bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does respiratory variation in inferior vena cava diameter predict fluid responsiveness in adult patients? A systematic review and meta-analysis of diagnostic accuracy studies
Authors: Unal Akoglu Ebru , Akoglu Haldun 
Published: July 2021

Objectives: To systematically review the diagnostic utility of the respiratory variation of the inferior vena cava diameter measured using ultrasonography for predicting fluid responsiveness in adult patients and compare the three commonly used equations, inferior vena cava distensibility, inferior vena cava collapsibility and inferior vena cava variability. Methods: We searched PubMed, Scopus, Web of Science and Cochrane library, and included studies investigating the diagnostic accuracy of the respiratory variation of the inferior vena cava measured using ultrasonography compared to a reference standard for measuring cardiac output after a fluid challenge for fluid responsiveness, and stratified participants as fluid responsive or not. We included studies conducted in the emergency department or intensive care unit. We excluded studies on paediatric, prehospital, cancer, pregnant, dialysis patients or healthy volunteers. Results: We retrieved 270 records and excluded 171 because of irrelevance, patient population or publication type. We screened the abstracts of 99 studies and then the full texts of 42 studies. Overall, 21 studies with 1321 patients were included, of whom 689 (52%) were fluid responsive. The mean threshold value for positive inferior vena cava distensibility, inferior vena cava collapsibility and inferior vena cava variability was 17%, 35% and 12%, respectively. The heterogeneity between studies was high. Bivariate diagnostic random-effects meta-analysis was used to calculate the summary receiver operating characteristics curves. The overall accuracy, sensitivity and specificity of respiratory variation of the inferior vena cava diameter were 0.85, 0.72 and 0.81, respectively. The accuracy of inferior vena cava distensibility and inferior vena cava collapsibility was similar. The diagnostic utility of respiratory variation of the inferior vena cava diameter was lower but not statistically significant in mechanically ventilated patients compared with spontaneous breathing for predicting fluid responsiveness. Conclusion: The respiratory variation of the inferior vena cava diameter has moderate diagnostic utility for predicting fluid responsiveness independent of the equation used.
Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: a multicenter retrospective study
Authors: Zhao Yannan , Xie Ning , Li Wei , Chen Wenyan , Lv Zheng , Zheng Yabing , Sun Tao , Liu Jieqiong , Zhang Jian , Hu Shihui , Wang Yajun , Gong Chengcheng , Li Yi , Xie Yizhao , Ge Rui , Xu Fei , Wang Biyun 
Published: July 2021

Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Patients and Methods: A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis ( p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusion: Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.
Shockwave Treatment Enhanced Extracellular Matrix Production in Articular Chondrocytes Through Activation of the ROS/MAPK/Nrf2 Signaling Pathway
Authors: Shen Po-Chih , Chou Shih-Hsiang , Lu Cheng-Chang , Huang Hsuan-Ti , Chien Song-Hsiung , Huang Peng-Ju , Liu Zi-Miao , Shih Chia-Lung , Su Shu-Jem , Chen Li-Min , Tien Yin-Chun 
Published: July 2021

Objective Shockwave application is a potential treatment for osteoarthritis (OA), but the underlying mechanism remains unknown. Oxidative stress and a counterbalancing antioxidant system might be the key to understanding this mechanism. We hypothesized that reactive oxygen species (ROS) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2),which is an important regulator of cellular redox homeostasis, are plausible elements. Design Porcine chondrocytes were cultured in a 3-dimensional pellet model and subjected to shockwaves. The effects of shockwaves with various energy-flux densities on optimal extracellular matrix (ECM) synthesis were assessed. ROS, mitogen-activated protein kinase (MAPK) signaling, and the redox activity of Nrf2 were measured. To investigate the signaling mechanism involved in the shockwave treatment in chondrocytes, specific inhibitors of ROS, MAPK signaling, and Nrf2 activity were targeted. Results Shockwaves increased ECM synthesis without affecting cell viability or proliferation. Furthermore, they induced transient ROS production mainly through xanthine oxidase. The phosphorylation of ERK1/2 and p38 and the nuclear translocation of Nrf2 were activated by shockwaves. By contrast, suppression of ROS signaling mitigated shockwave-induced MAPK phosphorylation, Nrf2 nuclear translocation, and ECM synthesis. Pretreatment of chondrocytes with the specific inhibitors of MEK1/2 and p38, respectively, mitigated the shockwave-induced nuclear translocation of Nrf2 and ECM synthesis. Nrf2 inhibition by both small hairpin RNA knockdown and brusatol reduced the shockwave-enhanced ECM synthesis. Conclusions Shockwaves activated Nrf2 activity through the induction of transient ROS signaling and subsequently enhanced ECM synthesis in chondrocytes. This study provided fundamental evidence confirming the potential of shockwaves for OA management.
ASSERT (Acute Sacral inSufficiEncy fractuRe augmenTation): Perceptions in the Assessment and Treatment of Pubic Rami and Sacral Fragility Fractures Amongst Healthcare Professionals in Geriatric Medicine and Surgery—A Qualitative Study
Authors: Sahota Opinder , Leighton Paul , Cameron Maribel , Taylor Rachael , Ong Terence , Drummond Avril , Hendrick Paul , Quraishi Nasir , Salem Khalid ,   On Behalf of the ASSERT Research Team
Published: July 2021

