bluuebunny/crossref_metadata_2025 huggingface dataset:
New species and new synonyms of Macromotettixoides (Orthoptera: Tetrigidae) with an updated key
Authors: DENG WEI-AN , XIN LEI , ZHANG RONG-JIAO , HUANG CHAO-MEI , XU HAI-QING , TAN LIU-SU , HUANG SU-QIN
Published: September 2020

The genus Macromotettixoides Zheng, Wei & Jiang, 2005 is reviewed. Four new species of the genus, M. daiyunshanensis Deng, sp. nov., M. curvicarina Deng, sp. nov., M. convexa Deng, sp. nov. and M. shengtangshanensis Deng, sp. nov. are described with detailed illustrations of external morphology. Two new synonyms are established: M. jinggangshanensis, syn. nov. is synonymized with M. jiuwanshanensis Zheng, Wei & Jiang, 2005; M. parvula Zha & Wen, 2017, syn. nov. is synonymized with M. undulatifemura Deng, Zheng & Yang, 2012. Additionally, an updated key to species of the genus is given.
Two new genera of Nearctic Chamaemyiidae (Diptera: Lauxanioidea) associated with Cinara aphids (Hemiptera: Aphididae) on Pinus
Authors: GAIMARI STEPHEN D.
Published: September 2020

Two new genera of Chamaemyiidae (Diptera: Lauxanioidea) are described and illustrated, including: Chamaethrix gen. nov. (type species Chamaethrix necopina sp. nov.), possibly a predator of Cinara ponderosae (Williams) on Pinus ponderosa in the southwestern United States; and Vitaleucopis gen. nov. (type species Vitaleucopis nidolkah sp. nov.; other included species Vitaleucopis astonea (McAlpine), comb. nov., and Vitaleucopis scopulus sp. nov.), predators of Cinara aphids and possibly adelgids on Pinaceae in western North America. Immature stages are discussed or described and illustrated for some taxa, including the eggs of Chamaethrix necopina and Vitaleucopis nidolkah; and the third instars and puparia of Vitaleucopis nidolkah.
New data on the fauna of China, part II: the millipede genus Nepalmatoiulus Mauriès, 1983 (Diplopoda, Julidae) in continental China and Taiwan, with descriptions of seven new species
Authors: MIKHALJOVA ELENA V.
Published: September 2020

Nepalmatoiulus is currently represented in continental China and Taiwan by twenty-five species. Seven new species of the genus are described from the China: Nepalmatoiulus lanpingensis sp. nov., Nepalmatoiulus uncinatus sp. nov., Nepalmatoiulus emarginatus sp. nov., Nepalmatoiulus deqenensis sp. nov., Nepalmatoiulus parvulus sp. nov., Nepalmatoiulus acutidentatus sp. nov., Nepalmatoiulus hexiensis sp. nov. Additional material for Nepalmatoiulus tianbaoshanensis Mikhaljova, 2020 is given. A key is given to all Nepalmatoiulus presently known from continental China and Taiwan Island. The distributions of Chinese and Taiwanese Nepalmatoiulus species are discussed. Taxonomic remarks are provided for nearly all new species.
Simulating Passenger Evacuation in Railway Station under Fire Emergency using Safe Zone Approach
Authors: Salarian Amir Hossein , Mashhadizadeh Aida , Bagheri Morteza
Published: September 2020

Railway stations are usually considered to be one of the main gathering centers of the city; thus, in the event of any incident, there will be significant casualties. The purpose of this study is to simulate strategies for reducing the evacuation time of the railway station in the event of fire using a safe zone approach with simulation software. To reduce the evacuation time, 18 scenarios were introduced and simulated according to (1) number of gates and exit doors, (2) width of the gates, (3) obstacles, (4) priority of the exit doors, and (5) safe zone. The results show that the best evacuation time occurs by increasing the number of exit doors from two to four and considering a safe zone simultaneously; the evacuation time is reduced by 7 min and 19 s. Using safe zones for emergency evacuation has a significant role in reducing evacuation time and improving service levels. Interestingly, the removal of gates and obstacles would increase the evacuation time of passengers. The proposed model could be used for renovating existing railway stations to decrease the consequences of accidents such as fire.
Using a Customer Relationship Management System to Manage a Quality Improvement Intervention
Authors: Pham-Singer Hang , Onakomaiya Marie , Cuthel Allison , De Leon Samantha , Shih Sarah , Chow Su , Shelley Donna
Published: September 2020

HealthyHearts New York City (HHNYC), one of 7 cooperatives funded through the Agency for Healthcare Research and Quality’s EvidenceNOW initiative, evaluated the impact of practice facilitation on implementation of the Million Hearts guidelines for cardiovascular disease prevention and treatment. Tracking the intervention required a system to facilitate process data collection that was also user-friendly and flexible. Coupled with protocols and training, a strategically planned and customizable customer relationship management system (CRMS) was implemented to support the quality improvement intervention with 257 small independent practices. Features of the CRMS and implementation protocols were customized to optimize program management, practice facilitation tracking and supervision, and data collection for performance feedback to practices and research. The CRMS was a valuable tool for tracking and managing the intervention systematically. Successful implementation of the HHNYC protocol also required an articulated implementation plan and adoption process.
Caregiver experiences of paediatric inpatient cardiac services: A qualitative systematic review
Authors: Knight Lozano Rachel , May Stephen , Clarkson Carl , Sarjeant Rebecca
Published: September 2020

Background

Advances in paediatric care have contributed to an increasing survival of children with complex heart disease. Yet, life-saving management demands prolonged inpatient admissions, which contribute to emotional and psychological distress for parents and other caregivers in a role of main custody.

