bluuebunny/crossref_metadata_2025 huggingface dataset:
TTI1 promotes non‐small‐cell lung cancer progression by regulating the mTOR signaling pathway
Authors: Zhang Ling‐Xian , Yang Xin , Wu Zhi‐Bo , Liao Zhong‐Min , Wang Ding‐Guo , Chen Shi‐Wei , Lu Feng , Wu Yong‐Bing , Zhu Shu‐Qiang
Published: November 2022

The role of TELO2‐interacting protein 1 (TTI1) in the progression of several types of cancer has been reported recently. The aim of this study was to estimate the expression and potential value of TTI1 in non‐small‐cell lung cancer (NSCLC) patients. The expression of TTI1 and its prognostic value in NSCLC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. To verify the bioinformatics findings, a tissue microarray containing 160 NSCLC and paired peritumoral tissues from NSCLC patients was analyzed by immunohistochemistry for TTI1. Subsequently, the roles of TTI1 in NSCLC cells were investigated in vivo by establishing xenograft models in nude mice and in vitro by transwell, CCK‐8, wound healing, and colony formation assays. In addition, quantitative real‐time polymerase chain reaction and western blot were applied to explore the underlying mechanism by which TTI1 promotes tumor progression. Finally, the relationship between TTI1 and Ki67 expression level in NSCLC was probed, and Kaplan–Meier and Cox analyses were performed to assess the prognostic merit of TTI1 and Ki67 in NSCLC patients. We found that the expression of TTI1 was significantly upregulated in NSCLC tissues compared to paired peritumoral tissues, which coincides with the bioinformatics findings from the TCGA and GEO databases. TTI1 was highly expressed in NSCLC patients with large tumors, advanced tumor stage, and lymphatic metastasis. In addition, the prognostic analysis identified TTI1 as an independent indication for poor prognosis of NSCLC patients. In vitro, upregulation of TTI1 in NSCLC cells could facilitate cell invasion, metastasis, viability, and proliferation. Mechanistically, our study verified that TTI1 could regulate mTOR activity, which has a pivotal role in human cancer. Consistently, the expressions of TTI1 and Ki67 had a positive relationship in NSCLC cells and tissues. Notably, patients with overexpression of TTI1 or Ki67 had a shorter overall survival rate and a higher disease‐free survival rate compared to patients with low expression of TTI1 or Ki67, and the combination of TTI1 and Ki67 was an independent parameter predicting the prognosis and recurrence of NSCLC patients. We conclude that TTI1 promotes NSCLC cell proliferation, metastasis, and invasion by regulating mTOR activity, and the combination of TTI1 and Ki67 is a valuable molecular biomarker for the survival and recurrence of NSCLC patients.
Association of hospital volume with postoperative outcomes in Crohn's disease
Authors: Williams Hannah , Alabbadi Sundos , Khaitov Sergey , Egorova Natalia , Greenstein Alexander
Published: November 2022

Aim

Most patients diagnosed with Crohn's disease (CD) require surgery during their lifetime. While the literature has shown that certain cancer patients have superior postoperative outcomes at high‐volume hospitals, there remains a paucity of data on the hospital volume–outcome relationship in CD. Given the complexities in both medical and surgical management, this study aims to determine whether patients with CD have superior postoperative outcomes at high‐volume hospitals.

Method

A retrospective analysis of patients undergoing abdominal surgery for CD in New York hospitals between 2012 and 2018 was performed using data from the Statewide Planning and Research Cooperation System. Outcomes included postoperative mortality, 30‐day readmission and postoperative complications. Using a penalized B‐spline plot, high‐volume centres were defined as those performing more than 160 abdominal surgeries for CD each year.

Results

A total of 13,221 surgeries were performed across 176 hospital centres in New York State. Of these, 73.9% of procedures occurred at low‐volume centres. High‐volume hospitals had lower in‐hospital mortality (0.5% vs. 1.5%; p < 0.001) and 30‐day readmission rates (8.3% vs. 10.4%; p < 0.001) than low‐volume centres. Major postoperative complications and reoperation rates did not differ by hospital volume. On multivariate analysis, patients at high‐volume hospitals had lower odds of in‐hospital mortality (OR 0.54, 95% CI 0.38–0.75) and 30‐day readmission (OR 0.79, 95%CI 0.64–0.98). Hospital volume remained an independent predictor of 30‐day readmission for emergent admissions (OR 0.72, 95% CI 0.61–0.85) and in‐hospital mortality for nonemergent admissions (OR 0.39, 95% CI 0.19–0.82).

Conclusion

Patients undergoing abdominal surgery for CD have lower odds of postoperative mortality and 30‐day readmission when the operation occurs at a high‐volume hospital. These findings suggest that surgical patients with CD may benefit from care at specialized centres.
RMCL: A deep learning based recursive malicious context learner in social networks
Authors: Tiwari Devisha Arunadevi
Published: November 2022

