bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Efficacy of Tonic Chinese Herbal Injections for Treating Sepsis or Septic Shock: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials
Authors: Xiao Lu , Niu Liqing , Xu Xinyi , Zhao Yuetong , Yue Linkai , Liu Xinqiao , Li Guiwei
Published: March 2022

Background: Sepsis has high mortality and is responsible for significant healthcare costs. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for sepsis. Therefore, this study assessed and ranked the effectiveness of CHIs to provide more sights for the selection of sepsis treatment.

Method: Eight databases were searched from their inception up to September 1, 2021. The methodological quality of included study was evaluated by the Revised Cochrane risk-of-bias tool for randomized trials. Then Bayesian network meta-analysis was performed by OpenBUGS 3.2.3 and STATA 14.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Publication bias was reflected by a funnel plot.

Results: A total of 50 eligible randomized controlled trials involving 3,394 participants were identified for this analysis. Five CHIs including Shenfu injection, Shenmai injection, Shengmai injection, Shenqifuzheng injection, and Huangqi injection were included. The results of the NMA and sensitivity analysis showed that Shenqifuzheng (MD = −4.48, 95% CI = −5.59 to −3.24), Shenmai (MD = −3.38, 95% CI = −4.38 to −2.39), Shenfu (MD = −2.38, 95% CI = −3.03 to −1.70) and Shengmai (MD = −1.90, 95% CI = −3.47 to −0.31) combined with Western medicine (WM) had a superior effect in improving the APACHE II score. Based on SUCRA values, Shenqifuzheng injection (95.65%) ranked highest in the APACHE II score, followed by Shenmai (74%), Shenfu (47.1%), Shengmai (35.3%) and Huangqi injection (33.2%). Among the secondary outcomes, Shenmai injection was the most favorable intervention in reducing PCT and CRP levels, and Shenqifuzheng injection was the second favorable intervention in reducing CRP level. Shenfu injection combined with WM was more effective than the other treatments in decreasing the serum IL-6 and TNF-α levels and lowering the 28-days mortality. Regarding the improvement of immune function, Shenqifuzheng injections had obvious advantages.

Conclusion: In conclusion, Shenqifuzheng injection was the optimum treatment regimen to improve APACHE II score, reduce CRP level, and regulate immune function. Shenfu injection was superior in reducing the expression of inflammatory factors and decreasing 28-days mortality. Nevertheless, more multicenter, diverse, and direct comparisons randomized controlled trials are needed to further confirm the results.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=254531, identifier CRD42021254531.
Bisphosphonates Targeting Ion Channels and Musculoskeletal Effects
Authors: Scala Rosa , Maqoud Fatima , Antonacci Marina , Dibenedetto Jacopo Raffaele , Perrone Maria Grazia , Scilimati Antonio , Castillo Karen , Latorre Ramón , Conte Diana , Bendahhou Saïd , Tricarico Domenico
Published: March 2022

Bisphosphonates (BPs) are the most used bone-specific anti-resorptive agents, often chosen as first-line therapy in several bone diseases characterized by an imbalance between osteoblast-mediated bone production and osteoclast-mediated bone resorption. BPs target the farnesyl pyrophosphate synthase (FPPS) in osteoclasts, reducing bone resorption. Lately, there has been an increasing interest in BPs direct pro-survival/pro-mineralizing properties in osteoblasts and their pain-relieving effects. Even so, molecular targets involved in these effects appear now largely elusive. Ion channels are emerging players in bone homeostasis. Nevertheless, the effects of BPs on these proteins have been poorly described. Here we reviewed the actions of BPs on ion channels in musculoskeletal cells. In particular, the TRPV1 channel is essential for osteoblastogenesis. Since it is involved in bone pain sensation, TRPV1 is a possible alternative target of BPs. Ion channels are emerging targets and anti-target for bisphosphonates. Zoledronic acid can be the first selective musculoskeletal and vascular KATP channel blocker targeting with high affinity the inward rectifier channels Kir6.1-SUR2B and Kir6.2-SUR2A. The action of this drug against the overactive mutants of KCNJ9-ABCC9 genes observed in the Cantu’ Syndrome (CS) may improve the appropriate prescription in those CS patients affected by musculoskeletal disorders such as bone fracture and bone frailty.
A Systematic Review of Utilisation of Diurnal Timing Information in Clinical Trial Design for Long QT Syndrome
Authors: Seed Lydia M. , Hearn Timothy J.
Published: March 2022

Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 h, and drug delivery. Despite guidelines having been issued around the analysis of 24-h ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.
Understanding the Adaptive Mechanisms of Plants to Enhance Phosphorus Use Efficiency on Podzolic Soils in Boreal Agroecosystems
Authors: Nadeem Muhammad , Wu Jiaxu , Ghaffari Hamideh , Kedir Amana Jemal , Saleem Shamila , Mollier Alain , Singh Jaswinder , Cheema Mumtaz
Published: March 2022

