bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurses’ turnover intention, hope and career identity: the mediating role of job satisfaction
Authors: Hu Huiling , Wang Chongkun , Lan Yue , Wu Xue
Published: February 2022

Background

A high turnover rate has become a critical issue in the field of nursing and how to tackle the problem of nursing turnover has received increased attention worldwide. Hope, career identity, job satisfaction may be useful for reducing turnover. The aim of this study is to explore the relationships among career identity, hope, job satisfaction, and the turnover intention of nurses, and to test the mediating role of job satisfaction on the associations of hope and career identity with turnover intention.

Methods

A descriptive cross-sectional design was used. A total of 500 nurses were recruited from five comprehensive tertiary hospitals using convenience sampling. The questionnaire included items about sociodemographic information as well as the Adult Dispositional Hope Scale, Nursing Career Identity Scale, Job Satisfaction Index Scale, and Nurse Turnover Intention Scale. Pearson’s correlation, multiple linear regression, and structural equation modeling were used to analyze the data. We describe the study in accordance with the STROBE statement.

Results

Hope (r = − 0.227, p < 0.001) and career identity (r = − 0.342, p < 0.001) were negatively correlated with turnover intention. Job satisfaction played a completely mediating role on the associations of hope and career identity with turnover intention (β1 = − 0.09, β2 = − 0.33).

Conclusions

Job satisfaction mediated the associations of career identity and hope with turnover intention. Thus, effective measures can be taken to enhance nurses’ hope and career identity in order to improve their job satisfaction and thereby reduce their turnover intention. Providing nurses with more support, helping them find a spiritual foundation, and holding mindful activities that stimulate positive emotions are helpful. In addition, colleges should pay more attention to instilling nursing students with career identity and nursing values.
Onchocerca lupi in imported dogs in the UK: implications for animal and public health
Authors: McGarry John W. , Carrozza Rossella , Bradley Claire , Latrofa Maria S. , Makepeace Benjamin L. , Otranto Domenico
Published: February 2022

Background

Onchocerca lupi is a filarial nematode affecting dogs, and occasionally cats and humans, in continental Europe, North Africa, the Middle East, and the USA. Adult worms are usually found in periocular nodules and enucleation is sometimes required if the infection fails to respond to other treatment options.

Case presentation

Here, we report the presence of O. lupi in the UK for the first time. Of two dogs re-homed from continental Europe, one developed an ocular nodule seven years after arrival from Portugal. The conjunctival perilimbal mass in its left eye was surgically removed but despite anthelminthic treatment, a further nodule developed in the same eye six months later. In the second case - a dog imported from Romania 12 months earlier - a perilimbal mass was excised from the left eye and prior anthelminthic treatment was supplemented with oral prednisolone and doxycycline. However, nodules recurred, and the left globe was subsequently enucleated. Conjunctival hyperaemia then appeared in the right eye and neither additional anthelminthic treatment nor removal of worm masses failed to prevent the further development of lesions. Excised adult worms were identified in both cases as O. lupi based on morphological characteristics, as well as PCR and sequencing of cytochrome c oxidase subunit I and 12S rRNA gene fragments.

Conclusion

O. lupi parasitosis can apparently remain cryptic in dogs for several years before any clinical signs manifest. Moreover, the progression of infection can be highly aggressive and recalcitrant to both surgical intervention and anthelminthic treatment. Increasingly, former stray dogs of unknown infection status are entering the UK, raising both veterinary and public health concerns.
Mortality analysis of captive red panda cubs within Chengdu, China
Authors: Liu Songrui , Li Yunli , Zhang Dongsheng , Su Xiaoyan , Yue Chanjuan , E.Ayala James , Yan Xia , Hou Rong , Li Lin , Xie Yi , Zhuo Guifu , McManamon Rita , Yang Kuixing
Published: February 2022

Background

The red panda has been classified as an endangered species due to the decreased number in the world and disease is considered as a great threat to the health and survival of the cubs in captivity.

Results

This study analyzed 32 red panda cub mortalities (15 females and 17 males, age less than two months) through gross necropsy, microbiological examination, and histopathological observation at the Chengdu Research Base of Giant Panda Breeding, China, during 2014–2020. The results showed that screenings for canine distemper virus, canine parvovirus, rotavirus and parasite infection were all negative, however bacteria such as Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli, Enterococcus faecalis, Pseudomonas were isolated from the tissue samples of some cubs. The major causes of death were respiratory (43.75%) and digestive system disease (28.13%), followed by cardiovascular disease (12.5%) and neonatal stillbirths (9.38%). Renal system diseases and trauma were also detected, at lower incidence (one case for each). The mortality rate within 15 days of birth was 68.75% and gradually decreased with age, there was no significant difference in gender.