Propagation of malicious content and its promotion is a recurrent problem prominent in social networks. Detection and interactive labeling of malicious context promotion on‐the‐fly is a very challenging and difficult task due to the lack of complete knowledge about the underlying context. Modern research in this field use neural networks and text encoders to analyze the information dynamically which is inefficient, in terms of time‐space consumed in the overall process. This article proposes an online active learning system to label the data streams on‐the‐fly by sampling them in the form of tweet‐retweet‐follow (trf) sequences in social networks. A heuristically pretrained recursive malicious context learner is fixed for knowledge acquisition, data accommodation and pseudonymization in the form of a transformer in the tree structured recursive neural network. The data stream is trained using recursive bidirectional training to capture long‐term dependencies. The COVID‐19 data streams are selectively sampled on‐the‐fly using psycho linguistic words in the proposed experiment and are labeled deceptive/nondeceptive based on knowledge learned during pretraining. The proposed recursive malicious context learner successfully resolves the problem of on‐the‐fly‐interactive labeling of a dynamically changing data stream.
Sutimlimab provides clinically meaningful improvements in patient‐reported outcomes in patients with cold agglutinin disease: Results from the randomised, placebo‐controlled, Phase 3 CADENZA study
Authors: Röth Alexander , Broome Catherine M. , Barcellini Wilma , Jilma Bernd , Hill Quentin A. , Cella David , Tvedt Tor Henrik Anderson , Yamaguchi Masaki , Lee Michelle , Shafer Frank , Wardęcki Marek , Jiang Xiaoyu , Patel Parija , Joly Florence , Weitz Ilene C.
Published: November 2022

Cold agglutinin disease (CAD) is a rare chronic autoimmune haemolytic anaemia, driven mainly by classical complement pathway activation, leading to profound fatigue and poor quality of life. In the Phase 3 CADENZA trial, sutimlimab—a C1s complement inhibitor—rapidly halted haemolysis, increased haemoglobin levels and improved fatigue versus placebo in patients with CAD without a recent history of transfusion. Patient‐reported outcomes (PROs) included Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐Fatigue), 12‐Item Short Form Health Survey (SF‐12), EuroQol visual analogue scale (EQ‐VAS), Patient Global Impression of Change (PGIC) and Patient Global Impression of (fatigue) Severity (PGIS). Sutimlimab resulted in significant rapid and meaningful improvements versus placebo in PROs. From Week 1, the FACIT‐Fatigue mean score increased >5 points above baseline (considered a clinically important change [CIC]). Least‐squares (LS) mean change in FACIT‐Fatigue score from baseline to treatment assessment timepoint was 10.8 vs. 1.9 points (sutimlimab vs. placebo; p < 0.001). Improvements in physical (PCS) and mental (MCS) component scores of the SF‐12 were also considered CICs (LS mean changes from baseline to Week 26: PCS 5.54 vs. 1.57 [p = 0.064]; MCS 5.65 vs. –0.48 [p = 0.065]). These findings demonstrate that in addition to improving haematologic parameters, sutimlimab treatment demonstrates significant patient‐reported benefits. Study registered at www.clinicaltrials.gov: NCT03347422.
Systemic light chain amyloidosis myopathy responsive to daratumumab monotherapy
Authors: Chitimus Diana Maria , Berling Edouard , Garderet Laurent , Venturelli Nadia , Malfatti Edoardo , Authier François Jérôme , Nicolas Guillaume , Laforêt Pascal , Lefeuvre Claire
Published: November 2022

Background and purpose

Amyloid myopathy is a rare and severe manifestation of systemic light chain (AL) amyloidosis. Early diagnosis and staging are mandatory for optimal therapy, given the rapid progression of muscle weakness. Despite the efficacy of bortezomib‐based treatment regimens, there is a lack of therapeutic alternatives in non‐responsive patients.

Method

The case report of a patient with systemic AL amyloidosis myopathy treated with daratumumab is presented.

Results

A 70‐year‐old man displayed severe proximal muscle weakness which had developed over a 10‐month period. Blood tests revealed an immunoglobulin A lambda monoclonal gammopathy, whilst muscle biopsy showed amyloid deposits within the arteriolar walls, confirming the diagnosis of amyloid myopathy associated with AL amyloidosis. Initial treatment with a bortezomib‐based regimen showed no clinical or hematological improvement. After switching to daratumumab monotherapy, our patient achieved a favorable evolution with respect to functional muscle scoring and a complete hematological response.

Conclusion

To our knowledge, this is the first case report of an amyloid myopathy showing a remarkable clinical improvement in response to daratumumab monotherapy. It thereby highlights the potential of daratumumab as a monotherapeutical approach to the treatment of amyloid myopathy complicating AL amyloidosis.
A LA‐ICP‐MS Comparison of Reference Materials Used in Cassiterite U‐Pb Geochronology
Authors: Carr Patrick A. , Moreira Emeline , Neymark Leonid , Norman Marc D. , Mercadier Julien
Published: November 2022

Laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS) is used to compare the suitability of four cassiterite (SnO2) materials (SPG, Yankee, AY‐4 and Jian‐1), and three matrix‐mismatched reference materials (NIST SRM 612, NIST SRM 614 and 91500 zircon) for normalisation of U‐Pb and Pb‐Pb isotope ratios in cassiterite. The excess variance of ages determined by LA‐ICP‐MS is estimated to be ±0.33% for 207Pb/206Pb vs. 208Pb/206Pb isochron ages and ± 1.8% and for U‐Pb ages. Incorporation of this excess variance in cassiterite ages is necessary for realistic uncertainties. 207Pb‐206Pb ages are advantageous for dating Precambrian cassiterite such as SPG compared with U‐Pb ages as matrix effect on instrumental mass fractionation of Pb isotopes are generally considered to be minor. We note minor bias in 207Pb/206Pb vs. 208Pb/206Pb isochron ages (~ 0.6%) when using either the NIST SRM 614 or 91500 zircon reference materials and emphasise the requirement for uncertainty propagation of all sources of error and reference materials with comparable U and Pb mass fraction to the cassiterite. The 238U/206Pb isotopic ratios from normalisation to matrix‐mismatched reference materials show varied results, which emphasises the need to use matrix‐matched reference materials for calculating U‐Pb ages. When cross‐calibrated against each other, LA‐ICP‐MS U‐Pb ages of the ca. 1535 Ma SPG, ca. 245 Ma Yankee and ca. 155 Ma Jian‐1 cassiterites are all consistent with their ID‐TIMS values.
Quantification of Cl, Br and I in Geological Materials by NH4F Digestion: Comparison with Rapid Acid Digestion
Authors: He Tao , Li Mufei , Hu Zhaochu , Zhang Wen , Chen Haihong , Wang Zaicong , Liu Yongsheng
Published: November 2022