Aim

The purpose of this study was to identify, appraise and synthesise qualitative studies exploring caregivers’ experiences of paediatric inpatient cardiac services, generating an understanding of their needs in hospital and informing priorities for change in healthcare delivery.

Methods

Searches were conducted in Medline, Allied and Complimentary Medicine Database, Cumulative Index of Nursing and Allied Health Literature, EMCARE, Scopus, PsychINFO, Proquest, OpenGrey and ETHOs from 2008–2019, reflecting recent advances in cardiac healthcare. Articles were selected using predetermined eligibility criteria dictating qualitative inquiry into caregiver perspectives whilst their child received hospital-based interventions for heart disease. All eligible studies underwent quality appraisal. Framework synthesis was used to analyse and summarise findings.

Results

Twenty-seven studies involving 689 caregivers from 11 countries were included. Three overarching themes were identified: ‘emotional capacity to care’, ‘practicalities of caring’, and ‘the bigger picture of caring’.

Conclusions

Through analysis and summary of qualitative primary research, this review captures the emotional challenges that caregivers face and practicalities of undertaking a caregiver role, whilst looking after their child with heart disease in hospital. The results widen the context of the caregiver role, encompassing the whole family unit beyond the hospital environment. This review exposes the impact of these challenges on caregiver competence, wellbeing and attachment to their unwell child, informing priorities for development of family-centred paediatric inpatient cardiac services.
Applying the COM-B behaviour model to overcome barriers to heart failure self-care: A practical application of a conceptual framework for the development of complex interventions (ACHIEVE study)
Authors: Whittal Amanda , Störk Stefan , Riegel Barbara , Herber Oliver Rudolf
Published: September 2020

Background

Effective interventions to enhance adherence to self-care recommendations in patients with heart failure have immense potential to improve health and wellbeing. However, there is substantial inconsistency in the effectiveness of existing self-management interventions, partly because they lack theoretical models underpinning intervention development.

Aim

To outline how the capability, opportunity and motivation behaviour model has been applied to guide the development of a theory-based intervention aiming to improve adherence to heart failure self-care recommendations.

Methods

The application of the capability, opportunity and motivation behaviour model involved three steps: (a) identification of barriers and facilitators to heart failure self-care from two comprehensive meta-studies; (b) identification of appropriate behaviour change techniques to improve heart failure self-care; and (c) involvement of experts to reduce and refine potential behaviour change techniques further.

Results

A total of 119 barriers and facilitators were identified. Fifty-six behaviour change techniques remained after applying three steps of the behaviour model for designing interventions. Expert involvement (n=39, of which 31 were patients (67% men; 45% New York Heart Association II)) further reduced and refined potential behaviour change techniques. Experts disliked some behaviour change techniques such as ‘anticipated regret’ and ‘salience of consequences’. This process resulted in a final comprehensive list consisting of 28 barriers and 49 appropriate behaviour change techniques potentially enhancing self-care that was put forward for further use.

Conclusion

The application of the capability, opportunity and motivation behaviour model facilitated identifying important factors influencing adherence to heart failure self-care recommendations. The model served as a comprehensive guide for the selection and design of interventions for improving heart failure self-care adherence. The capability, opportunity and motivation behaviour model enabled the connection of heart failure self-care barriers to particular behaviour change techniques to be used in practice.
Fostering international students’ sense of belonging and perceived social support through a semester-long experiential activity
Authors: Caligiuri Paula , DuBois Cathy L.Z. , Lundby Kyle , Sinclair Elizabeth A
Published: September 2020

We tested whether a semester-long classroom experiential activity designed to foster international and domestic student social interaction increases international students’ sense of belonging and perceived social support. Two studies were conducted testing the effectiveness of this experiential activity which was based on the theoretical underpinnings of how social attachment is formed. The first study was a controlled experiment with freshmen university students. When compared to the control group, the students participating in the experiential activity had an increased sense of belonging and perceived social support by the end of the semester, especially when they had lower levels of openness at the onset of starting college. The second study was a longitudinal study conducted with graduate students. The results found that students had an increase in their sense of belonging and perceived social support. These studies suggest that semester-long classroom experiential activities designed to foster international and domestic student social interaction can foster international students’ sense of belonging and social support.
Interferon-β alleviates delayed tPA-induced adverse effects via modulation of MMP3/9 production in ischemic stroke
Authors: Kuo Ping-Chang , Weng Wen-Tsan , Scofield Barbara A. , Furnas Destin , Paraiso Hallel C. , Intriago Alexander J. , Bosi Kristopher D. , Yu I-Chen , Yen Jui-Hung
Published: September 2020