Conclusion

This study can provide a scientific basis for the analysis of the cause of death among red panda cubs in captivity, so as to improve the survival rate, help build the captive population and further the ex-situ conservation management of this endangered species. Additionally, our research may also provide insights into the in-situ conservation of wild red pandas by identifying emerging disease threats within the wild population and potential treatment for rescued individuals.
Cumulative triglyceride-glucose index is a risk for CVD: a prospective cohort study
Authors: Cui Haozhe , Liu Qian , Wu Yuntao , Cao Liying
Published: February 2022

Background

Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and cardiovascular disease (CVD). However, the long-term effect of TyG index and incident CVD remains uncertain. This study aimed to investigate the association between cumulative TyG index and the risk of CVD.

Method

In this study, we recruited individuals participating in Kailuan Study from 2006 to 2013 without stroke, myocardial infarction, and cancer in the four consecutive examinations. Cumulative TyG index was calculated by multiplying the average TyG index and the time between the two consecutive examinations. Cumulative TyG index levels were categorized into four quartile groups: Q1 group, ≤ 50.65 (as reference group), Q2 group, 50.65–53.86, Q3 group, 53.86–57.44, Q4 group, > 57.44. The association between cumulative TyG index and the risk of CVD was estimated by multivariable Cox proportional hazard models.

Result

A total of 44,064 individuals participated in the final analysis. After a mean follow-up of 6.52 ± 1.14 years, incident CVD, MI and stroke occurred in 2057, 395 and 1695, respectively. The risk of developing CVD increased with the quartile of cumulative in TyG index, after adjustment for multiple potential confounders, the HR for CVD events were 1.25 (1.08–1.44) in Q2, 1.22 (1.05–1.40) in Q3 and 1.39 (1.21–1.61) in Q4, compared to Q1 group. The longer duration of higher TyG index exposure was significantly associated with increased CVD risk. Similar results were obtained in the subgroup and sensitivity analysis.

Conclusion

Cumulative TyG index was associated with increased risk of CVD. Maintaining an appropriate level of TG and FBG within the desirable range and better control of cumulative TyG index are important for prevention of CVD.
FERMT1 contributes to the migration and invasion of nasopharyngeal carcinoma through epithelial–mesenchymal transition and cell cycle arrest
Authors: Li Lingling , Li Piao , Zhang Wei , Zhou Haiting , Guo Ergang , Hu Guoqing , Zhang Linli
Published: February 2022

Background

Fermitin family member 1 (FERMT1) is significantly overexpressed in human cancers and associated with poor prognosis, but its contributions to tumorigenesis and nasopharyngeal carcinoma (NPC) progression remain unclear.

Methods

The public GEO database was examined to investigate the role of FERMT1. Immunohistochemistry (IHC) staining of FERMT1 was performed in NPC tissues to corroborate the results. Western blotting and qRT-PCR were performed to test the expression of related proteins and mRNAs. Cell counting kit-8 assay (CCK8 assay) and colony formation assays were carried out to investigate the association of FERMT1 expression with NPC cell proliferation. The wound healing assay and Transwell assay were used to detect the migration and invasion of NPC cells. Flow cytometric analysis was conducted to detect the cell cycle transition of NPC cells. Co-immunoprecipitation (Co-IP) was employed to identify the correlation of FEMRT1 and Nod-like receptor family protein 3 (NLRP3). Xenograft tumors were generated to investigate the effect of FERMT1 on the growth of NPC cells in vivo.

Results

Here, we found that FERMT1 was upregulated in NPC tissues and correlated with the clinicopathological characteristics of NPC patients. Moreover, knockdown of FERMT1 significantly decreased cell proliferation, migration and invasion by mediating epithelial–mesenchymal transition (EMT) and cell cycle arrest of NPC cells both in vitro and in vivo. Knockdown FERMT1 inhibited EMT through directly binding to the NLRP3 and inhibited NF-kB signaling pathway.

Conclusion

These data indicated that FERMT1 could be a good potential therapeutic target for NPC treatment.
Long non-coding RNAs as the critical regulators of epithelial mesenchymal transition in colorectal tumor cells: an overview
Authors: Hamidi Amir Abbas , Khalili-Tanha Ghazaleh , Nasrpour Navaei Zahra , Moghbeli Meysam
Published: February 2022

Colorectal cancer (CRC) is the second most common cause of cancer mortality and a major health challenge worldwide. Despite advances in therapeutic and diagnostic methods, there is still a poor prognosis in CRC patients. Tumor recurrence and metastasis are the main causes of high mortality rate in these patients, which are due to late diagnosis in advanced tumor stages. Epithelial-mesenchymal transition (EMT) is known to be the most important cause of CRC metastasis, during which tumor cells obtain metastasis ability by losing epithelial features and gaining mesenchymal features. Long non-coding RNAs (lncRNAs) are pivotal regulators of EMT process. Regarding the higher stability of lncRNAs compared with coding RNAs in body fluids, they can be used as non-invasive diagnostic markers for EMT process. In the present review, we summarized all of the lncRNAs involved in regulation of EMT process during CRC progression and metastasis. It was observed that lncRNAs mainly induced the EMT process in CRC cells by regulation of EMT-related transcription factors, Poly comb repressive complex (PRC), and also signaling pathways such as WNT, NOTCH, MAPK, and Hippo.
Methyltransferase like 7B is a potential therapeutic target for reversing EGFR-TKIs resistance in lung adenocarcinoma
Authors: Song Huibin , Liu Dongcheng , Wang Lingwei , Liu Kaisheng , Chen Chen , Wang Le , Ren Yi , Ju Bing , Zhong Fuhua , Jiang Xingyu , Wang Guangsuo , Chen Zhe-Sheng , Zou Chang
Published: February 2022

