bluuebunny/crossref_metadata_2025 huggingface dataset:
Heuristic shortest hyperpaths in cell signaling hypergraphs
Authors: Krieger Spencer , Kececioglu John
Published: May 2022

Background

Cell signaling pathways, which are a series of reactions that start at receptors and end at transcription factors, are basic to systems biology. Properly modeling the reactions in such pathways requires directed hypergraphs, where an edge is now directed between two sets of vertices. Inferring a pathway by the most parsimonious series of reactions corresponds to finding a shortest hyperpath in a directed hypergraph, which is NP-complete. The current state-of-the-art for shortest hyperpaths in cell signaling hypergraphs solves a mixed-integer linear program to find an optimal hyperpath that is restricted to be acyclic, and offers no efficiency guarantees.

Results

We present, for the first time, a heuristic for general shortest hyperpaths that properly handles cycles, and is guaranteed to be efficient. We show the heuristic finds provably optimal hyperpaths for the class of singleton-tail hypergraphs, and also give a practical algorithm for tractably generating all source-sink hyperpaths. The accuracy of the heuristic is demonstrated through comprehensive experiments on all source-sink instances from the standard NCI-PID and Reactome pathway databases, which show it finds a hyperpath that matches the state-of-the-art mixed-integer linear program on over 99% of all instances that are acyclic. On instances where only cyclic hyperpaths exist, the heuristic surpasses the state-of-the-art, which finds no solution; on every such cyclic instance, enumerating all source-sink hyperpaths shows the solution found by the heuristic was in fact optimal.

Conclusions

The new shortest hyperpath heuristic is both fast and accurate. This makes finding source-sink hyperpaths, which in general may contain cycles, now practical for real cell signaling networks.

Availability

Source code for the hyperpath heuristic in a new tool we call  (as well as for hyperpath enumeration, and all dataset instances) is available free for non-commercial use at .
In-hospital mortality associated with necrotizing soft tissue infection due to Vibrio vulnificus: a matched-pair cohort study
Authors: Chang Chih-Yao , Wu Kai-Hsiang , Wu Po-Han , Hung Shang-Kai , Hsiao Cheng-Ting , Wu Shu-Ruei , Chang Chia-Peng
Published: May 2022

Background

It remains unclear whether Vibrio vulnificus necrotizing soft tissue infection (NSTI) is associated with higher mortality compared with non-Vibrio NSTI. This study’s objective was to compare outcomes including in-hospital mortality and prognosis between patients with V. vulnificus NSTI and those with non-Vibrio NSTI.

Method

A retrospective 1:2 matched-pair cohort study of hospitalized patients with NSTI diagnosed by surgical finding was conducted in two tertiary hospitals in southern Taiwan between January 2015 and January 2020. In-hospital outcomes (mortality, length of stay) were compared between patients with and without V. vulnificus infection. We performed multiple imputation using chained equations followed by multivariable regression analyses fitted with generalized estimating equations to account for clustering within matched pairs. All-cause in-hospital mortality and length of stay during hospitalization were compared for NSTI patients with and without V. vulnificus.

Result

A total of 135 patients were included, 45 in V. vulnificus NSTI group and 90 in non-Vibrio group. The V. vulnificus NSTI patients had higher mortality and longer hospital stays. Multivariable logistic regression analysis revealed that V. vulnificus NSTI was significantly associated with higher in-hospital mortality compared with non-Vibrio NSTI (adjusted odds ratio = 1.52; 95% confidence interval 1.36–1.70; p < 0.01).

Conclusion

Vibrio vulnificus NSTI was associated with higher in-hospital mortality and longer hospital stay which may increase health care costs, suggesting that preventing V. vulnificus infection is essential.
The application of the WSES classification system for open pelvic fractures—validation and supplement from a nationwide data bank
Authors: Li Pei-Hua , Hsu Ting-An , Kuo Yu-Chi , Fu Chih-Yuan , Bajani Francesco , Bokhari Marissa , Mis Justin , Poulakidas Stathis , Bokhari Faran
Published: May 2022

Background

Open pelvic fractures are rare but complex injuries. Concomitant external and internal hemorrhage and wound infection-related sepsis result in a high mortality rate and treatment challenges. Here, we validated the World Society Emergency Society (WSES) classification system for pelvic injuries in open pelvic fractures, which are quite different from closed fractures, using the National Trauma Data Bank (NTDB).

Methods

Open pelvic fracture patients in the NTDB 2015 dataset were retrospectively queried. The mortality rates associated with WSES minor, moderate and severe injuries were compared. A multivariate logistic regression model (MLR) was used to evaluate independent factors of mortality. Patients with and without sepsis were compared. The performance of the WSES classification in the prediction of mortality was evaluated by determining the discrimination and calibration.

Results

A total of 830 open pelvic fracture patients were studied. The mortality rates of the mild, moderate and severe WSES classes were 3.5%, 11.2% and 23.8%, respectively (p < 0.001). The MLR analysis showed that the presence of sepsis was an independent factor of mortality (odds of mortality 9.740, p < 0.001). Compared with patients without sepsis, those with sepsis had significantly higher mortality rates in all WSES classes (minor: 40.0% vs. 3.1%, p < 0.001; moderate: 50.0% vs. 9.1%, p < 0.001; severe: 66.7% vs. 22.2%, p < 0.001). The receiver operating characteristic (ROC) curve showed an acceptable discrimination of the WSES classification alone for evaluating the mortality of open pelvic fracture patients [area under curve (AUC) = 0.717]. Improved discrimination with an increased AUC was observed using the WSES classification plus sepsis (AUC = 0.767).