Tissue plasminogen activator (tPA) is the only US Food and Drug Administration (FDA)–approved drug for ischemic stroke. However, delayed tPA administration is associated with increased risk of blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT). Interferon-β (IFNβ), an FDA-approved drug for the treatment of multiple sclerosis, is a cytokine with immunomodulatory properties. Previous studies, including ours, demonstrated that IFNβ or type I IFN receptor signaling conferred protection against ischemic stroke in preclinical models, suggesting IFNβ might have translational therapeutic potential for the treatment of ischemic stroke. Currently, whether IFNβ could be coadministered with tPA to alleviate delayed tPA-induced adverse effects remains unknown. To elucidate that, IFNβ was coadministered with delayed tPA to ischemic stroke animals, and the severity and pathology of ischemic brain injury were assessed. We found delayed tPA treatment exacerbated ischemic brain injury, manifested by aggravated BBB disruption and HT. Notably, IFNβ ameliorated delayed tPA–exacerbated brain injury and alleviated adverse effects. Mechanistic studies revealed IFNβ suppressed tPA-enhanced neuroinflammation and MMP3/9 production in the ischemic brain. Furthermore, we identified IFNβ suppressed MMP9 production in microglia and attenuated tight junction protein degradation in brain endothelial cells. Moreover, we observed that peripheral immune cells may participate to a lesser extent in delayed tPA–exacerbated brain injury during the early phase of ischemic stroke. In conclusion, we provide the first evidence that IFNβ can be coadministered with tPA to mitigate delayed tPA–induced adverse effects of BBB disruption and HT that could potentially extend the tPA therapeutic window for the treatment of ischemic stroke.
CRISPR-Based Diagnosis of Infectious and Noninfectious Diseases
Authors: Jolany vangah Somayeh , Katalani Camellia , Boone Hannah A. , Hajizade Abbas , Sijercic Adna , Ahmadian Gholamreza
Published: September 2020

Interest in CRISPR technology, an instrumental component of prokaryotic adaptive immunity which enables prokaryotes to detect any foreign DNA and then destroy it, has gained popularity among members of the scientific community. This is due to CRISPR’s remarkable gene editing and cleaving abilities. While the application of CRISPR in human genome editing and diagnosis needs to be researched more fully, and any potential side effects or ambiguities resolved, CRISPR has already shown its capacity in an astonishing variety of applications related to genome editing and genetic engineering. One of its most currently relevant applications is in diagnosis of infectious and non-infectious diseases. Since its initial discovery, 6 types and 22 subtypes of CRISPR systems have been discovered and explored. Diagnostic CRISPR systems are most often derived from types II, V, and VI. Different types of CRISPR-Cas systems which have been identified in different microorganisms can target DNA (e.g. Cas9 and Cas12 enzymes) or RNA (e.g. Cas13 enzyme). Viral, bacterial, and non-infectious diseases such as cancer can all be diagnosed using the cleavage activity of CRISPR enzymes from the aforementioned types. Diagnostic tests using Cas12 and Cas13 enzymes have already been developed for detection of the emerging SARS-CoV-2 virus. Additionally, CRISPR diagnostic tests can be performed using simple reagents and paper-based lateral flow assays, which can potentially reduce laboratory and patient costs significantly. In this review, the classification of CRISPR-Cas systems as well as the basis of the CRISPR/Cas mechanisms of action will be presented. The application of these systems in medical diagnostics with emphasis on the diagnosis of COVID-19 will be discussed.
Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro
Authors: Liu Jianzhou , Yang Qing , Xiao Kevin Chen , Dobleman Thomas , Hu Shen , Xiao Gary Guishan
Published: September 2020

Background

The human Obg-like ATPase 1 (OLA1) protein has been reported to play an important role in cancer cell proliferation. The molecular mechanism underlying OLA1 regulated oral metastasis is still unknown. We investigated in this study the regulatory role of OLA1 playing in oral squamous cell metastasis.

Results

A series of in vitro assays were performed in the cells with RNAi-mediated knockdown or overexpression to expound the regulatory function of OLA1 in oral cancer. We found that the endogenous level of OLA1 in a highly metastatic oral squamous cell line was significantly lower than that in low metastatic oral cells as well as in normal oral cells. Escalated expression of OLA1 resulted in a reduced ability of metastasis in highly metastatic cells, and enhanced its sensitivity to the paclitaxel treatment. Further analysis of the EMT markers showed that Snail, Slug, N-cadherin were up-expressed significantly. Meanwhile, E-cadherin was significantly down-regulated in the oral cancer cells with OLA1-knocked down, suggesting that OLA1 inactivated EMT process. Furthermore, we found that OLA1 suppressed oral squamous cell metastasis by suppressing the activity of a TGFβ/SMAD2/EMT pathway.

Conclusion

Our data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.
Differences in midgut transcriptomes between resistant and susceptible strains of Chilo suppressalis to Cry1C toxin
Authors: Chen Geng , Wang Yanhui , Liu Yanmin , Chen Fajun , Han Lanzhi
Published: September 2020

Background

Chilo suppressalisis a widespread rice pest that poses a major threat to food security in China. This pest can develop resistance to Cry toxins fromBacillus thuringiensis(Bt), threatening the sustainable use of insect-resistant transgenicBtrice. However, the molecular basis for the resistance mechanisms ofC. suppressalisto Cry1C toxin remains unknown. This study aimed to identify genes associated with the mechanism of Cry1C resistance inC. suppressalisby comparing the midgut transcriptomic responses of resistant and susceptibleC. suppressalisstrains to Cry1C toxin and to provide information for insect resistance management.

Results

AC. suppressalismidgut transcriptome of 139,206 unigenes was de novo assembled from 373 million Illumina HiSeq and Roche 454 clean reads. Comparative analysis identified 5328 significantly differentially expressed unigenes (DEGs) betweenC. suppressalisCry1C-resistant and -susceptible strains. DEGs encoding Bt Cry toxin receptors, aminopeptidase-P like protein, the ABC subfamily and alkaline phosphatase were downregulated, suggesting an association withC. suppressalisCry1C resistance. Additionally, Cry1C resistance inC. suppressalismay be related to changes in the transcription levels of enzymes involved in hydrolysis, digestive, catalytic and detoxification processes.