Background: Pubic rami fragility fractures are common in older people and result in significant morbidity and increased mortality. Co-existing fractures of the sacrum are common, but routinely missed. The aim of the study was to explore the perceptions in the assessment and treatment of pubic rami and sacral fragility fractures amongst healthcare professionals. Methods: We interviewed 14 participants about their experience in the assessment and treatment of patients presenting with pubic rami fragility fractures. Data was analyzed using an inductive thematic approach. Results: The majority of patients presenting with a pubic rami fragility fracture were managed by geriatricians. However, many of the geriatricians were not aware that these fractures have a high association with co-existing sacral fragility fractures. Furthermore, they were not aware of the limitations of standard x-ray imaging, nor of the potential benefits of surgical intervention for sacral fragility fractures. Spinal surgeons recommended that early, more specialist imaging in patients with pubic rami fragility fractures failing to mobilize, would change clinical management, if found to have a coexisting sacral fragility fracture, amenable to surgical intervention. Conclusions: The awareness, assessment and management of sacral fragility fractures in patients presenting with pubic rami fragility fractures is poor amongst healthcare professionals in geriatric medicine. Spinal surgeons in this study advocate early further imaging and surgical intervention in patients confirmed to have a concomitant sacral fragility fracture who are failing to mobilize.
Pangenome analysis and virulence profiling of Streptococcus intermedius
Authors: Sinha Dhiraj , Sun Xifeng , Khare Mudra , Drancourt Michel , Raoult Didier , Fournier Pierre-Edouard 
Published: July 2021

Abstract
Background
Streptococcus intermedius, a member of the S. anginosus group, is a commensal bacterium present in the normal microbiota of human mucosal surfaces of the oral, gastrointestinal, and urogenital tracts. However, it has been associated with various infections such as liver and brain abscesses, bacteremia, osteo-articular infections, and endocarditis. Since 2005, high throughput genome sequencing methods enabled understanding the genetic landscape and diversity of bacteria as well as their pathogenic role. Here, in order to determine whether specific virulence genes could be related to specific clinical manifestations, we compared the genomes from 27 S. intermedius strains isolated from patients with various types of infections, including 13 that were sequenced in our institute and 14 available in GenBank.

Results
We estimated the theoretical pangenome size to be of 4,020 genes, including 1,355 core genes, 1,054 strain-specific genes and 1,611 accessory genes shared by 2 or more strains. The pangenome analysis demonstrated that the genomic diversity of S. intermedius represents an “open” pangenome model. We identified a core virulome of 70 genes and 78 unique virulence markers. The phylogenetic clusters based upon core-genome sequences and SNPs were independent from disease types and sample sources. However, using Principal Component analysis based on presence/ absence of virulence genes, we identified the sda histidine kinase, adhesion protein LAP and capsular polysaccharide biosynthesis protein cps4E as being associated to brain abscess or broncho-pulmonary infection. In contrast, liver and abdominal abscess were associated to presence of the fibronectin binding protein fbp54 and capsular polysaccharide biosynthesis protein cap8D and cpsB.

