bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution transcription factor binding sites prediction improved performance and interpretability by deep learning method
Authors: Zhang Yongqing , Wang Zixuan , Zeng Yuanqi , Zhou Jiliu , Zou Quan
Published: June 2021

Transcription factors (TFs) are essential proteins in regulating the spatiotemporal expression of genes. It is crucial to infer the potential transcription factor binding sites (TFBSs) with high resolution to promote biology and realize precision medicine. Recently, deep learning-based models have shown exemplary performance in the prediction of TFBSs at the base-pair level. However, the previous models fail to integrate nucleotide position information and semantic information without noisy responses. Thus, there is still room for improvement. Moreover, both the inner mechanism and prediction results of these models are challenging to interpret. To this end, the Deep Attentive Encoder-Decoder Neural Network (D-AEDNet) is developed to identify the location of TFs–DNA binding sites in DNA sequences. In particular, our model adopts Skip Architecture to leverage the nucleotide position information in the encoder and removes noisy responses in the information fusion process by Attention Gate. Simultaneously, the Transcription Factor Motif Discovery based on Sliding Window (TF-MoDSW), an approach to discover TFs–DNA binding motifs by utilizing the output of neural networks, is proposed to understand the biological meaning of the predicted result. On ChIP-exo datasets, experimental results show that D-AEDNet has better performance than competing methods. Besides, we authenticate that Attention Gate can improve the interpretability of our model by ways of visualization analysis. Furthermore, we confirm that ability of D-AEDNet to learn TFs–DNA binding motifs outperform the state-of-the-art methods and availability of TF-MoDSW to discover biological sequence motifs in TFs–DNA interaction by conducting experiment on ChIP-seq datasets.
ADEIP: an integrated platform of age-dependent expression and immune profiles across human tissues
Authors: Liu Xuan , Chen Wenbo , Fang Yu , Yang Siqi , Chang Liuping , Chen Xingyu , Ye Haidong , Tang Xinyu , Zhong Shan , Zhang Wen , Dong Zhiqiang , Han Leng , He Chunjiang
Published: June 2021

Gene expression and immune status in human tissues are changed with aging. There is a need to develop a comprehensive platform to explore the dynamics of age-related gene expression and immune profiles across tissues in genome-wide studies. Here, we collected RNA-Seq datasets from GTEx project, containing 16 704 samples from 30 major tissues in six age groups ranging from 20 to 79 years old. Dynamic gene expression along with aging were depicted and gene set enrichment analysis was performed among those age groups. Genes from 34 known immune function categories and immune cell compositions were investigated and compared among different age groups. Finally, we integrated all the results and developed a platform named ADEIP (http://gb.whu.edu.cn/ADEIP or http://geneyun.net/ADEIP), integrating the age-dependent gene expression and immune profiles across tissues. To demonstrate the usage of ADEIP, we applied two datasets: severe acute respiratory syndrome coronavirus 2 and human mesenchymal stem cells-assoicated genes. We also included the expression and immune dynamics of these genes in the platform. Collectively, ADEIP is a powerful platform for studying age-related immune regulation in organogenesis and other infectious or genetic diseases.
The potential of serum neurofilament as biomarker for multiple sclerosis
Authors: Bittner Stefan , Oh Jiwon , Havrdová Eva Kubala , Tintoré Mar , Zipp Frauke
Published: June 2021

Multiple sclerosis is a highly heterogeneous disease, and the detection of neuroaxonal damage as well as its quantification is a critical step for patients. Blood-based serum neurofilament light chain (sNfL) is currently under close investigation as an easily accessible biomarker of prognosis and treatment response in patients with multiple sclerosis. There is abundant evidence that sNfL levels reflect ongoing inflammatory-driven neuroaxonal damage (e.g. relapses or MRI disease activity) and that sNfL levels predict disease activity over the next few years. In contrast, the association of sNfL with long-term clinical outcomes or its ability to reflect slow, diffuse neurodegenerative damage in multiple sclerosis is less clear. However, early results from real-world cohorts and clinical trials using sNfL as a marker of treatment response in multiple sclerosis are encouraging. Importantly, clinical algorithms should now be developed that incorporate the routine use of sNfL to guide individualized clinical decision-making in people with multiple sclerosis, together with additional fluid biomarkers and clinical and MRI measures. Here, we propose specific clinical scenarios where implementing sNfL measures may be of utility, including, among others: initial diagnosis, first treatment choice, surveillance of subclinical disease activity and guidance of therapy selection.
Tandem running by foraging Pachycondyla striata workers in field conditions vary in response to food type, food distance, and environmental conditions
Authors: Silva Janiele Pereira , Valadares Lohan , Vieira Maria Eduarda Lima , Teseo Serafino , Châline Nicolas
Published: June 2021