Conclusion

Our study identified genes potentially involved in Cry1C resistance inC. suppressalisby comparative transcriptome analysis. The assembled and annotated transcriptome data provide valuable genomic resources for further study of the molecular mechanisms ofC. suppressalisresistance to Cry toxins.
The preablation monocyte/ high density lipoprotein ratio predicts the late recurrence of paroxysmal atrial fibrillation after radiofrequency ablation
Authors: Chen She-an , Zhang Man-man , Zheng Meifang , Liu Fei , Sun Lei , Bao Zheng-yu , Chen Fu-kun , Li Hong-xiao , Gu Xiang
Published: September 2020

Background

The monocyte/high-density lipoprotein ratio (MHR) has emerged as a promising alternative biomarker in the fields of cardiovascular disease and atrial fibrillation (AF). This retrospective study was aimed to explore the predictive value of the MHR for the late recurrence of AF after radiofrequency ablation.

Methods

From April 2015 to October 2018, patients with paroxysmal AF who had undergone radiofrequency catheter ablation at Subei People’s Hospital of Jiangsu Province were enrolled in our study. All the participants were observed until November 2019 after the procedure. During the postoperative follow up, the patients were categorized into the recurrence group and maintenance of sinus rhythm group based on who had experienced AF recurrence.

Results

One hundred twenty-five patients were diagnosed with paroxysmal AF, with an average age of 61.2 ± 9.3 years. Forty-seven patients had developed late recurrence during a mean follow up of 25.1 ± 12.0 months. The AF recurrence event rates were significantly increased in the highest MHR tertile compared with those in the lowest MHR tertile (22.0% vs. 57.1%; P < 0.05). On multivariate logistic regression analysis, the preablation MHR (OR = 1.34; 95% CI = 1.12 ~ 1.60; P = 0.001) and left atrial diameter (LAD) (OR = 1.21, 95% CI = 1.08 ~ 1.35; P = 0.001) were independent risk factors predicting the recurrence of AF after radiofrequency ablation. Furthermore, receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) of the MHR was 0.712 (95% CI = 0.618 ~ 0.806; P = 0.000) and that of LAD was 0.739 (95% CI = 0.653 ~ 0.814; P = 0.000). Z-test found no significant difference between the MHR and LAD regarding the AUC (Z = 0.451; P = 0.652).

Conclusion

An elevated preablation MHR was associated with an increased risk of the postoperative recurrence of AF. Additionally, the MHR independently predicted the late recurrence of paroxysmal AF after radiofrequency ablation, with the same predictive value as LAD.
Gastric submucosal abscess caused by Edwardsiella tarda infection: a case report
Authors: Ota Koshi , Yamanoue Hiroki , Aizawa Nobuyuki , Suzuki Naoyuki , Ota Kanna , Takasu Akira
Published: September 2020

Background

Edwardsiella tarda is a motile, facultatively anaerobic gram-negative bacillus that is isolated from a wide spectrum of animals in aquatic environments but rarely causes infection in humans. Here, we describe the case of a gastric submucosal abscess caused by E. tarda infection.

Case presentation

The patient was a 74-year-old man with a history of hypertension and chronic alcohol consumption who was admitted to our hospital for abdominal pain, appetite loss and vomiting. Contrast-enhanced computed tomography (CT) revealed choledocholithiasis in the common bile duct, a gastric wall abscess and an intra-abdominal abscess. Endoscopic ultrasound (EUS)-guided drainage with antibiotics successfully cured the patient.

Conclusion

The combination of CT, endoscopy and EUS-guided drainage with antibiotic therapy might be effective for diagnosis and treatment of a gastric submucosal abscess caused by E. tarda infection.
Real-world patient-reported outcomes of women receiving initial endocrine-based therapy for HR+/HER2− advanced breast cancer in five European countries
Authors: Davie Alison , Carter Gebra Cuyun , Rider Alex , Pike James , Lewis Katie , Bailey Abigail , Price Gregory L. , Ringeisen Francois , Pivot Xavier
Published: September 2020

Background

Endocrine therapy (ET)-based regimens are the mainstay of treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer. With the introduction of new treatment classes, it is important to examine patient symptoms and health-related quality of life (HRQoL) at the start of this changing therapeutic landscape. This real-world study describes the patient-reported outcomes (PROs) of women with HR+/HER2− advanced breast cancer receiving ET-based regimens who were naïve to systemic treatment in the advanced setting across five European countries (EU5).

Methods

Data were collected between March and July 2017 from surveyed oncologists and their patients at a single time point using the multinational Adelphi Advanced Breast Cancer Disease Specific Programme™. Patients completed PRO questionnaires on HRQoL (EORTC QLQ-C30), pain severity and interference, and work and activity impairment. A multiple linear regression model explored factors associated with HRQoL.

Results

Across EU5, 226 physicians provided data on 781 women with HR+/HER2− advanced breast cancer taking their first ET-based regimen for advanced disease, of whom 252 provided PRO data. This subset had a mean age of 67.1 years, 94% were postmenopausal, 89% were diagnosed with advanced breast cancer at initial presentation, 79% had stage IV disease (66% of these patients had bone metastases and 38% had visceral metastases, including 18% with liver metastases) and 77% were on endocrine-only therapy as their initial treatment for advanced disease. The mean EORTC QLQ-C30 global health score (50.9) was worse than the reference value for patients with advanced breast cancer (60.2). Fatigue, pain, and insomnia were the most severe symptoms, and mean functioning scores were also worse than reference values. “Worst pain” and “pain interference” were moderate/severe for 42 and 80% of patients. Mean activity impairment was 44%, and greater activity impairment was associated with poorer HRQoL.