Conclusions

The WSES guidelines can be applied to evaluate patients with open pelvic fracture with accurate evaluation of outcomes. The presence of sepsis is recommended as a supplement to the WSES classification for open pelvic fractures.
Uncertainties of soil organic carbon stock estimation caused by paleoclimate and human footprint on the Qinghai Plateau
Authors: Liu Xia , Zhou Tao , Shi Peijun , Zhang Yajie , Luo Hui , Yu Peixin , Xu Yixin , Zhou Peifang , Zhang Jingzhou
Published: May 2022

Background

Quantifying the stock of soil organic carbon (SOC) and evaluating its potential impact factors is important to evaluating global climate change. Human disturbances and past climate are known to influence the rates of carbon fixation, soil physiochemical properties, soil microbial diversity and plant functional traits, which ultimately affect the current SOC storage. However, whether and how the paleoclimate and human disturbances affect the distribution of SOC storage on the high-altitude Tibetan Plateau remain largely unknown. Here, we took the Qinghai Plateau, the main component of the Tibetan Plateau, as our study region and applied three machine learning models (random forest, gradient boosting machine and support vector machine) to estimate the spatial and vertical distributions of the SOC stock and then evaluated the effects of the paleoclimate during the Last Glacial Maximum and the mid-Holocene periods as well as the human footprint on SOC stock at 0 to 200 cm depth by synthesizing 827 soil observations and 71 environmental factors.

Results

Our results indicate that the vegetation and modern climate are the determinant factors of SOC stocks, while paleoclimate (i.e., paleotemperature and paleoprecipitation) is more important than modern temperature, modern precipitation and the human footprint in shaping current SOC stock distributions. Specifically, the SOC stock was deeply underestimated in near natural ecosystems and overestimated in the strongly human disturbance ecosystems if the model did not consider the paleoclimate. Overall, the total SOC stock of the Qinghai Plateau was underestimated by 4.69%, 12.25% and 6.67% at depths of 0 to 100 cm, 100 to 200 cm and 0 to 200 cm, respectively. In addition, the human footprint had a weak influence on the distributions of the SOC stock. We finally estimated that the total and mean SOC stock at 200 cm depth by including the paleoclimate effects was 11.36 Pg C and 16.31 kg C m−2, respectively, and nearly 40% SOC was distributed in the top 30 cm.

Conclusion

The paleoclimate is relatively important for the accurate modeling of current SOC stocks. Overall, our study provides a benchmark for predicting SOC stock patterns at depth and emphasizes that terrestrial carbon cycle models should incorporate information on how the paleoclimate has influenced SOC stocks.
Poor education and urgent information need for emergency physicians about rare diseases in China
Authors: Zhou Lingli , Xu Jun , Yang Jing
Published: May 2022

Background

Rare diseases are serious and chronic diseases that affect no more than 1 person in 2000 (in European Union criteria). Patients suffering from RDs may come to the emergency department for life-threatening symptoms, such as acute aortic dissection, intracranial haemorrhage, and severe respiratory distress. Diagnostic delay of rare disease patients is common and often caused by low rare disease awareness among physicians. The main aim of this study was to investigate Chinese emergency physicians’ basic knowledge, information access and educational needs regarding rare diseases. An online questionnaire was completed by Chinese emergency physicians during January and March 2021.

Methods and results

A total of 539 emergency physicians, including 200 females and 339 males, responded to the questionnaire-based study. More than half of the respondents were from Tertiary A hospitals and had engaged in medical clinical work for more than 10 years. Only 4.27% of respondents correctly estimated the prevalence of rare diseases. A few respondents knew the exact number of RDs in the first official list of rare diseases in 2018. A total of 98.5% of respondents rated their knowledge about rare diseases as minimal or insufficient. Most emergency physicians preferred to obtain information through search engines instead of specialized websites on rare diseases. A lack of practice guidelines or consensus was considered the most important reason for the diagnostic delay of RD. Practice guidelines or consensus and professional websites on rare diseases are urgently needed for emergency physicians.

Conclusion

The investigation shows poor knowledge of rare diseases among emergency physicians. Practice guidelines and professional websites on rare diseases were the primary urgent needs for emergency physicians. Specialized RD courses should also be added to medical education.
Engineering the oleaginous yeast Candida tropicalis for α-humulene overproduction
Authors: Zhang Lihua , Yang Haiquan , Xia Yuanyuan , Shen Wei , Liu Liming , Li Qi , Chen Xianzhong
Published: May 2022

Background

α-Humulene is a plant-derived monocyclic sesquiterpenoid with multiple pharmacological activities, and far-reaching potential for the development of new drugs. Currently, the production of α-humulene is typically achieved via plant extraction, which is not sustainable and limited by low yields. The oleaginous yeast Candida tropicalis has recently emerged as a valuable host for producing high-value-added chemicals. However, the potential of C. tropicalis for terpenoid production has not been exploited.