Ants show collective and individual behavioral flexibility in their response to immediate context, choosing for example between different foraging strategies. In Pachycondyla striata, workers can forage solitarily or recruit and guide nestmates to larger food sources through tandem running. Although considered more ancestral and less efficient than pheromone trail-laying, this strategy is common especially in species with small colony size. What is not known is how the decision to recruit or follow varies according to the immediate context. That is, how fine adjustments in information transfer affect immediate foraging decisions at the colony level. Here, we studied individually marked workers and evaluated their foraging decisions when food items varied in nature (protein versus carbohydrate), size, and distance from the nest at different temperatures and humidity levels. Our results show that tandem run leaders and potential followers adjust their behavior according to a combination of external factors. While 84.2% of trips were solitary, most ants (81%) performed at least 1 tandem run. However, tandem runs were more frequent for nearby resources and at higher relative humidity. Interestingly, when food items were located far away, tandem runs were more successful when heading to protein sources (75%) compared with carbohydrate sources (42%). Our results suggest that the social information transfer between leaders and followers conveys more information than previously thought, and also relies on their experience and motivation.
Case report of isolated cardiac sarcoidosis presenting as hypertrophic obstructive cardiomyopathy—a clinical picture printed on lenticular paper
Authors: Mathias Isadora Sande , Oliveira Lima Filho Jorge Otávio , Culver Daniel A , Rodriguez E Rene , Tan Carmela D , Ribeiro Neto Manuel L , Jellis Christine L
Published: June 2021

Background

Cardiac sarcoidosis (CS) is an inflammatory granulomatous process of the myocardium that can be asymptomatic or have several different clinical phenotypes. One of its rarely described presentations consists of hypertrophy of the septal myocardium, similar to hypertrophic cardiomyopathy (HCM). Isolated cardiac sarcoidosis that haemodynamically mimics hypertrophic obstructive cardiomyopathy (HOCM) has been rarely described in the literature.

Case summary

A 64-year-old Caucasian female previously diagnosed with non-critical aortic stenosis presented with pre-syncope, and echocardiography showed significant obstruction based on left ventricular outflow tract gradients, confirmed by cardiac magnetic resonance (CMR), concerning for a phenocopy of HCM. Septal myectomy was performed and pathology specimen revealed non-caseating granulomata consistent with cardiac sarcoidosis. She was started on oral corticosteroids and initial cardiac fluorodeoxyglucose positron emission tomography (FDG-PET) done after 1 month of treatment was negative. Repeat FDG-PET 15 months later, in the setting of haemodynamic decompensation, demonstrated diffuse FDG uptake in the myocardium without extra-cardiac involvement.

Discussion

Our case brings together two entities: isolated cardiac sarcoidosis and its presentation mimicking HOCM, which has been very rarely described in the literature. And it also shows the scenario of surgical pathology diagnosis of sarcoidosis that was not suspected by initial CMR or FDG-PET, despite adequate preparation, only appearing on repeat FDG-PET done 15 months later. Isolated cardiac sarcoidosis should remain a differential diagnosis for any non-ischaemic cardiomyopathy without a clear cause, despite imaging evidence of HCM.
Simultaneous acute myocardial infarction, bilateral pulmonary embolism, and acute ischaemic cerebral stroke, a delayed complication in a patient with COVID-19 infection: case report
Authors: Chakir Mariame , El Jamili Mohammed , Boudhar Zainab , El Hattaoui Mustapha
Published: June 2021

Background

The simultaneous occurrence of acute myocardial infarction, pulmonary embolism, and acute cerebral stroke is a rare concomitant finding that requires thorough aetiological investigation. Multiple reports note delayed COVID-19 arterial and venous thromboembolic complications. However, to the best of our knowledge, this is the first report of such a simultaneous finding after COVID-19.

Case summary

A 60-year-old male patient, with a history of Type II diabetes and no risk factors for thromboembolism, experienced simultaneous acute myocardial infarction, bilateral pulmonary embolism, and acute ischaemic stroke. The occurrence of these multi-systemic thromboembolic events made us rule out differential diagnoses of thrombophilia, systemic lupus erythematosus, antiphospholipid syndrome, vasculitis, cancer, disseminated intravascular coagulation, and paradoxical embolism through a patent foramen ovale. On laboratory analysis, the patient was positive for IgG SARS-COV2 antibodies, but negative for IgM antibodies and had two negative nasal polymerase chain reaction swab tests. After thorough aetiological investigation, the most probable diagnosis was thought to be delayed complications of COVID-19 infection.

Discussion

Multiple mechanisms, such as endothelial dysfunction, complement activation, and virus-induced antiphospholipid syndrome, may explain the hypercoagulable state related to COVID-19. To the best of our knowledge, this is the first case of concomitant multi-systemic thrombosis development, recognized as a delayed complication of COVID-19 infection. This highlights a need among cardiologists for an increased awareness of such late-onset complications. It also emphasizes the importance of identifying the optimal duration and dose of prophylactic anticoagulation as well as the characteristics of the population that would benefit from it after COVID-19.
Case report of a coronary artery-right ventricular fistula following repeat endomyocardial biopsies in a heart transplant patient
Authors: Siebert Vincent R , John Alan , Manshad Ahmad , Darki Amir
Published: June 2021

Background

Endomyocardial biopsy (EMB) remains the gold standard for cellular rejection surveillance in heart transplant recipients. Coronary artery fistula formation is a rare late and potentially catastrophic complication of repeated endomyocardial biopsies, without contemporary evidence on incidence or management.

Case summary

A 47-year-old male was found to have a fistula between his right ventricle and his left anterior descending artery on an angiogram that was performed as a part of regular screening of coronary allograft vasculopathy. Given the low shunt fraction, asymptomatic nature, and lack of guidelines on definitive management, the patient is undergoing conservative management with regular surveillance.