Background

Identification of potential novel targets for reversing resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) holds great promise for the treatment of relapsed lung adenocarcinoma (LUAD). In the present study, we aim to investigate the role of methyltransferase-like 7B (METTL7B) in inducing EGFR-TKIs resistance in LUAD and whether it could be a therapeutic target for reversing the resistance.

Methods

METTL7B-overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX) and Patient-Derived tumor Xenograft (PDX) mouse models were employed to evaluate the role of METTL7B in TKIs resistance. Ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was used to identify the metabolites regulated by METTL7B. Methylated RNA immunoprecipitation (MeRIP)-qPCR analysis was performed to measure the N6-methyladenosine (m6A) status of mRNA of METTL7B targeted genes. Gold nanocluster-assisted delivery of siRNA targeting METTL7B (GNC-siMETTL7B) was applied to evaluate the effect of METTL7B in TKIs resistance.

Results

Increased expression of METTL7B was found in TKIs-resistant LUAD cells and overexpression of METTL7B in LUAD cells induced TKIs resistance both in vitro and in vivo. Activated ROS-metabolism was identified in METTL7B-overexpressed LUAD cells, accompanied with upregulated protein level of GPX4, HMOX1 and SOD1 and their enzymatic activities. Globally elevated m6A levels were found in METTL7B-overexpressed LUAD cells, which was reduced by knock-down of METTL7B. METTL7B induced m6A modification of GPX4, HMOX1 and SOD1 mRNA. Knock-down of METTL7B by siRNA re-sensitized LUAD cells to gefitinib and osimertinib both in vitro and in vivo.

Conclusions

This study uncovered a new critical link in METTL7B, glutathione metabolism and drug resistance. Our findings demonstrated that METTL7B inhibitors could be used for reversing TKIs resistance in LUAD patients.
Prognostic significance of visit-to-visit variability, and maximum and minimum LDL cholesterol in diabetes mellitus
Authors: Sheng Chang-Sheng , Miao Ya , Ding Lili , Cheng Yi , Wang Dan , Yang Yulin , Tian Jingyan
Published: February 2022

Background

Current guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 70 mg/dL. The present study investigated the prognostic significance of visit-to-visit variability in LDL-C, and minimum and maximum LDL-C during follow-up in diabetes mellitus.

Methods

The risk of outcomes in relation to visit-to-visit LDL-C variability was investigated in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. LDL-C variability indices were coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Multivariable Cox proportional hazards models were employed to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI).

Results

Compared with the placebo group (n=2667), the fenofibrate therapy group (n=2673) had a significantly (P<0.01) lower mean plasma triglyceride (152.5 vs. 178.6 mg/dL), and total cholesterol (158.3 vs.162.9 mg/dL) but a similar mean LDL-C during follow-up (88.2 vs. 88.6 mg/dL, P>0.05). All three variability indices were associated with primary outcome, total mortality and cardiovascular mortality both in the total population and in the fenofibrate therapy group but only with primary outcome in the placebo group. The minimum LDL-C but not the maximum during follow-up was significantly associated with various outcomes in the total population, fenofibrate therapy and placebo group. The minimum LDL-C during follow-up ≥70 mg/dL was associated with an increased risk for various outcomes.

Conclusions

Visit-to-visit variability in LDL-C was a strong predictor of outcomes, independent of mean LDL-C. Patients with LDL-C controlled to less than 70 mg/dL during follow-up might have a benign prognosis.

ClinicalTrials.gov number: NCT 00000620.
Effects of marine-derived and plant-derived omega-3 polyunsaturated fatty acids on erythrocyte fatty acid composition in type 2 diabetic patients
Authors: Liu Hechun , Wang Feng , Liu Xiaosong , Xie Yulan , Xia Hui , Wang Shaokang , Sun Guiju
Published: February 2022

Background

Dietary fatty acids intake affects the composition of erythrocyte fatty acids, which is strongly correlated with glycolipid metabolism disorders. This study aimed at investigating the different effects of marine-derived and plant-derived omega-3 polyunsaturated fatty acid (n-3 PUFA) on the fatty acids of erythrocytes and glycolipid metabolism in patients with type 2 diabetes mellitus (T2DM).