Conclusions

Despite receiving first-line ET-based regimens for advanced disease, these women had a poor HRQoL and high levels of symptoms, pain, pain interference and activity impairment. New treatments that maintain a stable disease state and reduce activity impairment may have a positive effect on the HRQoL of those living with advanced breast cancer.
From tobacco smoking to cancer mutational signature: a mediation analysis strategy to explore the role of epigenetic changes
Authors: Chen Zhishan , Wen Wanqing , Cai Qiuyin , Long Jirong , Wang Ying , Lin Weiqiang , Shu Xiao-ou , Zheng Wei , Guo Xingyi
Published: September 2020

Background

Tobacco smoking is associated with a unique mutational signature in the human cancer genome. It is unclear whether tobacco smoking-altered DNA methylations and gene expressions affect smoking-related mutational signature.

Methods

We systematically analyzed the smoking-related DNA methylation sites reported from five previous casecontrol studies in peripheral blood cells to identify possible target genes. Using the mediation analysis approach, we evaluated whether the association of tobacco smoking with mutational signature is mediated through altered DNA methylation and expression of these target genes in lung adenocarcinoma tumor tissues.

Results

Based on data obtained from 21,108 blood samples, we identified 374 smoking-related DNA methylation sites, annotated to 248 target genes. Using data from DNA methylations, gene expressions and smoking-related mutational signature generated from ~ 7700 tumor tissue samples across 26 cancer types from The Cancer Genome Atlas (TCGA), we found 11 of the 248 target genes whose expressions were associated with smoking-related mutational signature at a Bonferroni-correctionP < 0.001. This included four for head and neck cancer, and seven for lung adenocarcinoma. In lung adenocarcinoma, our results showed that smoking increased the expression of three genes,AHRR,GPR15, andHDGF, and decreased the expression of two genes,CAPN8, andRPS6KA1, which were consequently associated with increased smoking-related mutational signature. Additional evidence showed that the elevated expression ofAHRRandGPR15were associated with smoking-altered hypomethylations at cg14817490 and cg19859270, respectively, in lung adenocarcinoma tumor tissues. Lastly, we showed that decreased expression ofRPS6KA1, were associated with poor survival of lung cancer patients.

Conclusions

Our findings provide novel insight into the contributions of tobacco smoking to carcinogenesis through the underlying mechanisms of the elevated mutational signature by altered DNA methylations and gene expressions.
Pars plana vitrectomy combined with penetrating keratoplasty and transscleral-sutured intraocular lens implantation in complex eyes: a case series
Authors: Hayashi Takahiko , Yasutsugu Ida , Shimizu Toshiki , Kuroki Tsubasa , Kobashigawa Yuji , Iijima Yasuhito , Yuda Kentaro
Published: September 2020

Background

The aim of this study was to evaluate the clinical outcomes of pars plana vitrectomy (PPV) combined with penetrating keratoplasty (PKP) and transscleral-sutured intraocular lens (IOL) implantation (IOL-suture) in complex eyes.

Methods

In this prospective, consecutive interventional case series, patients who underwent PKP combined with PPV and IOL implantation from July 2014 to March 2018 at Yokohama Minami Kyosai Hospital were enrolled. The postoperative best corrected visual acuity (BCVA) (converted to logarithm of the minimal angle of resolution [logMAR] units), intraocular pressure (IOP, mmHg), endothelial cell density (ECD, cells/mm2), graft survival, complications, astigmatism, and spherical equivalent (dioptres [D]) were evaluated.

Results

This study included 11 eyes of 11 patients (three females and eight males; mean age, 61.8 ± 13.9 years) with an injury (n = 6) or bullous keratopathy (n = 5). The BCVA significantly improved from 1.50 ± 0.66 logMAR preoperatively to 0.78 ± 0.59 logMAR (p < 0.001) postoperatively. The baseline ECD significantly decreased from 2396 ± 238 cells/mm2 preoperatively to 1132 ± 323 cells/mm2 (p < 0.001) postoperatively. Despite two rejection episodes, graft survival rates were 100%. The mean follow-up period was 38.0 ± 20.5 months. Two patients required combined glaucoma surgery, and three patients underwent subsequent glaucoma surgery. Postoperative astigmatism and spherical equivalent were 3.9 ± 3.2 D and 0.29 ± 2.18 D, respectively.

Conclusion

The combination of PKP, PPV, and IOL-suture implantation could be a safe and effective approach for eyes requiring anterior segment surgery; however, these eyes are associated with a higher incidence of glaucoma surgery.
Exploring the efficacy of using hypertonic saline for nebulizing treatment in children with bronchiolitis: a meta-analysis of randomized controlled trials
Authors: Hsieh Chia-Wen , Chen Chiehfeng , Su Hui-Chuan , Chen Kee-Hsin
Published: September 2020

Background

Inhaled hypertonic saline (HS) has shown benefit in decreasing airway edema in acute bronchiolitis which is the most common lower respiratory infection resulting in dyspnea among infants under 2 years old. The aim of this systematic review and meta-analysis was to evaluate the efficacy and safety of HS in the implementation of treatment with nebulized HS among children with bronchiolitis.