Discussion

Coronary artery fistulas were once thought to be rare complications of repeated EMB, but the true prevalence is likely to be higher than previously believed. Ideal treatment and monitoring is unknown given the relative rarity of the condition.
Left ventricular mural thrombi with multisystem thrombosis in patients with COVID-19 and myocardial injury: a case series
Authors: Garg Aakash , Hakeem Hisham , Chennu Gouthami , Saeed Qaisra , Vucic Esad , Kats Yuliya , Waxman Sergio
Published: June 2021

Background

Cardiovascular and thromboembolic complications have been reported in patients with Coronavirus disease-2019 (COVID-19)-related severe respiratory distress syndrome. Although myocarditis associated with COVID-19 pneumonia has been described, evidence of left ventricular (LV) mural thrombi with other multisystem events has not been reported.

Case summary

We report two cases with severe COVID-19 pneumonia and myocardial injury with large LV thrombi and other multisystem thrombotic events. The first patient represents an unusual case of large LV apical thrombus without concordant regional wall motion abnormality and mildly reduced LV function. A subsequent inferior ST-elevation myocardial infarction (STEMI) was likely related to either an embolic event or in situ coronary thrombosis. We could not ascertain whether the acute right ventricular dysfunction was due to in situ pulmonary thrombosis or inferior STEMI. The catastrophic cerebrovascular accident was likely an embolic phenomenon. Similarly, the second patient demonstrated multiple large pedunculated thrombi occupying one-third of the LV cavity with moderately reduced LV function. A segmental pulmonary embolism was diagnosed on computed tomography chest, confirming multiple territories of in situ thrombosis.

Discussion

COVID-19-related inflammatory cytokine release has been linked to activation of coagulation pathways. Marked elevation of ferritin and C-reactive protein levels in both patients were consistent with evidence of a hyperinflammatory state with ‘cytokine storm’. Furthermore, the finding of elevated D-dimer levels lends support to the altered coagulation cascade that plausibly explains the multisystem thrombosis observed in our patients. The direct viral endothelial involvement and subsequent endothelial dysfunction may play an important role in the development of thrombosis in different vascular beds, as seen in our patients.
First-in-human high-density epicardial mapping and ablation through a left anterior minithoracotomy in an LVAD patient presenting in electrical storm: a case report
Authors: El Hamriti Mustapha , Fox Henrik , Sommer Philipp , Rojas Sebastian V
Published: June 2021

Background

Despite substantial technical improvements in long-term mechanical circulatory support, ventricular tachycardia (VT) remains a major challenge in left ventricular assist device (LVAD) patients. Recurrent VTs in LVAD patients are not only associated with limited quality of life, but also increased mortality. Although LVAD therapy improves VT tolerance of the left ventricle, haemodynamical deterioration of the right ventricle is the limiting factor in these patients.

Case summary 

We present a case report of a hybrid epicardial VT ablation of incessant VTs in a 53-year-old man with advanced heart failure and St.p. LVAD implantation. With this unique clinical case report, we describe an epicardial VT ablation using secondary surgical open-heart access in a patient with therapy-refractory VTs combing left-sided minithoracotomy with high-density (HD) mapping and catheter ablation.

Discussion 

To the best of our knowledge, the presented approach is the first interdisciplinary case of epicardial VT ablation using secondary surgical open-heart access in an LVAD patient with therapy-refractory VTs. By combing left-sided minithoracotomy with HD mapping and catheter ablation, we could to demonstrate that even in these complex patients epicardial VT ablations can be performed safely and improve quality of life of LVAD patients with recurrent implantable cardioverter-defibrillator shock therapies.
Cardiovascular magnetic resonance-based predictors of complete left ventricular systolic functional recovery after rhythm restoration in patients with atrial tachyarrhythmia
Authors: Stegmann Clara , Jahnke Cosima , Lindemann Frank , Oebel Sabrina , Richter Sergio , Bollmann Andreas , Dagres Nikolaos , Hindricks Gerhard , Paetsch Ingo
Published: June 2021

Aims

To establish a cardiovascular magnetic resonance (CMR)-based prediction model for complete systolic left ventricular ejection fraction (LVEF) recovery for the distinction of ‘arrhythmia-induced’ from ‘arrhythmia-mediated’ cardiomyopathy in patients with atrial tachyarrhythmias.

Methods and results

Two hundred and fifty-three tachyarrhythmia patients referred for catheter ablation were enrolled and underwent CMR baseline imaging; patients with a reduced LVEF <50% at baseline and CMR imaging at 3-month follow-up after successful rhythm restoration constituted the final study population (n = 134). CMR at baseline consisted of standard functional cine imaging, determination of extracellular volume, and late gadolinium enhancement (LGE) imaging; follow-up CMR comprised standard functional cine imaging. Left ventricular end-diastolic volume index (LVEDVI) measurements were categorized in ‘opposite’, ‘normal’, and ‘enlarged’. At follow-up, 80% (107/134) presented with complete LVEF recovery, while in 20% (27/134) persistent LVEF impairment was observed. LVEDVI and LGE were independent predictors of complete LVEF recovery with LGE adding significant incremental value on logistic regression modelling. Model-derived probabilities for complete LVEF recovery in LVEDVI categories of opposite, normal, and enlarged for LGE negativity and positivity were 94%, 85%, and 29% and 77%, 55%, and 8%, respectively.

