bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro selection of Neisseria gonorrhoeae unveils novel mutations associated with extended-spectrum cephalosporin resistance
Authors: Schörner Marcos André , Mesa Dany , Barazzetti Fernando Hartmann , Martins Jéssica Motta , Machado Hanalydia de Melo , Grisard Henrique Borges da Silva , Wachter Julia Kinetz , Starick Márick Rodrigues , Scheffer Mara Cristina , Palmeiro Jussara Kasuko , Bazzo Maria Luiza
Published: July 2022

The emergence of Neisseria gonorrhoeae strains resistant to extended-spectrum cephalosporins (ESCs) is a worldwide concern because this class of antibiotics represents the last empirical treatment option for gonorrhea. The abusive use of antimicrobials may be an essential factor for the emergence of ESC resistance in N. gonorrhoeae. Cephalosporin resistance mechanisms have not been fully clarified. In this study, we mapped mutations in the genome of N. gonorrhoeae isolates after resistance induction with cefixime and explored related metabolic pathways. Six clinical isolates with different antimicrobial susceptibility profiles and genotypes and two gonococcal reference strains (WHO F and WHO Y) were induced with increasing concentrations of cefixime. Antimicrobial susceptibility testing was performed against six antimicrobial agents before and after induction. Clinical isolates were whole-genome sequenced before and after induction, whereas reference strains were sequenced after induction only. Cefixime resistance induction was completed after 138 subcultures. Several metabolic pathways were affected by resistance induction. Five isolates showed SNPs in PBP2. The isolates M111 and M128 (ST1407 with mosaic penA-34.001) acquired one and four novel missense mutations in PBP2, respectively. These isolates exhibited the highest minimum inhibitory concentration (MIC) for cefixime among all clinical isolates. Mutations in genes contributing to ESC resistance and in other genes were also observed. Interestingly, M107 and M110 (ST338) showed no mutations in key determinants of ESC resistance despite having a 127-fold increase in the MIC of cefixime. These findings point to the existence of different mechanisms of acquisition of ESC resistance induced by cefixime exposure. Furthermore, the results reinforce the importance of the gonococcal antimicrobial resistance surveillance program in Brazil, given the changes in treatment protocols made in 2017 and the nationwide prevalence of sequence types that can develop resistance to ESC.
Multidrug-resistant Pseudomonas aeruginosa is predisposed to lasR mutation through up-regulated activity of efflux pumps in non-cystic fibrosis bronchiectasis patients
Authors: Ding Fengming , Han Lei , Xue Yishu , Yang Iris Tingshiuan , Fan Xinxin , Tang Rong , Zhang Chen , Zhu Miao , Tian Xue , Shao Ping , Zhang Min
Published: July 2022

Background

Multidrug-resistant (MDR) Pseudomonas aeruginosa is a frequent opportunistic pathogen that causes significant mortality in patients with non-cystic fibrosis bronchiectasis (NCFB). Although the quorum sensing (QS) system is a potential target for treatment, lasR mutants that present with a QS-deficient phenotype have been frequently reported among clinical P. aeruginosa isolates. We aimed to investigate whether antibiotic resistance would select for lasR mutants during chronic P. aeruginosa lung infection and determine the mechanism underlying the phenomenon.

Methods

We prospectively evaluated episodes of chronic P. aeruginosa lung infections in NCFB patients over a 2-year period at two centers of our institution. QS phenotypic assessments and whole-genome sequencing (WGS) of P. aeruginosa isolates were performed. Evolution experiments were conducted to confirm the emergence of lasR mutants in clinical MDR P. aeruginosa cultures.

Results

We analyzed episodes of P. aeruginosa infection among 97 NCFB patients and found only prior carbapenem exposure independently predictive of the isolation of MDR P. aeruginosa strains. Compared with non-MDR isolates, MDR isolates presented significantly QS-deficient phenotypes, which could not be complemented by the exogenous addition of 3OC12-HSL. The paired isolates showed that their QS-phenotype deficiency occurred after MDR was developed. Whole-genome sequencing analysis revealed that lasR nonsynonymous mutations were significantly more frequent in MDR isolates, and positive correlations of mutation frequencies were observed between genes of lasR and negative-efflux-pump regulators (nalC and mexZ). The addition of the efflux pump inhibitor PAβN could not only promote QS phenotypes of these MDR isolates but also delay the early emergence of lasR mutants in evolution experiments.

Conclusions

Our data indicated that MDR P. aeruginosa was predisposed to lasR mutation through the upregulated activity of efflux pumps. These findings suggest that anti-QS therapy combined with efflux pump inhibitors might be a potential strategy for NCFB patients in the challenge of MDR P. aeruginosa infections.
Potential Implications of the Lung Microbiota in Patients with Chronic Obstruction Pulmonary Disease and Non-Small Cell Lung Cancer
Authors: He Jia-Qi , Chen Qin , Wu Sheng-Jun , Wang De-Qin , Zhang Shen-Yingjie , Zhang Song-Zhao , Chen Rui-Lin , Wang Jia-Feng , Wang Zhen , Yu Chen-Huan
Published: July 2022