Being a macronutrient, phosphorus (P) is the backbone to complete the growth cycle of plants. However, because of low mobility and high fixation, P becomes the least available nutrient in podzolic soils; hence, enhancing phosphorus use efficiency (PUE) can play an important role in different cropping systems/crop production practices to meet ever-increasing demands in food, fiber, and fuel. Additionally, the rapidly decreasing mineral phosphate rocks/stocks forced to explore alternative resources and methods to enhance PUE either through improved seed P reserves and their remobilization, P acquisition efficiency (PAE), or plant's internal P utilization efficiency (IPUE) or both for sustainable P management strategies. The objective of this review article is to explore and document important domains to enhance PUE in crop plants grown on Podzol in a boreal agroecosystem. We have discussed P availabilities in podzolic soils, root architecture and morphology, root exudates, phosphate transporters and their role in P uptake, different contributors to enhance PAE and IPUE, and strategies to improve plant PUE in crops grown on podzolic soils deficient in P and acidic in nature.
Genome-Wide Identification of APETALA2/ETHYLENE RESPONSIVE FACTOR Transcription Factors in Cucurbita moschata and Their Involvement in Ethylene Response
Authors: Li Qingfei , Zhang Li , Chen Peiwen , Wu Chunhui , Zhang Huaixia , Yuan Jingping , Zhou Junguo , Li Xinzheng
Published: March 2022

APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF), a plant-specific transcription factor (TF) family, plays an essential role in the growth and development of plants, and in their response to biotic and abiotic stresses. However, information on AP2/ERF in Cucurbita moschata (pumpkin), an edible and medicinal vegetable used worldwide, is scarce. A total of 212 AP2/ERF genes were identified in the C. moschata genome (CmoAP2/ERFs). Based on phylogenetic analysis, they were divided into four groups—28 AP2s, 92 ERFs, 86 dehydration-responsive element-binding (DREB) factors, and 6 ABI3/VPs (RAV). The 212 AP2/ERF genes were unevenly distributed on the 20 chromosomes of C. moschata. The results of structural analysis showed the absence of introns on 132 CmoAP2/ERFs. Four pairs of tandem duplication and 155 pairs of segmental duplication events were identified, which indicated that segmental duplications might be the main reason for the expansion of the CmoAP2/ERF family. The analysis of cis-regulatory elements (CREs) showed that most of the CmoAP2/ERFs contained hormone response elements (ABREs, EREs) in their promoters, suggesting that AP2/ERFs could contribute to the processes regulated by ethylene and abscisic acid. By comparing the transcriptome of ethephon-treated and control plants, we found that 16 CmoAP2/ERFs were significantly upregulated after ethephon treatment. Furthermore, we determined the expression patterns of these genes at different developmental stages of female and male flowers. This study provides insights into the identification, classification, physicochemical property, phylogenetic analysis, chromosomal location, gene structure, motif identification, and CRE prediction of the AP2/ERF superfamily in C. moschata. Sixteen CmoAP2/ERF genes were identified as ethylene-inducible genes. The results of this study will be valuable for understanding the roles of CmoAP2/ERFs in ethylene response and should provide a foundation for elucidating the function of AP2/ERF TFs in C. moschata.
Loop-Mediated Isothermal Amplification for Detection of Plant Pathogens in Wheat (Triticum aestivum)
Authors: Gomez-Gutierrez Sandra V. , Goodwin Stephen B.
Published: March 2022

Wheat plants can be infected by a variety of pathogen species, with some of them causing similar symptoms. For example, Zymoseptoria tritici and Parastagonospora nodorum often occur together and form the Septoria leaf blotch complex. Accurate detection of wheat pathogens is essential in applying the most appropriate disease management strategy. Loop-mediated isothermal amplification (LAMP) is a recent molecular technique that was rapidly adopted for detection of plant pathogens and can be implemented easily for detection in field conditions. The specificity, sensitivity, and facility to conduct the reaction at a constant temperature are the main advantages of LAMP over immunological and alternative nucleic acid-based methods. In plant pathogen detection studies, LAMP was able to differentiate related fungal species and non-target strains of virulent species with lower detection limits than those obtained with PCR. In this review, we explain the amplification process and elements of the LAMP reaction, and the variety of techniques for visualization of the amplified products, along with their advantages and disadvantages compared with alternative isothermal approaches. Then, a compilation of analyses that show the application of LAMP for detection of fungal pathogens and viruses in wheat is presented. We also describe the modifications included in real-time and multiplex LAMP that reduce common errors from post-amplification detection in traditional LAMP assays and allow discrimination of targets in multi-sample analyses. Finally, we discuss the utility of LAMP for detection of pathogens in wheat, its limitations, and current challenges of this technique. We provide prospects for application of real-time LAMP and multiplex LAMP in the field, using portable devices that measure fluorescence and turbidity, or facilitate colorimetric detection. New technologies for detection of plant pathogen are discussed that can be integrated with LAMP to obtain elevated analytical sensitivity of detection.
The Search as Learning Spaceship: Toward a Comprehensive Model of Psychological and Technological Facets of Search as Learning
Authors: von Hoyer Johannes , Hoppe Anett , Kammerer Yvonne , Otto Christian , Pardi Georg , Rokicki Markus , Yu Ran , Dietze Stefan , Ewerth Ralph , Holtz Peter
Published: March 2022

Using a Web search engine is one of today’s most frequent activities. Exploratory search activities which are carried out in order to gain knowledge are conceptualized and denoted as Search as Learning (SAL). In this paper, we introduce a novel framework model which incorporates the perspective of both psychology and computer science to describe the search as learning process by reviewing recent literature. The main entities of the model are the learner who is surrounded by a specific learning context, the interface that mediates between the learner and the information environment, the information retrieval (IR) backend which manages the processes between the interface and the set of Web resources, that is, the collective Web knowledge represented in resources of different modalities. At first, we provide an overview of the current state of the art with regard to the five main entities of our model, before we outline areas of future research to improve our understanding of search as learning processes.
A Bibliometric Analysis of the Landscape of Problem-Based Learning Research (1981–2021)
Authors: Zhang Fan , Wang Hui , Bai Yan , Zhang Huachun
Published: March 2022

Background

Problem-Based Learning (PBL) is an instructional method of hands-on, active learning centered on investigating and resolving messy, real-world problems. This study aims to systematically analyze the current status and hotspots of PBL research and provide insights for research in the field.