Methods

The randomized double-blinded trial that was performed on 180 T2DM patients. The participants were randomly assigned to three groups for the six-month intervention. The participants were randomly assigned to three groups for the six-month intervention. The fish oil (FO) group was administered with FO at a dose of 3 g/day containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the perilla oil (PO) group was administered with PO at a dose of 3 g/day containing α-linolenic (ALA), the linseed and fish oil (LFO) group was administered with mixed linseed and fish oil at a dose of 3 g/day containing EPA, DHA and ALA. Demographic information were collected and anthropometric indices, glucose and lipid metabolism indexes, erythrocyte fatty acid composition were measured. Statistical analyses were performed using two-way ANOVA.

Results

A total of 150 patients finished the trial, with 52 of them in the FO group, 50 in the PO group and 48 in the LFO group. There were significant effects of time × treatment interaction on fast blood glucose (FBG), insulin, HOMA-IR and C-peptide, TC and triglyceride (TG) levels (P < 0.001). Glucose and C-peptide in PO and LFO groups decreased significantly and serum TG in FO group significantly decreased (P < 0.001) after the intervention. Erythrocyte C22: 5 n-6, ALA, DPA, n-6/n-3 PUFA, AA/EPA levels in the PO group were significantly higher than FO and LFO groups, while EPA, total n-3 PUFA and Omega-3 index were significantly higher in the FO and LFO groups compared to PO group.

Conclusion

Supplementation with perilla oil decreased FBG while fish oil supplementation decreased the TG level. Marine-based and plant-based n-3 PUFAs exhibit different effects on fatty acid compositions of erythrocytes and regulated glycolipid metabolism.

Trial registration

This trial was recorded under Chinese Clinical Trial Registry Center (NO: ChiCTR-IOR-16008435) on May 28 2016.
Controlling supramolecular filament chirality of hydrogel by co-assembly of enantiomeric aromatic peptides
Authors: Yang Xuejiao , Lu Honglei , Tao Yinghua , Zhang Hongyue , Wang Huaimin
Published: February 2022

Supramolecular chirality plays an indispensable role in living and synthetic systems. However, the generation and control of filament chirality in the supramolecular hydrogel of short peptides remains challenging. In this work, as the first example, we report that the heterodimerization of the enantiomeric mixture controls the alignment, chirality, and stiffness of fibrous hydrogels formed by aromatic building blocks. The properties of the resulting racemic hydrogel could not be achieved by either pure enantiomer. Cryo-EM images indicate that the mixture of L and D enantiomers forms chiral nanofibers, the percentage of which can be readily controlled through stoichiometric co-assembly of heterochiral enantiomers. 2D NOESY NMR and diffusion-ordered NMR spectroscopy reveal that heterodimerization of enantiomers plays a crucial role in the formation of chiral nanofibers. Further mechanistic studies unravel the mechanism of supramolecular chirality formation in this two-component system. Molecular dynamics simulations confirm that the intermolecular hydrogen bond and π–π interaction of heterodimers play important roles in forming a chiral hydrogel. Furthermore, regulation of the adhesion and morphology of mammalian cells is achieved by tuning the relative ratio of L and D enantiomers at the same concentration. This work illustrates a novel strategy to control the supramolecular chirality of aromatic peptide hydrogels for materials science.

Graphical Abstract
Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively
Authors: Tao Hong , Liu Zhe , Mu Jing , Gai Fei , Huang Zhan , Shi Liang
Published: February 2022

Introduction

Anaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing.

Case presentation

Case 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4‐ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib.

Conclusions

Our study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.
Optimized synthesis of layered double hydroxide lactate nanosheets and their biological effects on Arabidopsis seedlings
Authors: Wu Hongyang , Zhang He , Li Xinyu , Zhang Yu , Wang Jiankun , Wang Qiang , Wan Yinglang
Published: February 2022

Background

Layered double hydroxide lactate nanosheets (LDH-lactate-NS) are powerful carriers for delivering macro-molecules into intact plant cells. In the past few years, some studies have been carried out on DNA/RNA transformation and plant disease resistance, but little attention has been paid to these factors during LDH-lactate-NS synthesis and delamination, nor has their relationship to the DNA adsorption capacity or transformation efficiency of plant cells been considered.

Results

Since the temperature during delamination alters particle sizes and zeta potentials of LDH-lactate-NS products, we compared the LDH-lactate-NS stability, DNA adsorption rate and delivery efficiency of fluorescein isothiocyanate isomer I (FITC) of them, found that the LDH-lactate-NS obtained at 25 °C has the best characters for delivering biomolecules into plant cell. To understand the potential side effects and cytotoxicity of LDH-lactate-NS to plants, we compared the root growth rate between theArabidopsis thalianaseedlings grown in the culture medium with 1–300 μg/mL LDH-lactate-NS and equivalent raw material, Mg(lactate)2and Al (lactate)3. Phenotypic analysis showed LDH in a range of 1–300 μg/mL can enhance the root elongation, whereas the same concentration of raw materials dramatically inhibited root elongation, suggesting the nanocrystallization has a dramatical de-toxic effect to Mg(lactate)2and Al (lactate)3.Since enhancing of root elongation by LDH is an unexpected phenomenon, we further designed experiments to investigate influence of LDH to Arabidopsis seedlings. We further used the gravitropic bending test, qRT-PCR analysis of auxin transport proteins, non-invasive micro-test technology and liquid chromatography-mass spectrometry to investigate the auxin transport and distribution in Arabidopsis root. Results indicated that LDH-lactate-NS affect root growth by increasing the polar auxin transport.