Recently, chronic obstructive pulmonary disease (COPD) has been considered as a common risk factor of non-small cell lung cancer (NSCLC). However, very few studies have been conducted on the effects of COPD on the lung microbiota in patients with NSCLC. To identify the lung microbiota in patients with COPD and NSCLC (CN), the microbiome of the induced sputa of 90 patients was analyzed using 16S rDNA sequencing. The results showed no significant differences in the bacterial diversities of induced sputa among patients with COPD, NSCLC, and CN and no intrinsic differences among patients with different pathological types of lung cancer. After surgical operation, the diversities of the induced sputa in patients with CN significantly decreased. More remarkably, both the microbial community phenotypes and the components of the induced sputa in patients with CN obviously differed from those in patients with COPD or NSCLC. The relative abundances of Streptococcus, Veillonella, Moraxella, and Actinomyces significantly decreased, but those of Neisseria and Acinetobacter significantly increased in patients with CN compared with those in patients with COPD or NSCLC alone, resulting in increased Gram-negative microbiota and, therefore, in potential pathogenicity and stress tolerance, as well as in enhancement of microbial glycolipid metabolism, amino acid metabolism, and oxidative stress. Although COPD did not affect the number of pulmonary flora species in patients with NSCLC, these significant alterations in the microbial populations, phenotypes, and functions of induced sputa due to COPD would contribute to inflammation-derived cancer progression in patients with CN.
Uncovering inclusivity gaps in design pedagogy through the digital design marginalization framework
Authors: Sin Jaisie , Munteanu Cosmin , Nixon Michael , Pandeliev Velian , Tigwell Garreth W. , Shinohara Kristen , Tang Anthony , Szigeti Steve
Published: July 2022

Designers play a key role in the design of inclusive and socially conscious interfaces. Thus, it is imperative for designers to be thoughtful of the ethical and social implications of design. However, gaps in the foundational training that designers receive (e.g., as university students) can negatively impact their ability to consider the social implications of their design practice. This can result in consequences such as digital marginalization, which, as defined by the Digital Design Marginalization (DDM) framework, is the “pushing away”, whether intentional or not, of a defined group of users from a digital or online service or system, where the exclusion has additional, indirect, and long-lasting social consequences on that particular user group. Designers can contribute, even unintentionally, to digital marginalization through their design practices and the design choices they make. We argue that our role as educators includes ensuring not only that our design pedagogy is inclusive, but that the designers we train now are prepared to conduct their future design practice in a manner that is inclusive to all users. As such, we propose to use the Digital Design Marginalization as a lens to guide a reflection-based approach to identify gaps in our pedagogy that may lead to designers becoming ill-equipped to identify how their designs may lead to digital marginalization. Through seven case studies from our own teaching practice, we demonstrate the use of the DDM framework to guide marginalization-focused introspective reflections of curricula. These reflections through the DDM lens revealed gaps in our pedagogy with respect to providing future designers with training that enables them to consider the broader societal and individual implications of the design choices they will make in future practice. Based on our experience using the DDM framework, we then discuss in greater depth how reflection of social consequences of design pedagogy can be operationalized within institutions to reduce educational gaps that may be associated with design-mediated digital marginalization. Finally, we comment on avenues for further development of pedagogical reflection using DDM.
Toward privacy-aware federated analytics of cohorts for smart mobility
Authors: Gjoreski Martin , Laporte Matías , Langheinrich Marc
Published: July 2022

Location-based Behavioral Analytics (LBA) holds a great potential for improving the services available in smart cities. Naively implemented, such an approach would track the movements of every citizen and share their location traces with the various smart service providers—similar to today's Web analytics systems that track visitors across the web sites they visit. This study presents a novel privacy-aware approach to location-based federated analytics that removes the need for individuals to share their location traces with a central server. The general approach is to model the behavior of cohorts instead of modeling specific users. Using a federated approach, location data is processed locally on user devices and only shared in anonymized fashion with a server. The server aggregates the data using Secure Multiparty Computation (SMPC) into service-defined cohorts, whose data is then used to provide cohort analytics (e.g., demographics) for the various smart service providers. The approach was evaluated on three real-life datasets with varying dropout rates, i.e., clients not being able to participate in the SMPC rounds. The results show that our approach can privately estimate various cohort demographics (e.g., percentages of male and female visitors) with an error between 0 and 8 percentage points relative to the actual cohort percentages. Furthermore, we experimented with predictive models for estimating these cohort percentages 1-week ahead. Across all three datasets, the best-performing predictive model achieved a Pearson's correlation coefficient above 0.8 (strong correlation), and a Mean Absolute Error (MAE) between 0 and 10 (0 is the minimum and 100 is the maximum). We conclude that privacy-aware LBA can be achieved using existing mobile technologies and federated analytics.
Evaluation of left ventricular myocardial stratified strain in patients with Kawasaki disease using two-dimensional speckle tracking imaging
Authors: Hu Jinling , Zheng Qiaojin , Ren Weidong
Published: July 2022