Methods

Problem-based learning-related publications were retrieved from the Web of Science Core Collection using “Problem-Based Learning”. Annual publications, countries, institutions, authors, journals, references, and keywords in the field were visually analyzed using the R, VOSviewer, and Microsoft Excel 2019 software.

Results

A total of 2,790 articles and reviews were analyzed, with a steady increase in publications in the field of PBL. Overall, the United States was the major contributor to the study of PBL. Van Der Vleuten CPM was the key researcher in this field. Moreover, most of the publications were published in Medical Education. Keyword analysis showed that current research hotspots focus on the extensions of PBL teaching mode, application of PBL teaching method, and reform of PBL.

Conclusion

Research on PBL is flourishing. Cooperation and exchange between countries and institutions should be strengthened in the future. These findings will provide a better understanding of the state of PBL research and inform future research ideas.
How Flow Experience and Self-Efficacy Define Students’ Online Learning Intentions: View From Task Technology Fit (Framework)
Authors: Huang Hai , Wang Yong
Published: March 2022

The ongoing pandemic has transformed communication modes globally. Especially in the case of higher education, where countermeasures against coronavirus disease 2019 (COVID-19) have affected students’ learning experience. This study emphasized the case of business simulation games, where critical factors were underlined to define learners’ intention to use an online learning environment through the lens of task technology fit (TTF) as a theoretical stance. This study considered the statistical analysis of 523 students who attended the business simulation module online at the tertiary level of education. Findings conclude that flow experience is the most critical factor to define learners’ perceived TTF in the case of an online learning experience. However, the learners’ self-efficacy is significant enough to map learners’ intentions to use an online environment for learning. The study discussed several theoretical and practical implications for learners’ educators and policymakers.
Correlations of Resource Bricolage and Exaptation With Low-Cost Breakthrough Innovations: Moderating Effect of Organizational Agility
Authors: Tang Chaoyong , Shi Yongzhi , Cai Ruilin
Published: March 2022

The mechanism influencing resource bricolage driving low-cost breakthrough innovations remains unclear. By introducing exaptation and organizational agility, this study creates a regulated mediation model, explores effects of resource bricolage on low-cost breakthrough innovations, and analyzes the moderating effect of organizational agility and mediation effect of exaptation. The results revealed that resource bricolage exerted a significant positive impact on low-cost breakthrough innovations, and exaptation played a mediation role between resource bricolage and low-cost breakthrough innovations. In addition, both marketing agility and operational agility positively regulated the correlation between resource bricolage and exaptation. Further research revealed that the mediation effect of exaptation was positively regulated by marketing agility and operational agility, respectively. Overall, this study enriches the discussion of the impact mechanism of breakthrough innovations by resource bricolage and provides valuable enlightenment for enterprises to implement innovation-driven development strategies in the context of economic transformation.
English as a Foreign Language Teachers’ Well-Being, Their Apprehension, and Stress: The Mediating Role of Hope and Optimism
Authors: Yang Hui-min
Published: March 2022

Studies have shown that teachers’ wellbeing has a positive effect on teachers’ learning quality and learners’ performance. Nevertheless, teaching is a stressful and exhausting profession at all academic level with special difficulties about the nature of language education. Tension and fear are still classic challenges in learning, though the concepts such as hope and optimism are core issues in assisting teachers to feel happy during instruction and work longer. The present review makes efforts to provide the most current confirmation on the interface of hope and optimism with educational issues since they are progressively documented as significant emotional capitals for educational success, job growth, and presentation. It is worth mentioning that the current review of research can benefit educational administrations, and other stakeholders and officials in the educational community to contemplate the functions of constructive emotions in the process of learning to decrease and even diminish stress and apprehension that consequently lead to flourishing.
Psychological Interventions for Prenatal Anxiety in Latinas and Black Women: A Scoping Review and Recommendations
Authors: Ponting Carolyn , Urizar Guido G. , Dunkel Schetter Christine
Published: March 2022

Anxiety symptoms are common among pregnant women worldwide. In the United States, prenatal anxiety symptoms tend to be elevated among Black and Latin American women as compared to non-Latina White women. Despite the high prevalence of anxiety and associations with adverse maternal and offspring outcomes, interventions have not been developed or tailored sufficiently to Black women or Latinas who need efficacious treatment. This article provides a scoping review of articles published since 2017 that test the effects of randomized and non-randomized psychological interventions designed to reduce prenatal anxiety in samples comprised primarily of ethnic/racial minority women. We also review published protocols of planned psychological interventions to reduce prenatal anxiety in order to highlight novel approaches. In addition to summarizing intervention efficacy and participant acceptability, we highlight gaps in the literature which, if addressed, could improve perinatal mental health equity. Finally, we discuss future directions in prenatal anxiety intervention science beginning preconception including intervention design and prevention models.
How to Deal With Vaccine Breakthrough Infection With SARS-CoV-2 Variants
Authors: Guo Ying , Meng Jun , Liu Caide , Chen Guosheng , Chi Yuhua , Zheng Shiliang , Wang Haixia
Published: March 2022