The lack of analytical techniques for halogens in geological materials is mainly due to the loss of analytes during sample preparation. This study describes a rapid bulk rock digestion method (NH4F digestion) for determination of the abundances of Cl, Br and I in geological materials by SF‐ICP‐MS. During high temperature (200–240 °C) digestion, NH3 released from the decomposition of molten NH4F can effectively prevent the loss of halogens released from geological samples. Chlorine, Br and I were not lost during NH4F digestion at 220 °C for 0.25–6 h. The limits of quantitation for NH4F digestion were 2.8, 0.018 and 0.003 μg g‐1 Cl, Br and I, respectively. Most results for halogens in geological reference materials by NH4F digestion were in agreement with their certified values, confirming that the high‐performance rapid bulk rock NH4F digestion has sufficient digestion capability to extract Cl, Br and I from rocks, sediments and soils. In comparison, results obtained following acid digestion showed that HNO3 + HF digestion could effectively extract Br and I from soil and sediment samples, and that HNO3 acid digestion is only suitable to use for the determination of Br and I in soil samples.
Outcome of partial and full pulpotomy in cariously exposed mature molars with symptoms indicative of irreversible pulpitis: A randomized controlled trial
Authors: Jassal Ashima , Nawal Ruchika Roongta , Yadav Seema , Talwar Sangeeta , Yadav Sudha , Duncan Henry Fergus
Published: November 2022

Aim

The aim of this study was to assess and compare the clinical and radiographic outcome of partial pulpotomy and full pulpotomy using Biodentine in cariously exposed mature molar teeth with symptoms indicative of irreversible pulpitis.

Methodology

This study is an unicentric, double‐arm, randomized superiority clinical trial with parallel experimental groups, registered under CTRI (CTRI/2019/12/022559). Fifty mature permanent molar teeth with carious exposures with symptoms indicative of irreversible pulpitis were randomly allocated equally into two groups. Partial pulpotomy (PP) and full pulpotomy (FP) were performed in the first and second group, respectively, following standardized protocols. Exposed pulp tissue was removed up to a depth of 2–3 mm for partial pulpotomy, whereas complete coronal pulp tissue was removed up to the level of root orifices for full pulpotomy. Haemostasis was achieved with placement of 2.5% sodium hypochlorite‐moistened cotton pellets placed on amputated pulp tissue for a maximum of 10 min. Biodentine was used as the pulp capping material. Pain scores were evaluated using 11‐point Visual Analogue Scale (VAS) preoperatively, at 24 h, 48 h and 7th day after the intervention(s). Clinical and radiographic evaluation was done at 3 months, 6 months and 1 year. The data were statistically analysed using chi‐squared test, Mann–Whitney U‐test, Friedman's test and Wilcoxon signed‐rank test. The significance level was pre‐determined at p < .05. Cumulative survival probabilities were assessed at 12 months using Kaplan–Meier analysis.

Results

Intra‐group analysis of pain scores revealed significant reduction in pain scores preoperatively and at 24 h, 48 h and 7th day in both the groups. However, the difference in the pain score(s) reduction between both the groups was not statistically significant at any time interval (p > .05). At 1‐year follow‐up, the success rate was 88% (22/25) and 91.6% (22/24) for PP and FP respectively (p > .05).

Conclusions

Partial pulpotomy showed comparable results to full pulpotomy in terms of clinical/radiographic treatment outcome. If the long‐term results remain the same, partial pulpotomy can be proposed as an alternative treatment modality for mature teeth with cariously exposed pulp tissue presenting with signs of symptomatic irreversible pulpitis.
Does it burn? The effect of guar gum addition on ginger beer's sensory properties
Authors: Knowles Sophie , Gorman Mackenzie , McSweeney Matthew B.
Published: November 2022

Consumer demand for ginger beer has grown within the last few years due to health benefits associated with ginger consumption identified in recent studies and its low‐calorie content. However, non‐alcoholic ginger beer, like other non‐alcoholic beverages, does not possess the same mouthfeel as its alcoholic counterparts. As such, the aim of this study was to evaluate how the addition of guar gum impacted the sensory perception, spiciness, and consumer acceptability of non‐alcoholic ginger beer. Two different formulations of ginger beer were created, one without the addition of guar gum (control) and the other with 1.9 g/L guar gum added. Samples, along with carbonated water, were presented in pairs with a 20‐s wait and no‐rinse in between to observe sensitisation and desensitisation. The participants (n = 103) evaluated each sample for spiciness, burning or stinging sensation, along with bitterness, sweetness, sourness, overall flavour intensity, liking of flavour and mouthfeel, and overall liking. The addition of guar gum significantly impacted the perception of spiciness, burning, and stinging sensation in addition to the overall flavour intensity. The guar gum addition also negatively impacted the acceptability of the ginger beer.
Structural changes of cellulosic polysaccharides in sesame kernels during roasting
Authors: Liu Xiao‐Yan , Zhao Xiao‐Juan , Qin Jing‐Wen , Qin Zhao , Liu Hua‐Min , Ma Yu‐Xiang , Wang Xue‐De
Published: November 2022