Conclusions
Based on the virulence gene content of 27 S. intermedius strains causing various diseases, we identified putative disease-specific genetic profiles discriminating those causing brain abscess or broncho-pulmonary infection from those causing liver and abdominal abscess. These results provide an insight into S. intermedius pathogenesis and highlights putative targets in a diagnostic perspective.
Development of a liquid biopsy based purely quantitative digital droplet PCR assay for detection of MLH1 promoter methylation in colorectal cancer patients
Authors: Wang Danyi , O’Rourke Dennis , Sanchez-Garcia Jorge F. , Cai Ti , Scheuenpflug Juergen , Feng Zheng 
Published: July 2021

Abstract
Background
MutL Homolog 1 (MLH1) promotor methylation is associated with microsatellite instability high colorectal cancer (CRC). The strong correlation between methylation status and cancer development and progression has led to a growing interest in the use of methylation markers in circulating tumor DNA (ctDNA) for early cancer detection and longitudinal monitoring. As cancer-specific DNA methylation changes in body fluids are limited, it is particularly challenging to develop clinically applicable liquid biopsy methodologies with high sensitivity and specificity. The purpose of this study was to develop a fit-for-purpose methylation sensitive restriction enzyme (MSRE) based digital droplet PCR (ddPCR) assay to examine MLH1 promoter methylation in ctDNA in advanced CRC.

Methods
Primers and probes were designed to amplify CpG sites of the MLH1 promoter. Methylated and unmethylated control genomic DNA were sheared to mimic ctDNA and subjected to MSRE HpaII digestion. Plasma samples from 20 healthy donors and 28 CRC patients were analyzed with the optimized MSRE procedure using ddPCR.

Results
Using methylated and unmethylated controls, we optimized the conditions for HpaII enzyme digestion to ensure complete digestion and avoid false positives. Based on the results from the ddPCR assay using 1 ng circulating cell-free DNA (cfDNA) input from healthy donors or CRC samples, ROC curves were generated with an area under the curve (AUC) value of 0.965 (95% CI: 0.94, 0.99). The statistically optimal assay sensitivity and specificity was achieved when 8 positive droplets were used as acceptance criteria (78% sensitivity and 100% specificity, 95% CI: 0.45, 0.95). A tiered-based cutoff (20, 50, 80% percentile based) was applied to distinguish CRC samples with different methylation level.

Conclusions
Our study demonstrated that the liquid biopsy assay for MLH1 promoter methylation detection using purely quantitative ddPCR is a simple and highly sensitive procedure that provides reliable methylation detection in ctDNA. The MSRE ddPCR approach can also be applied to other genes of interest where methylation patterns could reveal clinically relevant information for future clinical biomarker and/or companion diagnostic development.
Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)
Authors: Nakayama Takahiro , Yoshinami Tetsuhiro , Yasojima Hiroyuki , Kittaka Nobuyoshi , Takahashi Masato , Ohtani Shoichiro , Kim Seung Jin , Kurakami Hiroyuki , Yamamoto Naoko , Yamada Tomomi , Takata Takehiko , Masuda Norikazu 
Published: July 2021

Abstract
Background
Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer.

Methods
In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken.

Results
Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months.

Conclusions
In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings.

Trial registration
UMIN000038296; registered on 15 October 2019.
Laboratory evaluation of the potential masking of color changes produced by silver diamine fluoride in primary molars
Authors: Hamdy Dina , Giraki Maria , Abd Elaziz Amr , Badran Amira , Allam Gehan , Ruettermann Stefan 
Published: July 2021

Abstract
Background
The importance of Silver diamine fluoride (SDF) as a minimally invasive and nonaerosolizing management during COVID-19 pandemic has highly increased. SDF is a caries-arresting agent that causes staining of tooth structure. Managing this discoloration will increase its acceptance in treating primary teeth. The main aim of this study was to quantify the color change associated with the application of SDF on extracted carious primary molars, the potential masking of this color change by potassium iodide (KI), composite (CMP) and glass ionomer cement (GI) and the effect of aging on this color masking effect.

Methods
An in-vitro study in which 52 carious primary molars were collected, prepared, and distributed randomly into four groups equally as follows: Group A: SDF 38%; Group B: SDF 38% + KI; Group C: SDF 38% + CMP; Group D: SDF 38% + GI. Color changes were recorded for each sample at baseline, and after application of the tested materials. Moreover, all samples had undergone Suntest aging followed by a third color reading. CIELAB values L*, a*, b*, ΔL, Δa, and Δb were measured, ΔE was calculated, and data were analyzed using multivariate analysis of variance (MANOVA) and post-Hoc Scheffé test (p < 0.05).