Novel Coronary Pneumonia is the most infectious disease with the highest number of morbidity and mortality in 100 years. Despite aggressive and effective COVID-19 prevention and control measures, countries have been unable to stop its outbreaks. With the widespread use of vaccines, the occurrence of COVID-19 has declined markedly. April 21, 2021, New York scholars reported Vaccine Breakthrough Infections with SARS-CoV-2 Variants, which immediately attracted widespread attention. In this mini-review, we focus on the characteristics of SARS-CoV-2 and its mutant strains and vaccine breakthrough infections. We have found that outbreaks of vaccine-breaking SARS-CoV-2 Delta infections in many countries are primarily the result of declining vaccine-generated antibody titers and relaxed outbreak management measures. For this reason, we believe that the main response to vaccine-breaking infections with the SARS-CoV-2 variant is to implement a rigorous outbreak defense policy and vaccine application. Only by intensifying the current vaccination intensity, gradually improving the vaccine and its application methods, and strengthening non-pharmaceutical measures such as travel restrictions, social distancing, masking and hand hygiene, can the COVID-19 outbreak be fully controlled at an early date.
Association Between Fatigue and Falls Risk Among the Elderly Aged Over 75 Years in China: The Chain Mediating Role of Falls Efficacy and Lower Limb Function
Authors: He Yudi , Zhang Huaguo , Song Mi , Wu Hongyi , Pi Hongying
Published: March 2022

Background

Although fatigue has been shown to be strongly associated with falls risk, very few studies have focused on its mechanism involved in community-dwelling older subjects. The purpose of this study was to explore the relationship between fatigue and falls risk and its internal mechanism by constructing a chain mediation model.

Methods

A cross-sectional study design was adopted. A convenience sample of 270 older adults was recruited from July to October 2021 in an urban community, in Beijing, China. The participants completed the 14-item Fatigue Scale (FS-14), Falls Efficacy Scale International (FES-I), the Short Physical Performance Battery (SPPB) and Fall-Risk Self-Assessment Questionnaire (FRQ) to measure fatigue, falls efficacy, lower limb function and falls risk. The theory of unpleasant symptoms was used as a conceptual framework. Structural equation modeling (SEM) was utilized to test the hypothetical model.

Results

The overall fit of final model was found to be satisfactory: χ2/df = 1.61, CFI = 0.971, TLI = 0.962, RMSEA = 0.049 (95% CI 0.030/0.066) and SRMR = 0.023. Fatigue had a direct effect on falls risk (β = 0.559, S.E. = 0.089, 95% CI 0.380/0.731), and it also had indirect effects on falls risk (β = 0.303, S.E. = 0.072, 95% CI 0.173/0.460) through mediating factors. Falls efficacy and lower limb function were the main mediating variables, and there was a chain mediating effect (β = 0.015, S.E. = 0.010, 95% CI 0.003/0.046).

Conclusions

Our study suggests that fatigue can influence falls risk among the elderly in China. There are many mediating paths between fatigue and falls risk. These results may help healthcare professionals to better understand the inherent relationship between fatigue and fall risk that may benefit older adults.
Fusobacterium nucleatum Subspecies Differ in Biofilm Forming Ability in vitro
Authors: Muchova Maria , Balacco Dario L. , Grant Melissa M. , Chapple Iain L. C. , Kuehne Sarah A. , Hirschfeld Josefine
Published: March 2022

Development of dysbiosis in complex multispecies bacterial biofilms forming on teeth, known as dental plaque, is one of the factors causing periodontitis. Fusobacterium nucleatum (F. nucleatum) is recognised as a key microorganism in subgingival dental plaque, and is linked to periodontitis as well as colorectal cancer and systemic diseases. Five subspecies of F. nucleatum have been identified: animalis, fusiforme, nucleatum, polymorphum, and vincentii. Differential integration of subspecies into multispecies biofilm models has been reported, however, biofilm forming ability of individual F. nucleatum subspecies is largely unknown. The aim of this study was to determine the single-subspecies biofilm forming abilities of F. nucleatum ATCC type strains. Static single subspecies F. nucleatum biofilms were grown anaerobically for 3 days on untreated or surface-modified (sandblasting, artificial saliva, fibronectin, gelatin, or poly-L-lysine coating) plastic and glass coverslips. Biofilm mass was quantified using crystal violet (CV) staining. Biofilm architecture and thickness were analysed by scanning electron microscopy and confocal laser scanning microscopy. Bioinformatic analysis was performed to identify orthologues of known adhesion proteins in F. nucleatum subspecies. Surface type and treatment significantly influenced single-subspecies biofilm formation. Biofilm formation was overall highest on poly-L-lysine coated surfaces and sandblasted glass surfaces. Biofilm thickness and stability, as well as architecture, varied amongst the subspecies. Interestingly, F. nucleatum ssp. polymorphum did not form a detectable, continuous layer of biofilm on any of the tested substrates. Consistent with limited biofilm forming ability in vitro, F. nucleatum ssp. polymorphum showed the least conservation of the adhesion proteins CmpA and Fap2 in silico. Here, we show that biofilm formation by F. nucleatum in vitro is subspecies- and substrate-specific. Additionally, F. nucleatum ssp. polymorphum does not appear to form stable single-subspecies continuous layers of biofilm in vitro. Understanding the differences in F. nucleatum single-subspecies biofilm formation may shed light on multi-species biofilm formation mechanisms and may reveal new virulence factors as novel therapeutic targets for prevention and treatment of F. nucleatum-mediated infections and diseases.
Can the Ratio SUVmax of the Lesion/SUVmax of Mediastinal Tissues Guide the Choice of Surgical Access for the Resection of Thymic Epithelial Tumors?
Authors: Moraitis Sotirios D. , Agrafiotis Apostolos C. , Skoura Evangelia , Kalkanis Dimitrios , Moraitis Dimitrios , Tomos Periklis , Liakakos Theodoros , Angouras Dimitrios
Published: March 2022