Conclusion

CMR-derived assessment of LVEDVI category and LGE allowed for identification of arrhythmia-induced cardiomyopathy with acceptable discriminative performance. Probabilities for complete LVEF recovery for the combination of opposite LVEDVI/LGE negativity and enlarged LVEDVI/LGE positivity were 94% and 8%, respectively. The CMR-based prediction model of complete LVEF recovery can be used to perform upfront stratification in atrial tachyarrhythmia-related LVEF impairment.
Involving older people in co-designing an intervention to reverse frailty and build resilience
Authors: Travers John , Romero-Ortuno Roman , Ní Shé Éidin , Cooney Marie-Therese
Published: June 2021

Background

An essential consideration in health research is to conduct research with members of the public rather than for them. Public and patient involvement (PPI) of older people in research can improve enrolment, relevance and impact. However, few studies with PPI in frailty research have been identified. PPI has fallen during the Covid-19 pandemic.

Objective

We aimed to involve older people in co-designing a randomised control trial (RCT) intervention to reverse frailty and build resilience. We also wished to encourage wider use of PPI with older people by outlining our approach.

Methods

Involvement of older people was undertaken in three stages. Eighteen over 65-year-olds helped co-design an exercise intervention in two group discussions using the Socratic education method. Ninety-four contributed intervention feedback in one-on-one telephone interviews over nine months. Ten contributors helped optimise the intervention in three online workshops. Multidisciplinary team input and systematic review supported co-design.

Results

Eleven home-based resistance exercises were co-designed by group discussion contributors (mean age 75, 61% female). Frailty intervention format, gender balance and GP follow-up were shaped in telephone interviews (mean age 77, 63% female). Dietary guidance and patient communication were co-designed in workshops (mean age 71, 60% females). Technology proved no barrier to PPI. The co-designed frailty intervention is being evaluated in a definitive RCT.

Conclusions

We enabled meaningful the involvement of 112 older people in the co-design of an intervention to reverse frailty and build resilience in diverse ways. Inclusive involvement can be achieved during a pandemic. Feedback enhanced intervention feasibility for real-world primary-care.
Exploring microbial communities, assessment methodologies and applications of animal's carcass decomposition: a review
Authors: Hilal Mian Gul , Yu Qiaoling , Zhou Rui , Wang Yijie , Feng Tianshu , Li Xiangkai , Li Huan
Published: June 2021

Animals are an essential part of the ecosystem, and their carcasses are the nutrient patches or hotspots where nutrients accumulate for a long time. After death, the physical and chemical properties undergo alterations inside the carcass. The animal carcass is decomposed by many decomposers such as bacteria, fungi, microeukaryotes and insects. The role of microbial symbionts in living organisms is well explored and studied, but there is a scarcity of knowledge and research related to their role in decomposing animal carcasses. Microbes play an important role in carcass decomposition. The origins of microbial communities associated with a carcass, including the internal and external microbiome, are discussed in this review. The succession and methods used for the detection and exploration of decomposition-associated microbial communities have been briefly described. Also, the applications of carcass-associated microbial taxa have been outlined. This review is intended to understand the dynamics of microbial communities associated with the carcass and pave the way to estimate postmortem interval and its role in recycling nutrients.
Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients
Authors: Pilapitiya Devaki H , Harris Paul W R , Hanson-Manful Paulina , McGregor Reuben , Kowalczyk Renata , Raynes Jeremy M , Carlton Lauren H , Dobson Renwick C J , Baker Michael G , Brimble Margaret , Lukomski Slawomir , Moreland Nicole J
Published: June 2021

Acute rheumatic fever (ARF) is a serious post-infectious immune sequelae of Group A streptococcus (GAS). Pathogenesis remains poorly understood, including the events associated with collagen autoantibody generation. GAS express streptococcal collagen-like proteins (Scl) that contain a collagenous domain resembling human collagen. Here, the relationship between antibody reactivity to GAS Scl proteins and human collagen in ARF was investigated. Serum IgG specific for a representative Scl protein (Scl1.1) together with collagen-I and collagen-IV mimetic peptides were quantified in ARF patients (n = 36) and healthy matched controls (n = 36). Reactivity to Scl1.1 was significantly elevated in ARF compared to controls (P < 0.0001) and this was mapped to the collagen-like region of the protein, rather than the N-terminal non-collagenous region. Reactivity to collagen-1 and collagen-IV peptides was also significantly elevated in ARF cases (P < 0.001). However, there was no correlation between Scl1.1 and collagen peptide antibody binding, and hierarchical clustering of ARF cases by IgG reactivity showed two distinct clusters, with Scl1.1 antigens in one and collagen peptides in the other, demonstrating that collagen autoantibodies are not immunologically related to those targeting Scl1.1. Thus, anti-collagen antibodies in ARF appear to be generated as part of the autoreactivity process, independent of any mimicry with GAS collagen-like proteins.
Evaluation of Bayesian alphabet and GBLUP based on different marker density for genomic prediction in Alpine Merino sheep
Authors: Zhu Shaohua , Guo Tingting , Yuan Chao , Liu Jianbin , Li Jianye , Han Mei , Zhao Hongchang , Wu Yi , Sun Weibo , Wang Xijun , Wang Tianxiang , Liu Jigang , Tiambo Christian Keambou , Yue Yaojing , Yang Bohui
Published: June 2021