Results

In this study, C. tropicalis was engineered for de novo synthesis of α-humulene from glucose. To improve α-humulene production, the codon-optimised α-humulene synthase gene and the entire endogenous farnesyl diphosphate synthesis pathway were co-overexpressed. Furthermore, bottlenecks in the α-humulene synthase pathway were identified and relieved by overexpressing α-humulene synthase, acetoacetyl-CoA thiolase and NADH-dependent HMG-CoA reductase. Combined with fermentation medium optimisation, the engineered strain produced 195.31 mg/L of α-humulene in shake flasks and 4115.42 mg/L in a bioreactor through fed-batch fermentation, a 253- and 5345-fold increase over the initial production, respectively.

Conclusions

This study demonstrates the potential of C. tropicalis for α-humulene production, and presents a platform for the biosynthesis of other terpenoids.
Allergological study in patients vaccinated against COVID-19 with suspected allergic reactions
Authors: Jover Cerdá Vicente , Rodríguez Pacheco Ramón , Doménech Witek Joan , Alonso Hernández Sonia , Durán García Rafael , Real Panisello Marina , Marco de la Calle Francisco Manuel
Published: May 2022

Background

One of the main barriers to vaccination against SARS-CoV-2 is the fear of developing hypersensitivity reactions to any of its components. Although these reactions are very rare, it is necessary to establish an effective protocol to detect patients at risk of developing them. The aim of this study was to evaluate hypersensitivity reactions in vaccinated patients in order to allow or not to complete the vaccination protocol.

Methods

Descriptive and cross-sectional study in which patients with suspected hypersensitivity to SARS-CoV-2 vaccines were evaluated. All patients underwent skin prick test (SPT) and/or intradermal test (IDT) with the vaccines and their excipients. In patients with positive IDT with the vaccine, a histopathological and immunohistochemical study was performed by skin biopsy. A basophil activation test (BAT) and a lymphoblastic transformation test (LTT) were also performed.

Results

Sixteen patients with suspected hypersensitivity to SARS-CoV-2 vaccine (12 received Comirnaty®, 3 received Vaxzevria®, and 1 received Spikevax®) were evaluated. Half had immediate hypersensitivity reactions and half had delayed reactions. All SPTs to excipients and vaccines were negative. IDTs with all excipients were negative. IDTs with vaccines were positive in 11 patients and negative in 5. The histological and immunohistochemical study of the two selected patients with positive IDT with vaccine showed T-lymphocyte involvement. BAT and LTT were negative in both cases. The vaccination protocol could be completed in 7 of 16 patients (44%) studied. The remaining 9 patients did not receive the second dose: 5 because vaccination was not required and 4 because they refused to be vaccinated.

Conclusions

Thanks to the allergological and immunohistochemical study, the vaccination protocol could be completed in about half of the patients who presented suspected hypersensitivity reactions to SARS-CoV-2 vaccines. IDTs with vaccines could be a valuable method for assessing the immunogenicity of the vaccines.
Increasing the publicness of riversides as public space development on Kebena River, Addis Ababa, Ethiopia
Authors: Getachew Abebe , Asnake Kalkidan , Desta Hayal
Published: May 2022

Introduction

Public space development is important for the socio-economic and ecological conditions of cities. This study evaluated the publicness of riversides as public space development on the Kebena River in Addis Ababa, Ethiopia. The study identified the potentials and challenges of open spaces for public space development along the riversides of the Kebena River to increase the publicness of the riversides.

Methods

A comparative analysis of the publicness level of three selected open spaces along the riversides of Kebena River, namely, Wisdom Park, Minister Meda, and Agoza Meda, were done using the star model. Quantitative data were collected using site observations, document reviews, and questionnaire surveys with 169 interviewees. The land use and land cover (LULC) change detections were done for the years 2002 and 2020. Data were analyzed using SPSS, ArcGIS (Geographic Information Systems) software, and the Star model of the publicness analysis tool. Both qualitative and quantitative data were used to examine the riversides of the Kebena River.

Result

The results from the star model revealed that the riversides of the Kebena River could not be considered public spaces in their present conditions. This could be attributable to the abuse by the illegal settlers and urban agriculture activities.

Conclusion

The study depicted that the publicness of the Kebena riverside areas is very low and has a very poor public life. Publicness-oriented public spaces should be established and developed to improve and enhance the publicness level of the riversides of the Kebena River. The study contributes to scientific communities and policymakers to enhance the development of open green spaces, which may contribute towards climate change mitigation and adaptation strategies.
VeriSIM: A model-based learning pedagogy for fostering software design evaluation skills in computer science undergraduates
Authors: Prasad Prajish , Iyer Sridhar
Published: May 2022