Kawasaki disease (KD) is an acute autoimmune self-limited disease of unknown etiology. We aimed to evaluate the left ventricular myocardial stratified strains in children with KD in different stages using two-dimensional speckle tracking imaging, and to find the index that can early predict myocardial function injury in children with KD. A total of 73 children with KD were divided into acute, convalescent, and chronic stages according to the disease course. All children had no coronary artery damage. Further, 64 normal children were selected as the control group. The longitudinal and circumferential strain peaks of each myocardium were recorded, and the left ventricular global longitudinal strain (LVGLS), global circumferential strain (LVGCS), and transmural gradient between endocardium and epicardium (ΔGLS, ΔGCS) were calculated. Compared with the control group, LVGLS, GLS-Endo, GLS-Mid, GLS-Epi, and ΔGLS decreased in acute KD; LVGLS, GLS-Endo, GLS-Mid, GLS-Epi, ΔGLS, LVGCS, GCS-Mid, and GCS-Epi decreased in the convalescent stage; and only GLS-Endo was lower in children with chronic KD (P < 0.05). ROC curve was used to calculate the stratified strain parameters so as to predict left ventricular systolic function in children with acute KD; the area under the LVGLS curve was the largest (AUC = 0.953, P < 0.001). When the cutoff value of LVGLS was −19.89%, the sensitivity and specificity were 95.8% and 83.2%, respectively.

Conclusions

The systolic function of the whole layer of the myocardium decreased to varying degrees in children with KD. With the extension of the disease course, the myocardial function gradually recovered, but the subendocardial myocardium was still damaged. LVGLS could identify the abnormity of left ventricular contractility in patients with KD at the acute stage. Thus, it has the promising prospect of clinical diagnosis.
Deployment and validation of an AI system for detecting abnormal chest radiographs in clinical settings
Authors: Nguyen Ngoc Huy , Nguyen Ha Quy , Nguyen Nghia Trung , Nguyen Thang Viet , Pham Hieu Huy , Nguyen Tuan Ngoc-Minh
Published: July 2022

Background

The purpose of this paper is to demonstrate a mechanism for deploying and validating an AI-based system for detecting abnormalities on chest X-ray scans at the Phu Tho General Hospital, Vietnam. We aim to investigate the performance of the system in real-world clinical settings and compare its effectiveness to the in-lab performance.

Method

The AI system was directly integrated into the Hospital's Picture Archiving and Communication System (PACS) after being trained on a fixed annotated dataset from other sources. The system's performance was prospectively measured by matching and comparing the AI results with the radiology reports of 6,285 chest X-ray examinations extracted from the Hospital Information System (HIS) over the last 2 months of 2020. The normal/abnormal status of a radiology report was determined by a set of rules and served as the ground truth.

Results

Our system achieves an F1 score—the harmonic average of the recall and the precision—of 0.653 (95% CI 0.635, 0.671) for detecting any abnormalities on chest X-rays. This corresponds to an accuracy of 79.6%, a sensitivity of 68.6%, and a specificity of 83.9%.

Conclusions

Computer-Aided Diagnosis (CAD) systems for chest radiographs using artificial intelligence (AI) have recently shown great potential as a second opinion for radiologists. However, the performances of such systems were mostly evaluated on a fixed dataset in a retrospective manner and, thus, far from the real performances in clinical practice. Despite a significant drop from the in-lab performance, our result establishes a reasonable level of confidence in applying such a system in real-life situations.
The role of interleukin-1β in type 2 diabetes mellitus: A systematic review and meta-analysis
Authors: Alfadul Hend , Sabico Shaun , Al-Daghri Nasser M.
Published: July 2022

Type 2 diabetes mellitus (T2DM) is a multifactorial non-communicable disease that is characterized by insulin resistance and chronic sub-clinical inflammation. Among the emerging inflammatory markers observed to be associated with β-cell damage is interleukin 1β (IL1β), a proinflammatory cytokine that modulates important metabolic processes including insulin secretion and β-cell apoptosis. The present systematic review and meta-analysis gathers available evidence on the emerging role of IL1β in T2DM. PubMed and Embase were searched for human studies that assessed 1L1β in T2DM individuals from 2016-2021. Thirteen studies (N=2680; T2DM=1182, controls=1498) out of 523 were included in the systematic review and only 3 studies in the meta-analysis. Assays were the most commonly used quantification method and lipopolysaccharides as the most common stimulator for IL1β upregulation. Random and fixed effects meta-analysis showed non-significant mean differences of IL1β concentrations between the T2DM and controls. Given the high heterogeneity and small subset of studies included, caution is advised in the interpretation of results. The present systematic review and meta-analysis highlights the limited evidence available that could implicate 1L1β as a potent biomarker for T2DM. Standardization of 1L1β assays with larger sample sizes are encouraged in future observational and prospective studies.
Clinical Characteristics of Inpatients With New-Onset Diabetes Mellitus in Eastern China: Based on Novel Clustering Analysis
Authors: Song Xueke , Lv Yingqi , Huang Nan , Sun Jinfang , Yang Ting , Wang Xiaoyuan , Zhang Jianan , Zhou Ziwei , Gao Huihua , Li Jie , Zhang Wei , Yin Han , Wei Qiong , Wang Kun , Li Ling
Published: July 2022

Introduction

This study aimed to explore the novel classification of inpatients with new-onset diabetes in Eastern China by the cluster-based classification method and compare the clinical characteristics among the different subgroups.

