1, 4, and 12 weeks after discharge. Feasibility was determined regarding predetermined progression criteria.

Results

Twenty-two participants were randomized. Both groups performed the minimum number of sessions (> 18), and retention was adequate (73–91%). SET-participants performed more sessions than MAT-participants (30.8 vs. 22.7) and stayed longer in the facility (34.2 vs. 31.6 days). Non-eligibility of admitted pwMS was high (74% non-eligible), mainly due to high EDSS and inability to attend pool-based sessions. Consequently, recruitment (1.8/month) was slower than the predetermined progression criterium. Baseline assessments took longer than required (only 50% completed within 3 days). Short-term fatigue reduction was similar for both groups. Motor fatigability also improved in both groups, whereas cognitive fatigability deteriorated. In MAT, average improvement in walking endurance (43.9 m) exceeded minimal important change values for individuals (> 26.9 m).

Conclusions

Progressing to a definitive RCT necessitates adaptation of eligibility criteria. In the present design it will also be difficult to attain similar dosing of interventions. A multicenter RCT focused only on gym-based MAT might be another option to assess the effect of MAT. The primary outcome measure should be able to measure change in perceived fatigue more robustly.

Trial registration

German Clinical Trials Register: DRKS00023943, date of registration: 23 September 2021.
You & Me: Test and Treat study protocol for promoting COVID-19 test and treatment access to underserved populations
Authors: D’Agostino Emily M. , Rosenberg Lauren M. , Richmond Alan , Damman Allyn , Brown-Lowery Camille , Abbot-Grimes Princess , Siddiqui Saira , Fadika Tigidankay , Ward Mark , Cooper Mia , Sutton Sonya , Kenton Lindsay , Spaziano Bob , Kasper Janet , Barnes Nicole , Hornik Christoph
Published: October 2023

Background

Infections and deaths from the COVID-19 pandemic have disproportionately affected underserved populations. A community-engaged approach that supports decision making around safe COVID-19 practices is needed to promote equitable access to testing and treatment. You & Me: Test and Treat (YMTT) will evaluate a systematic and scalable community-engaged protocol that provides rapid access to COVID-19 at-home tests, education, guidance on next steps, and information on local resources to facilitate treatment in underserved populations.

Methods

This direct-to-participant observational study will distribute at-home, self-administered, COVID-19 testing kits to people in designated communities. YMTT features a Public Health 3.0 framework and Toolkit prescribing a tiered approach to community engagement. We will partner with two large community organizations, Merced County United Way (Merced County, CA) and Pitt County Health Department (Pitt County, NC), who will coordinate up to 20 local partners to distribute 40,000 COVID tests and support enrollment, consenting, and data collection over a 15-month period. Participants will complete baseline questions about their demographics, experience with COVID-19 infection, and satisfaction with the distribution event. Community partners will also complete engagement surveys. In addition, participants will receive guidance on COVID-19 mitigation and health-promoting resources, and accessible and affordable therapeutics if they test positive for COVID-19. Data collection will be completed using a web-based platform that enables creation and management of electronic data capture forms. Implementation measures include evaluating 1) the Toolkit as a method to form community-academic partnerships for COVID-19 test access, 2) testing results, and 3) the efficacy of a YMTT protocol coupled with local resourcing to provide information on testing, guidance, treatment, and links to resources. Findings will be used to inform innovative methods to address community needs in public health research that foster cultural relevance, improve research quality, and promote health equity.

Discussion

This work will promote access to COVID-19 testing and treatment for underserved populations by leveraging a community-engaged research toolkit. Future dissemination of the toolkit can support effective community-academic partnerships for health interventions in underserved settings.

Trial registration

ClinicalTrials.gov Identifier: NCT05589376. Registered 21 October 2022.
Short-term outcomes associated with the use of a new powered circular stapler for rectal reconstructions: a retrospective study comparing it to manual circular staplers using inverse probability of treatment weight analysis
Authors: Matsuhashi Nobuhisa , Tajima Jesse Yu , Yokoi Ryoma , Kiyama Shigeru , Endo Masahide , Sato Yuta , Kuno Masashi , Hayashi Hirokatsu , Asai Ryuichi , Fukada Masahiro , Yasufuku Itaru , Tanaka Yoshihiro , Okumura Naoki , Murase Katsutoshi , Ishihara Takuma , Takahashi Takao
Published: October 2023

Background

The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J).