Methods

A systematic literature search was conducted using Cochrane Library, PubMed, EMBASE and Airiti Library (Chinese Database) for randomized controlled trials from inception to July 2019. We calculated pooled risk ratios (RR), mean difference (MD) and 95% CI using RevMan 5.3 for meta-analysis.

Results

There were 4186 children from 32 publications included. Compared to the control group, the HS group exhibited significant reduction of severity of respiratory distress, included studies used the Clinical Severity Score (n = 8; MD, − 0.71; 95% CI, − 1.15 to − 0.27; I2 = 73%) and full stop after Respiratory Distress Assessment Instrument (n = 5; MD, − 0.60; 95% CI, − 0.95 to − 0.26; I2 = 0%) for evaluation respectively. Further, the HS group decreased the length of hospital stay 0.54 days (n = 20; MD, − 0.54; 95% CI, − 0.86 to − 0.23; I2 = 81%).

Conclusions

We conclude that nebulization with 3% saline solution is effective in decreasing the length of hospital stay and the severity of symptoms as compared with 0.9% saline solution among children with acute bronchiolitis. Further rigorous randomized controlled trials with large sample size are needed.
Adaptive tutorials versus web-based resources in radiology: a mixed methods analysis in junior doctors of efficacy and engagement
Authors: Wade Stuart W. T. , Moscova Michelle , Tedla Nicodemus , Moses Daniel A. , Young Noel , Kyaw Merribel , Velan Gary M.
Published: September 2020

Background

Radiology education is limited in undergraduate Medicine programs. Junior doctors might not have the necessary background to effectively order and interpret diagnostic imaging investigations. Furthermore, junior doctors are often time-poor, balancing clinical commitments with ongoing learning, leadership and teaching responsibilities. Previous studies have demonstrated the efficacy of radiology-themed online adaptive tutorials for senior medical students. Such adaptive tutorials might therefore be an efficient and effective form of radiology education for junior doctors.

Methods

A randomised controlled crossover trial was performed to evaluate the impact of adaptive tutorials on learning the indications for, and interpretation of, basic imaging studies, compared with peer-reviewed web-based resources. Ninety-one volunteer junior doctors, comprising 53 postgraduate year 1 (PGY 1) and 38 postgraduate year 2 (PGY 2), were randomly allocated into two groups. In the first phase of the trial, focusing on head CT, one group accessed adaptive tutorials while the other received web-based resources. In the second phase of the trial, focusing on chest CT, the groups crossed over. Following each phase of the trial, participants completed exam-style online assessments. At the conclusion of the study, participants also completed an online questionnaire regarding perceived engagement and efficacy of each type of educational resource.

Results

Junior doctors completed the adaptive tutorials significantly faster than the relevant web-based resources for both head CT and chest CT (p = 0.03 and < 0.01 respectively). Mean quiz scores were higher in the groups receiving adaptive tutorials on head CT and chest CT (86.4% vs 83.5 and 77.7% vs 75% respectively). However, in contrast to previous studies in senior medical students, these differences were not statistically significant. Participants reported higher engagement and perceived value of adaptive tutorials, compared with web-based resources.

Conclusions

Adaptive tutorials are more time-efficient than existing web-based resources for learning radiology by junior doctors, while both types of resources were equally effective for learning in this cohort. Junior doctors found the adaptive tutorials more engaging and were more likely to recommend these resources to their colleagues.
Repositioning liothyronine for cancer immunotherapy by blocking the interaction of immune checkpoint TIGIT/PVR
Authors: Zhou Xiuman , Du Jiangfeng , Wang Hongfei , Chen Chunxia , Jiao Ling , Cheng Xiangrui , Zhou Xiaowen , Chen Shaomeng , Gou Shanshan , Zhao Wenshan , Zhai Wenjie , Chen Junhui , Gao Yanfeng
Published: September 2020

Background

Inhibitors targeting immune checkpoint were proved effective in cancer immunotherapy, such as PD-1/PD-L1 blockade. The novel immune checkpoint TIGIT/PVR plays critical roles in suppressing the anti-tumor effects of CD8+ T and NK cells, and dual blockade of TIGIT/PVR and PD-1/PD-L1 by antibody can elicit synergistic effects in tumor models and clinical trials. However, small molecules for TIGIT/PVR blockade have not been investigated.

Methods

The expression of PVR in tumors were analyzed by using TCGA, Oncomine and GEO database, and in cancer cell lines examined by flow cytometry. Natural product compounds were docked to PVR for virtual screening by using the software Molecular Operating Environment (MOE). Candidate compounds were further tested by biolayer interferometry-based binding assay, microscale thermophoresis assay and cell based blocking assay. The in vitro activity of the candidate compound was determined by MTT, peripheral blood mononuclear cells (PBMCs) activation assay and coculture assay. The anti-tumor effects and mechanism were also investigated by using MC38 tumor-bearing mice model and immune cell depletion tumor model.

Results

PVR was over-expressed in many tumor tissues and cancer cell lines, making it a promising therapeutic target. Through virtual screening, binding, and blocking assay, liothyronine was discovered to bind PVR and block the interaction of TIGIT/PVR. Liothyronine could enhance the function of CD4+ and CD8+ T cells in PBMCs. Besides, in the Jurkat-hTIGIT and CHOK1-hPVR coculture assay, liothyronine could reverse the IL-2 secretion inhibition resulted by TIGIT/PVR ligation. Although had no influence on the proliferation of tumor cells in vitro, liothyronine could significantly inhibit tumor growth when administrated in vivo, by enhancing CD8+ T cell infiltration and immune responses in the tumor bearing mice. The immune cell depletion model showed that the anti-tumor effects of liothyronine depends on CD4+ T cells, CD8+ T cells and NK cells.