Methods

A total of 1017 Inpatients with new-onset diabetes of five hospitals in Eastern China were included in the study. Clustering analysis was used to cluster the data into five subgroups according to six basic variables. The differences in clinical characteristics, treatments, and the prevalence of diabetes-related diseases among the five subgroups were analyzed by multiple groups comparisons and pairwise comparisons. The risk of diabetes-related diseases in the five subgroups was compared by calculating odd ratio (OR). P value < 0.05 was considered significant.

Results

Five subgroups were obtained by clustering analysis with the highest proportion of patients with severe insulin-deficient diabetes (SIDD) 451 (44.35%), followed by patients with mild age-related diabetes (MARD) 236 (23.21%), patients with mild obesity-related diabetes (MOD) 207 (20.35%), patients with severe insulin-resistant diabetes (SIRD) 81 (7.96%), and patients with severe autoimmune diabetes (SAID) 42 (4.13%). Five subtypes had their own unique characteristics and treatments. The prevalence and risk of diabetes-related complications and comorbidities were also significantly different among the five subtypes. Diabetic kidney disease (DKD) was the most common in SIRD group. Patients in SIDD, SIRD, and MARD groups were more likely to develop cardiovascular disease (CVD) and/or stroke, diabetic peripheral vascular disease (DPVD), and diabetic distal symmetric polyneuropathy (DSPN). The prevalence and risk of metabolic syndrome (MS) were the highest in MOD and SIRD groups. Patients in SAID group had the highest prevalence and risk of diabetic ketoacidosis (DKA). Patients with MOD were more likely to develop non-alcoholic fatty liver disease (NAFLD).

Conclusions

The inpatients with new-onset diabetes in Eastern China had the unique clustering distribution. The clinical characteristics, treatments, and diabetes-related complications and comorbidities of the five subgroups were different, which may provide the basis for precise treatments of diabetes.
Changes in temperature and precipitation extremes in the arid regions of China during 1960–2016
Authors: Wang Xuyang , Li Yuqiang , Yan Meng , Gong Xiangwen
Published: July 2022

Extreme climate events have a greater impact on natural and human systems than average climate. The spatial and temporal variation of 16 temperature and nine precipitation extremal indices was investigated using the daily maximum and minimum surface air temperature and precipitation records from 113 meteorological stations in China’s arid regions from 1960 to 2016. The warmth indices [warm spell duration (WSDI); numbers of warm nights, warm days, tropical nights (TR), and summer days (SU)] increased significantly. On the contrary, the cold indices [numbers of frost days (FD), ice days (ID), cool days, and cool nights; cold spell duration (CSDI)] decreased significantly. The number of FD decreased fastest (−3.61 days/decade), whereas the growing season length (GSL) increased fastest (3.17 days/decade). The trend was strongest for diurnal temperature range (DTR) (trend rate = −7.29, P < 0.001) and minimum night temperature (trend rate = 7.70, P < 0.001). The cold extreme temperature events increased with increasing latitude, but the warm extreme temperature events decreased. Compared with temperature indices, the precipitation indices exhibited much weaker changes and less spatial continuity. Overall, changes in precipitation extremes present wet trends, although most of the changes are insignificant. The regionally averaged total annual precipitation for wet days increased by 4.78 mm per decade, and extreme precipitation events have become more intense and frequent during the study period. The spatial variability of extreme precipitation in the region was primarily influenced by longitude. Furthermore, the climate experienced a warm-wet abrupt climate change during 1990s.
Molecular characterization of thioester-containing proteins in Biomphalaria glabrata and their differential gene expression upon Schistosoma mansoni exposure
Authors: Marquez J. , Dinguirard N. , Gonzalez A. , Kane A.E. , Joffe N.R. , Yoshino T.P. , Castillo M.G.
Published: July 2022

Schistosomiasis is a disease caused by trematode parasites of the genus Schistosoma that affects approximately 200 million people worldwide. Schistosomiasis has been a persistent problem in endemic areas as there is no vaccine available, currently used anti-helmintic medications do not prevent reinfection, and most concerning, drug resistance has been documented in laboratory and field isolates. Thus, alternative approaches to curtail this human disease are warranted. Understanding the immunobiology of the obligate intermediate host of these parasites, which include the freshwater snail Biomphalaria glabrata, may facilitate the development of novel methods to stop or reduce transmission to humans. Molecules from the thioester-containing protein (TEP) superfamily have been shown to be involved in immunological functions in many animals including corals and humans. In this study we identified, characterized, and compared TEP transcripts and their expression upon S. mansoni exposure in resistant and susceptible strains of B. glabrata snails. Results showed the expression of 11 unique TEPs in B. glabrata snails. These transcripts present high sequence identity at the nucleotide and putative amino acid levels between susceptible and resistant strains. Further analysis revealed differences in several TEPs’ constitutive expression levels between resistant and susceptible snail strains, with C3-1, C3-3, and CD109 having higher constitutive expression levels in the resistant (BS90) strain, whereas C3-2 and TEP-1 showed higher constitutive expression levels in the susceptible (NMRI) strain. Furthermore, TEP-specific response to S. mansoni miracidia exposure reiterated their differential expression, with resistant snails upregulating the expression of both TEP-4 and TEP-3 at 2 h and 48 h post-exposure, respectively. Further understanding the diverse TEP genes and their functions in invertebrate animal vectors will not only expand our knowledge in regard to this ancient family of immune proteins, but also offer the opportunity to identify novel molecular targets that could aid in the efforts to develop control methods to reduce schistosomiasis transmission.
The efficacy and safety of IL-13 inhibitors in atopic dermatitis: A systematic review and meta-analysis
Authors: Zhang Yan , Jing Danrong , Cheng Jun , Chen Xiang , Shen Minxue , Liu Hong
Published: July 2022

Background

Several clinical trials have evaluated the efficacy and safety of interleukin-13 (IL-13) with lebrikizumab and tralokinumab in patients with moderate to severe atopic dermatitis (AD). However, the safety and efficacy of IL-13 inhibitors as a potent biologic for AD remain elusive.