Materials and methods

This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database.

Result

One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34–0.98 and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.58; 95% Confidence Interval(CI), 0.34–0.98; p = 0.044). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65–1.18; p = 0.394) and grade III or higher (OR, 0.45; 95%CI, 0.28–0.73; p = 0.001) were significantly remarkable lower in powered circular stapling group.

Conclusion

In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.
Impact of COVID-19 on patient follow-up during supportive periodontal therapy: a retrospective study based on phone call survey
Authors: Wang Mengli , Xu Yuxin , Fang Wen , Pan Weiyi , Wang Qianting
Published: October 2023

Background

COVID-19 and the subsequent intermittent lockdown measures from 2020 to 2022 in China critically disrupted regular medical activities, including dental care. This study aimed to investigate the impact of COVID-19 on long-term follow-up at the Stomatology Hospital, Zhejiang University School of Medicine and to evaluate potential causes of loss to follow-up.

Methods

A total of 1062 patients with periodontitis who visited the hospital from January 2019 to June 2022 were included in this study, and patient information was collected retrospectively in the form of a telephone questionnaire. The questionnaire consisted of 19 questions in four areas: demographic characteristics, clinical periodontal parameters, oral hygiene habits, and follow-up-related open-ended questions (specific reasons for loss to follow-up, attitudes toward follow-up and suggestions for increasing participation in future follow-ups). Regression analysis of factors influencing the follow-up of patients with periodontitis were analyzed by regression analysis using R (v4.2.3) software.

Results

A total of 536 (50.47%) valid questionnaires were collected from 1062 patients. Personal factors (42.5%), instead of the COVID-19 epidemic (20.0%), were the main factors that impacted the loss to follow-up in long-term periodontal treatment, while work factors (19.8%), hospital factors (16.4%), and transportation or distance factors (14.7%) were all important factors. A family history of periodontitis [odds ratio (OR) = 0.567, 95% confidence interval (CI): 0.393, 0.817, p = 0.002], as well as frequent use of dental devices (OR = 0.540, 95% CI: 0.375, 0.777, p = 0.001), were significantly associated with a “negative” attitude toward follow-up visits.

Conclusion

This survey suggests that the COVID-19 epidemic factor was an important cause contributed to the loss to follow-up during supportive periodontal therapy (SPT) among a variety of potential factors. Majority of patients had negative attitudes toward subsequent continued participation in supportive care.
Human papillomavirus vaccine uptake and associated factors among adolescent girls in high schools of Nekemte city, Western Ethiopia, 2020
Authors: Hailu Genet , Wirtu Desalegn , Tesfaye Tariku , Getachew Motuma
Published: October 2023

Background

Cervical cancer is the leading cause of cancer death in adult women in the developing world including Ethiopia. To combat cervical cancer, the World Health Organization (WHO) recommends that girls aged 9–14 years have to take the human papillomavirus vaccine. However, there is a lack of information regarding the uptake of human papillomavirus vaccine in the study area. Therefore, this study aimed to assess the Human Papilloma Virus vaccine uptake and associated factors among adolescent girls in high schools of Nekemte City, Western Ethiopia, 2020.

Methods

A cross-sectional study design was employed among adolescent girls attending grade 9 and age 15 enrolled at schools in Nekemte City from July 15–30, 2020. Six hundred twenty-six (626) randomly selected adolescent girls were interviewed. The data were entered into Epi Info 7 and analyzed by SPSS 25. Multivariable analysis was computed and a P-value < 0.05 was taken as a cut-off point to declare the statistically significant association.

Result

The uptake of the HPV vaccine was 61.2%, 95%CI (57.2%, 65%). The Place where adolescents grow up (AOR = 3.46, 95%CI [1.95,6.15]), having a mobile phone(AOR = 1.71, 95%CI [1.05, 2.79]), ever heard about HPV (AOR = 5.69, 95%CI [1.33, 24.27]), ever heard about HPV vaccine(AOR = 1.917, 95%CI [1.002, 3.667]), Ever had sexual intercourse (AOR = 3.04, 95% [1.49,6.20]) and Perceived risk of towards HPV(AOR = 4.63 [2.49, 8.63]) has shown statistically significant association with Uptake of the HPV vaccine.