The marker density, the heritability level of trait and the statistical models adopted are critical to the accuracy of genomic prediction (GP) or selection (GS). If the potential of GP is to be fully utilized to optimize the effect of breeding and selection, in addition to incorporating the above factors into simulated data for analysis, it is essential to incorporate these factors into real data for understanding their impact on GP accuracy, more clearly and intuitively. Herein, we studied the GP of six wool traits of sheep by two different models, including Bayesian Alphabet (BayesA, BayesB, BayesCπ, and Bayesian LASSO) and genomic best linear unbiased prediction (GBLUP). We adopted fivefold cross-validation to perform the accuracy evaluation based on the genotyping data of Alpine Merino sheep (n = 821). The main aim was to study the influence and interaction of different models and marker densities on GP accuracy. The GP accuracy of the six traits was found to be between 0.28 and 0.60, as demonstrated by the cross-validation results. We showed that the accuracy of GP could be improved by increasing the marker density, which is closely related to the model adopted and the heritability level of the trait. Moreover, based on two different marker densities, it was derived that the prediction effect of GBLUP model for traits with low heritability was better; while with the increase of heritability level, the advantage of Bayesian Alphabet would be more obvious, therefore, different models of GP are appropriate in different traits. These findings indicated the significance of applying appropriate models for GP which would assist in further exploring the optimization of GP.
Identification of the sex chromosome system in a sand fly species,Lutzomyia longipalpiss.l
Authors: Vigoder Felipe M , Araripe Luciana O , Carvalho Antonio Bernardo
Published: June 2021

In many animal species, sex determination is accomplished by heterogamety i.e., one of the sexes produces two types of gametes, which upon fertilization will direct the development toward males or females. Both male (“XY”) and female (“ZW”) heterogamety are known to occur and can be easily distinguished when the sex-chromosomes are morphologically different. However, this approach fails in cases of homomorphic sex chromosomes, such as the sand fly Lutzomyia longipalpis s.l. (Psychodidae, Diptera), which is the main vector of visceral leishmaniosis in Brazil. In order to identify the heterogametic sex in L. longipalpis s.l., we did a whole-genome sequencing of males and females separately and used the “Y chromosome Genome Scan” (YGS) method to find sex-specific sequences. Our results, which were confirmed by PCR, show that L. longipalpis s.l. has XY system. The YGS method can be especially useful in situations in which no morphological difference is observed in the sex-chromosomes or when fresh specimens are not readily available.
Deacetylated sialic acids modulates immune mediated cytotoxicity via the sialic acid-Siglec pathway
Authors: Grabenstein Susan , Barnard Karen N , Anim Mathias , Armoo Albert , Weichert Wendy S , Bertozzi Carolyn R , Parrish Colin R , Willand-Charnley Rachel
Published: June 2021

Cancers utilize glycans to evade the immune system via the Sialic acid (Sia)-Siglec (Sialic-acid-binding immunoglobulin-like lectins) pathway. Specifically, atypical structural forms of sialic acid bind to inhibitory Siglec receptors on natural killer (NK) cells resulting in the suppression of immune cell mediated cytotoxicity. The mechanism of action that governs the Sia-Siglec pathway in cancers is not understood. Specifically, how deviations from the typical form of Sia mechanistically contribute. Here, we focused on modulating 9-O and 7, 9-O-acetylation of Neu5Ac, via CRISPR-Cas9 gene editing, a functional group that is absent from Sias on many types of cancer cells. The two genes that are responsible for regulating the level of acetylation on Neu5Ac, are Sialic acid acetylesterase (SIAE) and Sialic acid acetyltransferase (CASD1). These genes modulated Siglec binding in colon, lung and a noncancerous kidney cell line. In the absence of SIAE, Neu5Ac is acetylated, engagement of cancer associated Siglecs is reduced while binding was increased when the ability to acetylate was removed via CASD1 knock out. In the absence of SIAE NK mediated cytotoxicity increased in both colon and lung cancer cells. In addition to modulating Siglec binding, SIAE expression modulates the level of Sias in a cell, and the α2–6-linkage of Sias—which is specifically upregulated and associated with cancers. Uncovering how functional group alterations on Neu5Ac contribute mechanistically to both Siglec receptor binding, the Sia-Siglec immune evasion pathway, and the production of cancer associated glycosidic linkages—offers a promising avenue for targeted cancer immune therapies in the future.
Impact evaluation of a maternal and neonatal health training intervention in private Ugandan facilities
Authors: Baumgartner Joy Noel , Headley Jennifer , Kirya Julius , Guenther Josh , Kaggwa James , Kim Min Kyung , Aldridge Luke , Weiland Stefanie , Egger Joseph
Published: June 2021