Conclusions

A small molecule liothyronine was discovered to serve as a potential candidate for cancer immunotherapy by blocking the immune checkpoint TIGIT/PVR.

Graphical abstract
Perspectives in melanoma: meeting report from the “Melanoma Bridge” (December 5th–7th, 2019, Naples, Italy)
Authors: Ascierto Paolo A. , Puzanov Igor , Agarwala Sanjiv S. , Blank Christian , Carvajal Richard D. , Demaria Sandra , Dummer Reinhard , Ernstoff Marc , Ferrone Soldano , Fox Bernard A. , Gajewski Thomas F. , Garbe Claus , Hwu Patrick , Lo Roger S. , Long Georgina V. , Luke Jason J. , Osman Iman , Postow Michael A. , Sullivan Ryan J. , Taube Janis M. , Trinchieri Giorgio , Zarour Hassane M. , Caracò Corrado , Thurin Magdalena
Published: September 2020

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including sequential or combination treatment are being tested. Approaches to overcome resistance and to potentiate the immune response are being developed. Increasing evidence emerges that tissue and blood-based biomarkers can predict the response to a therapy. The latest findings in melanoma research, including insights into the tumor microenvironment and new biomarkers, improved understanding of tumor immune response and resistance, novel approaches for combination strategies and the role of neoadjuvant and adjuvant therapy, were the focus of discussions at the Melanoma Bridge meeting (5–7 December, 2019, Naples, Italy), which are summarized in this report.
Toward a hemorrhagic trauma severity score: fusing five physiological biomarkers
Authors: Bhat Ankita , Podstawczyk Daria , Walther Brandon K. , Aggas John R. , Machado-Aranda David , Ward Kevin R. , Guiseppi-Elie Anthony
Published: September 2020

Background

To introduce the Hemorrhage Intensive Severity and Survivability (HISS) score, based on the fusion of multi-biomarker data; glucose, lactate, pH, potassium, and oxygen tension, to serve as a patient-specific attribute in hemorrhagic trauma.

Materials and methods

One hundred instances of Sensible Fictitious Rationalized Patient (SFRP) data were synthetically generated and the HISS score assigned by five clinically active physician experts (100 [5]). The HISS score stratifies the criticality of the trauma patient as; low(0), guarded(1), elevated(2), high(3) and severe(4). Standard classifier algorithms; linear support vector machine (SVM-L), multi-class ensemble bagged decision tree (EBDT), artificial neural network with bayesian regularization (ANN:BR) and possibility rule-based using function approximation (PRBF) were evaluated for their potential to similarly classify and predict a HISS score.

Results

SVM-L, EBDT, ANN:BR and PRBF generated score predictions with testing accuracies (majority vote) corresponding to 0.91 ± 0.06, 0.93 ± 0.04, 0.92 ± 0.07, and 0.92 ± 0.03, respectively, with no statistically significant difference (p > 0.05). Targeted accuracies of 0.99 and 0.999 could be achieved with SFRP data size and clinical expert scores of 147[7](0.99) and 154[9](0.999), respectively.

Conclusions

The predictions of the data-driven model in conjunction with an adjunct multi-analyte biosensor intended for point-of-care continual monitoring of trauma patients, can aid in patient stratification and triage decision-making.
Impact of different omega-3 fatty acid sources on lipid, hormonal, blood glucose, weight gain and histopathological damages profile in PCOS rat model
Authors: Komal Fiza , Khan Muhammad Kamran , Imran Muhammad , Ahmad Muhammad Haseeb , Anwar Haseeb , Ashfaq Usman Ali , Ahmad Nazir , Masroor Amna , Ahmad Rabia Shabir , Nadeem Muhammad , Nisa Mahr Un
Published: September 2020

Background

Omega-3 fatty acids (Ω-3 PUFAs) may help to improve health status in polycystic ovarian syndrome (PCOS) by reducing numerous metabolic disorders (insulin sensitivity, hyperinsulinemia, lipid profile, obesity and inflammation). To evaluate the current objective, 16 weeks (6 weeks of adjustment period followed by 10 weeks of collection period) research trial was planned to check the impact of different sources of Ω-3 PUFAs (synthetic Ω-3, flaxseed and fish oil) on nutrient digestibility, weight gain, productive (lipid profile, glucose and insulin), reproductive profile (progesterone, follicle stimulating hormone (FSH), estrogen, luteinizing hormone (LH) and prolactin) and histological study of ovarian tissues in Wistar female rats.

Methods

Forty-five rats of 130 ± 10 g weight were divided into 5 groups, each having 9 rats: NC (negative control without PCOS), PC (positive control with PCOS), SO (synthetic omega-3 containing ALA, EPA and DHA), FO (flaxseed oil) and F (fish oil) fed at 300 mg/kg/orally/daily of these sources were added in the basal diets while PC and NC received only the basal diet. Food and water were offered ad libitum. PCOS was induced in the rats fed of PC, SO, FO and F diets group by single intramuscular injection of estradiol-valerate (4 mg/rat/IM). Body weight and blood glucose was recorded weekly. At 16thweek of trial, blood samples were collected for lipid and hormonal analysis. Ovarian tissues were removed for pathological evaluation. Digestibility was measured by total collection method.