Conclusion

Nearly two-thirds of the study participants had taken at least one dose of the HPV vaccine. It is better if health information on HPV is disseminated considering the available technology like mobile phones and reaching rural girls.
Mechanism of furfural toxicity and metabolic strategies to engineer tolerance in microbial strains
Authors: Jilani S. Bilal , Olson Daniel G.
Published: October 2023

Lignocellulosic biomass represents a carbon neutral cheap and versatile source of carbon which can be converted to biofuels. A pretreatment step is frequently used to make the lignocellulosic carbon bioavailable for microbial metabolism. Dilute acid pretreatment at high temperature and pressure is commonly utilized to efficiently solubilize the pentose fraction by hydrolyzing the hemicellulose fibers and the process results in formation of furans—furfural and 5-hydroxymethyl furfural—and other inhibitors which are detrimental to metabolism. The presence of inhibitors in the medium reduce productivity of microbial biocatalysts and result in increased production costs. Furfural is the key furan inhibitor which acts synergistically along with other inhibitors present in the hydrolysate. In this review, the mode of furfural toxicity on microbial metabolism and metabolic strategies to increase tolerance is discussed. Shared cellular targets between furfural and acetic acid are compared followed by discussing further strategies to engineer tolerance. Finally, the possibility to use furfural as a model inhibitor of dilute acid pretreated lignocellulosic hydrolysate is discussed. The furfural tolerant strains will harbor an efficient lignocellulosic carbon to pyruvate conversion mechanism in presence of stressors in the medium. The pyruvate can be channeled to any metabolite of interest by appropriate modulation of downstream pathway of interest. The aim of this review is to emphasize the use of hydrolysate as a carbon source for bioproduction of biofuels and other compounds of industrial importance.
Triglyceride-glucose index on risk of adverse events after drug-coated balloon angioplasty
Authors: Lin Zhaorong , He Xi , Lin Maosen , Chen Lianglong
Published: October 2023

Background

The pathogenetic mechanism of atherosclerotic cardiovascular diseases is associated with insulin resistance (IR), which serves as a metabolic risk factor. As a novel indication for IR, triglyceride-glucose (TyG) index may predict cardiovascular disease outcomes.

Methods

In current study, a cohort of 157 individuals with newly developed de novo lesions who received DCB angioplasty between January 2017 and May 2021 were included. The midterm follow-up clinical results consisted of the presence of vessel-oriented composite endpoint (VOCE). The baseline TyG index was divided into three groups by tertiles. This study compared various clinical characteristics and parameters among different groups during DCB angioplasty. A multivariate Cox regression model was built to investigate the potential predictors.

Results

Higher TyG index indicated an increased risk of VOCE according to the adjusted model (HR = 4.0, 95%Cl: 1.0-15.4, P = 0.047). A non-linear correlation was uncovered between the index and VOCE from the smooth curve. Based on Kaplan-Meier curve, individuals in the highest TyG index group were more likely to develop VOCE (P < 0.05 for log-rank).

Conclusions

The incidence of VOCE was shown to be independently and positively correlated with an elevated TyG index in individuals with de novo coronary lesions who received DCB angioplasty.
A carrier-free supramolecular nano-twin-drug for overcoming irinotecan-resistance and enhancing efficacy against colorectal cancer
Authors: Yuan Miaomiao , Chen Tong , Jin Lu , Zhang Peng , Xie Luoyijun , Zhou Shuyi , Fan Lianfeng , Wang Li , Zhang Cai , Tang Ning , Guo LiHao , Xie Chengmei , Duo Yanhong , Li Ling , Shi Leilei
Published: October 2023

Irinotecan (Ir) is commonly employed as a first-line chemotherapeutic treatment for colorectal cancer (CRC). However, tremendous impediments remain to be addressed to surmount drug resistance and ameliorate adverse events. Poly-ADP-Ribose Polymerase (PARP) participates in the maintenance of genome stability and the repair of DNA damage, thus playing a critical role in chemotherapy resistance. In this work, we introduce a novel curative strategy that utilizes nanoparticles (NPs) prepared by dynamic supramolecular co-assembly of Ir and a PARP inhibitor (PARPi) niraparib (Nir) through π-π stacking and hydrogen bond interactions. The Ir and Nir self-assembled Nano-Twin-Drug of (Nir-Ir NPs) could enhance the therapeutic effect on CRC by synergistically inhibiting the DNA damage repair pathway and activating the tumor cell apoptosis process without obvious toxicity. In addition, the Nir-Ir NPs could effectively reverse irinotecan-resistance by inhibiting the expression of multiple resistance protein-1 (MRP-1). Overall, our study underscores the distinctive advantages and potential of Nir-Ir NPs as a complementary strategy to chemotherapy by simultaneously overcoming the Ir resistance and improving the anti-tumor efficacy against CRC.
Prognostic value of ascites in patients with liver cirrhosis undergoing cardiac surgery
Authors: Cizmic Amila , Rahmanian Parwis Baradaran , Gassa Asmae , Kuhn Elmar , Mader Navid , Wahlers Thorsten
Published: October 2023