Background

There are studies showing the utility of the 18-fluorodeoxyglucose positron emission tomography (18FDG PET) scan in the management of patients with thymic epithelial tumors. It seems to be a correlation between the standard uptake value (SUVmax) of thymic epithelial tumors and the histological type and the stage. This study aims to use the ratio of the SUVmax of the lesion to the SUVmax of the adjacent mediastinal tissues in order to guide the choice of the surgical access.

Methods

All patients who presented an anterior mediastinal lesion with a high suspicion of being of thymic origin were included in a prospective database. A ratio inferior to 1 could predict a benign nature and less aggressive behavior, and a minimally invasive approach was performed. A ratio superior to 1 suggested a malignant and aggressive behavior, and a median sternotomy (or a thoracotomy) was performed.

Results

There were 15 male (mean age 44.6 ± 16.26 years, range 25–73) and 15 female patients (mean age 50.1 ± 16.94 years, range 25–76). When the ratio is inferior to 1, it predicts benign disease in 80% of cases. When it is superior to 1, it predicts in half of cases advanced histological types (high risk thymomas and thymic carcinomas). On the contrary, it can quite accurately predict advanced Masaoka–Koga stages.

Conclusions

The protocol of this study is in accordance with the current literature showing the utility of 18FDG PET scan in the treatment of thymic epithelial tumors. This study goes one step further since the choice of surgical access is based on the SUVmax values. The ratio SUVmax of the lesion/SUVmax of the mediastinal tissues could be a new marker, more pertinent than absolute SUVmax values.
Survival After Lobectomy vs. Sublobar Resection for Stage IA Large-Cell Neuroendocrine Carcinoma of the Lung: A Population-Based Study
Authors: Yu Xiangyang , Zhang Mengqi , Wang Feifei , Guo Xiaotong , Ma Kai , Wang Lixu , Zhao Hongbo , Xiao Hua , Huang Chujian , Du Longde , Jia Ran , Yang Yikun , Zhang Lanjun , Yu Zhentao
Published: March 2022

Objective

Due to the low incidence of pulmonary large cell neuroendocrine carcinoma (LCNEC), the survival analysis for comparing lobectomy and sublobar resection (SLR) for stage IA LCNEC remains scarce.

Methods

Patients diagnosed with pathological stage IA LCNEC between 1998 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The oncological outcomes were cancer-specific survival (CSS) and overall survival (OS). Kaplan–Meier analysis and Cox multivariate analysis were used to identify the independent prognostic factors for OS and CSS. Furthermore, propensity score matching (PSM) was performed between SLR and lobectomy to adjust the confounding factors.

Results

A total of 308 patients with stage IA LCNEC met the inclusion criteria: 229 patients (74.4%) received lobectomy and 79 patients (25.6%) received SLR. Patients who underwent SLR were older (P < 0.001), had smaller tumor size (P = 0.010), and less lymph nodes dissection (P < 0.001). The 5-year CSS and OS rates were 56.5 and 42.9% for SLR, and 67.8 and 55.7% for lobectomy, respectively (P = 0.037 and 0.019, respectively). However, multivariate analysis did not identify any differences between the SLR group and lobectomy group in CSS (P = 0.135) and OS (P = 0.285); and the PSM also supported these results. In addition, the age at diagnosis and laterality of tumor were identified as significant predictors for CSS and OS, whereas the number of lymph nodes dissection was a significant predictor for CSS.

Conclusions

Although SLR is not inferior to lobectomy in terms of oncological outcomes for patients with stage IA LCNEC, more lymph nodes can be dissected or sampled during lobectomy. Lobectomy should still be considered as a standard procedure for patients with early-stage LCNEC who are able to withstand lobectomy.
Influence of Fine Management Combined With PDCA Cycle Method on Disinfection Qualified Rate and Performance Grade of Ophthalmic Precision Instruments
Authors: Zeng Fanli , Wang Xiuling , Gao Yan , Hu Ling
Published: March 2022

Objective

The aim of this study is to explore the influence of fine management combined with the plan-do-check-action (PDCA) cycle method on the management of ophthalmic precision instruments.

Methods

The ophthalmic precision instruments centralized in the disinfection supply room of our hospital were selected as the research objects and divided into groups A and B. Traditional instrument management method was adopted in group A, and fine management combined with the PDCA cycle method based on the group A was adopted in group B. The instrument management risk scores, the qualified rate of disinfection, instrument performance grade, and incidence of toxic anterior segment syndrome (TASS) of the two groups were compared.