Global and country-specific targets for reductions in maternal and neonatal mortality in low-resource settings will not be achieved without improvements in the quality of care for optimal facility-based obstetric and newborn care. This global call includes the private sector, which is increasingly serving low-resource pregnant women. The primary aim of this study was to estimate the impact of a clinical and management-training programme delivered by a non-governmental organization [LifeNet International] that partners with clinics on adherence to global standards of clinical quality during labour and delivery in rural Uganda. The secondary aim included describing the effect of the LifeNet training on pre-discharge neonatal and maternal mortality. The LifeNet programme delivered maternal and neonatal clinical trainings over a 10-month period in 2017–18. Direct clinical observations of obstetric deliveries were conducted at baseline (n = 263 pre-intervention) and endline (n = 321 post-intervention) for six faith-based, not-for-profit primary healthcare facilities in the greater Masaka area of Uganda. Direct observation comprised the entire delivery process, from initial client assessment to discharge, and included emergency management (e.g. postpartum haemorrhage and neonatal resuscitation). Data were supplemented by daily facility-based assessments of infrastructure during the study periods. Results showed positive and clinically meaningful increases in observed handwashing, observed delayed cord clamping, partograph use documentation and observed 1- and/or 5-minute APGAR assessments (rapid scoring system for assessing clinical status of newborn), in particular, between baseline and endline. High-quality intrapartum facility-based care is critical for reducing maternal and early neonatal mortality, and this evaluation of the LifeNet intervention indicates that their clinical training programme improved the practice of quality maternal and neonatal healthcare at all six primary care clinics in Uganda, at least over a relatively short-term period. However, for several of these quality indicators, the adherence rates, although improved, were still far from 100% and could benefit from further improvement via refresher trainings and/or a closer examination of the barriers to adherence.
Venovenous extracorporeal membrane oxygenation during high-risk airway interventions
Authors: Stokes John W , Katsis James M , Gannon Whitney D , Rice Todd W , Lentz Robert J , Rickman Otis B , Avasarala Sameer K , Benson Clayne , Bacchetta Matthew , Maldonado Fabien
Published: June 2021

OBJECTIVES

Practice patterns for the use of extracorporeal membrane oxygenation (ECMO) during high-risk airway interventions vary, and data are limited. We aim to characterize our recent experience using ECMO for procedural support during whole-lung lavage (WLL) and high-risk bronchoscopy for central airway obstruction (CAO).

METHODS

We performed a retrospective cohort study of adults who received ECMO during WLL and high-risk bronchoscopy from 1 July 2018 to 30 March 2020. Our primary end point was successful completion of the intervention. Secondary end points included ECMO-associated complications and hospital survival.

RESULTS

Eight patients received venovenous ECMO for respiratory support during 9 interventions; 3 WLLs for pulmonary alveolar proteinosis were performed in 2 patients, and 6 patients underwent 6 bronchoscopic interventions for CAO. We initiated ECMO prior to the intervention in 8 cases and during the intervention in 1 case for respiratory decompensation. All 9 interventions were successfully completed. Median ECMO duration was 17.8 h (interquartile range, 15.9–26.6) for the pulmonary alveolar proteinosis group and 1.9 h (interquartile range, 1.4–8.1) for the CAO group. There was 1 cannula-associated deep vein thrombosis; there were no other ECMO complications. Seven patients (87.5%) and 4 (50.0%) patients survived to discharge and 1 year postintervention, respectively.

CONCLUSIONS

Use of venovenous ECMO to facilitate high-risk airway interventions is safe and feasible. Planned preprocedural ECMO initiation may prevent avoidable respiratory emergencies and extend therapeutic airway interventions to patients otherwise considered too high-risk to treat. Guidelines are needed to inform the utilization of ECMO during high-risk bronchoscopy and other airway interventions.
Asymptotic Hecke Algebras and Lusztig–Vogan Bijection via Affine Matrix-Ball Construction
Authors: Kim Dongkwan , Pylyavskyy Pavlo
Published: June 2021

The affine matrix-ball construction (abbreviated AMBC) was developed by Chmutov, Lewis, Pylyavskyy, and Yudovina as an affine generalization of the Robinson–Schensted correspondence. We show that AMBC gives a simple way to compute a distinguished involution in each Kazhdan–Lusztig cell of an affine symmetric group. We then use AMBC to give the 1st known canonical presentation for the asymptotic Hecke algebras of extended affine symmetric groups. As an application, we show that AMBC gives a conceptual way to compute the Lusztig–Vogan bijection. For the latter, we build upon prior works of Achar and Rush.
Social Power and the Politics of Reservations and Objections in Human Rights Treaties
Authors: Eldredge Cody D , Shannon Megan
Published: June 2021

States often file reservations to human rights treaties with the goal of reducing their legal commitments under the treaty. Other states within the treaty have the right to declare objections in response to states making reservations. This is a potentially powerful tool for objecting states, and has numerous consequences for relations within and outside the human rights institution. So why do only some states lodge formal objections, while others do not? We argue that states consider the degree of social power they wield over a reserving state when formulating the decision to lodge an objection, because higher levels of social power amplify the effects of an objection. To evaluate our expectation, we gather data on all states’ reserving and objecting behaviors within the Convention against Torture. Controlling for a number of factors, we find that the measure of social power significantly increases the likelihood that a state will object to another state's reservation. This research calls attention to the power of objections as a legal tool, and suggests areas of future research for the effects of objections on the legality of human rights agreements.
Eco-Friendly Chromatographic Methods for Determination of Acemetacin and Indomethacin; Greenness Profile Assessment
Authors: Moaaz Eman M , Abdel-Moety Ezzat M , Rezk Mamdouh R , Fayed Ahmed S
Published: June 2021

Background

The green chemistry approach was developed for the purpose of saving the environment by using green solvents. Applying green analytical chemistry principles to traditional methods is considered a challenge. Acemetacin is a commonly used analgesic prodrug that bioactivates to indomethacin.

Objective

Developing two simple, eco-friendly chromatographic methods for simultaneous determination of acemetacin and indomethacin.

Method

The first method is HPLC-DAD. Separation was performed on a Waters XBridge® Shield RP18 (250 × 4.6 mm, 5 µm) analytical column with ethanol–ammonium acetate buffer (50 mM, pH 3.5 ± 0.1; 60:40, v/v) as a mobile phase at a flow rate of 1 mL/min at 25 ± 0.5°C and UV detection at 254 nm. The other method is TLC coupled with densitometric quantification using pre-coated silica TLC plates and butanol–ethyl acetate (70:30, v/v) elution system. The plates were scanned at 254 nm.

