bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining and evaluating the Hawthorne effect in primary care, a systematic review and meta-analysis
Authors: Berkhout Christophe , Berbra Ornella , Favre Jonathan , Collins Claire , Calafiore Matthieu , Peremans Lieve , Van Royen Paul
Published: November 2022

In 2015, we conducted a randomized controlled trial (RCT) in primary care to evaluate if posters and pamphlets dispensed in general practice waiting rooms enhanced vaccination uptake for seasonal influenza. Unexpectedly, vaccination uptake rose in both arms of the RCT whereas public health data indicated a decrease. We wondered if the design of the trial had led to a Hawthorne effect (HE). Searching the literature, we noticed that the definition of the HE was unclear if stated. Our objectives were to refine a definition of the HE for primary care, to evaluate its size, and to draw consequences for primary care research. We designed a Preferred Reporting Items for Systematic reviews and Meta-Analyses review and meta-analysis between January 2012 and March 2022. We included original reports defining the HE and reports measuring it without setting limitations. Definitions of the HE were collected and summarized. Main published outcomes were extracted and measures were analyzed to evaluate odds ratios (ORs) in primary care. The search led to 180 records, reduced on review to 74 for definition and 15 for quantification. Our definition of HE is “an aware or unconscious complex behavior change in a study environment, related to the complex interaction of four biases affecting the study subjects and investigators: selection bias, commitment and congruence bias, conformity and social desirability bias and observation and measurement bias.” Its size varies in time and depends on the education and professional position of the investigators and subjects, the study environment, and the outcome. There are overlap areas between the HE, placebo effect, and regression to the mean. In binary outcomes, the overall OR of the HE computed in primary care was 1.41 (95% CI: [1.13; 1.75]; I2 = 97%), but the significance of the HE disappears in well-designed studies. We conclude that the HE results from a complex system of interacting phenomena and appears to some degree in all experimental research, but its size can considerably be reduced by refining study designs.
Blood monocyte counts as a prognostic biomarker and predictor in Chinese patients with idiopathic pulmonary fibrosis
Authors: Zhang Xinran , Ren Yanhong , Xie Bingbing , Ye Qiao , Ban Chenjun , Zhang Shu , Zhu Min , Liu Yan , Wang Shiyao , Geng Jing , He Xuan , Jiang Dingyuan , He Jiarui , Shu Shi , Luo Sa , Wang Xin , Song Dingyun , Fan Mingming , Sun Haishuang , Dai Huaping
Published: November 2022

Objectives

We sought to evaluate the prognostic value of blood routine parameters and biochemical parameters, especially inflammation-related biomarkers, and establish an inflammation-related prognostic model in Chinese patients with idiopathic pulmonary fibrosis (IPF).

Material/methods

Patients diagnosed as IPF at Beijing Chaoyang Hospital and aged 40 years and older were consecutively enrolled from June 2000 to March 2015, and finally, a total of 377 patients were enrolled in the derivation cohort. The follow-up ended in December 2016. We used Cox proportional hazard model to calculate the hazard ratio (HR) and establish the prognostic model. The discrimination and calibration of the prognostic model were evaluated in an independent validation cohort enrolled from China-Japan Friendship Hospital between January 2015 and December 2019.

Results

Multivariate analysis revealed that patients with elevated monocyte-to-red blood cell count ratio (MRR) and monocyte counts showed increased risk of mortality. The clinical-physiological-biomarker (CPB) index and CPB stage we established in this study were a significant predictor, and the C-index for CPB index and CPB stage in the validation cohort was 0.635 (95% CI: 0.558–0.712) and 0.619 (95% CI: 0.544–0.694), respectively. Patients in CPB stage III had the poorest survival.

Conclusion

We developed and validated a new inflammation-related prognostic model (CPB index and CPB stage) which was integration of age, gender, FVC (%, predicted), DLCO (%, predicted), Charlson Comorbidity Index, and blood monocyte counts. This prediction model exhibited strong ability in predicting mortality in Chinese patients with IPF.
Developing a competing risk nomogram that predicts the survival of patients with a primary hepatic neuroendocrine tumor
Authors: Lin Jianyang , Li Xiang , Ding Xin , Chen Zhihong , Wu Yinyan , Zhao Kun
Published: November 2022