This study investigated the structural changes of sesame kernel cellulosic polysaccharides during roasting and identified the volatile products produced from the degradation of cellulosic polysaccharides. The results showed that rhamnose and galacturonic acid of cellulosic polysaccharides were more susceptible to non‐enzymatic browning reaction than glucose. The degradation of cellulosic polysaccharides in the roasting temperature range of 180–220°C resulted in decreasing in their molecular weight from 163 270 to 125 477 Da. The crystallinity increased from 16.4% to 32.5% revealing that mainly the amorphous regions of cellulosic polysaccharides were degraded during roasting. In addition, the volatiles from degradation of the amorphous region were rich in aldehydes (10.17–33.33%) and furans (12.84–41.55%). This study provides a new perspective for improving the quality of sesame kernel products in the food industry.
Effects of different ablation settings on lesion dimensions in an ex vivo swine heart model: Baseline impedance, irrigant, and electrode configuration
Authors: Jiang Xi , Li Sijie , Xiong Qingsong , Zhang Changzhi , Peng Lijuan , Chen Weijie , Cai Yangwei , Yin Yuehui , Chen Shaojie , Ling Zhiyu
Published: November 2022

Introduction

Intramural or epicardial locations of the arrhythmogenic substrate are regarded as one of the main reasons for radiofrequency (RF) catheter ablation failure. This study aims to conduct a comprehensive analysis of various factors including baseline impedance, irrigant and electrode configuration at similar ablation index (AI) value.

Methods

In 12 ex vivo swine hearts, RF ablation was performed at a target AI value of 500 and a multistep impedance load (100–180 Ω) in 4 settings: (1) conventional unipolar configuration with an irrigant of normal saline (NS); (2) conventional unipolar configuration with an irrigant of half normal saline (HNS); (3) bipolar configuration with an irrigant of NS; (4) sequential unipolar configuration with an irrigant of NS. The relationships between lesion dimensions and above factors were examined.

Results

Baseline impedance had a strong negative linear correlation with lesion dimensions at a certain AI. The correlation coefficient between baseline impedance and depth, width, and volume were R = −0.890, R = −0.755 and R = −0.813, respectively (p < .01). There were 10 (total: 10/100, 10%; bipolar: 10/25, 40%) transmural lesions during the whole procedure. Bipolar ablation resulted in significantly deeper lesion than other electrode configurations. Other comparisons in our experiment did not achieve statistical significance.

Conclusion

There is a strong negative linear correlation between baseline impedance and lesion dimensions at a certain AI value. Baseline impedance has an influence on the overall lesion dimensions among irrigated fluid and ablation configurations. Over a threshold impedance of 150 Ω, the predictive accuracy of AI can be compromised.
WD repeat domain 48 promotes hepatocellular carcinoma progression by stabilizing c‐Myc
Authors: Li Bo , Zhang Ye‐wei , Cao Kun , Li Chao , Chen Qian , Jiang Yi‐heng , Luo Lu‐ling , Zuo Shi
Published: November 2022

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto‐oncogene transcriptional regulator c‐Myc and stabilizes c‐Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.
MicroRNA‐205‐5p: A potential therapeutic target for influenza A
Authors: Bao Yanyan , Shi Yujing , Zhou Lirun , Gao Shuangrong , Yao Rongmei , Guo Shanshan , Geng Zihan , Bao Lei , Zhao Ronghua , Cui Xiaolan
Published: November 2022

We are committed to finding host targets for influenza A therapeutics. The nucleoprotein (NP) plays an important role in influenza A virus replication and is an indispensable part of viral transcription and replication. Exploring endogenous substances that can modulate NP is critical for finding host targets. MicroRNAs (miRNAs, miR) are a novel class of powerful, endogenous gene expression regulators. Herein, we used miRanda to analyse the base complementarity between the NP gene and the 14 host miRNAs reported previously by us. MiRanda predicted that miR‐431‐5p, miR‐744‐3p and miR‐205‐5p could complement the NP gene. To understand the effect of these miRNAs on NP expression, we co‐transfected 293 T cells with NP gene sequence containing above miRNAs binding site or full sequence of NP gene (transfected into pmirGlo or pcDNA3.1 vectors, respectively), and mimics of miR‐205‐5p, miR‐431‐5p and miR‐744‐3p. Dual luciferase reporter gene or Western blotting assays confirmed that miR‐205‐5p and miR‐431‐5p inhibit NP expression by binding with the miRNA binding site of NP gene. Further, we infected Mouse Lung Epithelial (MLE‐12) cells overexpressing miR‐205‐5p and miR‐431‐5p with influenza A virus and performed Western blotting to examine NP expression. We found that NP expression was significantly reduced in MLE‐12 cells overexpressing miR‐205‐5p during influenza A infection. The miR‐205‐5p overexpression‐induced inhibition of influenza A replication could be attributed to the inhibition of NP expression. Further, we administered oseltamivir and Jinchai Antiviral Capsules (JC, an anti‐influenza Chinese medicine) to influenza A virus‐infected MLE‐12 cells and mice. We found that miR‐205‐5p was significantly decreased increased in infected cells and lung tissues, and oseltamivir and JC could up‐regulate miR‐205‐5p. In conclusion, we provide new evidence that miR‐205‐5p plays a role in regulating viral NP protein expression in combating influenza A and may be a potential target for influenza A therapy.
Interaction among dietary n‐3 and n‐6 polyunsaturated fatty acid intake, fatty acid desaturase 2 genetic variants, and low‐density lipoprotein cholesterol levels in type 2 diabetes patients
Authors: Huang Pei‐Chi , Cheng Hsuan , Su Yu‐Ting , Huang Meng‐Chuan , Hsu Chih‐Cheng , Hwang Shang‐Jyh , Shin Shyi‐Jang , Chang Wen‐Tsan
Published: November 2022