Evaluating a software design is an important practice of expert software designers. They spend significant time evaluating their solution, by developing an integrated mental model of the software design and the requirements. However, sufficient emphasis has not been given on teaching and learning of evaluation practices in software design courses, and hence, graduating students find it difficult to critically analyse an existing design and improve upon it. In this paper, we describe a model-based learning pedagogy for teaching–learning of software design evaluation. Model-based learning has been extensively used in science education and entails helping students construct, refine, revise, evaluate, and validate scientific models. We argue that modelling practices in software design evaluation are analogous to these practices. We adapted the model-based learning paradigm and operationalised it into a technology-enhanced learning environment (TELE) for fostering software design evaluation skills in computer science undergraduates. We conducted a research study with 22 undergraduate students to explore how the TELE and its features help students effectively evaluate a given software design. Students attempted a pre-test and post-test which asked them to identify defects in the design. We used the content analysis method to identify categories of defects from student responses in the pre-test and post-test. We also analysed student interaction logs and conducted focus group interviews to identify how features in the TELE contributed towards student learning. Findings from the study showed that students’ understanding of evaluation improved, from merely adding new functionalities and requirements, to a process which involved identifying alternate scenarios in the design which violate the given requirements. Students perceived that pedagogical features of the TELE were useful in helping them effectively evaluate software designs. Findings from the study provide evidence for the model-based learning paradigm as an appropriate pedagogy for software design and also opens the space for researchers to investigate model-based learning in other aspects of software design, such as designs of different types and varying complexities.
Emotional intelligence and academic motivation in primary school students
Authors: Arias Julia , Soto-Carballo Jorge G. , Pino-Juste Margarita R.
Published: May 2022

The role of emotions in the educational context is one of the lines of research that has generated most interest in recent years. This study explores the level of emotional intelligence (EI) and motivation towards studying of primary school (PS) students, as well as the relationship between both variables. For this, a quasi-experimental design has been used with an accidental sample of 541 students from public centers in the province of Pontevedra (Spain). The instruments used were a School Motivation Scale and an EI questionnaire for primary school students, based on the five areas of Goleman EI. The results maintain a mid to high level of EI in all of the factors (self-conscience, self-control, emotional use, empathy and social skills) and a good level of academic motivation. Therefore, they show a positive and significant correlation of both variables. Girls have a higher emotional intelligence index and there is no difference in academic motivation in terms of gender. Based on these results, it is suggested to implement programs that consolidate emotional competences given their importance in the psychoevolutionary development of students and their relationship with academic motivation.
Fibronectin extra domain A as a drug delivery targeting epitope for rheumatoid arthritis
Authors: Sun Victor Z. , Melim Terry L. , Mitra Soumya , Erickson Jamie E. , Bryant Shaughn H. , Farnham Avery , Westmoreland Susan , Knight Heather , Zhang Liang , Ritacco Wendy , Homan Kristoff , Benatuil Lorenzo , Sterman Annette J. Schwartz , Goodearl Andrew D.
Published: May 2022

Objectives

To assess the ability of monoclonal antibodies (mAbs) specific for fibronectin extra-domain A (FnEDA) to target diseased tissues of mouse collagen induced arthritis (mCIA) models. To explore the parameters of the targeting exhibited by anti-FnEDA mAbs including timing and location.

Methods

Targeting capabilities of anti-FnEDA mAbs were demonstrated by biodistribution study where i.v. injected antibodies were detected by conjugated near-infrared (NIR) fluorophore, 125I label and immunohistochemistry (IHC) of the injected antibody. Location of FnEDA expression in both mCIA and human RA tissue were mapped by IHC. Quantification of anti-FnEDA mAbs targeted to disease tissue was measured by whole-body autoradiography (WBA). Timing of the targeting was interrogated with fluorescent and confocal microscopy using anti-FnEDA mAbs labeled with different fluorophores and injected at different times.

Results

Anti-FnEDA mAbs show specific targeting to diseased paws of mCIA animal. The targeting was focused on inflamed synovium which is consistent with FnEDA expression profile in both mCIA and human RA tissues. Anti-FnEDA mAbs accumulated in diseased tissue at pharmacologically relevant concentrations, the targeting was sustained for up to 14 days and FnEDA was able to support targeting of multiple doses of anti-FnEDA mAbs given 5 days apart.

Conclusion

FnEDA is specifically upregulated in the inflamed tissues of mCIA. Antibodies specific for FnEDA can be useful as molecular delivery vehicles for disease specific targeting of payloads to inflamed joint tissue.
Identifying drivers of breast cancer metastasis in progressively invasive subpopulations of zebrafish-xenografted MDA-MB-231
Authors: Xiao Jerry , McGill Joseph R. , Nasir Apsra , Lekan Alexander , Johnson Bailey , Wilkins Devan J. , Pearson Gray W. , Tanner Kandice , Goodarzi Hani , Glasgow Eric , Schlegel Richard , Agarwal Seema
Published: May 2022

Cancer metastasis is the primary cause of the high mortality rate among human cancers. Efforts to identify therapeutic agents targeting cancer metastasis frequently fail to demonstrate efficacy in clinical trials despite strong preclinical evidence. Until recently, most preclinical studies used mouse models to evaluate anti-metastatic agents. Mouse models are time-consuming and expensive. In addition, an important drawback is that mouse models inadequately model the early stages of metastasis which plausibly leads to the poor correlation with clinical outcomes.