Introduction

Mild or moderate liver cirrhosis increases the risk of complications after cardiac surgery. Ascites is the most common complication associated with liver cirrhosis. However, the prognostic value of ascites on postoperative morbidity and mortality after cardiac surgery remains uninvestigated.

Methods

A retrospective study included 69 patients with preoperatively diagnosed liver cirrhosis who underwent cardiac surgery between January 2009 and January 2018 at the Department of Cardiothoracic Surgery, University Hospital of Cologne, Germany. The patients were divided into ascites and non-ascites groups based on preoperatively diagnosed ascites. Thirty-day mortality, postoperative complications, length of stay, and blood transfusions were analyzed postoperatively.

Results

Out of the total of 69 patients, 14 (21%) had preoperatively diagnosed ascites. Ascites group had more postoperative complications such as blood transfusions (packed red blood cells: 78.6% vs. 40.0%, p = 0.010; fresh frozen plasma: 57.1% vs. 29.1%, p = 0.049), acute kidney injury (78.6% vs. 45.5%, p = 0.027), longer ICU stay (8 vs. 3 days, p = 0.044) with prolonged mechanical ventilation (57.1% vs. 23.6%, p = 0.015) and tracheotomy (28.6% vs. 3.6%, p = 0.003). The 30-day mortality rate was significantly higher in the ascites group than in the non-ascites group (35.7% vs. 5.5%, p = 0.002).

Conclusion

Ascites should be implemented in preoperative risk score assessments in cirrhotic patients undergoing cardiac surgery. Preoperative treatment of ascites could reduce the negative impact of ascites on postoperative complications after cardiac surgery. However, this needs to be thoroughly investigated in prospective randomized clinical trials.

Graphical abstract
Efficacy of poly (ADP-ribose) polymerase inhibitors monotherapy and the impact to subsequent platinum-based chemotherapy in breast cancer susceptibility genes1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse
Authors: Ma Yana , Liu Jiale , Li Ning , Bu Hualei , Huang Yongwen , Jin Chengjuan , Wen Hao , Feng Shuai , Zhang Hui , Yang Xiaorong , Kong Beihua , Wu Lingying , Song Kun
Published: October 2023

Background

The therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse.

Methods

BRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse.

Results

A total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p=0.766) and PFS (median: 11.2 vs. 11.0 months, p=0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p=0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p=0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p=0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p=0.002) could prolong PRS for patients with secondary platinum-sensitive relapse.

Conclusions

PARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.
Characteristics of pulmonary artery catheter use in multicenter ICUs in Japan and the association with mortality: a multicenter cohort study using the Japanese Intensive care PAtient Database
Authors: Fukano Kentaro , Iizuka Yusuke , Nishiyama Seiya , Yoshinaga Koichi , Uchino Shigehiko , Sasabuchi Yusuke , Sanui Masamitsu
Published: October 2023

Background

It has been 50 years since the pulmonary artery catheter was introduced, but the actual use of pulmonary artery catheters in recent years is unknown. Some randomized controlled trials have reported no causality with mortality, but some observational studies have been published showing an association with mortality for patients with cardiogenic shock, and the association with a pulmonary artery catheter and mortality is unknown. The aim of this study was to investigate the utilization of pulmonary artery catheters (PACs) in the intensive care unit (ICU) and to examine their association with mortality, taking into account differences between hospitals.

Methods

This is a retrospective analysis using the Japanese Intensive care PAtient Database, a multicenter, prospective, observational registry in Japanese ICUs. We included patients aged 16 years or older who were admitted to the ICU for reasons other than procedures. We excluded patients who were discharged within 24 h or had missing values. We compared the prognosis of patients with and without PAC. The primary outcome was hospital mortality. We performed propensity score analysis to adjust for baseline characteristics and hospital characteristics.