Results

Both methods were validated according to International Conference on Harmonization guidelines. Linearity was confirmed for both over a concentration range of 1–100 µg/mL for the HPLC method and 0.2–7 µg/band for TLC-densitometric method. The methods’ greenness was evaluated by the National Environmental Methods Index, Eco-Scale, Green Analytical Procedure Index metrics and Analytical GREEnness Metric Approach.

Conclusions

The proposed methods were found to be suitable for determination of studied drugs in their marketed formulations and is suggested for routine analysis in quality control laboratories.

Highlights

The developed HPLC method shortened the elution time of the analyzed drugs saving more time and money and the TLC method lowered the drugs’ detection limit. HPLC and TLC methods were validated for the assay of acemetacin and indomethacin. The methods’ greenness was evaluated and compared to published methods. The developed HPLC method shortened the elution time of the analyzed drugs, saving time and money and the TLC method lowered the drugs’ detection limit.
Salivary neopterin and related pterins: their comparison to those in plasma and changes in individuals
Authors: Ikemoto Kazuhisa , Sumi-Ichinose Chiho , Suganuma Yui , Kano Taiki , Ihira Noriko , Nagatsu Toshiharu , Kondo Kazunao
Published: June 2021

Neopterin (NP), biopterin (BP) and monapterin (MP) exist in saliva. The physiological role of salivary NP as well as the pathophysiological role of increased NP in the immune-activated state has been unclear. Saliva is a characteristic specimen different from other body fluids. In this study, we analysed salivary NP and related pterin compounds, BP and MP and revealed some of its feature. High-performance liquid chromatography (HPLC) analysis of saliva and plasma obtained from 26 volunteers revealed that salivary NP existed mostly in its fully oxidized form. The results suggested that salivary NP as well as BP would mostly originate from the oral cavity, perhaps the salivary glands, and that salivary NP levels might not reflect those in the plasma. We also found that a gender difference existed in correlations between concentrations of salivary total concentrations of NP (tNP) and BP (tBP). HPLC analysis of saliva obtained from 5 volunteers revealed that the concentrations of salivary tNP as well as tBP fluctuated in an irregular fashion in various individuals. MP, a diastereomer of NP, might have come from oral cavity NP itself or its precursor. These results indicated that the nature of salivary NP might be different from that of NP in the blood or urine.
Paternity After Treatment for Testicular Germ Cell Cancer: A Danish Nationwide Population-Based Cohort Study
Authors: Bandak Mikkel , Jensen Allan , Dehlendorff Christian , Lauritsen Jakob , Kreiberg Michael , Wagner Thomas , Rosenvilde Josephine , Daugaard Gedske
Published: June 2021

Background

Testicular germ cell cancer (TC) incidence peaks during reproductive age, but knowledge on fertility after treatment is insufficient. The aim was to evaluate paternity after today’s TC treatment.

Methods

Clinical data were extracted from the Danish Testicular Cancer database, and patients were divided into 4 groups: 1) surveillance; 2) bleomycin, etoposide, and cisplatin (BEP); 3) BEP + postchemotherapy retroperitoneal surgery (BEP + surgery); and 4) abdominal radiotherapy. For each patient, 10 men matched on date of birth were randomly sampled from the normal population. Paternity was defined as date of birth of first child after TC treatment with or without the use of assisted reproductive technology and was assessed by linkage to the Danish Medical Birth Register and the Danish in vitro fertilization register.

Results

We included 4846 unilateral TC patients and 48 456 men from the normal population. The 20-year predicted chance of obtaining fatherhood for a 30-year-old man was 39.7% in TC patients compared with 42.5% in the normal population. The chance of obtaining fatherhood was statistically significantly decreased after BEP (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.78 to 0.97) and BEP + surgery (HR = 0.74, 95% CI = 0.63 to 0.87), but not after radiotherapy (HR = 0.89, 95% CI = 0.75 to 1.06) or surveillance (HR = 0.95, 95% CI = 0.89 to 1.02). The risk of needing assisted reproductive technology to obtain fatherhood was increased after all treatment modalities.

Conclusions

The chance of obtaining fatherhood after TC treatment was substantially higher than previously reported. Patients followed on a surveillance program had a similar chance of obtaining fatherhood as noncancerous men.
In-line monitoring and endpoint determination of percolation process of herbal medicine using ultraviolet spectroscopy combined with convolutional neural network
Authors: Zhang Sheng , Yan Xu , Fu Hao , Li Wenlong , Qu Haibin
Published: June 2021

Objectives

As a common step in the herbal medicine production process, percolation usually lacks effective process monitoring methods and is often conducted with fixed process parameters. In this study, an in-line ultraviolet (UV) spectroscopy was used for monitoring the Caulis Sinomenii percolation process.

Methods

The spectra and concentration data of 156 percolation samples from five batches were collected. Convolutional neural networks (CNNs) were used to develop quantitative calibration models. The mean squared error (MSE), mean absolute percentage error (MAPE) and mean absolute error (MAE) were compared to select the proper loss function for developing the CNN models. Meanwhile, partial least square regression (PLSR) was also used to develop calibration models for performance comparison.