Conclusions

Optimal synthesized LDH-lactate-NS can delivery biomolecules into intact plant cells with high efficiency and low cytotoxity. The working solution of LDH-lactate-NS can promote root elongation via increase the polar auxin transport in Arabidopsis roots.
A feasibility study for in vivo treatment verification of IMRT using Monte Carlo dose calculation and deep learning-based modelling of EPID detector response
Authors: Zhang Jun , Cheng Zhibiao , Fan Ziting , Zhang Qilin , Zhang Xile , Yang Ruijie , Wen Junhai
Published: February 2022

Background

This paper describes the development of a predicted electronic portal imaging device (EPID) transmission image (TI) using Monte Carlo (MC) and deep learning (DL). The measured and predicted TI were compared for two-dimensional in vivo radiotherapy treatment verification.

Methods

The plan CT was pre-processed and combined with solid water and then imported into PRIMO. The MC method was used to calculate the dose distribution of the combined CT. The U-net neural network-based deep learning model was trained to predict EPID TI based on the dose distribution of solid water calculated by PRIMO. The predicted TI was compared with the measured TI for two-dimensional in vivo treatment verification.

Results

The EPID TI of 1500 IMRT fields were acquired, among which 1200, 150, and 150 fields were used as the training set, the validation set, and the test set, respectively. A comparison of the predicted and measured TI was carried out using global gamma analyses of 3%/3 mm and 2%/2 mm (5% threshold) to validate the model's accuracy. The gamma pass rates were greater than 96.7% and 92.3%, and the mean gamma values were 0.21 and 0.32, respectively.

Conclusions

Our method facilitates the modelling process more easily and increases the calculation accuracy when using the MC algorithm to simulate the EPID response, and has potential to be used for in vivo treatment verification in the clinic.
Knowledge, attitude, and practice of artificial intelligence in emergency and trauma surgery, the ARIES project: an international web-based survey
Authors: De Simone Belinda , Abu-Zidan Fikri M. , Gumbs Andrew A. , Chouillard Elie , Di Saverio Salomone , Sartelli Massimo , Coccolini Federico , Ansaloni Luca , Collins Toby , Kluger Yoram , Moore Ernest E. , Litvin Andrej , Leppaniemi Ari , Mascagni Pietro , Milone Luca , Piccoli Micaela , Abu-Hilal Mohamed , Sugrue Michael , Biffl Walter L. , Catena Fausto
Published: February 2022

Aim

We aimed to evaluate the knowledge, attitude, and practices in the application of AI in the emergency setting among international acute care and emergency surgeons.

Methods

An online questionnaire composed of 30 multiple choice and open-ended questions was sent to the members of the World Society of Emergency Surgery between 29th May and 28th August 2021. The questionnaire was developed by a panel of 11 international experts and approved by the WSES steering committee.

Results

200 participants answered the survey, 32 were females (16%). 172 (86%) surgeons thought that AI will improve acute care surgery. Fifty surgeons (25%) were trained, robotic surgeons and can perform it. Only 19 (9.5%) were currently performing it. 126 (63%) surgeons do not have a robotic system in their institution, and for those who have it, it was mainly used for elective surgery. Only 100 surgeons (50%) were able to define different AI terminology. Participants thought that AI is useful to support training and education (61.5%), perioperative decision making (59.5%), and surgical vision (53%) in emergency surgery. There was no statistically significant difference between males and females in ability, interest in training or expectations of AI (p values 0.91, 0.82, and 0.28, respectively, Mann–Whitney U test). Ability was significantly correlated with interest and expectations (p < 0.0001 Pearson rank correlation, rho 0.42 and 0.47, respectively) but not with experience (p = 0.9, rho − 0.01).

Conclusions

The implementation of artificial intelligence in the emergency and trauma setting is still in an early phase. The support of emergency and trauma surgeons is essential for the progress of AI in their setting which can be augmented by proper research and training programs in this area.
Mineral medicine: from traditional drugs to multifunctional delivery systems
Authors: Zhong Xiaoqing , Di Zhenning , Xu Yuanxin , Liang Qifan , Feng Kuanhan , Zhang Yuting , Di Liuqing , Wang Ruoning
Published: February 2022

Mineral drugs are an important constituent of traditional Chinese medicine (TCM). Taking minerals that contain heavy metals as drugs is a very national characteristic part of TCM. However, the safety and scientific nature of mineral drugs are controversial owing to their heavy metals and strong toxicity. In 2000, the Food and Drug Administration (FDA) authorized arsenic trioxide (ATO) as first-line therapy for acute promyelocytic leukemia. This makes the development and utilization of mineral drugs become a research hotspot. The development of nanomedicine has found a great prospect of mineral drugs in nano-delivery carriers. And that will hold promise to address the numerous biological barriers facing mineral drug formulations. However, the studies on mineral drugs in the delivery system are few at present. There is also a lack of a detailed description of mineral drug delivery systems. In this review, the advanced strategies of mineral drug delivery systems in tumor therapy are summarized. In addition, the therapeutic advantages and research progress of novel mineral drug delivery systems are also discussed. Here, we hope that this will provide a useful reference for the design and application of new mineral drug delivery systems.