Results

Among 184,705 patients in this registry from April 2015 to December 2020, 59,922 patients were included in the analysis. Most patients (94.0%) with a PAC in place had cardiovascular disease. There was a wide variation in the frequency of PAC use between hospitals, from 0 to 60.3% (median 14.4%, interquartile range 2.2–28.6%). Hospital mortality was not significantly different between the PAC use group and the non-PAC use group in patients after adjustment for propensity score analysis (3.9% vs 4.3%; difference, − 0.4%; 95% CI − 1.1 to 0.3; p = 0.32). Among patients with cardiac disease, those with post-open-heart surgery and those in shock, hospital mortality was also not significantly different between the two groups (3.4% vs 3.7%, p = 0.45, 1.7% vs 1.7%, p = 0.93, 4.8% vs 4.9%, p = 0.87).

Conclusions

The frequency of PAC use varied among hospitals. PAC use for ICU patients was not associated with lower hospital mortality after adjusting for differences between hospitals.
The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial
Authors: Vestager Maria Linander , Hansen Mathias Lühr , Rasmussen Marie Isabel , Hahn Gitte Holst , Hyttel-Sørensen Simon , Pellicer Adelina , Heuchan Anne Marie , Hagmann Cornelia , Dempsey Eugene , Dimitriou Gabriel , Pichler Gerhard , Naulaers Gunnar , Fuchs Hans , Tkaczyk Jakub , Mintzer Jonathan , Fumagalli Monica , Nesargi Saudamini , Fredly Siv , Szczapa Tomasz , Gluud Christian , Jakobsen Janus Christian , Greisen Gorm
Published: October 2023

Background

The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants’ lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns.

Methods/design

SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery.

A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children’s Abilities-Revised (PARCA-R) at 2 years of corrected age.

Discussion

There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns.

Trial registration

The protocol is registered at www.clinicaltrials.gov (NCT05907317; registered 18 June 2023).
Polymorphism of virulence genes and biofilm associated with in vitro induced resistance to clarithromycin in Helicobacter pylori
Authors: Rosli Naim Asyraf , Al-Maleki Anis Rageh , Loke Mun Fai , Chua Eng Guan , Alhoot Mohammed Abdelfatah , Vadivelu Jamuna
Published: October 2023

Background

Clarithromycin-containing triple therapy is commonly used to treat Helicobacter pylori infections. Clarithromycin resistance is the leading cause of H. pylori treatment failure. Understanding the specific mutations that occur in H. pylori strains that have evolved antibiotic resistance can help create a more effective and individualised antibiotic treatment plan. However, little is understood about the genetic reprogramming linked to clarithromycin exposure and the emergence of antibiotic resistance in H. pylori. Therefore, this study aims to identify compensatory mutations and biofilm formation associated with the development of clarithromycin resistance in H. pylori. Clarithromycin-sensitive H. pylori clinical isolates were induced to develop clarithromycin resistance through in vitro exposure to incrementally increasing concentration of the antibiotic. The genomes of the origin sensitive isolates (S), isogenic breakpoint (B), and resistant isolates (R) were sequenced. Single nucleotide variations (SNVs), and insertions or deletions (InDels) associated with the development of clarithromycin resistance were identified. Growth and biofilm production were also assessed.

Results

The S isolates with A2143G mutation in the 23S rRNA gene were successfully induced to be resistant. According to the data, antibiotic exposure may alter the expression of certain genes, including those that code for the Cag4/Cag protein, the vacuolating cytotoxin domain-containing protein, the sel1 repeat family protein, and the rsmh gene, which may increase the risk of developing and enhances virulence in H. pylori. Enhanced biofilm formation was detected among R isolates compared to B and S isolates. Furthermore, high polymorphism was also detected among the genes associated with biofilm production.

Conclusions

Therefore, this study suggests that H. pylori may acquire virulence factors while also developing antibiotic resistance due to clarithromycin exposure.
Exploring the impact of professional soccer substitute players on physical and technical performance
Authors: Pan Pengyu , Li Fangbin , Han Bo , Yuan Bo , Liu Tianbiao
Published: October 2023

Background

Substitutions are generally used to promote the match performance of the whole team. This study aimed to analyze the performance of substitute players and explore the performance difference among substitute players, completed players, and replaced players across each position.