Aims/Introduction

Fatty acid desaturase (FADS) genetic polymorphisms are strongly correlated with the risk of dyslipidemia and cardiovascular disease. In this study, we examined the impact of FADS1 and FADS2 genetic variants on plasma lipid status, and assessed interactions between FADS genetic polymorphisms and plasma n‐3/n‐6 fatty acids regarding lipid status within a population of 816 Taiwanese patients with type 2 diabetes.

Materials and Methods

Selected tag single‐nucleotide polymorphisms (FADS1 rs174546 [T/C]; FADS2 rs174602 [A/G] and rs2072114 [A/G]) were genotyped (n = 816).

Results

The distribution of genotypes were compared with reports publicly available in the Genome Aggregation Database for East Asian populations (https://gnomad.broadinstitute.org). In the subgroup of patients not taking lipid‐lowering medications (n = 192), we observed that the G allele of FADS2 rs174602 was statistically significantly correlated with lower low‐density lipoprotein cholesterol (LDL‐C) concentrations (P = 0.001), whereas the G allele of rs2072114 was marginally associated with LDL‐C concentrations (P = 0.091). Using a general linear model adjusted for confounding factors, statistically significant interactions (P = 0.016) between single‐nucleotide polymorphisms in rs2072114 and a low alpha‐linolenic acid (18:3n‐3)/linoleic acid (18:2n‐6) ratio; the G allele correlated with lower LDL‐C levels among individuals with a low alpha‐linolenic acid/linoleic acid ratio. Interaction between rs174602 single‐nucleotide polymorphisms and low alpha‐linolenic acid/linoleic acid values on LDL‐C was only marginally significant (P = 0.063).

Conclusions

Our results show the role of n‐3/n‐6 dietary polyunsaturated fatty acids in modifying the effects of genetic susceptibility on lipoprotein concentrations in patients with type 2 diabetes. Our findings highlight the potential of interventions with dietary polyunsaturated fatty acids regarding developing individualized prevention strategies for type 2 diabetes presenting with co‐occurring dyslipidemia and cardiovascular diseases.
Association between serum gamma glutamyl transferase and fasting blood glucose in Chinese people: A 6‐year follow‐up study
Authors: Teng Fei , Ye Yan , Wang Liying , Qin Ruihao , Liu Xuekui , Geng Houfa , Xu Wei , Lai Peng , Liang Jun
Published: November 2022

Aims/Introduction

In this study, we aimed to investigate the relationships between gamma‐glutamyl transferase (GGT) and fasting blood glucose (FBG) during a 6‐year follow‐up study of participants, and to determine whether GGT is a risk factor for FBG.

Materials and Methods

A total of 1,369 individuals from the health examination survey in the urban area of Xuzhou, central China, were followed up for 6 years. The patients were divided into four groups based on their baseline GGT levels (in quartiles). The one‐way analysis of variance (anova) method was used to compare the differences between the variables and baseline. The relationship between GGT and FBG levels was investigated using repeated measurements anova.

Results

The grouping of baseline GGT levels affected the changes in blood glucose during the 6‐year follow‐up study. In the GGT quartile subgroups, the annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. This trend was even more aggregated in the highest baseline GGT group. Interactions among time course, baseline FBG and GGT groups in different participants together affected the change of FBG levels during the follow‐up period. The repeated measures anova suggested that different baseline GGT groups were still significantly associated with increased FBG levels. GGT is a risk factor that affects FBG levels(P < 0.001).

Conclusions

The annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. Higher baseline GGT levels resulted in a faster annual mean increase in FBG. Thus, GGT can be used for the early detection of FBG‐related disorders of glucose metabolism for clinical application.
Trend of gastric cancer incidence and death rate in adolescents and young adults: A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database
Authors: Wen Jie , Shen Huiqin
Published: November 2022

Background and Aim

Less attentions are paid into the adolescents and young adults (AYAs) diagnosed with gastric cancer (GC). Our study aims to explore incidence rate trend, death rate trend, and prognostic factors for overall survival (OS) and cancer‐specific survival (CSS) in AYAs with GC.

Methods

A retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database was performed. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) with 95% confidence interval (CI) for incidence and death rate trends. Prognostic factors for OS and CSS were investigated using Cox proportional hazard model and gray test, respectively, with results shown as hazard ratio (HR) with 95% CI.