Graphical Abstract
Integrating rare disease management in public health programs in India: exploring the potential of National Health Mission
Authors: Choudhury Mohua Chakraborty , Chaube Pragya
Published: February 2022

Rare diseases (RD) are conditions that affect a small number of people and hence do not get the focus on government health priorities in a resource-constrained setting such as India. Therefore, it is essential to focus on strengthening and utilizing the existing public health framework for the optimal usage of healthcare resources. In this regard, National Health Mission (NHM) is one of the crucial programs initiated by the government of India to address the health needs of the under-served. As Phase 1 of the NHM moves towards completion, we explored the Reproductive, Maternal, Newborn, Child, and Adolescent Health (RMNCH + A) program under NHM to assess their potential and limitations to aid RD care. We found that some of the disease-prevention initiatives of NHM address certain RDs and can easily be expanded to manage many such preventable RDs. In addition, NHM programs can provide a unique epidemiological data repository to strengthen the National Rare Disease Registry. These programs can also play important role in providing a continuum of care for many RDs that need lifelong management. However, existing programs have a limited scope to provide specialized RD-related treatments, which is better served in a more focused system. Thus, considering RDs in the design of the existing programs may help RD management better through prevention, data collection, and providing a continuum of care.
Is physical activity a future therapy for patients with Marfan syndrome?
Authors: Jouini Steeve , Milleron Olivier , Eliahou Ludivine , Jondeau Guillaume , Vitiello Damien
Published: February 2022

Introduction

The international recommendations tend to avoid physical activity (PA) for patients with Marfan syndrome (MFS). However, exceptions have recently been made in the most recent recommendations for these patients, suggesting benefits from doing PA at low intensity only. Furthermore, there is no evidence that moderate aerobic or weight training can worsen the disease symptoms and increase mortality of MFS patients. The present review sums up the work carried out in the field of PA and MFS. The review aims to (1) identify the different types of exercise testing and training protocols and (2) discuss the feasibility and potentially beneficial nature of PA as an innovative way to manage MFS patients.

Methods

The scientific literature was reviewed using the following words: Marfan syndrome, training, physical activity, evaluation, weight training, arterial disease, aneurysms, lung damage, aortic dissection, rupture. A total of 345 studies were prospected and 43 studies were included.

Conclusions

A limited number of studies were done in humans, however one demonstrated the feasibility of the management of MFS patients with PA. There were potential beneficial effects of PA on arterial structures, but this review also showed deleterious effects when PA was conducted at high intensities, corresponding to 75–85% of the maximal oxygen uptake. However, these effects have only been reported in animal studies.
A natural marmoset model of genetic generalized epilepsy
Authors: Yang Xiangyu , Chen Zhitang , Wang Ziying , He Guang , Li Zhiqiang , Shi Yongyong , Gong Neng , Zhao Binglei , Kuang Yifang , Takahashi Eiki , Li Weidong
Published: February 2022

Epilepsy has been extensively studied as a common neurological disease. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs for treatment. However, the features of current epilepsy models cannot fully mimic different types of epilepsy in humans, hence non-human primate models of epilepsy are required. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we present a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operations in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that the epileptic phenotype can be inherited. These marmosets were more sensitive to the epilepsy inducers pentylenetetrazol. Using electrocorticogram (ECoG) recordings, we detected epileptiform discharge in marmosets with a history of seizures. In summary, we report a family of marmosets with generalized seizures induced by handling operations. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods.
Cerebral mechanism of opposing needling for managing acute pain after unilateral total knee arthroplasty: study protocol for a randomized, sham-controlled clinical trial
Authors: Zhao Chi , Xu Hui , A Xinyu , Kang Bingxin , Xie Jun , Shen Jun , Sun Songtao , Zhong Sheng , Gao Chenxin , Xu Xirui , Zhou Youlong , Xiao Lianbo
Published: February 2022

Background

Opposing needling is a unique method used in acupuncture therapy to relieve pain, acting on the side contralateral to the pain. Although opposing needling has been used to treat pain in various diseases, it is not clear how opposing needling affects the activity of the central nervous system to relieve acute pain. We herein present the protocol for a randomized sham-controlled clinical trial aiming to explore the cerebral mechanism of opposing needling for managing acute pain after unilateral total knee arthroplasty (TKA).