Primary hepatic neuroendocrine tumor (PHNET) is rare liver cancer and related prognostic factors are unclear. The aim of this study was to analyze the prognostic risk factors of patients with PHNETs and establish an assessment model for prognosis. The clinical information of 539 patients with PHNETs who met the criteria for inclusion was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly assigned to the training (269 cases) and validation sets (270 cases). Prognostic factors in patients with PHNETs were screened using the Cox proportional regression model and Fine–Gray competing risk model. Based on the training set analysis using the Fine–Gray competing risk model, a nomogram was constructed to predict cumulative probabilities for PHNET-specific death. The performance of the nomogram was measured by using receiver operating characteristic curves, the concordance index (C-index), calibration curves, and decision curve analysis (DCA). No differences in clinical baseline characteristics between the training and validation sets were observed, and the Fine–Gray analysis showed that surgery and more than one primary malignancy were associated with a low cumulative probability of PHNET-specific death. The training set nomograms were well-calibrated and had good discriminative ability, and good agreement between predicted and observed survival was observed. Patients with PHNETs with a high-risk score had a significantly increased risk of PHNET-specific death and non-PHNET death. Surgical treatment and the number of primary malignancies were found to be independent protective factors for PHNETs. The competing risk nomogram has high accuracy in predicting disease-specific survival (DSS) for patients with PHNETs, which may help clinicians to develop individualized treatment strategies.
Whole-genome sequence of the filamentous diazotrophic cyanobacterium Tolypothrix sp. PCC 7712 and its comparison with non-diazotrophic Tolypothrix sp. PCC 7601
Authors: Bozan Mahir , Popp Denny , Kallies Rene , da Rocha Ulisses Nunes , Klähn Stephan , Bühler Katja
Published: November 2022

Cyanobacteria are highly promising microorganisms in forthcoming biotechnologies. Besides the systematic development of molecular tools for genetic engineering, the design of chassis strains and novel reactor concepts are in focus. The latter includes capillary biofilm reactors (CBR), which offer a high surface area-to-volume ratio and very high cell densities. In this context, Tolypothrix sp. PCC 7712 was found to be highly suited for this reactor system due to maximal surface coverage, extraordinarily strong biofilm attachment, and high biomass formation. Here, we provide the genome sequence of Tolypothrix sp. PCC 7712 to potentially allow targeted strain engineering. Surprisingly, it was almost identical to an available incomplete genome draft of Tolypothrix sp. PCC 7601. Thus, we completely sequenced this strain as well and compared it in detail to strain PCC 7712. Comparative genome analysis revealed 257 and 80 unique protein-coding sequences for strains PCC 7601 and PCC 7712, respectively. Clustering genomes based on average nucleotide identity (ANI) and 16S rRNA homology showed 99.98% similarity and only minor distance, respectively, between the two strains in contrast to 21 other cyanobacterial genomes. Despite these high similarities, both strains differ in the ability to fix atmospheric nitrogen and show specific sequence variations, which are discussed in the paper.
Enrichment of antibiotic resistance genes within bacteriophage populations in saliva samples from individuals undergoing oral antibiotic treatments
Authors: Andersson Tilde , Makenga Geofrey , Francis Filbert , Minja Daniel T. R. , Overballe-Petersen Soren , Tang Man-Hung Eric , Fuursted Kurt , Baraka Vito , Lood Rolf
Published: November 2022

Spread of antibiotic resistance is a significant challenge for our modern health care system, and even more so in developing countries with higher prevalence of both infections and resistant bacteria. Faulty usage of antibiotics has been pinpointed as a driving factor in spread of resistant bacteria through selective pressure. However, horizontal gene transfer mediated through bacteriophages may also play an important role in this spread. In a cohort of Tanzanian patients suffering from bacterial infections, we demonstrate significant differences in the oral microbial diversity between infected and non-infected individuals, as well as before and after oral antibiotics treatment. Further, the resistome carried both by bacteria and bacteriophages vary significantly, with blaCTX-M1 resistance genes being mobilized and enriched within phage populations. This may impact how we consider spread of resistance in a biological context, as well in terms of treatment regimes.
A new method for the rapid detection of the antibacterial and bacteriostatic activity of disinfectants based on Propidium Monoazide combined with real-time PCR
Authors: Liu Yanrong , Huang Shuting , Zhou Jungui , Zhang Chi , Hu Feijie , Xiao Youyu , Qiu Haopu , Yang Yao
Published: November 2022

Rapid detection of antibacterial and bacteriostatic properties is an important part of the quality and safety supervision of disinfectants. In this study, propidium monoazide (PMA) was used in combination with real-time PCR (PMA-qPCR) to detect the antibacterial and bacteriostatic activity of disinfectants against three commonly used indicator bacteria, Escherichia coli, Staphylococcus aureus, and Candida albicans, utilizing specifically designed primers. The method for preparing membrane-damaged bacteria was optimized to improve the ability of the PMA dye to distinguish between live and dead indicator bacteria. Finally, this method could simultaneously detect viable numbers of the indicator bacteria after the disinfectants were used. The R2 values of the PMA-qPCR standard curves were 0.9986, 0.9980, and 0.9962 for E. coli, S. aureus, and C. albicans, respectively, and the detection range was 103 ~ 106 CFU/ml, showing no significant difference in accuracy compared to that of the plate counting method (p > 0.05). The method established here is the first application of PMA-qPCR to detect the antibacterial and bacteriostatic activity of disinfectants. This technique markedly simplifies the detection steps of antibacterial and bacteriostatic activity, reduces the detection time (3 h compared to 48 ~ 72 h for the plate counting method), improves the quality supervision efficiency of disinfectants, and guarantees healthy and safe lives.
Framework for field-scale application of molecular biological tools to support natural and enhanced bioremediation
Authors: Key Trent A. , Sorsby Skyler J. , Wang Yingnan , Madison Andrew S.
Published: November 2022