Results
MANOVA revealed the significant influence of the factor ‘material’. SDF caused an obvious color change compared to the color of carious dentin. Regarding ΔL, the color change of groups C and D was not significant directly after application of the tested materials. After aging, it was significant among all groups, including groups C and D. In Δa there was a difference between SDF and groups B and C after application of the tested materials, and aging produced the same results. The color shifts of Δb of all tested groups varied significantly from one another. After aging, there was no difference between group D and either group A or B.

Conclusions
Treatment with SDF caused obvious discoloration of carious dentin. Directly after SDF application, all tested materials could effectively mask the color change associated with the application of SDF. CMP was the only material whose color masking effect was not completely reversed by aging.
The effect of fascia iliaca block on postoperative pain and analgesic consumption for patients undergoing primary total hip arthroplasty: a meta-analysis of randomized controlled trials
Authors: Dai Wenli , Leng Xi , Hu Xiaoqing , Cheng Jin , Ao Yingfang 
Published: July 2021

Abstract
Background
The primary aim of this systematic review and meta-analysis was to compare postoperative pain, analgesic consumption, and complications after fascia iliaca block (FIB) versus control for patients undergoing primary total hip arthroplasty (THA). Second, we compared the outcomes of FIB versus placebo. Finally, we sought to evaluate pain and analgesic consumption after preoperative and postoperative FIB.

Methods
We performed a systematic literature search in MEDLINE, Embase, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and CENTRAL through February 2021 to identify randomized controlled trials (RCTs) that evaluated the efficacy of FIB versus control for patients undergoing primary THA. All analyses were conducted on intent-to-treat data with a random-effects model.

Results
Twelve RCTs with a total of 815 patients were included. There was no difference in postoperative pain (P = 0.64), analgesic consumption (P = 0.14), or complication rate (P = 0.99) between FIB and control groups. Moreover, no difference in postoperative pain (P = 0.26), analgesic consumption (P = 0.06), or complication rate (P = 0.71) was found between FIB and placebo. Moreover, sensitivity analysis suggested that no significant difference in postoperative pain, analgesic consumption, or complication rate was present between FIB and control in studies that used preoperative and postoperative FIB.

Conclusion
FIB was not found to be superior to placebo or various anesthetic techniques for patients undergoing primary THA, as measured by postoperative pain, analgesic consumption, and complications.
Mechanistic insights into the inhibitory effect of theaflavins on virulence factors production in Streptococcus mutans
Authors: Kong Junhao , Xia Kai , Su Xiaoqin , Zheng Xuan , Diao Chunhua , Yang Xiufang , Zuo Xiaobo , Xu Jun , Liang Xinle 
Published: July 2021

AbstractStreptococcus mutans is the primary etiological agent associated with cariogenic process. The present study aimed to investigate the antibacterial and anti-virulence activities of theaflavins (TFs) to Streptococcus mutans UA159 as well as the underlying mechanisms. The results showed that TFs were capable of suppressing the acid production, cell adherence, water-insoluble exopolysaccharides production, and biofilm formation by S. mutans UA159 with a dosage-dependent manner while without influencing the cell growth. By a genome-wide transcriptome analysis (RNA-seq), we found that TFs attenuated the biofilm formation of S. mutans UA159 by inhibiting glucosyltransferases activity and the production of glucan-binding proteins (GbpB and GbpC) instead of directly blocking the expression of genes coding for glucosyltransferases. Further, TFs inhibited the expression of genes implicated in peptidoglycan synthesis, glycolysis, lipid synthesis, two-component system, signaling peptide transport (comA), oxidative stress response, and DNA replication and repair, suggesting that TFs suppressed the virulence factors of S. mutans UA159 by affecting the signal transduction and cell envelope stability, and weakening the ability of cells on oxidative stress resistance. In addition, an upregulated expression of the genes involved in protein biosynthesis, amino acid metabolism, and transport system upon TFs treatment indicated that cells increase the protein synthesis and nutrients uptake as one self-protective mechanism to cope with stress caused by TFs. The results of this study increase our current understanding of the anti-virulence activity of TFs on S. mutans and provide clues for the use of TFs in the prevention of dental caries.