Methods

This is a randomized sham-controlled single-blind clinical trial. Patients will be allocated randomly to two parallel groups (A: opposing electroacupuncture group; B: sham opposing electroacupuncture group). The Yinlingquan (SP9), Yanglingquan (GB34), Futu (ST32), and Zusanli (ST36) acupoints will be used as the opposing needling sites in both groups. In group A, the healthy lower limbs will receive electroacupuncture, while in group B, the healthy lower limbs will receive sham electroacupuncture. At 72 h after unilateral TKA, patients in both groups will begin treatment once per day for 3 days. Functional magnetic resonance imaging will be performed on all patients before the intervention, after unilateral TKA, and at the end of the intervention to detect changes in brain activity. Changes in pressure pain thresholds will be used as the main outcome for the improvement of knee joint pain. Secondary outcome indicators will include the visual analogue scale (including pain during rest and activity) and a 4-m walking test. Surface electromyography, additional analgesia use, the self-rating anxiety scale, and the self-rating depression scale will be used as additional outcome indices.

Discussion

The results will reveal the influence of opposing needling on cerebral activity in patients with acute pain after unilateral TKA and the possible relationship between cerebral activity changes and improvement of clinical variables, which may indicate the central mechanism of opposing needling in managing acute pain after unilateral TKA.

Trial registration

Study on the brain central mechanism of opposing needling analgesia after total kneearthroplasty based on multimodal MRI ChiCTR2100042429. Registered on January 21, 2021
A sensitive, accurate, and high-throughput gluco-oligosaccharide oxidase-based HRP colorimetric method for assaying lytic polysaccharide monooxygenase activity
Authors: Wu Shuaishuai , Tian Juan , Xie Ning , Adnan Muhammad , Wang Juan , Liu Gang
Published: February 2022

Background

The AA9 (auxiliary activities) family of lytic polysaccharide monooxygenases (AA9 LPMOs) is a ubiquitous and diverse group of enzymes in the fungal kingdom. They catalyse the oxidative cleavage of glycosidic bonds in lignocellulose and exhibit great potential for biorefinery applications. Robust, high-throughput and direct methods for assaying AA9 LPMO activity, which are prerequisites for screening LPMOs with excellent properties, are still lacking. Here, we present a gluco-oligosaccharide oxidase (GOOX)-based horseradish peroxidase (HRP) colorimetric method for assaying AA9 LPMO activity.

Results

We cloned and expressed a GOOX gene from Sarocladium strictum in Trichoderma reesei, purified the recombinant SsGOOX, validated its properties, and developed an SsGOOX-based HRP colorimetric method for assaying cellobiose concentrations. Then, we expressed two AA9 LPMOs from Thielavia terrestris, TtAA9F and TtAA9G, in T. reesei, purified the recombinant proteins, and analysed their product profiles and regioselectivity towards phosphoric acid swollen cellulose (PASC). TtAA9F was characterized as a C1-type (class 1) LPMO, while TtAA9G was characterized as a C4-type (class 2) LPMO. Finally, the SsGOOX-based HRP colorimetric method was used to quantify the total concentration of reducing lytic products from the LPMO reaction, and the activities of both the C1- and C4-type LPMOs were analysed. These LPMOs could be effectively analysed with limits of detection (LoDs) less than 30 nmol/L, and standard curves between the A515 and LPMO concentrations with determination coefficients greater than 0.994 were obtained.

Conclusions

A novel, sensitive and accurate assay method that directly targets the main activity of both C1- and C4-type AA9 LPMOs was established. This method is easy to use and could be performed on a microtiter plate for high-throughput screening of AA9 LPMOs with desirable properties.
Childhood glaucoma registry in Germany: initial database, clinical care and research (pilot study)
Authors: Aghayeva Fidan A. , Schuster Alexander K. , Diel Heidi , Chronopoulos Panagiotis , Wagner Felix M. , Grehn Franz , Pirlich Nina , Schweiger Susann , Pfeiffer Norbert , Hoffmann Esther M.
Published: February 2022

Objective

The aim of this prospective pilot study is to establish an initial database to register patients diagnosed with different types of childhood glaucoma and the set-up of a national registry for childhood glaucoma (ReCG) in Germany. 28 children with different types of diagnosed childhood glaucoma, who were admitted and treated at the Childhood Glaucoma Center of the University Medical Center Mainz, Germany were included. Main outcome measures were the type of childhood glaucoma, mean intraocular pressure (IOP) and genetic data of the patients.

Results

The documents and questionnaires for each individual included: informed consent form of the parents, medical history form of the child, patient’s gestational history questionnaire and general anesthesia examination form. Primary congenital and secondary childhood glaucoma were revealed in 11 (39%) and 17 (61%) patients, respectively. The mean IOP measured with Perkins tonometer in all patients under general anesthesia at the time of inclusion was 17.5 ± 11.8 mmHg in the right and 17 ± 8.9 mmHg in the left eyes. In 33% of children with glaucoma mutations in the CYP1B1, FOXC1, LTBP2 and TEK genes were found. The development of specific questionnaires for childhood glaucoma provides detailed baseline data to establish a ReCG in Germany for the first time.
RNA recovery from specimens of duct-washing cytology performed contemporaneously with mammary ductoscopy
Authors: Jikuzono Tomoo , Manabe Eriko , Kure Shoko , Akasu Haruki , Ishikawa Tomoko , Fujiwara Yoko , Makita Masujiro , Ishibashi Osamu
Published: February 2022