Here, we report an in vivo model based on xenografted zebrafish embryos where we select for progressively invasive subpopulations of MDA-MB-231 breast cancer cells. A subpopulation analogous to circulating tumor cells found in human cancers was selected by injection of MDA-MB-231 cells into the yolk sacs of 2 days post-fertilized zebrafish embryos and selecting cells that migrated to the tail. The selected subpopulation derived from MDA-MB-231 cells were increasingly invasive in zebrafish. Isolation of these subpopulations and propagation in vitro revealed morphological changes consistent with activation of an epithelial-mesenchymal transition program. Differential gene analysis and knockdown of genes identified gene-candidates (DDIT4, MT1X, CTSD, and SERPINE1) as potential targets for anti-metastasis therapeutics. Furthermore, RNA-splicing analysis reinforced the importance of BIRC5 splice variants in breast cancer metastasis. This is the first report using zebrafish to isolate and expand progressively invasive populations of human cancer cells. The model has potential applications in understanding the metastatic process, identification and/or development of therapeutics that specifically target metastatic cells and formulating personalized treatment strategies for individual cancer patients.
Toward Equitable Access to Tertiary Cancer Care in Rwanda: A Geospatial Analysis
Authors: Fadelu Temidayo , Nadella Pranay , Iyer Hari S. , Uwikindi Francois , Shyirambere Cyprien , Manirakiza Achille , Triedman Scott A. , Rebbeck Timothy R. , Shulman Lawrence N.
Published: May 2022

PURPOSE

Geographic access to care is an important measure of health equity. In this study, we describe geographic access to cancer care centers (CCCs) in Rwanda with the current facilities providing care and examine how access could change with expanded care infrastructure.

METHODS

Health facilities included are public hospitals administered by the Rwanda Ministry of Health. The WorldPop Project was used to estimate population distribution, and OpenStreetMap was used to determine travel routes. On the basis of geolocations of the facilities, AccessMod 5 was used to estimate the percentage of the population that live within 1 hour, 2 hours, and 4 hours of CCCs under the current (two facilities) and expanded care (seven facilities) scenarios. Variations in access by region, poverty, and level of urbanization were described.

RESULTS

Currently, 13%, 41%, and 85% of Rwandans can access CCCs within one, two, and 4 hours of travel, respectively. With expansion of CCCs to seven facilities, access increases to 37%, 84%, and 99%, respectively. There is a substantial variation in current geographic access by province, with 1-hour access in Kigali at 98%, whereas access in the Western Province is 0%; care expansion could increase 2-hour access in the Western Province from 1% to 71%. Variation in access is also seen across the level of urbanization, with current 1-hour access in urban versus rural areas of 45% and 8%, respectively. Expanded care results in improvement of 1-hour access to 67% and 33%, respectively. Similar trends were also noted across poverty levels.

CONCLUSION

Geographical access to CCCs varies substantially by province, level of urbanization, and poverty. These disparities can be alleviated by strategic care expansion to other tertiary care facilities across Rwanda.
Finding the Lowest-Cost Pharmacy for Cancer Supportive Care Medications: Not So Easy
Authors: Etteldorf Andrew , Rotolo Shannon , Sedhom Ramy , Vogel Rachel I. , Blaes Anne , Dusetzina Stacie B. , Virnig Beth , Gupta Arjun
Published: May 2022

PURPOSE:

To decrease the financial burden on people with cancer, clinicians and patients increasingly use medication price comparison websites to seek pharmacies where medications may be cheaper. Shopping around at different pharmacies can add additional time and logistic burden to patients and care partners. We sought to determine whether a single pharmacy consistently offered the lowest price for symptom control medications.

METHODS:

We compiled medications/formulations used to manage two common cancer-associated symptoms: nausea/vomiting and anorexia/cachexia. We extracted discounted, lowest price with coupon prices for a typical fill of these medications at nine pharmacies in Minneapolis, MN, using GoodRx. We compared prices across formulations and pharmacies to assess whether a pharmacy consistently offered the lowest price.

RESULTS:

We included 24 formulations for nausea/vomiting (14 generic and 10 brand-name) and 19 for anorexia/cachexia (12 generic and seven brand-name). Prices for brand-name formulations were similar across pharmacies, but prices of generic formulations varied widely across pharmacies. For example, the prices of a seven-unit fill of generic 5-mg olanzapine tablets ranged from $4 to $57 US dollars. No single pharmacy consistently offered the lowest price across the formulations studied. For example, for the 12 generic formulations for anorexia/cachexia, one pharmacy had the highest price for four formulations and the lowest price for two others.

CONCLUSION:

In this study of discounted medication prices, we found that no single pharmacy in an urban zip code consistently offered the lowest price for medications used to manage two common cancer-associated symptoms. Well-intentioned efforts to pursue the cheapest source of each medication by visiting multiple pharmacies may add extra time and logistic toxicity to patients and care partners. This approach can increase redundant scripts and expose patients to medication-related adverse events.
Zero-TE MRI: principles and applications in the head and neck
Authors: Wiesinger Florian , Ho Mai-Lan
Published: May 2022

Zero echo-time (ZTE) MRI is a novel imaging technique that utilizes ultrafast readouts to capture signal from short-T2 tissues. Additional sequence advantages include rapid imaging times, silent scanning, and artifact resistance. A robust application of this technology is imaging of cortical bone without the use of ionizing radiation, thus representing a viable alternative to CT for both rapid screening and “one-stop-shop” MRI. Although ZTE is increasingly used in musculoskeletal and body imaging, neuroimaging applications have historically been limited by complex anatomy and pathology. In this article, we review the imaging physics of ZTE including pulse sequence options, practical limitations, and image reconstruction. We then discuss optimization of settings for ZTE bone neuroimaging including acquisition, processing, segmentation, synthetic CT generation, and artifacts. Finally, we examine clinical utility of ZTE in the head and neck with imaging examples including malformations, trauma, tumors, and interventional procedures.
Case Report: A case report of multiple co-infections (melioidosis, paragonimiasis, Covid-19 and tuberculosis) in a patient with diabetes mellitus and thalassemia-trait in Myanmar
Authors: Chit Yee December , Aung Htet Ko Ko , Mg Mg Banyar , Htun Win Pa Pa , Janurian Naw , Bancone Germana , Watthanaworawit Wanitda , Proux Stephane , Pyae Phyo Aung , Nosten François
Published: May 2022