Results

Cholesterol, triglycerides and low-density lipoproteins were reduced in SO, FO and F groups when compared with rats of PC group. However, increasing trend of high-density lipoprotein (HDL) was found in same groups. The highest HDL (36.83 ± 0.72 mg/dL) was observed in rats fed F diet. In case of a hormonal profile, testosterone, LH and insulin levels showed a significant reduction after treatments. Blood glucose results showed significantly reducing trend in all the rats fed with Ω-3 PUFAs sources than PC from 5 to 10th week of trial. However, similar trend was noticed in rat’s body weight at the end of 6th week. In ovarian morphology, different stages of follicles were observed in groups fed SO, FO and F diets. Nutrient digestibility in PCOS induced rats was remained non-significant.

Conclusions

The three sources of Ω-3 PUFAs had effective role in improving lipid and hormonal profile, reducing blood glucose, weight gain and histopathological damages in PCOS rats. However, fish oil source might be an innovative approach to cure PCOS via reducing the weight and metabolic anomalies due to EPA and DHA.
A phase 2 study of combined chemo-immunotherapy with cisplatin-pembrolizumab and radiation for unresectable vulvar squamous cell carcinoma
Authors: Yeku Oladapo , Russo Andrea L. , Lee Hang , Spriggs David
Published: September 2020

Background

Unresectable or metastatic vulvar cancer has relatively poor outcomes despite chemotherapy-sensitized radiation therapy and combination cytotoxic therapy. Despite the virus-associated and immunogenic nature of this disease, novel immunotherapy options that exploit this advantage are currently lacking. Platinum agents such as cisplatin have been shown to prime dendritic cells for T-cell costimulation, promote downregulation of inhibitory checkpoint molecules, and sensitize tumor cells to cytotoxic T-cell killing. Radiation therapy has also been shown to promote immunogenetic cell death as monotherapy and in combination with cisplatin. In combination with pembrolizumab, cisplatin-sensitized radiation is hypothesized to increase overall response rates and recurrence-free survival in patients with vulvar cancer, via induction of an anti-tumor inflammatory response.

Methods

We propose a single-arm phase II clinical trial of pembrolizumab combined with cisplatin-sensitized radiation therapy for women with unresectable, locally advanced, or metastatic vulvar cancer. The first three patients with locally advanced or unresectable disease will receive cycle 1 of pembrolizumab followed by a break and resumption of pembrolizumab at cycle 4 and as part of a safety cohort. All other patients, including the fourth patient with locally advanced/unresectable disease, will receive weekly cisplatin and pembrolizumab every 3 weeks, concurrently with daily radiation therapy. Following the completion of Cis-RT, patients will continue pembrolizumab maintenance for a total of 12 cycles. Archived tissue will be used for HPV status, MSI status, PD-L1, and TIL stratification post hoc. Imaging will be performed at baseline and every 3 cycles (21-day cycles) as per standard-of-care. Laboratory analysis will occur on the first day of each cycle.

Discussion

The combination of cisplatin-sensitized radiation and immune checkpoint blockade has not been evaluated in the upfront setting for vulvar cancer. In this rare malignancy, there are limited interventional clinical trials. This trial is designed to be as accessible as possible by allowing patients to receive cisplatin and radiation locally according to accepted standard-of-care while receiving pembrolizumab and adverse event monitoring at a centralized site. A robust suite of translational correlative studies has also been built into the trial to evaluate tumor-directed immune activation.

Trial registration NCT04430699
Exploring perspectives, preferences and needs of a telemonitoring program for women at high risk for preeclampsia in a tertiary health facility of Karachi: a qualitative study protocol
Authors: Feroz Anam , Saleem Sarah , Seto Emily
Published: September 2020

Background

In Pakistan, deaths from preeclampsia/eclampsia (PE/E) represent one-third of maternal deaths reported at tertiary care hospitals. To reduce the morbidity and mortality associated with PE/E, an accessible strategy is to support pregnant women at high risk for preeclampsia (HRPE) by closely monitoring their blood pressures at home (i.e., telemonitoring) for the earliest signs of preeclampsia. This could lead to the earliest possible detection of high blood pressure, resulting in early intervention such as through medications, hospitalization, or delivery of the baby. The study aims to explore the perspectives, preferences and needs of telemonitoring (TM) for pregnant women at HRPE in Karachi, to inform future implementation strategies.

Methods

The study will employ an exploratory qualitative research design. The study will be conducted at the Jinnah Postgraduate Medical Centre (JPMC) hospital and Aga Khan University Hospital (AKUH) in Karachi, Sindh, Pakistan. Data will be collected through key-informant interviews (KIIs) and in-depth patient interviews (IDPIs). IDPIs will be conducted with the pregnant women at HRPE who are visiting the out-patient department/ antenatal clinics of JPMC hospital for antenatal check-ups and immunizations. KIIs will be conducted with the obstetricians, Maternal, neonatal and child health (MNCH) specialists and health care providers at JPMC, as well as TM experts from Karachi. Study data will be analyzed through conventional content analysis. Interviews are anticipated to begin in April 2020 and to be completed during the summer of 2020.

Discussion

This is the first study to explore the use of TM program for pregnant women at HRPE in a tertiary health facility in Karachi. The research will help explore perceived benefits associated with the use of a TM program alongside potential facilitators and barriers that may help inform the future implementation of a TM program for pregnant women at HRPE in Karachi.