Key findings

The CNN models with MAPE or MAE as the loss function could provide accurate predictions for all samples. However, CNN models adopting MSE as the loss function tended not to predict low-concentration samples accurately. The CNN models mostly achieved satisfactory results without any preprocessing techniques and surpassed PLSR models in all the performance metrics.

Conclusions

An in-line UV spectroscopy system combining the CNN algorithm was implemented to monitor the percolation process of Caulis Sinomenii. The system can accurately determine the endpoint of the percolation process.
Oculomotor nerve palsy following coronary artery bypass graft surgery: can pituitary apoplexy complicate the post-operative course of cardiac surgery?
Authors: Alkhaibary Ali , Alsubaie Noura , Alharbi Ahoud , Alghanim Noor , Khairy Sami , Almuntashri Makki , Alwohaibi Mohammed , Alarifi Abdulaziz , Aloraidi Ahmed , Alkhani Ahmed
Published: June 2021

Oculomotor nerve palsy, due to pituitary apoplexy, has been previously reported in the literature. However, the association with coronary artery bypass graft surgery (CABG) is rarely investigated. This article reports a case of pituitary apoplexy presenting with oculomotor nerve palsy following CABG. A 65-year-old male, known to have ischemic heart disease, diabetes mellitus and hypertension, presented with ptosis, diplopia and anisocoria that developed after 1 day of CABG. Radiological imaging demonstrated a pituitary adenoma with acute/subacute hemorrhage causing mild mass effect on the cavernous sinus. Considering the acute state of bypass surgery and pre-existing cardiac co-morbidities, expectant management was considered. The visual acuity and palsy gradually improved. Pituitary apoplexy, following CABG, is a rare phenomenon in the post-operative period. High index of suspicious is required to promptly identify high-risk patients to avoid further neurological sequelae.
Physalis floridana CRABS CLAWmediates neofunctionalization ofGLOBOSAgenes in carpel development
Authors: Gong Pichang , Song Chunjing , Liu Hongyan , Li Peigang , Zhang Mingshu , Zhang Jisi , Zhang Shaohua , He Chaoying
Published: June 2021

Floral B-function MADS-box genes, such as GLOBOSA (GLO), function in corolla and stamen organ identity specification. The functions of these genes outside these floral whorls are rarely reported. DOLL1 is a GLO gene controlling corolla and androecium organ identity. In this study we found that, in Physalis floridana double-layered-lantern 1 (doll1) mutant pollinated with wild-type pollen, fruit set was extremely low, indicating that doll1 females are dysfunctional. Stigma and style structure, stigma receptivity, pollen tube guidance, and embryo sac development were also impaired in doll1. P. floridana CRABS CLAW (PFCRC), predominantly expressed in carpels, was repressed in doll1 native carpels. Loss-of-function of PFCRC altered carpel meristem determinacy, carpel closure, and ovule number, and the resultant ‘pistil’ consisted of multiple spirally-arranged dorsiventral carpels occasionally with 1–2 naked ovules on the margin and trichomes at each mutated carpel tip, implying an alteration of carpel organ identity. Regulatory and genetic interactions between B-class MADS-box genes and PFCRC were revealed in a context-dependent manner in floral development. Our work reveals a new role for the B-function genes in carpel and ovule development via regulating PFCRC, providing a new understanding of genetic regulatory networks between MADS-domain and CRC transcription factors in mediating carpel organ specification, functionality, and origin.
Association of Medication-Assisted Treatment and Age With Treatment Completion Among Veterans Seeking Non-VA Treatment for Opioid use Disorder at Non-Veterans Health Administration Facilities
Authors: Pickard Joseph G , van den Berk-Clark Carissa , Matthieu Monica M
Published: June 2021

Background

Medication-assisted treatment has been shown to be effective in treating opioid use disorder among both older adults and veterans of U.S. Armed Forces. However, limited evidence exists on MAT’s differential effect on treatment completion across age groups. This study aims to ascertain the role of MAT and age in treatment completion among veterans seeking treatment in non–Department of Veterans Affairs healthcare facilities for opioid use disorder.

Methods

We used the Treatment Episode Data Set—Discharges (TEDS-D; 2006-2017) to examine trends in treatment and MAT usage over time and TEDS-2017 to determine the role of age and MAT in treatment completion. We examined a subset of those who self-identified as veterans and who sought treatment for an opioid use disorder.

Results

Veterans presented in treatment more often as heroin users than prescription opioid users, and older veterans were more likely to get MAT than younger veterans. We found that before propensity score matching, MAT initially appeared to be associated with a lower likelihood of treatment completion in inpatient ($\beta $ = −1.47, 95% CI −1.56 to −1.39) and outpatient ($\beta $ = −1.40, 95% CI −2.21 to −0.58) settings, and age (50+ years) appeared to mediate the effect of MAT on treatment completion ($\beta $ = −0.54, 95% CI −0.87 to −0.21). After matching, older veterans were more likely to complete substance use disorder treatment ($\beta $ = 0.21, 95% CI 0.01-0.42), while age no longer mediated the effect of MAT, and MAT had a significant positive impact on treatment completion in detox settings ($\beta $ = 1.36, 95% CI 1.15-1.50) and inpatient settings ($\beta $ = 1.54, 95% CI 1.37 -1.71).

Conclusion

The results show that age plays an important role in outpatient treatment completion, while MAT plays an important role in inpatient treatment completion. Implications for veterans are discussed.