Burkholderia pseudomallei is a soil-dwelling aerobic bacterium prevalent in tropical and subtropical regions, particularly in Southeast Asia and Northern Australia. It is the causal organism of melioidosis, a severe infection that can manifest as chronic debilitating pneumonia resembling pulmonary tuberculosis. Here, we report a case of melioidosis, pulmonary tuberculosis, covid-19, and paragonimus co-infection in a 50-year-old male with poorly controlled diabetes mellitus and β-thalassemia trait. The patient recovered with intravenous antibiotics and standard anti-tuberculosis treatment.
Maternal reports of morbidity during the index ALSPAC pregnancy
Authors: Ellis Genette , Fraser Abigail , Golding Jean , Iles-Caven Yasmin , Northstone Kate
Published: May 2022

Within the ALSPAC (Avon Longitudinal Study of Parents and Children) resource, information concerning the health of the mother during pregnancy is available from three sources: (i) computerised data collected by midwives after the delivery of the baby, known as the STORK database; (ii) data abstracted by ALSPAC staff from detailed medical obstetric records, and (iii) reports by mothers during pregnancy, and shortly after delivery using structured questionnaires completed at home. In this Data Note we focus on source (iii), and detail the information obtained from these mothers concerning their health, signs and symptoms together with medications and supplements taken during pregnancy. We also describe how the data can be accessed.
Optimising care for UK patients with acute myeloid leukaemia
Authors: Pagliuca Antonio , Khwaja Asim , Dillon Richard , Evans Paul AS , Mohite Unmesh
Published: May 2022

This article has been commissioned and funded by Astellas Pharma Ltd. Astellas Pharma Ltd also had editorial input in the writing of this article.

 

Job code XOS_2022_0036_UK. Date of preparation: June 2022

 

Acute myeloid leukaemia is a rare cancer, with about 3000 cases diagnosed each year in the UK. Diagnosis is based on patient history, blood and bone marrow tests and, in some cases, imaging. Chemotherapy is the mainstay of treatment for acute myeloid leukaemia, with eligible patients also undergoing allogeneic haematopoietic stem cell transplantation, which can be curative. However, patients must be carefully evaluated by the multidisciplinary team before they are put forward for transplant to ensure they are able to tolerate the conditioning therapy required. Improvements in transplant technology have increased donor availability and reduced transplant toxicity. At the same time, greater understanding of the cytogenetics and molecular genetics of acute myeloid leukaemia have helped to ensure that patients receive treatment that gives them the best chance of survival. A recent roundtable discussion considered how current diagnostic and treatment pathways might be adapted or enhanced to leverage good outcomes for the greatest numbers of patients.
Arbuscular Mycorrhizal Fungi Community Dynamics and Functioning in Diff erent Rice Cultivation Systems
Authors:   Faculty of Applied Sciences, Rajarata University of Sri Lanka, Sri Lanka, Kalamulla Ruwanthika , Karunarathna Samantha C. ,   Center for Mountain Futures, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 65201 P.R. China, Kumla Jaturong ,   Research Center of Microbial Diversity and Sustainable Utilization, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand, Yapa Neelamanie ,   Faculty of Applied Sciences, Rajarata University of Sri Lanka, Sri Lanka
Published: May 2022

As a main component of soil microbiota arbuscular mycorrhizal fungi (AMF) play a benefi cial role in the agro-ecosystems. Introduction of AMF inoculum as a biofertilizer to the rice cultivation system is one of the environmentally healthy solutions that may increase crop productivity and yield, when compare to the non-AMF relationships. Within an ecosystem, both biotic and abiotic factors affect the diversity, distribution, and ecological role of AMF. Here we reviewed the effect of the variables including production area, environmental conditions, agricultural management systems, rice varieties, and different growth stages of the host on dynamics and structure of the AMF community mainly in the rice fi elds. Understanding of this co-relation is required to explore their future enrolment in agriculture. To ensure food security, identifi cation of all variables that may make indigenous AMF presence and active in different rice growing systems needs to be done in order to explore this specifi c fungus-root interaction.
Electoral repression cycles
Authors: Adam Antonis
Published: May 2022

This article examines whether there is an increase in repression in the election year in electoral autocracies. First, we build a simple theoretical model of an electoral autocracy. We assume that autocratic rulers want to maximise the expected rents from office. As a higher vote share in the election is translated into a higher probability of remaining in power, they use repression to exclude those opposing the ruler from the electoral body. Then, in the empirical section, we use a data set of autocracies to examine the existence of an electoral cycle in repression. We use a dynamic inverse probability weighting regression adjustment model, which models the dynamics of elections on the respect of human rights and considers that elections are non-random events. All results, and several robustness tests, indicate a strong presence of an electoral cycle in repression consistent with our theoretical model and priors. Additionally, we find that when it comes to autocracies, this cyclical increase in repression is more pronounced than the pre-electoral increase in government spending.
Mode selection and amplification from optical frequency combs by optical injection locking: a numerical study of noise
Authors: Liu Chenhao , Jin Haoshu , Liu Hui , Bai Jintao
Published: May 2022