Microorganisms naturally present at environmental contaminated sites are capable of biodegrading, biotransforming, or removing contaminants in soil and groundwater through bioremediation processes. Cleanup strategies and goals for site remediation can be effectively achieved by bioremediation leveraging the capabilities of microorganisms to biotransform contaminants into lesser or non-toxic end products; however, reproducible success can be limited by inadequate design or performance monitoring. A group of biological analyses collectively termed molecular biological tools (MBTs) can be used to assess the contaminant-degrading capabilities and activities of microorganisms present in the environment and appropriately implement bioremediation approaches. While successful bioremediation has been demonstrated through previously described lab-scale studies and field-scale implementation for a variety of environmental contaminants, design and performance monitoring of bioremediation has often been limited to inferring biodegradation potential, occurrence, and pathways based on site geochemistry or lab-scale studies. Potential field-scale application of MBTs presents the opportunity to more precisely design and monitor site-specific bioremediation approaches. To promote standardization and successful implementation of bioremediation, a framework for field-scale application of MBTs within a multiple lines of evidence (MLOE) approach is presented. The framework consists of three stages: (i) “Assessment” to evaluate naturally occurring biogeochemical conditions and screen for potential applicability of bioremediation, (ii) “Design” to define a site-specific bioremediation approach and inform amendment selection, and (iii) “Performance Monitoring” to generate data to measure or infer bioremediation progress following implementation. This framework is introduced to synthesize the complexities of environmental microbiology and guide field-scale application of MBTs to assess bioremediation potential and inform site decision-making.
The effectiveness and safety of repetitive transcranial magnetic stimulation on spasticity after upper motor neuron injury: A systematic review and meta-analysis
Authors: Fan Jin , Fu Hui , Xie Xiaolong , Zhong Dongling , Li Yuxi , Liu Xiaobo , Zhang Huiling , Zhang Jun , Huang Jiaxi , Li Juan , Jin Rongjiang , Zheng Zhong
Published: November 2022

To systematically evaluate the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) on spasticity after upper motor neuron (UMN) injury. Eight electronic databases were searched from inception to August 6, 2022. Randomized controlled trials (RCTs) investigating the effectiveness and safety of rTMS on spasticity after UMN injury were retrieved. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. Review Manager 5.3 and Stata 14.0 software were used to synthesize data. The certainty of the evidence was appraised with the Grade of Recommendation, Assessment, Development and Evaluation tool. Forty-two studies with a total of 2,108 patients were included. The results of meta-analysis revealed that, compared with control group, rTMS could significantly decrease scores of the Modified Ashworth Scale (MAS) in patients with UMN injury. The subgroup analysis discovered that rTMS effectively decreased the MAS scores in patients with stroke. Meanwhile, rTMS treatment > 10 sessions has better effect and rTMS could decrease the MAS scores of upper limb. Thirty-three patients complained of twitching facial muscles, headache and dizziness, etc. In summary, rTMS could be recommended as an effective and safe therapy to relieve spasticity in patients with UMN injury. However, due to high heterogeneity and limited RCTs, this conclusion should be treated with caution.
Flexor carpi radialis H-reflex in different body positions in patients with post-stroke
Authors: Ma Jia-Yin , Wu Jia-Jia , Zheng Mou-Xiong , Hua Xu-Yun , Shan Chun-Lei , Xu Jian-Guang
Published: November 2022

Background

Spinal stretch reflex (SSR) hyperexcitability reflected by the H-reflex has been reported in more strongly affected extremities after stroke. The H-reflex in the lower extremities is modulated by body position normally and alternatively modulated post-stroke.

Objective

This study aimed to preliminarily explore how upper extremity (UE) H-reflexes are modulated by body position after stroke, which remains unknown.

Materials and methods

Three patients after stroke with hemiparesis/hemiplegia were included. Bilateral flexor carpi radialis (FCR) H-reflexes were examined in the supine position while standing. Other clinical evaluations include the modified Ashworth scale (MAS) and postural stability measurement.

Results

The three cases herein showed that (1) SSR excitability was higher in more strongly affected UEs than less-affected UEs, (2) down-modulation of SSR excitability occurred in less-affected UEs in static standing compared with the supine position, but modulation of SSR excitability in more-affected UEs varied, and (3) bilateral UE SSR excitability in case 3 was down-modulated the most. Moreover, case 3 showed no difference in muscle tone of the more affected UE between supine and standing positions, and case 3 showed the best postural stability.

Conclusion

Spinal stretch reflex hyperexcitability in strongly affected UEs could commonly occur in different phases of recovery after stroke. Down-modulation of SSR excitability could occur in less-affected UEs in the standing position compared with the supine position, while modulation of SSR excitability might be altered in strongly affected UEs and vary in different phases of recovery. There could be some correlation between postural control and UE SSR hyperexcitability. The H-reflex may help to offer a new perspective on rehabilitation evaluation and interventions to promote UE motor control after stroke.
The prevalence and clinical significance of intracranial vertebral artery terminated in posterior inferior cerebellar artery: A multicenter hospital-based study in China
Authors: Zhu Juehua , Huang Ruiyun , Ye Kaiwen , Chen Hongbing , Dai Zheng , Jiang Yongjun
Published: November 2022

Objective

Intracranial vertebral artery terminated in the posterior inferior cerebellar artery (PICA-VA) is the most popular variant of the posterior inferior cerebellar artery, while its prevalence and clinical significance remained unclear. In the present study, we aimed to investigate the prevalence and clinical significance of PICA-VA.