Results

The risk scores of instrument management and incidence of TASS in group B were lower than those in group A (p < 0.05). The qualified rate of disinfection and instrument performance grades in group B were higher than those in group A (p < 0.05).

Conclusion

Fine management combined with the PDCA cycle method can improve the qualified rate of disinfection of ophthalmic precision instruments, optimize the performance of instruments, reduce the risk of instrument management, and reduce the incidence of TASS.
Qualitative and Quantitative Changes in Total Lipid Concentration and Lipid Fractions in Liver Tissue of Periparturient German Holstein Dairy Cows of Two Age Groups
Authors: Theinert Kirsten B. , Snedec Teja , Pietsch Fabian , Theile Sabrina , Leonhardt Anne-Sophie , Spilke Joachim , Pichelmann Stefan , Bannert Erik , Reichelt Kristin , Dobeleit Gabriele , Fuhrmann Herbert , Baumgartner Walter , Schären-Bannert Melanie , Starke Alexander
Published: March 2022

Fatty liver syndrome (FLS) is a common disease in high-producing dairy cows. Studies in humans suggest that the different hepatic lipid fractions play a role in this context. In dairy cows, little is known about the composition of fat stored in the liver, its periparturient dynamics, and the effect of cows' age. Therefore, our goal was to generate primary data in healthy cows to serve as reference values for future studies. Eight healthy German Holstein cows (2nd lactation, n = 3; ≥3rd lactation, n = 5) were examined 14 d antepartum and 7, 28, and 42 d postpartum. The examinations included clinical assessment, liver biopsy, blood sampling, and recording of milk yield. Total lipids (TL) in liver tissue were measured gravimetrically. The TL were separated into lipid fractions (triacylglycerol, TAG; phospholipids, PL; non-esterified fatty acids, NEFA; and cholesterol esters) using thin-layer chromatography, followed by gas chromatography for fatty acid determination. Concentrations of NEFA, ß-hydroxybutyrate, and cholesterol were analyzed in blood. Concentrations of TL, TAG, NEFA, and cholesterol esters in liver tissue and NEFA in blood increased in the periparturient period. The older cows had higher hepatic TL, TAG, and PL concentrations, higher relative hepatic concentrations of TAG in TL, higher NEFA concentrations in blood, a greater decrease in body condition, and higher milk yields between d 9 and 40 than the younger cows. We proposed that due to higher milk yield, older cows mobilized and deposited more fat in the liver, and the increase in hepatic TAG concentration was longer-lasting than in younger cows. Higher levels of structural lipids (PL) in older cows could be explained by higher demand for storage of TAG and cholesterol esters in lipid droplets or for the export of TAG via very-low-density lipoproteins. Results show that hepatic fat storage is a reversible process and does not necessarily cause clinical disease. Nevertheless, older cows have a more sustained and greater increase in hepatic TAG concentration, which may explain their increased risk of FLS. The results are limited in their extrapolation due to the small sample size and thereby possible selection bias but present a valuable basis for future studies.
Comparison of the Evaluation of Combination of Ultrasonography of the Reproductive Tract With Hormone Administration on Dairy Cow Fertility
Authors: Wang Bingke , Xiao Jinbang , Ma Yongjie , Gao Chuxi , Li Hanbing , Jia Yonghong , Jin Yaping , Lin Pengfei
Published: March 2022

Further optimization of reproduction management programs in dairy cows is a contemporary research topic. In this context, our study aimed to compare a hormone program, named “uterus-ovary monitoring and classified use of hormone program” (M+C), with the Pre-OvSynch program. The M+C was based on regular application of B-mode ultrasonography during a voluntary waiting period to monitor the uterus and ovaries, while using various treatments under different conditions. Results of the 30–33-day and 60-day pregnancy/artificial insemination after the first AI of M+C were significantly better than the Pre-OvSynch (p < 0.05). The pregnancy rates within 180 days in milk after M+C was significantly higher than that after Pre-OvSynch (p < 0.05). The total number of inseminations used for M+C was significantly lower than that for Pre-OvSynch (p < 0.01). The number of open days was fewer after M+C than after the Pre–OvSynch throughout the experimental period with highly significant differences (p < 0.01). In summary, the use of M+C enhances reproductive benefits and reduces the need for hormone drugs among cows.
The “WWHow” Concept for Prospective Categorization of Post-operative Severity Assessment in Mice and Rats
Authors: Tappe-Theodor Anke , Pitzer Claudia , Lewejohann Lars , Jirkof Paulin , Siegeler Katja , Segelcke Astra , Drude Natascha , Pradier Bruno , Pogatzki-Zahn Esther , Hollinderbäumer Britta , Segelcke Daniel
Published: March 2022

The prospective severity assessment in animal experiments in the categories' non-recovery, mild, moderate, and severe is part of each approval process and serves to estimate the harm/benefit. Harms are essential for evaluating ethical justifiability, and on the other hand, they may represent confounders and effect modifiers within an experiment. Catalogs and guidelines provide a way to assess the experimental severity prospectively but are limited in adaptation due to their nature of representing particular examples without clear explanations of the assessment strategies. To provide more flexibility for current and future practices, we developed the modular Where-What-How (WWHow) concept, which applies findings from pre-clinical studies using surgical-induced pain models in mice and rats to provide a prospective severity assessment. The WWHow concept integrates intra-operative characteristics for predicting the maximum expected severity of surgical procedures. The assessed severity categorization is mainly congruent with examples in established catalogs; however, because the WWHow concept is based on anatomical location, detailed analysis of the tissue trauma and other intra-operative characteristics, it enables refinement actions, provides the basis for a fact-based dialogue with authority officials and other stakeholders, and helps to identify confounder factors of study findings.
Experimental and Numerical Study on Residual Strength of Honeycomb Sandwich Composite Structure after Lightning Strike
Authors: Wang Yongwei , Zhou Deng , Yan Gang , Wang Zhuangjie
Published: March 2022