Noise, except for residual side modes, in mode selection and amplification from optical frequency combs by optical injection locking has not been studied in detail, to our knowledge. We report a numerical study of noise behaviors, including both residual side modes and the noise between them. It reveals that comb laser injection can introduce excessive noise, compared to optical injection with a single mode master laser through the interference between residual side modes and resonances within Arnol’d tongues created by periodic forcing in the optical phase, which can be a severe problem for the case of sub-GHz comb mode spacing. The dependences of residual side mode rejection and phase noise variance on comb mode spacing, seeding power, and detuning are discussed to help in low-noise system design and operation.
Continuous-wave microcavity quantum cascade lasers in whispering-gallery modes up to 50 °C
Authors: Guo Qiangqiang , Zhang Jinchuan , Yin Ran , Zhuo Ning , Lu Quanyong , Zhai Shenqiang , Liu Junqi , Wang Lijun , Liu Shuman , Liu Fengqi
Published: May 2022

Micro-resonator-based lasers are well suited for high-density optoelectronic integration because of their small volumes and low thresholds. However, microcavity quantum cascade lasers for on-chip sensing have high thermal loads that make continuous-wave operation challenging. In this work, we designed an selective thermal dissipation scheme for the selective electrical isolation process to improve the thermal conductivity of the devices. The lasers operated at 50 °C, with 4.7-µm emission. They were fabricated as a notched elliptical resonator, resulting in a highly unidirectional far-field profile with an in-plane beam divergence of 1.9°. Overall, these directional-emission quantum cascade lasers pave the way for portable and highly integrated sensing applications.
Light trapping gratings for solar cells: an analytical period optimization approach
Authors: Bläsi Benedikt , Hanser Mario , Jäger Klaus , Höhn Oliver
Published: May 2022

Solar cells can harvest incident sunlight very efficiently by utilizing grating-based light trapping. As the working principle of such gratings strongly depends on the number as well as the propagation directions of the diffraction orders, the grating period is a key parameter. We present an analytical model for optimizing the grating period, focusing on its impact on light path enhancement and outcoupling probability. Based on the presented model, we formulate guidelines to maximize light trapping in state-of-the-art high-end solar cells. The model increases the understanding of the grating performance in systems like the III-V//Si triple junction solar cell achieving record efficiency.
Four-mode parallel silicon multimode waveguide crossing scheme based on the asymmetric directional couplers
Authors: Zhang Runsen , Sun Shangsen , Zhang Fengchun , Chen Kaixuan , Liu Liu , Zhu Ning
Published: May 2022

We theoretically propose and experimentally demonstrate a novel ultra-compact four-mode silicon waveguide crossing device based on the asymmetric directional couplers for densely integrated on-chip mode division multiplexing systems. The crossing is based on the parallel crossing scheme where the two access waveguides are parallel to each other to have minimal area. The device utilizes an idle high order mode inside one bus waveguide to drop subsequently all the guided modes inside another bus waveguide, with the help of the asymmetric directional couplers (ADCs). We also optimize the structural parameters of these ADCs by using the particle swarm optimization method to obtain higher conversion efficiency and smaller coupling length. The simulation results show that the insertion losses of the input 1-8 ports are no more than 0.5 dB at the central wavelength of 1550 nm. And the crosstalks are less than −20 dB in the broadband from 1530 nm to 1580 nm with a footprint of only 25 × 70 µm2. Furthermore, our scheme can be easily extended to accommodate more modes by cascading more ADCs for mode dropping and crossing, without obviously deteriorating the performance and greatly increasing the overall footprint.
A recombinant monoclonal-based Taenia antigen assay that reflects disease activity in extra-parenchymal neurocysticercosis
Authors: Corda Madelynn , Sciurba Joshua , Blaha Jiana , Mahanty Siddhartha , Paredes Adriana , Garcia Hector H. , Nash Theodore E. , Nutman Thomas B. , O’Connell Elise M.
Published: May 2022

Background

Antigen tests for diagnosis and disease monitoring in some types of neurocysticercosis (NCC) are useful but access to testing has been limited by availability of proprietary reagents and/or kits.

Methods/Principal findings

Three previously identified IgM-secreting hybridomas whose IgM products demonstrated specificity to Taenia solium underwent variable heavy and light chain sequencing and isotype conversion to mouse IgG. Screening of these recombinantly expressed IgG anti-Ts hybridomas, identified one (TsG10) with the highest affinity to crude Taenia antigen. TsG10 was then used as a capture antibody in a sandwich antigen detection immunoassay in combination with either a high titer polyclonal anti-Ts antibody or with biotinylated TsG10 (termed TsG10*bt). Using serum, plasma, and CSF samples from patients with active NCC and those from NCC-uninfected patients, ROC curve analyses demonstrated that the TsG10-TsG10-*bt assay achieved a 98% sensitivity and 100% specificity in detecting samples known to be antigen positive and outperformed the polyclonal based assay (sensitivity of 93% with 100% specificity). By comparing levels of Ts antigen (Ag) in paired CSF (n = 10) or plasma/serum (n = 19) samples from well-characterized patients with extra-parenchymal NCC early in infection and at the time of definitive cure, all but 2 (1 from CSF and 1 from plasma) became undetectable. There was a high degree of correlation (r = 0.98) between the Ag levels detected by this new assay and levels found by a commercial assay. Pilot studies indicate that this antigen can be detected in the urine of patients with active NCC.