Methods

This was a multicenter hospital-based cross-sectional study. Patients were enrolled for cerebral MRI and MRA within 1 week of stroke onset. Clinical characteristics were recorded. PICA-VA is termed as a vertebral artery that does not communicate with the basilar artery but terminates in an ipsilateral PICA. We observed the prevalence of PICA-VA and identified a relationship between PICA-VA and vertebrobasilar stroke.

Results

From 1 August 2015 to 31 May 2017, a total of 2,528 patients were enrolled in the present study. Among them, 95 patients (3.76%, 95/2,528) had the variation of PICA-VA, 51 of which (53.7%) were located on the right side. The prevalence of vertebrobasilar stroke was considerably higher in patients with PICA-VA than those without (40.2%, 37/92 vs. 17.1%, 417/2,436, p < 0.01). PICA-VA was an independent risk for vertebrobasilar stroke after being adjusted for a history of intracranial hemorrhage, diabetes, body mass index, and triglyceride.

Conclusion

The present study showed that 3.76% of patients with acute stroke had PICA-VA, which independently increased the risk of acute vertebrobasilar stroke.
Effects of stent-assisted coiling in comparison with flow diversion on intracranial aneurysms
Authors: Guo Hao , Liu Jian-Feng , Li Cong-Hui , Wang Ji-Wei , Li Hui , Gao Bu-Lang
Published: November 2022

Objective

The aim of this study was to investigate the efficacy and complications of stent-assisted coiling in comparison with flow diversion for wide-necked intracranial aneurysms.

Methods

Patients with wide-necked intracranial aneurysms who were treated with stent-assisted coiling or flow diversion were respectively, enrolled into the stent-assisted coiling or flow diversion treatment group. The clinical and angiographic data were analyzed.

Results

A total of 61 patients with intracranial aneurysms underwent stent-assisted coiling, including 35 (57.4%) female and 26 (42.6%) male patients with 21 (34.4%) ruptured and 40 (65.6%) unruptured aneurysms. Also, 53 patients underwent deployment of flow-diverting devices, including 30 (56.6%) female and 23 (43.4%) male patients with 25 (47.2%) ruptured and 28 (52.8%) unruptured aneurysms. Stent-assisted coiling was performed successfully in 60 patients with 63 stents deployed, and immediate aneurysm occlusion was complete occlusion in 38 (62.3%) aneurysms, residual neck in 12 (19.7%), and residual aneurysm in 10 (16.4%). Procedure-related complications included in-stent thrombosis in three (4.9%) patients, coil protrusion in three (4.9%), and re-rupture of one (1.6%) aneurysm, with a total complication rate of 11.5%. In the flow diversion group, a pipeline embolization device alone was deployed in each of the 24 (45.3%) patients, adjunctive coiling combined with a pipeline device in 29 (54.7%), and double pipeline devices in each of the 6 (11.3%) patients. Immediately after treatment, complete occlusion was achieved in 3 (5.7%) patients with adjunctive coiling, residual neck in 3 (5.7%), and residual aneurysm in 47 (88.7%). Procedure-related complications included aneurysm rebleeding in one patient (1.9%). Clinical and angiographic follow-up was performed 13–49 months (median 29) after the procedure for 49 (80.3%) patients with stent-assisted coiling, with complete aneurysm occlusion in 27 (55.1%) aneurysms, residual neck in 3 (6.1%), residual aneurysm in 5 (10.2%), and recurrence in 14 (28.6%). Follow-up was performed for 14–37 (median 25) months in 45 (84.9%) patients with flow diversion treatment, with complete occlusion in 39 (86.7%) patients, residual neck in 5 (11.1%), residual aneurysm in 1 (2.2%), and no aneurysm recurrence.

Conclusions

Stent-assisted coiling comes with more complications but fewer permanent aneurysm occlusions than flow diverters, and flow diverters are superior to stent-assisted coiling in the treatment of wide-necked intracranial aneurysms, especially in the long-term effect.
Rethinking statistical learning as a continuous dynamic stochastic process, from the motor systems perspective
Authors: Vaskevich Anna , Torres Elizabeth B.
Published: November 2022