Results

Although no statistical significance, incidence rate trend showed a tendency to an increase in AYAs (AAPC = 0.2, 95% CI: −0.2–0.6). All‐cause death rate trends were declined both in AYAs and middle‐aged and elderly people (MAEP), with AAPC value of −0.6 (95% CI: −0.8 to −0.5) and −0.5 (95% CI: −0.6 to −0.4), respectively. AYAs had a lower risk of all‐cause death (HR: 0.87, 95% CI: 0.84–0.90) but a higher risk of GC‐specific death (HR: 1.11, 95% CI: 1.07–1.15) than MAEP. Chemotherapy (HR: 1.27, 95% CI: 1.16–1.40) and intraoperative radiation (HR: 2.89, 95% CI: 1.13–7.37) were, respectively, identified as risk factors for worse OS and CSS in AYAs.

Conclusions

AYAs had a higher risk of GC‐specific death, indicating more attention should be paid into AYAs with GC.
Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4‐sclerosing cholangitis: Based on a Japanese nationwide study
Authors: Kubota Kensuke , Kamisawa Terumi , Nakazawa Takahiro , Tanaka Atsushi , Naitoh Itaru , Kurita Yusuke , Takikawa Hajime , Unno Michiaki , Kawa Shigeyuki , Masamune Atsushi , Nakamura Seiji , Okazaki Kazuichi ,   Collaborators
Published: November 2022

Objective

IgG4‐related sclerosing cholangitis (IgG4‐SC) is recognized as a benign steroid‐responsive disease; however, little is known about the risk of development of cancer in patients with IgG4‐SC and about how to counter this risk.

Design

We conducted a retrospective review of the data of 924 patients with IgG4‐SC selected from a Japanese nationwide survey. The incidence, type of malignancy, and risk of malignancy in these patients were examined. Then, the standardized incidence ratio (SIR) of cancer in patients with IgG4‐SC was calculated.

Results

Relapse was recognized in 19.7% (182/924) of patients, and cancer development was noted in 15% (139/924) of patients. Multivariate analysis identified only relapse as an independent risk factor for the development of cancer. In most of these patients with pancreato‐biliary cancer, the cancer developed within 8 years after the diagnosis of IgG4‐SC. The SIR for cancer after the diagnosis of IgG4‐SC was 12.68 (95% confidence interval [CI] 6.89–8.79). The SIRs of cancers involving the biliary system and pancreas were 27.35 and 18.43, respectively. The cumulative survival rate was significantly better in the group that received maintenance steroid treatment (MST) than in the group that did not; thus, MST influenced the prognosis of these patients.

Conclusion

Among the cancers, the risk of pancreatic and biliary cancers is the highest in these patients. Because of the elevated cancer risk, surveillance after the diagnosis and management to prevent relapse are important in patients with IgG4‐SC to reduce the risk of development of cancer.
A viewpoint on aldosterone andBMIrelated brain morphology in relation to treatment outcome in patients with major depression
Authors: Murck Harald , Lehr Lisa , Jezova Daniela
Published: November 2022

An abundance of knowledge has been collected describing the involvement of neuroendocrine parameters in major depression. The hypothalamic–pituitary–adrenocortical (HPA) axis regulating cortisol release has been extensively studied; however, attempts to target the HPA axis pharmacologically to treat major depression have failed. This review focuses on the importance of the adrenocortical stress hormone aldosterone, which is released by adrenocorticotropic hormone and angiotensin, and the mineralocorticoid receptor (MR) in depression. Depressed patients, in particular those with atypical depression, have signs of central hyperactivation of the aldosterone sensitive MR, potentially as a consequence of a reactive aldosterone release induced by low blood pressure and as a result of low sensitivity of peripheral MR. This is reflected in reduced heart rate variability, increased salt appetite and sleep changes in this group of patients. In addition, enlarged brain ventricles, compressed corpus callosum and changes of the choroid plexus are associated with increased aldosterone (in relation to cortisol). Furthermore, subjects with these features often show obesity. These characteristics are related to a worse antidepressant treatment outcome. Alterations in choroid plexus function as a consequence of increased aldosterone levels, autonomic dysregulation, metabolic changes and/or inflammation may be involved. The characterization of this regulatory system is in its early days but may identify new targets for therapeutic interventions.
Advancing mycorrhizal trait‐based ecology using both pure cultures and community‐level traits
Authors: Chagnon Pierre‐Luc
Published: November 2022

Traits are the intermediate by which species respond to environmental filters and influence ecosystem functions. With the myriad of biogeochemical processes controlled by fungi, the past decade has witnessed a rising interest in applying trait‐based approaches, core to the toolkit of plant and animal ecophysiologists, to fungi. One of the first challenges to tackle when working on fungal ecophysiology is to circumscribe the very definition of what we consider a fungal trait. Traits are characteristics/features possessed by an individual that can influence how it interacts with its environment. Here, the individual scale is both important, and problematic. Important because the very goal of comparative ecology is to measure traits on individuals belonging to known species. This allows us to populate trait databases, and syntheses of such databases can reveal key trade‐offs and trait syndromes that govern species' life‐histories. The scale of the individual is problematic, however, because it is hard to define for soil fungi, and because a rare minority of fungi can be sampled at the individual scale in the environment (e.g., macroscopic sporocarps, ectomycorrhizal root tips, lichen thalli). Beyond this minority, the individual organisms can only be accessed/sampled through establishing fungal cultures, which probably represents one of the main bottlenecks in the development of fungal trait databases. In this issue of Molecular Ecology, Zhang et al. (2022) show how interesting insights in fungal trait‐based ecology can be gained by working at the community level.
Coaches in postgraduate training: A difficult choice
Authors: Jackson Dawn , Lörwald Andrea C. , Huwendiek Sören , Hennel Eva K.
Published: November 2022