Conclusions/Significance

A newly developed recombinant monoclonal antibody-based Ts Ag detection immunoassay is extremely sensitive in the detection of extra-parenchymal NCC and can be used to monitor the success of treatment in the CSF, serum/plasma and urine. The ability to produce recombinant TsG10 at scale should enable use of this antigen detection immunoassay wherever NCC is endemic.

Clinical Trial Registration

ClinicalTrials.gov Identifiers: NCT00001205 - & NCT00001645.
Application of quantile regression to examine changes in the distribution of Height for Age (HAZ) of Indian children aged 0–36 months using four rounds of NFHS data
Authors: Mokalla Thirupathi Reddy , Rao Mendu Vishnu Vardhana
Published: May 2022

Background

The prevalence of stunting among under- three Indian children though decreased, still it is considered to be alarmingly high. In most of the previous studies, traditional (linear and logistic) regression analyses were applied. They were limited to encapsulated cross-distribution variations. The objective of the current study was to examine how the different determinants were heterogeneous in various percentiles of height for age (HAZ) distribution.

Methods and findings

This article examined the change in the HAZ distribution of children and examined the relationships between the key co-variate trends and patterns in HAZ among children aged <3 years over a period of 24 years. Four successive rounds of the National Family Health Survey data 1992–93, 1998–99, 2005–06, and 2015–16 were used for analysis. The final study included 206579 children aged <3 years (N = 106136 male, 100443 female). To explain and analyse differences in the HAZ distribution, the lambda-mu-sigma (LMS) method was used. Trends in height for age (HAZ) distribution over time were analysed using separate gender-stratified quantile regression (QR). The selected socio-economic, demographic and other predictors were considered for this analysis. The quantile regressions have indicated that mothers who have higher than primary level education were more proactive in mitigating malnutrition among children at the lower end of the distribution. The age, birth order, mother’s body-mass-index (BMI) and economic status, among children, were some more determining factors for HAZ. Results of selected quantile regression were estimated at the 5th, 10th, 25th, 50th, 75th, 90th, and 95thquantiles.

Conclusions

The outcome of various covariates working differently across the HAZ distribution was suggested by quantile regression. The major discrepancies in different aspects were underlined by socioeconomic and demographic aspects among the Indian population. The heterogeneity of this effect was shown using quantile regression. Policymakers may choose to concentrate on the most important factors when formulating policies to lessen the prevalence of stunting in India.
Analysis on single nucleotide polymorphisms of the PeTPS-(-)Apin gene in Pinus elliottii
Authors: Lei Lei , Zhang Lu , Cai Junhuo , Yi Min , Zhao Heng , Ma Jikai , Lai Meng , Jin Cangfu
Published: May 2022

Background

Resin-tapping forests of slash pine (Pinus elliottii) have been set up across Southern China owing to their high production and good resin quality, which has led to the rapid growth of the resin industry. In this study, we aimed to identify molecular markers associated with resin traits in pine trees, which may help develop marker-assisted selection (MAS).

Methods

PeTPS-(-)Apin gene was cloned by double primers (external and internal). DnaSP V4.0 software was used to evaluate genetic diversity and linkage disequilibrium. SHEsis was used for haplotype analysis. SPSS was used for ANOVA and χ2 test. DnaSP v4.0 software was used to evaluate genetic diversity.

Results

The full length PeTPS-(-)Apin gene was characterized and shown to have 4638 bp, coding for a 629-amino acid protein. A total of 72 single nucleotide polymorphism (SNP) loci were found. Three SNPs (CG615, AT641 and AG3859) were significantly correlated with α -pinene content, with a contribution rate > 10%. These SNPs were used to select P. elliottii with high α-pinene content, and a 118.0% realistic gain was obtained.

Conclusions

The PeTPS-(-)Apin gene is not uniquely decisive for selection of plus slash pines with stable production, high yield, and good quality, but it can be used as a reference for selection of other resin-producing pines and other resin components.
Differential Hebbian learning with time-continuous signals for active noise reduction
Authors: Möller Konstantin , Kappel David , Tamosiunaite Minija , Tetzlaff Christian , Porr Bernd , Wörgötter Florentin
Published: May 2022

Spike timing-dependent plasticity, related to differential Hebb-rules, has become a leading paradigm in neuronal learning, because weights can grow or shrink depending on the timing of pre- and post-synaptic signals. Here we use this paradigm to reduce unwanted (acoustic) noise. Our system relies on heterosynaptic differential Hebbian learning and we show that it can efficiently eliminate noise by up to -140 dB in multi-microphone setups under various conditions. The system quickly learns, most often within a few seconds, and it is robust with respect to different geometrical microphone configurations, too. Hence, this theoretical study demonstrates that it is possible to successfully transfer differential Hebbian learning, derived from the neurosciences, into a technical domain.