The brain integrates streams of sensory input and builds accurate predictions, while arriving at stable percepts under disparate time scales. This stochastic process bears different unfolding dynamics for different people, yet statistical learning (SL) currently averages out, as noise, individual fluctuations in data streams registered from the brain as the person learns. We here adopt a new analytical approach that instead of averaging out fluctuations in continuous electroencephalographic (EEG)-based data streams, takes these gross data as the important signals. Our new approach reassesses how individuals dynamically learn predictive information in stable and unstable environments. We find neural correlates for two types of learners in a visuomotor task: narrow-variance learners, who retain explicit knowledge of the regularity embedded in the stimuli. They seem to use an error-correction strategy steadily present in both stable and unstable environments. This strategy can be captured by current optimization-based computational frameworks. In contrast, broad-variance learners emerge only in the unstable environment. Local analyses of the moment-by-moment fluctuations, naïve to the overall outcome, reveal an initial period of memoryless learning, well characterized by a continuous gamma process starting out exponentially distributed whereby all future events are equally probable, with high signal (mean) to noise (variance) ratio. The empirically derived continuous Gamma process smoothly converges to predictive Gaussian signatures comparable to those observed for the error-corrective mode that is captured by current optimization-driven computational models. We coin this initially seemingly purposeless stage exploratory. Globally, we examine a posteriori the fluctuations in distributions’ shapes over the empirically estimated stochastic signatures. We then confirm that the exploratory mode of those learners, free of expectation, random and memoryless, but with high signal, precedes the acquisition of the error-correction mode boasting smooth transition from exponential to symmetric distributions’ shapes. This early naïve phase of the learning process has been overlooked by current models driven by expected, predictive information and error-based learning. Our work demonstrates that (statistical) learning is a highly dynamic and stochastic process, unfolding at different time scales, and evolving distinct learning strategies on demand.
Identification of hub genes of Parkinson's disease through bioinformatics analysis
Authors: Yang Yajun , Wang Yi , Wang Ce , Xu Xinjuan , Liu Cai , Huang Xintao
Published: November 2022

Parkinson's disease (PD) is a common neurodegenerative disease, and there is still a lack of effective diagnostic and treatment methods. This study aimed to search for hub genes that might serve as diagnostic or therapeutic targets for PD. All the analysis was performed in R software. The expression profile data of PD (number: GSE7621) was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) associated with PD were screened by the “Limma” package of the R software. Key genes associated with PD were screened by the “WGCNA” package of the R software. Target genes were screened by merging the results of “Limma” and “WGCNA.” Enrichment analysis of target genes was performed by Gene Ontology (GO), Disease Ontology (DO), and Kyoto Enrichment of Genes and Genomes (KEGG). Machine learning algorithms were employed to screen for hub genes. Nomogram was constructed using the “rms” package. And the receiver operating characteristic curve (ROC) was plotted to detect and validate our prediction model sensitivity and specificity. Additional expression profile data of PD (number: GSE20141) was acquired from the GEO database to validate the nomogram. GSEA was used to determine the biological functions of the hub genes. Finally, RPL3L, PLEK2, PYCRL, CD99P1, LOC100133130, MELK, LINC01101, and DLG3-AS1 were identified as hub genes of PD. These findings can provide a new direction for the diagnosis and treatment of PD.
2′-Fucosyllactose Ameliorates Inflammatory Bowel Disease by Modulating Gut Microbiota and Promoting MUC2 Expression
Authors: Yao Qianqian , Fan Linlin , Zheng Nan , Blecker Christophe , Delcenserie Véronique , Li Huiying , Wang Jiaqi
Published: November 2022

Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2′-fucosyllactose (2′-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2′-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2′-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2′-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group (p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2′-FL group. In addition, the data revealed that 2′-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae, and Bacteroides vulgatus. PAS and immunofluorescence staining showed that 2′-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2′-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2′-FL in colon tissue. In conclusion, this study suggests that 2′-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.
The prognostic impact of preoperative body mass index changes for patients with esophageal squamous cell carcinoma who underwent esophagectomy: A large-scale long-term follow-up cohort study
Authors: Gu Yi-Min , Shang Qi-Xin , Zhang Han-Lu , Yang Yu-Shang , Wang Wen-Ping , Yuan Yong , Hu Yang , Che Guo-Wei , Chen Long-Qi
Published: November 2022

Background

This study aims to investigate the relationship between preoperative body mass index changes (ΔBMI) and prognosis in patients with esophageal squamous cell carcinoma who underwent esophagectomy.

Methods

We identified 1,883 patients with esophageal squamous cell carcinoma who underwent curative resection in our department between January 2005 and December 2013. Patients were grouped into a stable body mass index (ΔBMI = 0) group and a decreased body mass index (ΔBMI < 0) group. Risk factors for ΔBMI were assessed using logistic regression analysis. The impact of ΔBMI on survival was investigated using Kaplan–Meier curves and Cox regression. A nomogram for survival prediction was constructed and validated.

Results

The results showed that T stage (OR: 1.30, 95% CI: 1.16–1.45, P < 0.001) and N stage (OR: 1.24, 95% CI: 1.11–1.38, P < 0.001) were independent risk factors for ΔBMI. The ΔBMI < 0 group had worse overall survival than the stable body mass index group (HR: 1.25, 95% CI: 1.08–1.44, P = 0.002). When stratified by stage, ΔBMI had the greatest prognostic impact in stage I tumors (HR: 1.82, 95%: 1.05–3.15, P = 0.033). In addition, multiple comparisons showed that decreasing ΔBMI correlated with worse prognosis. The ΔBMI-based nomogram presented good predictive ability with a C-index of 0.705.