The authors discuss challenges inherent to playing the role of coach in postgraduate training by reflecting on role conflicts and benefits with regard to feedback's impact on professional development.
Learners and EHRs: A path forward
Authors: Bell Amanda , Chung Han‐Oh
Published: November 2022

Effective EHR utilization requires organizational culture transformation, leading to suggestions that learners be included early in EHR transitions for successful implementation, effective use, and future benefits.
Digital wellbeing: Are educational institutions paying enough attention?
Authors: Nageswaran Priyanka , Leedham‐Green Kay , Nageswaran Harris , Madeira Teixeira Baptista Ana V.
Published: November 2022

This commentary questions the impacts of over‐using technology in medical education and highlights the consideration of digital wellbeing when developing new teaching strategies
Infrastructure‐level traffic micro‐simulation for probabilistic analysis of bridge loads
Authors: Testa Giusiana , Zaccaria Gaetano , Montanino Marcello , Baltzopoulos Georgios , Bilotta Antonio , Iervolino Iunio , Punzo Vincenzo
Published: November 2022

In state‐of‐the‐art building codes, the traffic loads for the design or assessment of bridges should derive from a probabilistic characterization. However, because traffic depends on the vehicle flow peculiar to the transportation infrastructure of interest, the frequency of exceedance of code‐assigned loads is factually unknown. This study presents a methodology to probabilistically characterize the traffic loads on bridges based on network‐level traffic micro‐simulation and its application to the A56, that is, the urban highway connecting Naples’ (Italy) districts. One year of traffic simulations, in conjunction with structural modeling of the bridges featured in the infrastructure, enabled the probabilistic characterization of the traffic‐induced structural demand and the determination of the bridge‐specific safety margins along the highway. The results of the study and of the application to A56 ultimately show that: (i) traffic micro‐simulation appears to be a suitable approach to bridge‐specific structural safety assessment; (ii) structural actions deriving from code‐assigned loads tend to be conservative with respect to their traffic‐simulation‐derived counterparts; and (iii) structural demand induced by traffic loads can vary along the same transportation infrastructure.
A dynamically bi‐orthogonal solution method for a stochastic Lighthill‐Whitham‐Richards traffic flow model
Authors: Fan Tianxiang , Wong S. C. , Zhang Zhiwen , Du Jie
Published: November 2022

Macroscopic traffic flow modeling is essential for describing and forecasting the characteristics of traffic flow. However, the classic Lighthill–Whitham–Richards (LWR) model only provides equilibrium values for steady‐state conditions and fails to capture common stochastic variabilities, which are a necessary component of accurate modeling of real‐time traffic management and control. In this paper, a stochastic LWR (SLWR) model that randomizes free‐flow speed is developed to account for the stochasticity incurred by the heterogeneity of drivers, while holding individual drivers’ behavior constant. The SLWR model follows a conservation law of stochastic traffic density and flow and is formulated as a time‐dependent stochastic partial differential equation. The model is solved using a dynamically bi‐orthogonal (DyBO) method based on a spatial basis and stochastic basis. Various scenarios are simulated and compared with the Monte Carlo (MC) method, and the results show that the SLWR model can effectively describe dynamic traffic evolutions and reproduce some commonly observed traffic phenomena. Furthermore, the DyBO method shows significant computational advantages over the MC method.
Medication‐related osteonecrosis of the jaw triggered by endodontic failure in oncologic patients
Authors: Tempesta Angela , Capodiferro Saverio , Di Nanna Simona , D'Agostino Silvia , Dolci Marco , Scarano Antonio , Gambarini Gianluca , Maiorano Eugenio , Favia Gianfranco , Limongelli Luisa
Published: November 2022

Objectives

To describe the association between endodontic treatment failure and medication‐related osteonecrosis of the jaw (MRONJ) in a cohort of oncologic patients in therapy with antiresorptive and antiangiogenic drugs.

Materials and Methods

Patients were selected as affected by MRONJ in absence of the common local risk factors (oral surgical procedures or ill‐fitting dentures) but showing failure of previous endodontic treatment performed at least 6 months before the starting of antiresorptive/antiangiogenic therapies. Jaw lesions were all surgically treated and patients underwent a strict clinical and radiological follow‐up.

Results

Among 18 patients, who developed 18 MRONJ, the only detectable local risk factor was the presence of teeth with failed endodontic treatment (more precisely, root canal underfilling in eight cases, root canal overfilling in two cases, root perforation in three cases, root fracture in five cases). All patients completely healed after surgical procedure and no recurrence was observed.

Conclusions

Endodontic treatment failure should be considered a local risk factor for MRONJ development in oncologic patients. For such reason, it is mandatory to carefully evaluate them prior than the beginning of antiresorptive and antiangiogenic drugs administration.
Changing trend of oral cancer disease burden in China from 1990 to 2019 and the forecast for the next 20 years
Authors: Xie Long , Shang Zhengjun
Published: November 2022

Objective

This study aimed to explore the trend of oral cancer (OC) disease burden in China from 1990 to 2019 and predict the disease burden in the next 20 years.

Methods

OC data collected for 15 years old in China from 1990 to 2019 were obtained from the 2019 Global Burden of Disease Study. Estimated annual percentage changes (EAPCs), with respective 95% CI, were used to assess incidence, mortality, disability‐adjusted life‐year (DALY), and their trends.