Methods

Chinese Super Soccer League (CSL) matches in the season 2018 including 5871 individual observation from 395 professional soccer players were analyzed by establishing linear mixed models to quantify the performance difference among substitute players (SP) (n = 1,071), entire match players (EMP) (n = 3,454), and replaced players (RP) (n = 1,346), and then separately for each position (central defenders, fullbacks, central midfielders, wide midfielders, and attackers).

Results

The results show SP display higher high intensity distance and sprint distance significantly (p < 0.05) relative to playing time than RP and EMP. SP in offensive positions (attackers, wide midfielders) showed significantly higher (p < 0.05) passing and organizing performance such as passes, ball control, short passes, and long passes than RP or EMP. The scoring performances of central midfielders of SP including goals, shots, and shots on target are significantly higher (p < 0.05) than RP or EMP. Central defenders of SP showed higher shot blocks and pass blocks (p < 0.05) while lower passing and organizing performance (p < 0.05).

Conclusion

Depending on different playing positions, substitute players could indeed improve physical and technical performance related to scoring, passing, and defending as offensive substitute players can boost organizing performance and substitute defenders enhance defending performance. These could help coaches better understand substitute players’ influence on match performance and optimize the substitution tactic.
Increased binding of anti-dsDNA antibodies to short oligonucleotides modified with topoisomerase I reveals a potential new enzyme function independent from DNA relaxation
Authors: Frese-Schaper Manuela , Voll Reinhard E. , Frese Steffen
Published: October 2023

Objective

Topoisomerase I (topo I) is a highly conserved enzyme which is known to reduce torsional stress at double-stranded (ds) DNA. Torsional stress induced by supercoiling of dsDNA requires either very long dsDNA existing in genomic DNA or circulation as presented in plasmid DNA. To enable DNA relaxation, topo I induce a transient single-strand break followed by stress-relieving rotation of the released DNA strand. Our group found by serendipity that the topo I inhibitor irinotecan is able to suppress murine systemic lupus erythematosus (SLE), an autoimmune disease which is characterized by the existence of pathogenic anti-dsDNA antibodies (abs). As a possible mechanism we demonstrated in the absence of immunosuppression an increased binding of anti-dsDNA abs to long genomic or circulated plasmid dsDNA modified with topo I.

Results

Here we show that this effect requires active site tyrosine of topo I which is known to facilitate DNA relaxation activity. Moreover, topo I enhanced anti-dsDNA abs binding to short linear oligonucleotides down to a size of 42 bp. Since oligonucleotides of such length are devoid of torsional stress and relaxation respectively, our results suggest a new and unknown function for the enzyme topo I.
Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum
Authors: Goossens Julie , Cervantes González Alba , Dewit Nele , Lidón Laia , Fortea Juan , Alcolea Daniel , Lleó Alberto , Belbin Olivia , Vanmechelen Eugeen
Published: October 2023

Background

Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer’s disease (AD). Vesicle-associated membrane protein 2 (VAMP-2) has emerged as a promising biomarker of AD-related synapse degeneration in cerebrospinal fluid (CSF). The aim of this study was to explore the CSF profile of VAMP-2 across the AD continuum in relation to core AD biomarkers, other synaptic proteins, neurogranin (Ng) and synaptosomal-associated Protein-25 kDa (SNAP-25) and cognitive performance.

Methods

We developed a digital immunoassay on the Single Molecule Array platform to quantify VAMP-2 in CSF and used existing immunoassays to quantify Ng, SNAP-25 and core CSF AD biomarkers. The clinical study included 62 cognitively unimpaired AD biomarker-negative subjects and 152 participants across the AD continuum from the SPIN cohort (Sant Pau Initiative on Neurodegeneration). Cognitive measures of episodic, semantic, executive and visuospatial domains and global cognition were included. Statistical methods included χ2 tests, spearman correlation, and ANCOVA analyses.

Results

The VAMP-2 assay had a good analytical performance (repeatability 8.9%, intermediate precision 10.3%). Assay antibodies detected native VAMP-2 protein in human brain homogenates. CSF concentrations of VAMP-2, neurogranin and SNAP-25 were lower in preclinical AD stage 1 compared to controls and higher at later AD stages compared to AD stage 1 and were associated with core AD biomarkers, particularly total tau (adj. r2 = 0.62 to 0.78, p < 0.001). All three synaptic proteins were associated with all cognitive domains in individuals on the AD continuum (adj. r2 = 0.04 to 0.19, p < 0.05).

Conclusions

Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.