Conclusion

This study demonstrates that ΔBMI < 0 had an adverse impact on the long-term survival of patients with esophageal squamous cell carcinoma undergoing esophagectomy. These results may support further investigation of preoperative nutrition support.
The role of the endoscopic grading of gastric intestinal metaplasia in assessing gastric cancer risk: A systematic review and meta-analysis
Authors: Fang Shuangshuang , Fu Yuhan , Du Sijing , Wang Lin , Qing Xiangli , Luo Xiaoying , Song Gengqing , Yang Yang , Wei Wei
Published: November 2022

Background and aim

Patients with gastric intestinal metaplasia (IM) are at increased risk of gastric cancer (GC). The endoscopic grading of gastric intestinal metaplasia (EGGIM) with high-definition endoscopes has shown the potential to facilitate GC risk stratification. However, a comprehensive review and meta-analysis of published articles are lacking. We conducted a meta-analysis to access the value of EGGIM in the assessment of histological IM.

Materials

Studies were selected from PubMed, Medline, Embase, and Cochrane (last selection, Jun 2022). We extracted relevant data to calculate the accuracy of EGGIM compared with the operative link of gastric intestinal metaplasia (OLGIM) and to calculate pooled odds ratio (OR) with a 95% confidence interval (CI) assessing GC risk with different grading.

Results

Four diagnostic studies and three case-control clinical trials were included in the analysis, which included 665 patients and 738 patients, respectively. Compared with OLGIM III/IV, EGGIM(5-10) had a pooled sensitivity and specificity of 0.92(95%CI 0.86-0.96) and 0.90(95%CI 0.88-0.93), and the area under the curve(AUC) was 0.9702. In assessing early GC, the pooled OR of patients with EGGIM(5-10) was 7.46(95%CI 3.41-16.31) compared with that of EGGIM(0-4).

Conclusions

EGGIM is highly consistent with OLGIM, and patients with EGGIM(5-10) are at a higher risk for early GC. Some heterogeneity in the current research suggests that we need to carry out more strict control of confounding factors.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=248691], (Prospero registration number:248691)
Deep-learning-based generation of synthetic 6-minute MRI from 2-minute MRI for use in head and neck cancer radiotherapy
Authors: Wahid Kareem A. , Xu Jiaofeng , El-Habashy Dina , Khamis Yomna , Abobakr Moamen , McDonald Brigid , O’ Connell Nicolette , Thill Daniel , Ahmed Sara , Sharafi Christina Setareh , Preston Kathryn , Salzillo Travis C. , Mohamed Abdallah S. R. , He Renjie , Cho Nathan , Christodouleas John , Fuller Clifton D. , Naser Mohamed A.
Published: November 2022

Background

Quick magnetic resonance imaging (MRI) scans with low contrast-to-noise ratio are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-quality synthetic images from low-quality images.

Methods

We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (~20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and 6mMRI as output. Eighteen image sets were used to test model performance. Similarity metrics, including the mean squared error (MSE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR) were calculated between normalized synthetic 6mMRI and ground-truth 6mMRI for all test cases. In addition, a previously trained OAR DL auto-segmentation model was used to segment the right parotid gland, left parotid gland, and mandible on all test case images. Dice similarity coefficients (DSC) were calculated between 2mMRI and either ground-truth 6mMRI or synthetic 6mMRI for each OAR; two one-sided t-tests were applied between the ground-truth and synthetic 6mMRI to determine equivalence. Finally, a visual Turing test using paired ground-truth and synthetic 6mMRI was performed using three clinician observers; the percentage of images that were correctly identified was compared to random chance using proportion equivalence tests.

Results

The median similarity metrics across the whole images were 0.19, 0.93, and 33.14 for MSE, SSIM, and PSNR, respectively. The median of DSCs comparing ground-truth vs. synthetic 6mMRI auto-segmented OARs were 0.86 vs. 0.85, 0.84 vs. 0.84, and 0.82 vs. 0.85 for the right parotid gland, left parotid gland, and mandible, respectively (equivalence p<0.05 for all OARs). The percent of images correctly identified was equivalent to chance (p<0.05 for all observers).

Conclusions

Using 2mMRI inputs, we demonstrate that DL-generated synthetic 6mMRI outputs have high similarity to ground-truth 6mMRI, but further improvements can be made. Our study facilitates the clinical incorporation of synthetic MRI in MRI-guided radiotherapy.
Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer
Authors: Wang Li-ting , Zeng Qiu-ling , Jiang Shao-lan , Chen Zhen-yu , Wang Xiao-ling , Li Ling , Li Xiaolong
Published: November 2022

Objective

This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.

Methods

Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan–Meier technique, Cox regression analysis, LinkedOmics, Pearson’s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein–protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.

Results

In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.