Honeycomb sandwich composite structures are widely used in various aircraft structures due to their unique performance. However, honeycomb sandwich composite structures are prone to lightning damage that threatens the structure safety. Therefore, it is necessary to assess the residual mechanical properties of honeycomb sandwich composite structures after a lightning strike. In this study, simulated lightning strike tests were first conducted for honeycomb sandwich panels with and without carbon nanotube film (CNTF) to obtain different damage scenarios and study the protection effect of CNTF. Then, the residual compressive strength of the panels with lightning strike damage was predicted using a progressive damage analysis method and verified with the experimental results. It was found that the numerical prediction results agree with the experimental results. The size and extent of lightning damage have an important effect on the compression damage mode of honeycomb sandwich panel with closed edges.
On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics
Authors: Wilson N. R. C. , Veatch Olivia J. , Johnson Steven M.
Published: March 2022

This review offers an overview of the relationship between diabetes, obstructive sleep apnea (OSA), obesity, and heart disease. It then addresses evidence that the traditional understanding of this relationship is incomplete or misleading. In the process, there is a brief discussion of the evolutionary rationale for the development and retention of OSA in light of blood sugar dysregulation, as an adaptive mechanism in response to environmental stressors, followed by a brief overview of the general concepts of epigenetics. Finally, this paper presents the results of a literature search on the epigenetic marks and changes in gene expression found in OSA and diabetes. (While some of these marks will also correlate with obesity and heart disease, that is beyond the scope of this project). We conclude with an exploration of alternative explanations for the etiology of these interlinking diseases.
Pain Coping Strategies in Pediatric Patients with Acute Leukemias in the First Month of Therapy: Effects of Treatments and Implications on Procedural Analgesia
Authors: Tremolada Marta , Tasso Giulia , Incardona Roberta Maria , Tumino Manuela , Putti Maria Caterina , Biffi Alessandra , Pillon Marta
Published: March 2022

Children with leukemia experience difficulties adapting to medical procedures and to the chemotherapy’s adverse effects. Study’s objectives were to identify which coping strategies could be associated with the treatments’ factors and with the dosage of sedation analgesic drugs during bone marrow aspirates. A total of 125 patients (mean = 6.79 years; standard deviation = 3.40), majority with acute lymphoblastic leukemia (90.4%) and their parents received, one month after diagnosis, the Pediatric Pain Coping Inventory. Data on the severe treatment effects and on the dosage of drugs in sedation-analgesia were also collected. An ANCOVA model (R2 = 0.25) showed that, weighing the age factor (F = 3.47; df = 3; p = 0.02), the number of episodes of fever (F = 4.78; df = 1; p = 0.03), nausea (F = 4.71; df = 1; p = 0.03) and mucositis (F = 5.81; df = 1; p = 0.02) influenced the use of distraction. Cognitive self-instructions (R2 = 0.22) were influenced by the number of hospitalizations (F = 5.14; df = 1; p = 0.03) and mucositis (F = 8.48; df = 3; p = 0.004) and by child’s age (F = 3.76; df = 3; p = 0.01). Children who sought parental support more frequently (F = 9.7; df = 2; p = 0.0001) and who tended not to succumb to a catastrophic attitude (F = 13.33; df = 2; p = 0.001) during the induction treatment phase required lower drug dosages, especially propofol. The clinical application of these results could be to encourage the use of cognitive self-instructions and search for social support.
Targeting Proliferating Tumor-Infiltrating Macrophages Facilitates Spatial Redistribution of CD8+ T Cells in Pancreatic Cancer
Authors: Yang Xiaobao , Lin Jinrong , Wang Guanzheng , Xu Dakang
Published: March 2022

Tumor-associated macrophages (TAMs) play crucial roles in cancer progression, but the contributions and regulation of different macrophage subpopulations remain unclear. Here, we report a high level of TAM infiltration in human and mouse pancreatic ductal adenocarcinoma (PDAC) models and that the targeting of proliferating F4/80+ macrophages facilitated cytotoxic CD8+ T-cell-dependent antitumor immune responses. A well-defined KPC-derived PDAC cell line and the murine Panc02 PDAC cell line were used. Treatment of PDAC-bearing mice with clodronate liposomes, an agent that chemically depletes macrophages, did not impact macrophage subpopulations in the local tumor microenvironment (TME). However, further investigation using both BrdU and Ki67 to evaluate proliferating cells showed that clodronate liposomes treatment reduced proliferating macrophages in the KPC and Panc02 models. We further evaluated the distance between CD8+ T cells and PanCK+ tumor cells, and clodronate liposomes treatment significantly increased the number of CD8+ T cells in close proximity (<30 µm) to PanCK+ PDAC cells, with increased numbers of tumor-infiltrating IFN-γ+CD8+ T cells. This study suggests that targeting proliferating tumor-infiltrating macrophages may increase CD8+ cytotoxic lymphocyte (CTL) infiltration and facilitate the spatial redistribution of CD8+ T cells in tumors, contributing to the antitumor effect.
Fertility Sparing Surgery and Borderline Ovarian Tumours
Authors: Kasaven Lorraine S. , Chawla Mehar , Jones Benjamin P. , Al-Memar Maya , Galazis Nicolas , Ahmed-Salim Yousra , El-Bahrawy Mona , Lavery Stuart , Saso Srdjan , Yazbek Joseph
Published: March 2022