Objective

Conventional cytological diagnosis including duct-washing cytology (DWC) is sometimes performed using ductal epithelial cells collected during mammary ductoscopy; it is useful for detection of early-stage breast cancer such as ductal carcinoma in situ (DCIS). However, conventional cytological diagnosis focuses exclusively on cellular morphology; false negatives and false positives may be caused by inadequate specimen preparation (triggering cell degeneration) or poor examiner diagnostic skills. Molecular diagnosis using RNA biomarkers is expected to compensate for the weaknesses of cytological diagnosis. We previously employed microarray analysis to identify highly expressed genes in DCIS, suggesting that they may be useful for DCIS diagnosis. Here, we explored whether DWC samples yielded RNA of sufficient quantity and quality for RNA biomarker-based diagnosis.

Results

We extracted RNAs from 37 DWC samples. RNA from 12 samples exhibited RNA integrities of  ≥ 6, indicative of moderate-to-high quality. We then showed that cocaine and amphetamine regulated transcript prepropeptide (CARTPT) and breast cancer-associated transcript 54 (BRCAT54) mRNA—previously shown by microarray analysis to be highly expressed in DCIS—were detectable in these samples. Therefore, DWC samples may be useful for molecular diagnosis involving RNA biomarkers.
Characteristics of patients referred to Canary Island pneumology outpatient services for chronic obstructive pulmonary disease: the EPOCan study
Authors: Figueira-Gonçalves Juan Marco , Hernández-Pérez José María , Cabrera-López Carlos , Wangüemert-Pérez Aurelio Luis , García-Talavera Ignacio , Ramallo-Fariña Yolanda , Ramos-Izquierdo Carolina , González-García Luis Manuel , Guanche-Dorta Sara
Published: February 2022

Objective

Assessing patients with chronic obstructive pulmonary disease (COPD) accounts for 30% of all pneumology outpatient evaluations. COPD is a heterogeneous disease and generates a massive public health problem. Overall morbidity, particularly cardiovascular disease, challenges patient management. This is an observational, multicentre study, performed at four hospitals in the Canary Islands (Spain), aimed at characterising patients with COPD referred to pneumology outpatient services. Demographic variables, lung function, and morbidity were assessed.

Results

Of the 877 included patients, 44.9% were active smokers with a mean (± SD) age of 68.2 ± 10.3 years. The median (IQR) score for the Charlson comorbidity index was 2 (2), and 70.6% of the patients were assigned high risk according to the Spanish Guidelines for COPD (GesEPOC) 2021. The degree of airflow obstruction defined by the GOLD 2021 stages 1, 2, 3, and 4 corresponded to 13.6%, 49%, 31%, and 6.3% of patients, respectively. The most frequently associated morbidities were arterial hypertension (59.5%), dyslipidaemia (54.3%), and type 2 diabetes mellitus (31.2%); 32% of the patients suffered heart disease. There is a high prevalence of active smoking, type 2 diabetes mellitus, and heart disease in patients referred for COPD to Canary Island pneumology outpatient services.
Results from the first culturally tailored, multidisciplinary diabetes education in Lebanese adults with type 2 diabetes: effects on self-care and metabolic outcomes
Authors: Sukkarieh-Haraty Ola , Egede Leonard E. , Khazen Georges , Abi Kharma Joelle , Farran Natali , Bassil Maya
Published: February 2022

Objective

Diabetes self-management education (DSME) is an essential component of lifestyle management needed for diabetes care. This pilot-study tested the effect of culturally-tailored education targeting diabetes selfcare on glycemia and cardiovascular risk factors of Lebanese with type 2 diabetes mellitus (T2DM) (n = 27; Age: 61 ± 10 yrs, 59% males, HbA1c: 8.98 ± 1.38%).

Results

Diabetes self-care (Diet, Self-Monitoring Blood Glucose and foot care) improved after 6 months, which was reflected in a significant drop in glycemic levels (HbA1c:-0.5%; FPG: − 38 mg/dl), and cholesterol/HDL ratio (4.45 ± 1.39 vs. 4.06 ± 1.29). Waist circumference decreased at 6 months compared to 3 months (p < 0.05). This is the first effective culturally-tailored intervention that improved self-care, glycemic control, body adiposity and lipid profile of Lebanese with T2DM. Larger scale implementation with representative sample is warranted.
Considerations regarding a diagnosis of Alzheimer’s disease before dementia: a systematic review
Authors: van der Schaar Jetske , Visser Leonie N. C. , Bouwman Femke H. , Ket Johannes C. F. , Scheltens Philip , Bredenoord Annelien L. , van der Flier Wiesje M.
Published: February 2022

Background

The NIA-AA research framework proposes a purely biological definition of Alzheimer’s disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia.

Methods

A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer’s disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis.

Results

We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects.

Conclusions

We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.