Results

From 1990 to 2019, the age‐standardized rate of incidence, mortality, and DALY of OC in China showed an upward trend with EAPCs of 2.33 (95% CI = 2.01–2.63), 1.44 (95% CI = 1.15–1.73), and 1.24 (95% CI = 0.95–1.52), respectively. The main risk factors for OC in China were smoking and alcohol consumption. New cases, deaths, and DALYs due to OC are predicted to increase >1.5 times over the next 20 years.

Conclusion

The number of cases, deaths, and DALYs will continue to increase in the next 20 years. Therefore, the control of risk factors, such as tobacco and alcohol consumption, needs to be strengthened to reduce the burden of OC in China.
Ectoparasites population dynamics are affected by host body size but not host density or water temperature in a 32‐year long time series
Authors: Henriksen Eirik H. , Frainer André , Poulin Robert , Knudsen Rune , Amundsen Per‐Arne
Published: November 2022

Host density, host body size and ambient temperature have all been positively associated with increases in parasite infection. However, the relative importance of these factors in shaping long‐term parasite population dynamics in wild host populations is unknown due to the absence of long‐term studies. Here, we examine long‐term drivers of gill lice (Copepoda) infections in Arctic charr (Salmonidae) over 32 years. We predicted that host density and body size and water temperature would all positively affect parasite population size and population growth rate. Our results show that fish size was the main driver of gill lice infections in Arctic charr. In addition, Arctic charr became infected at smaller sizes and with more parasites in years of higher brown trout population size. Negative intraguild interactions between brown trout and Arctic charr appear to drive smaller Arctic charr to seek refuge in deeper areas of the lake, thus increasing infection risk. There was no effect of host density on the force of infection, and the relationship between Arctic charr density and parasite mean abundance was negative, possibly due to an encounter‐dilution effect. The population densities of host and parasite fluctuated independently of one another. Water temperature had negligible effects on the temporal dynamics of the gill lice population. Understanding long‐term drivers of parasite population dynamics is key for research and management. In fish farms, artificially high densities of hosts lead to vast increases in the transmission of parasitic copepods. However, in wild fish populations fluctuating at natural densities, the surface area available for copepodid attachment might be more important than the density of available hosts.
Novel findings of an old algorithm: PVC response “Atrial Pace’’ initiates atrial arrhythmias in Abbott ICD and CRT‐D devices
Authors: Sane Markus , Marjamaa Annukka , Kuusisto Jouni , Raatikainen Pekka , Karvonen Jarkko
Published: November 2022

Background

Many algorithms have been developed to ensure the safety and accuracy of cardiac implantable electric devices (CIED). A specific algorithm designed to prevent pacemaker induced tachycardia (PMT) after a premature ventricular complex (PVC response) is available in all Abbott (former St. Jude Medical) CIED. However, a few case reports suggest that this algorithm may be proarrhythmic when programmed to Atrial Pace (A‐Pace on PVC).

Methods

We analyzed the data of all (n = 333) Abbot implantable cardioverter defibrillator (ICD) and cardiac resynchronization defibrillator (CRT‐D) devices followed remote using the Merlin.net Patient Care Network in our institute in 2020. Status of the PVC response algorithm A‐Pace on PVC or Off was collected, and all atrial mode switch (AMS) episodes longer than 30 s were thoroughly evaluated. Data on clinical characteristics of the patients was collect from the electronic patient records.

Results

A total of 173 patients had A‐Pace on PVC and twenty‐five of them (14%) had at least one atrial high rate episode (AHRE) >30 s (AHRE) triggered by the action of this algorithm. The median PVC count was higher in patients who had algorithm triggered AHRE than in those with no algorithm‐triggered AHRE (1.7% [IQR 0–3.2] vs. 0% [IQR 0–1.1], p < .0001). The major clinical characteristics were comparable in the two groups.

Conclusion

The A‐Pace on PVC setting was frequently used in our patients. Our study shows that a considerable number of patients had at least one AHRE triggered by the algorithm. The use of this algorithm should be carefully reconsidered.
CRISPR‐induced miRNA156‐recognition element mutations in TaSPL13 improve multiple agronomic traits in wheat
Authors: Gupta Ajay , Hua Lei , Zhang Zhengzhi , Yang Bing , Li Wanlong
Published: November 2022

Increase in grain yield is always a major objective of wheat genetic improvement. The SQUAMOSA promoter‐binding protein‐like (SPL) genes, coding for a small family of diverse plant‐specific transcription factors, represent important targets for improving grain yield and other major agronomic traits in rice. The function of the SPL genes in wheat remains to be investigated in this respect. In this study, we identified 56 wheat orthologues of rice SPL genes belonging to 19 homoeologous groups. Like in rice, nine orthologous TaSPL genes harbour the microRNA156 recognition elements (MRE) in their last exons except for TaSPL13, which harbour the MRE in its 3′‐untranslated region (3′UTR). We modified the MRE of TaSPL13 using CRISPR‐Cas9 and generated 12 mutations in the three homoeologous genes. As expected, the MRE mutations led to an approximately two‐fold increase in the TaSPL13 mutant transcripts. The phenotypic evaluation showed that the MRE mutations in TaSPL13 resulted in a decrease in flowering time, tiller number, and plant height, and a concomitantly increase in grain size and number. The results show that the TaSPL13 mutants exhibit a combination of different phenotypes observed in Arabidopsis AtSPL3/4/5 mutants and rice OsSPL13/14/16 mutants and hold great potential in improving wheat yield by simultaneously increasing grain size and number and by refining plant architecture. The novel TaSPL13 mutations generated can be utilized in wheat breeding programmes to improve these agronomic traits.