Objective

To assess the efficacy and safety of IL-13 inhibitors in moderate to severe AD.

Method

Randomized clinical trials (RCTs), comparing IL-13 inhibitors vs placebo treatment in patients with moderate to severe AD, were identified from public database from its inception to November 9th, 2021. The study was registered in PROSPERO (CRD42021254920).

Results

Six studies reporting 7 RCTs involving 2946 patients with moderate-to-severe AD were included for the pooled analysis. Compared with placebo, antagonizing IL-13 with lebrikizumab and tralokinumab showed a greater improvement in percentage change of EASI (MD -20.37, 95%CI -32.28, -8.47), and a larger proportion of patients achieving numerical rating scale (NRS) with more than 4-points improvement (RR 1.59, 95%CI 1.23, 2.05). Additionally, IL-13 inhibitors also improved impaired dermatology life quality index (DLQI) (MD -14.49, 95%CI -19.23, -9.75). In terms of safety, both lebrikizumab and tralokinumab were well tolerated, with the except that they were linked to an increased risk of conjunctivitis compared to placebo treatment.

Conclusion

Antagonizing IL-13 with lebrikizumab and tralokinumab have demonstrated encouraging clinical efficacy against moderate-to-severe AD with excellent safety profile, albeit they did come with a higher risk of conjunctivitis than placebo treatment.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier ID=CRD42021254920.
Novel approaches for long-term lung transplant survival
Authors: Miller Cynthia L. , O Jane M. , Allan James S. , Madsen Joren C.
Published: July 2022

Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.
Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
Authors: Shi Changying , Li Yulong , Yang Cheng , Qiao Liang , Tang Liukang , Zheng Yuting , Chen Xue , Qian Youwen , Yang Jiamei , Wu Dong , Xie Feng
Published: July 2022

Background

Currently, no second-line systemic treatment regimen has been recommended in advanced biliary tract cancer (BTC). Cumulative clinical evidence showed that systemic treatment with tyrosine kinase inhibitors (TKIs) in combination with immunotherapy may shed light on the dim clinical outcome in advanced BTC.

Objective

The aim of this study is to evaluate the anticancer efficacy of lenvatinib plus programmed cell death protein-1 (PD-1) antibody in patients with BTC who progressed after first-line cisplatin/gemcitabine (CisGem) chemotherapy.

Methods

Patients with advanced BTCs who progressed after CisGem were recruited. A combination regimen of lenvatinib (8/12 mg daily) plus PD-1 antibody (200/240 mg injection every 3 weeks) was prescribed. Clinicopathological information and therapeutic outcome, including tumor subtypes, biomarkers, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated.

Results

A total of 351 patients with BTCs were reviewed and 74 were recruited eventually: 35 had intrahepatic cholangiocarcinoma (47.3%), 4 had extrahepatic cholangiocarcinoma (5.4%), and 35 had gallbladder cancer (47.3%). The median administered cycles of PD-1 antibody were 6.43 (95% CI: 5.83–7.04) cycles, and the median duration of lenvatinib medication was 21.0 weeks (95% CI: 18.04–23.93). Twenty-eight patients (37.83%) experienced detectable objective response per RECIST1.1 within a median follow-up duration of 15.0 months. The objective response rate (ORR) was 20.27% (95% CI: 10.89%–29.65%), and the disease control rate (DCR) was 71.62% (95% CI: 61.11%–82.14%). The median PFS and OS were 4.0 months (95% CI: 3.5–5.0) and 9.50 months (95% CI: 9.0–11.0), respectively. Seventy-three patients (98.64%) reported AEs and 39 (52.70%) experienced ≥grade 3 AEs. In subgroup analyses, tumoral PD-L1 expression ≥50% and tumor mutation burden (TMB) ≥2.5 Muts/Mb were associated with prolonged PFS.

Conclusion

Lenvatinib plus PD-1 antibody treatment shows an active trend towards improving survival in patients with advanced BTCs after failure with CisGem chemotherapy. The treatment-related AEs are worthy of attention and are manageable.
Long-Term Monitoring of In-Water Abundance of Juvenile Pelagic Loggerhead Sea Turtles (Caretta caretta): Population Trends in Relation to North Atlantic Oscillation and Nesting
Authors: Dellinger Thomas , Zekovic Vladimir , Radeta Marko
Published: July 2022