Conclusion

FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.
Inconsistent clinical outcomes following afatinib treatment in NSCLC patients harboring uncommon epidermal growth factor receptor mutation
Authors: Dong Wei , Wang Congjie , Wang Chunsheng , Zhao Kewei , Ma Zhao , Hu Shanliang
Published: November 2022

Background

Uncommon epidermal growth factor receptor (EGFR) mutations consist of a heterogeneous population of molecular alterations, and the available clinical data on the outcomes of patients with non-small-cell lung cancer (NSCLC) harboring uncommon EGFR mutations following afatinib treatment are limited. The purpose of this pooled analysis was to investigate the clinicopathological features of patients with uncommon EGFR mutations (um-EGFRms) along with their treatment response and survival outcomes following afatinib treatment.

Methods

We performed a literature search in the NCBI PubMed database to identify relevant articles and conducted this pooled analysis based on 70 studies. The relationships between patient clinical characteristics, EGFR mutation type and the response to afatinib treatment were analyzed using univariate chi-square analysis, and survival analysis was performed using the Kaplan–Meier method.

Results

Data from a total of 99 patients were included in the pooled analysis. The objective response rate (ORR) to treatment with afatinib was53.5%, with a median progression-free survival (mPFS) of 9.0 months. For patients administered first-line afatinib treatment, the ORR and median PFS were 73.5% and 15.6 months, respectively, which were both superior to those of patients treated with second- or later-line treatments (ORR:37.0%, p < 0.001; mPFS: 6.0months, p = 0.001). Moreover, patients with a single um-EGFRm were more likely to have a favorable response and prognosis benefit after treatment with afatinib than patients with multiple one (ORR: 63.3% vs 38.5%, p=0.017; mPFS: 15.6 months vs 6.0 months,p=0.010). Moreover, single um-EGFRm were independent predictive factors for better treatment response and superior PFS. Subgroup analysis indicated that patients harboring major um-EGFRms (i.e., L861Q, G719X, and S768I) exhibited the best treatment responses and prognoses (ORR: 74.1%, mPFS: 15.6 months), by contrast, patients harboring multiple um-EGFRms comprising 19del/L858R had the worst treatment responses and prognoses (ORR: 23.5%, mPFS: 5.6months).

Conclusions

Patients with um-EGFRms exhibit favorable but inconsistent responses and survival outcomes following afatinib treatment, which closely related to the mutation pattern and cooccurring partner mutant genes. Administering afatinib for the treatment of patients with um-EGFRm might be considered an effective treatment option in some circumstances, but this recommendation requires further clinical studies for verification.
Comparison of laparoscopic pyeloplasty vs. robot-assisted pyeloplasty for the management of ureteropelvic junction obstruction in children
Authors: Pérez-Marchán Marcos , Pérez-Brayfield Marcos
Published: November 2022

Background

Ureteropelvic junction obstruction (UPJO) is a commonly observed abnormality in pediatric urology. Minimally invasive approaches have gained popularity in recent years. Studies have demonstrated excellent results with both laparoscopic pyeloplasty (LAP) and robot-assisted pyeloplasty (RAP). Few studies have compared the experience of both procedures performed in a single institution. Our objective is to compare laparoscopic pyeloplasty and robot-assisted pyeloplasty in the Puerto Rican pediatric population.

Methods

We conducted a retrospective cohort study using our clinic's database on patients with UPJO that were operated by the same surgeon (MPB) from 2008 to 2019. Statistical analysis was conducted of demographics, preoperative studies, perioperative data and complications of both procedures. This study was approved by our local IRB committee.

Results

A total of 86 patients that underwent pyeloplasty with at least 3 years of follow up were recorded for this study. Laparoscopic pyeloplasty and robot-assisted pyeloplasty were performed in 44 (51.1%) and 42 (48.8%) patients, respectively. Patient age ranged between 4 months and 17 years (LAP group - mean age of 6.19 years/RAP group - mean age of 7.07 years). Success rates was high in this series (LAP - 100% and RAP −95%). Using Wilcoxon signed rank test and Mann whitney sum test, significant differences between preoperative and postoperative hydronephrosis grading were observed in both LAP and RAP groups. However, no significant difference was seen regarding reduction of hydronephrosis grading when comparing both groups. No intraoperative complications were seen on either group.

Conclusion

Both LAP and RAP are safe and effective procedures that can properly manage UPJO. Our study shows that, under experienced hands, pure laparoscopic pyeloplasty achieves comparable results to robotic assisted laparoscopic pyeloplasty. Pediatric urologists should be comfortable offering either of these approaches as they demonstrate high success rates in our pediatric population. Selection of LAP vs. RAP approach depends on the Surgeon's preference or experience, and on institutional availability. Minimally invasive therapies will continue to gain popularity with future advances in laparoscopic and robotic technology.
Nonlinear relationship between early postnatal weight gain velocity and neurodevelopmental outcomes in very-low birth weight preterm infants: A secondary analysis based on a published prospective cohort study
Authors: Luo Zhongchen , You Beibei , Zhang You , Tang Jiao , Zheng Zehong , Jia Yuling , Wang Li , Zeng Dan , Li Hong , Wang Xiuhong
Published: November 2022

Background

Extrauterine growth restriction among the very-low birth weight preterm infants (VLBWPIs) is associated with poorer cognitive development outcome, while the rapid weight gain in infancy increases the long-term risk of obesity and noncommunicable disease among VLBWPIs. However, the results of research on the association between early postnatal growth velocity and neurodevelopmental outcomes in VLBWPIs are still limited and controversial.