To determine the oncological outcomes following fertility-sparing surgery (FSS) for the management of Borderline Ovarian Tumours (BOTs). A retrospective analysis of participants diagnosed with BOTs between January 2004 and December 2020 at the West London Gynaecological Oncology Centre was conducted. A total of 172 women were diagnosed; 52.3% (90/172) underwent FSS and 47.7% (82/172) non-FSS. The overall recurrence rate of disease was 16.9% (29/172), of which 79.3% (23/29) presented as the recurrence of serous or sero-mucinous BOTs and 20.7% (6/29) as low-grade serous carcinoma (LGSC). In the FSS group, the recurrence rate of BOTs was 25.6% (23/90) presenting a median 44.0 (interquartile range (IQR) 41.5) months, of which there were no episodes of recurrence presenting as LGSC reported. In the non-FSS group, all recurrences of disease presented as LGSC, with a rate of 7.7% (6/78), following a median of 47.5 months (IQR 47.8). A significant difference between the type of surgery performed (FSS v Non-FSS) and the association with recurrence of BOT was observed (Pearson Chi-Square: p = 0.000; x = 20.613). Twelve women underwent ultrasound-guided ovarian wedge resection (UGOWR) as a novel method of FSS. Recurrence of BOT was not significantly associated with the type of FSS performed (Pearson Chi- Square: x = 3.166, p = 0.379). Non-FSS is associated with negative oncological outcomes compared to FSS, as evidenced by the higher rate of recurrence of LGSC. This may be attributed to the indefinite long-term follow up with ultrasound surveillance all FSS women undergo, enabling earlier detection and treatment of recurrences.
WISP2/CCN5 Suppresses Vasculogenic Mimicry through Inhibition of YAP/TAZ Signaling in Breast Cancer Cells
Authors: Ferrand Nathalie , Fert Aude , Morichon Romain , Radosevic-Robin Nina , Zaoui Maurice , Sabbah Michèle
Published: March 2022

Vasculogenic mimicry (VM) formed by aggressive tumor cells to create vascular networks connected with the endothelial cells, plays an important role in breast cancer progression. WISP2 has been considered as a tumor suppressor protein; however, the relationship between WISP2 and VM formation remains unclear. We used the in vitro tube formation assay and in vivo immunohistochemical analysis in a mouse model, and human breast tumors were used to evaluate the effect of WISP2 on VM formation. Here we report that WISP2 acts as a potent inhibitor of VM formation in breast cancer. Enforced expression of WISP2 decreased network formation while knockdown of WISP2 increased VM. Mechanistically, WISP2 increased retention of oncogenic activators YAP/TAZ in cytoplasm, leading to decreased expression of the angiogenic factor CYR61. Studies using an in vivo mouse model and human breast tumors confirmed the in vitro cell lines data. In conclusion, our results indicate that WISP2 may play a critical role in VM and highlight the critical role of WISP2 as a tumor suppressor.
Comparison of MTA versus Biodentine in Apexification Procedure for Nonvital Immature First Permanent Molars: A Randomized Clinical Trial
Authors: Tolibah Yasser Alsayed , Kouchaji Chaza , Lazkani Thuraya , Ahmad Ibrahim Ali , Baghdadi Ziad D.
Published: March 2022

This study aimed to evaluate the radiological and clinical outcomes of Biodentine apical plugs compared to mineral trioxide aggregate (MTA) in treating immature molars with apical lesions in children. Materials and Methods: Thirty immature roots of 24 permanent lower first molars with apical lesions were randomly divided into two groups: group 1 (15 roots) treated with MTA apical plugs and group 2 (15 roots) treated with Biodentine apical plugs. Treatment radiological outcomes were assessed using the periapical index (PAI) scale after 6 and 12 months of treatment. The presence or absence of apical calcified barrier (ACB) was assessed after 12 months of treatment. The visual analog scale (VAS) was used to compare the postoperative pain between the two groups after 1, 3, 7, and 14 days of treatment. PAI scores between the two groups were compared using the Mann–Whitney U test, the presence or absence of the ACB was compared using the chi-square test, and the VAS scores were compared using the t-test. The statistical significance threshold was set at 0.05. Results: There were no statistically significant differences in the PAI between the two groups at 6 and 12 months postoperatively. After 12 months, four cases in the Biodentine group showed ACB formation, whereas ACB was not found in any case treated with MTA. The VAS scores were statistically lower in the MTA group on the first day after treatment. Nevertheless, these scores were not statistically significantly different after 3, 7, and 14 days of treatment between the two groups. Conclusions: Biodentine can be used as an apical plug to treat immature permanent molars with apical lesions in a single visit in children. Biodentine showed favorable outcomes in apical lesions healing, which was comparable to MTA but with a decreased treatment time associated with its use.