Sea turtles have various life-stages, typically being oceanic foragers as juveniles while shifting to more coastal habitats as they mature. The present study focuses on the least studied and well known of these, the juvenile oceanic life stage for the loggerhead sea turtle,Caretta caretta. Loggerhead sea turtles remain threatened by fisheries and their distribution and habitat change in the North Atlantic remains poorly understood. After hatching and swimming out to sea, turtles spend 7 or more years in the pelagic life stage. Madeira Island has an advantage of being situated in the middle of the North Atlantic developmental habitat for loggerheads originating both from the US, as well as, from Cape Verde and other mixed source rookeries. Understanding the demographics of this oceanic life stage has been described as a research priority. We here present a population trendline and the abundance variation of oceanic stage loggerheads, measured at a single geographic spot in Madeiran waters, over the period of 15 years. We find that the observed loggerhead distribution results from combined effects of physical and biological processes within the North Atlantic. We explore physical phenomena that influence abundance variability, and find that oscillations in climate affect the turtle migrations, as does the population recruitment from the nesting rookeries. For this, we use novel cost-effective census methods that take advantage of platforms of opportunity from the blue ecotourism industry. To study the time series and their correlations we use spectral analysis, a method not commonly used in traditional population assessments, including Wavelet and Fourier Transformations (WT and FFT), and Digital Signal Processing (DSP) techniques. A strong anti-correlation between sea turtle sightings and North Atlantic Oscillation seasonal components was found, which implies that loggerhead sea turtles are less abundant during positive NAO phases. We also detected long period trends in the sighting data which we relate to La Niña and El Niño oscillations. Source rookeries also influenced the sighting data with a time-lag of ~ 7years, which coincides with the average time that turtles spend as oceanic juveniles.
Effects and Mechanism of Two Nanoparticles (Titanium Dioxide and Silver) to Moina mongolica Daday (Crustacea, Cladocera)
Authors: Huang Jianrong , Li Shaojing , Lin Yuanshao
Published: July 2022

The nearshore and estuary are the main gathering areas of nanoparticles (NPs), and salinity change is a crucial characteristic in these marine areas. Moina mongolica Daday is an important open-ended bait in the nearshore aquaculture environment. Investigating the toxicity mechanism of NPs to M. mongolica under different salinity conditions is crucial to exploring the biological impact of NPs in the nearshore environment. Two typical metal oxide and metal NPs of TiO2 and Ag were used in this study to test the acute, chronic, and reproductive toxicities of M. mongolica (Cladocera) in marine environments of different salinity gradients. The toxic effects and mechanisms of the two NPs on M. mongolica were discussed by ecotoxicology and transcriptional analysis, respectively. A total of 27,274 genes were assembled, and 11,056 genes were successfully compared. Results suggested that TiO2 and Ag NPs showed particle toxicity with oxidation generation and immune emergencies on M. mongolica. Compared with TiO2, Ag NPs showed strong toxicity with reproductive toxicity due to the release of Ag+, resulting in a reduction in reproduction, which is a decrease in the number of offspring and the rm. Critical DEGs involved in carapace showed carapace damage of M. mongolica, due to adhesion and accumulation (approximately 40%–60% of all accumulation) on carapace, which was one of the toxic mechanisms of the two NPs. The salinity factor caused the aggregation of both NPs, and Ag+ release of Ag NPs. The toxicity of TiO2 NPs to M. mongolica increases with salinity, but that of Ag NPs decreases.
Sources of nitrate in a heavily nitrogen pollution bay in Beibu Gulf, as identified using stable isotopes
Authors: Cai Shangjun , Lao Qibin , Jin Guangzhe , Chen Chunqing , Zhou Xin , Zhu Qingmei , Lu Xuan
Published: July 2022

Eutrophication, mainly caused by the oversupply of inorganic nitrogen and phosphate, has increased and become a serious environmental problem in the coastal bays of Beibu Gulf, a newly developing industry and port in South China. However, the sources of nitrate are poorly understood in the gulf. In this study, nitrate dual isotopes (δ15N-NO3- and δ18O-NO3-) and ammonium isotopes (δ15N-NH4+) were measured during the rainy season to identify the nitrate sources and elucidate their biogeochemical processes in Xi Bay, a semi-enclosed bay that is strongly affected by human activities in the Beibu Gulf. The results showed that a high dissolved inorganic nitrogen (DIN, 10.24-99.09 µmol L-1) was observed in Xi Bay, particularly in the bay mouth. The concentrations of DIN in the bay were 1.5 times higher than that in Qinzhou Bay and 1.7 times than that in Tieshangang Bay, which mainly influenced by the intensive human activities (i.e., industrial and port activities). In addition, lower values of δ15N-NO3- and δ18O-NO3- and higher values of δ15N-NH4+ were observed in the upper bay, suggesting that microbial nitrification occurs in the upper bay, which was the dominant nitrate source in the upper bay (39%). In addition to nitrification, external sources, including sewage and manure (33%), soil N (15%) and fertilizer (11%), contributed to the higher nutrients in the upper bay. In the lower bay, severe nitrogen pollution led to a weaker impact of biological processes on isotopic fractionation, although a high Chl a level (average of 7.47 µg L-1) was found in this region. The heavy nitrate pollution in the lower bay mainly originated from sewage and manure (54%), followed by soil N (26%) and fertilizer (17%). The contribution of the nitrate source from atmospheric deposition was relatively low in the bay (<3%). This study suggests that biogeochemical processes have little impact on nitrate dual isotopes under heavy nitrogen pollution, and isotopes are an ideal proxy for tracing nitrogen sources.
Interventions to reduce the incidence of medical error and its financial burden in health care systems: A systematic review of systematic reviews
Authors: Ahsani-Estahbanati Ehsan , Sergeevich Gordeev Vladimir , Doshmangir Leila
Published: July 2022

Background and aim

Improving health care quality and ensuring patient safety is impossible without addressing medical errors that adversely affect patient outcomes. Therefore, it is essential to correctly estimate the incidence rates and implement the most appropriate solutions to control and reduce medical errors. We identified such interventions.