Objective

We aimed to explore the association between the growth velocity in early postnatal and neurodevelopmental impairment (NDI) among VLBWPIs.

Methods

This study was a secondary analysis of a previously published prospective cohort. It was based on data on 1,791 premature infants with a birth weight of less than 1500 g, registered in the database of the Premature Baby Foundation of Taiwan between 2007 and 2011. A binary logistic regression model was used to evaluate the association between the weight gain velocity in different periods [from birth to 6 months corrected age (CA), 6 to 12 months CA, and 12 to 24 months CA] and NDI, respectively. The generalized additive model and the smooth curve fitting (penalized spline method) were used to address nonlinearity, and a two-piece-wise binary logistic regression model was added to explain the nonlinearity further.

Results

Nonlinearities were observed between NDI and the weight gain velocity from birth to 6 months CA [inflection point 20.36, inflection point: OR = 1.01, 95% CI 0.97–1.05], 6–12 months CA [inflection point 9.44, inflection point: OR = 1.05, 95% CI 1.05–(1.00, 1.11)], and 12–24 months CA [inflection point 16.00, inflection point: OR = 1.75, 95% CI 1.05–(0.96, 3.08)].

Conclusion

The neurodevelopmental benefits from a rapid weight gain velocity from birth to 24 months CA might be limited once the growth pace reaches an optimum level. It would help find a pattern of growth that facilitates optimal neurodevelopment, yet minimizes negative health consequences associated with overnutrition further.
Role of microbes in colorectal cancer therapy: Cross-talk between the microbiome and tumor microenvironment
Authors: Xia Cong , Cai Yantao , Ren Shuangyi , Xia Chenglai
Published: November 2022

The human gut microbiota is associated with the development and progression of colorectal cancer, and manipulation of the gut microbiota is a novel strategy for the prevention and treatment of colorectal cancer. Some bacteria have antitumor activity against colorectal cancer, where specific bacteria can improve the tumor microenvironment, activate immune cells including dendritic cells, helper T cells, natural killer cells, and cytotoxic T cells, and upregulate the secretion of pro-tumor immune cytokines such as interleukin-2 and interferon. In this paper, we summarize some bacteria with potential benefits in colorectal cancer and describe their roles in the tumor microenvironment, demonstrate the application of gut microbes in combination with immunosuppressive agents, and provide suggestions for further experimental studies and clinical practice applications.
Combined effect of traditional Chinese herbal-based formulations Jing Si herbal tea and Jing Si nasal drop inhibits adhesion and transmission of SARS-CoV2 in diabetic SKH-1 mice
Authors: Chiang Chien-Yi , Kuo Wei-Wen , Lin Yu-Jung , Kuo Chia-Hua , Shih Cheng-Yen , Lin Pi-Yu , Lin Shinn-Zong , Ho Tsung-Jung , Huang Chih-Yang , Shibu Marthandam Asokan
Published: November 2022

Multiple studies show increased severity of SARS-CoV2-infection in patients with comorbidities such as hypertension and diabetes. In this study, we have prepared two herbal-based formulations, a pleiotropic herbal drink (Jin Si Herbal Tea, JHT) and a nasal drop (Jin Si nasal drop, JND), to provide preventive care against SARS-CoV2 infection. The effect of JHT and JND was determined in SARS-CoV2-S-pseudotyped lentivirus-infected bronchial and colorectal cell lines and in SKH-1 mouse models. For preliminary studies, ACE2 receptor abundant bronchial (Calu-3) and colorectal cells (Caco-2) were used to determine the effect of JHT and JND on the host entry of various variants of SARS-CoV2-S-pseudotyped lentivirus. A series of experiments were performed to understand the infection rate in SKH-1 mice (6 weeks old, n = 9), find the effective dosage of JHT and JND, and determine the combination effect of JHT and JND on the entry and adhesion of various variant SARS-CoV2-S-pseudotyped lentiviruses, which included highly transmissible delta and gamma mutants. Furthermore, the effect of combined JHT and JND was determined on diabetes-induced SKH-1 mice against the comorbidity-associated intense viral entry and accumulation. In addition, the effect of combined JHT and JND administration on viral transmission from infected SKH-1 mice to uninfected cage mate mice was determined. The results showed that both JHT and JND were effective in alleviating the viral entry and accumulation in the thorax and the abdominal area. While JHT showed a dose-dependent decrease in the viral load, JND showed early inhibition of viral entry from day 1 of the infection. Combined administration of 48.66 mg of JHT and 20 µL of JND showed rapid reduction in the viral entry and reduced the viral load (97–99%) in the infected mice within 3 days of treatment. Moreover, 16.22 mg of JHT and 20 µL JND reduced the viral infection in STZ-induced diabetic SKH-1 mice. Interestingly, combined JHT and JND also inhibited viral transmission among cage mates. The results, therefore, showed that combined administration of JHT and JND is a novel and an efficient strategy to potentially prevent SARS-CoV2 infection.