Methods

We conducted a systematic review of systematic reviews by searching four databases (PubMed, Scopus, Ovid Medline, and Embase) until January 2021 to elicit interventions that have the potential to decrease medical errors. Two reviewers independently conducted data extraction and analyses.

Results

Seventysix systematic review papers were included in the study. We identified eight types of interventions based on medical error type classification: overall medical error, medication error, diagnostic error, patients fall, healthcare-associated infections, transfusion and testing errors, surgical error, and patient suicide. Most studies focused on medication error (66%) and were conducted in hospital settings (74%).

Conclusions

Despite a plethora of suggested interventions, patient safety has not significantly improved. Therefore, policymakers need to focus more on the implementation considerations of selected interventions.
A multicenter prospective cohort study of cardiac ultrasound phenotypes in patients with sepsis: Study protocol for a multicenter prospective cohort trial
Authors: Zhang Hongxuan , Wang Xiaoting , Yin Wanhong , Zhang Hongmin , Liu Lixia , Pan Pan , Zhu Ying , Huang Wei , Xing Zhiqun , Yao Bo , Wang Cui , Lin Tianlai , Yu Rongguo , Shang Xiuling
Published: July 2022

Background

Sepsis-induced cardiomyopathy significantly increased the mortality of patients with sepsis. The diagnostic criteria for septic cardiomyopathy has not been unified, which brings serious difficulties to clinical treatment. This study aimed to provide evidence for the early identification and intervention in patients with sepsis by clarifying the relationship between the ultrasound phenotype of septic cardiomyopathy and the prognosis of patients with sepsis.

Methods

This was a multicenter, prospective cohort study. The study population will consist of all eligible consecutive patients with sepsis or septic shock who meet the Sepsis 3.0 diagnostic criteria and were aged ≥18 years. Clinical data and echocardiographic measurements will be recorded within 2 h, at the 24th hour, at the 72nd hour, and on the 7th day after admission. The prevalence of each phenotype will be described as well, and their association with prognosis will be analyzed statistically.

Discussion

To achieve early recognition, prevent reinjury, achieve precise treatment, and reduce mortality in patients with sepsis, it is important to identify septic cardiac alterations and classify the phenotypes at all stages of sepsis. First, there is a lack of studies on the prevalence of each phenotype in Chinese populations. Second, each phenotype and its corresponding prognosis are not clear. In addition, the prognosis of patients with normal cardiac ultrasound phenotypes vs. those with suppressed or hyperdynamic cardiac phenotypes is unclear. Finally, this study was designed to collect data at four specific timing, then the timing of occurrence, duration, changes over time, impact to outcomes of each phenotype will probably be found. This study is expected to establish a standard and objective method to assess the ultrasound phenotype of septic cardiomyopathy due to its advantages of visualization, non-invasiveness and reproducibility, and to provide more precise information for the hemodynamic management of septic patients. In addition, this research will promote the clinical application of critical care ultrasound, which will play an important role in medical education and make ultrasound the best method to assess cardiac changes in sepsis.

Trial registration

https://clinicaltrials.gov/ct2/show/NCT05161104, identifier NCT05161104.
Identification and Characterization of Potato Zebra Chip Resistance Among Wild Solanum Species
Authors: Mora Victoria , Ramasamy Manikandan , Damaj Mona B. , Irigoyen Sonia , Ancona Veronica , Avila Carlos A. , Vales Maria Isabel , Ibanez Freddy , Mandadi Kranthi K.
Published: July 2022

Potato zebra chip (ZC) disease, associated with the uncultured phloem-limited bacterium, Candidatus Liberibacter solanacearum (CLso), is transmitted by the potato psyllid Bactericera cockerelli. Potato ZC disease poses a significant threat to potato production worldwide. Current management practices mainly rely on the control of the psyllid to limit the spread of CLso. The present study investigated new sources of ZC resistance among wild Solanum species. A taxonomically diverse collection of tuber-bearing Solanum species was screened; one ZC-resistant accession and three ZC-tolerant accessions were identified among the 52 screened accessions. Further characterization of the resistant accession showed that the resistance was primarily associated with antibiosis effects due to differences in leaf trichome density and morphology of the wild accession, which could limit the psyllid feeding and oviposition. This germplasm offers a good resource for further understanding ZC and psyllid resistance mechanisms, contributing to potato breeding efforts to develop ZC resistance cultivars. Alternatively, it could be used as a potential trap crop to manage psyllid and control ZC disease.
Taxonomy and Multi-Gene Phylogeny of Poroid Panellus (Mycenaceae, Agaricales) With the Description of Five New Species From China
Authors: Zhang Qiu-Yue , Liu Hong-Gao , Papp Viktor , Zhou Meng , Wu Fang , Dai Yu-Cheng
Published: July 2022

Panellus is an Agaricales genus with both lamellate and poroid hymenophore. The poroid species are readily overlooked because of their tiny basidiocarps. The Chinese samples of poroid Panellus are studied, and five species, namely Panellus alpinus, Panellus crassiporus, Panellus longistipitatus, Panellus minutissimus, and Panellus palmicola are described as new species based on morphology and molecular phylogenetic analyses inferred from an nrITS dataset and a multi-gene dataset (nrITS + nrLSU + mtSSU + nrSSU + tef1). Panellus alpinus is characterized by its round to ellipsoid pores measuring 4–6 per mm and oblong ellipsoid basidiospores measuring 4.8–6 μm × 2.8–3.6 μm; P. crassiporus differs from other poroid species in the genus by the irregular pores with thick dissepiments and globose basidiospores measuring 8–9.8 μm × 6.9–8 μm; P. longistipitatus is distinguished by its long stipes, pyriform cheilocystidia, and broadly ellipsoid to subglobose basidiospores measuring 7–9.8 μm × 5–7 μm; P. minutissimus is characterized by its tiny and gelatinous basidiocarps, 5–20 pores per basidiocarp, and ellipsoid basidiospores measuring 6–8 μm × 3.2–4.2 μm; P. palmicola is characterized by its round pores measuring 2–4 per mm, the presence of acerose basidioles, and globose basidiospores measuring 7–9.5 μm × 6.2–8.2 μm. An identification key to 20 poroid species of Panellus is provided.
Few Amino Acid Mutations in H6 Influenza A Virus From South American Lineage Increase Viral Replication Efficiency in Poultry
Authors: Rimondi Agustina , Olivera Valeria S. , Soria Ivana , Parisi Gustavo D. , Rumbo Martin , Perez Daniel R.
Published: July 2022

In chickens, infections due to influenza A virus (IAV) can be mild to severe and lethal. The study of IAV infections in poultry has been mostly limited to strains from the North American and Eurasian lineages, whereas limited information exists on similar studies with strains from the South American lineage (SAm). To better evaluate the risk of introduction of a prototypical SAm IAV strain into poultry, chickens were infected with a wild-type SAm origin strain (WT557/H6N2). The resulting virus progeny was serially passaged in chickens 20 times, and the immunopathological effects of the last passage virus, 20Ch557/H6N2, in chickens were compared to those of the parental strain. A comparison of complete viral genome sequences indicated that the 20Ch557/H6N2 strain contained 13 amino acid differences compared to the wild-type strain. Five of these mutations are in functionally relevant regions of the viral surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). However, despite higher and more prolonged virus shedding in chickens inoculated with the 20Ch557/H6N2 strain compared to those that received the WT557/H6N2 strain, transmission to naïve chickens was not observed for either group. Analyses by flow cytometry of mononuclear cells and lymphocyte subpopulations from the lamina propria and intraepithelial lymphocytic cells (IELs) from the ileum revealed a significant increase in the percentages of CD3+TCRγδ+ IELs in chickens inoculated with the 20Ch557/H6N2 strain compared to those inoculated with the WT557/H6N2 strain.
Cognition impairment and risk of subclinical cardiovascular disease in older adults: The atherosclerosis risk in communities study
Authors: Li Dongze , Jia Yu , Yu Jing , Liu Yi , Li Fanghui , Zhang Wei , Gao Yongli , Liao Xiaoyang , Wan Zhi , Zeng Zhi , Zeng Rui
Published: July 2022

Background

Clinical cardiovascular disease (CVD) and cognition impairment are common and often coexist in aging populations, and CVD is associated with greater cognition impairment risk; however, the association between cognition impairment and CVD risk is inconsistent. It is unknown if pathways that contribute to CVD are caused by impaired cognition. We hypothesized that cognition impairment would be associated with greater subclinical CVD including subclinical myocardial damage [assessed by high-sensitivity cardiac troponin T (hs-cTnT)] and cardiac strain or dysfunction [assessed by N-terminal pro-B-type natriuretic peptide (NT-proBNP)].

Methods

This analysis included Atherosclerosis Risk in Communities Study (ARIC) participants who underwent global cognition z-score tests between 1991 and 1993. Cardiac biomarkers were measured from stored plasma samples collected between 1996 and 1999. Logistic regression models were used to determine the association of cognitive function with subclinical CVD risk.

Results

There were 558/9216 (6.1%) and 447/9097 (5.0%) participants with incident elevated hs-CTnT (≥14 ng/L) and NT-proBNP (≥300 pg/mL) levels, respectively. Comparing the lowest and highest quartiles of global cognition z-scores, a higher incidence of elevated hs-CTnT [odds ratio (OR) = 1.511, 95% confidence interval (CI): 1.093–2.088, P = 0.013] and NT-proBNP (OR = 1.929, 95% CI: 1.350–2.755, P < 0.001) were observed, respectively. In structural equation modeling, the indirect effect of global cognition z-score on major adverse cardiac events was 42.1% (P < 0.05).

Conclusion

Impairments in baseline cognitive function were associated with subclinical myocardial damage or wall strain. Although future studies are warranted to investigate the pathophysiological mechanisms behind these associations, our study suggests common pathways between cognitive and cardiac dysfunction.