bluuebunny/crossref_metadata_2025 huggingface dataset:
The transposable element-rich genome of the cereal pest Sitophilus oryzae
Authors: Parisot Nicolas , Vargas-Chávez Carlos , Goubert Clément , Baa-Puyoulet Patrice , Balmand Séverine , Beranger Louis , Blanc Caroline , Bonnamour Aymeric , Boulesteix Matthieu , Burlet Nelly , Calevro Federica , Callaerts Patrick , Chancy Théo , Charles Hubert , Colella Stefano , Da Silva Barbosa André , Dell’Aglio Elisa , Di Genova Alex , Febvay Gérard , Gabaldón Toni , Galvão Ferrarini Mariana , Gerber Alexandra , Gillet Benjamin , Hubley Robert , Hughes Sandrine , Jacquin-Joly Emmanuelle , Maire Justin , Marcet-Houben Marina , Masson Florent , Meslin Camille , Montagné Nicolas , Moya Andrés , Ribeiro de Vasconcelos Ana Tereza , Richard Gautier , Rosen Jeb , Sagot Marie-France , Smit Arian F. A. , Storer Jessica M. , Vincent-Monegat Carole , Vallier Agnès , Vigneron Aurélien , Zaidman-Rémy Anna , Zamoum Waël , Vieira Cristina , Rebollo Rita , Latorre Amparo , Heddi Abdelaziz
Published: November 2021

Background

The rice weevil Sitophilus oryzae is one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains. S. oryzae has an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacterium Sodalis pierantonius and is a valuable model to decipher host-symbiont molecular interactions.

Results

We sequenced the Sitophilus oryzae genome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show that S. oryzae has undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state. S. oryzae has undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 kyear), S. pierantonius relies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino acids required for insect development and cuticle biosynthesis.

Conclusions

Here we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition, S. oryzae may be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes.
Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension
Authors: Xanthouli Panagiota , Theobald Vivienne , Benjamin Nicola , Marra Alberto M. , D’Agostino Anna , Egenlauf Benjamin , Shaukat Memoona , Ding Cao , Cittadini Antonio , Bossone Eduardo , Kögler Maria , Grünig Ekkehard , Muckenthaler Martina U. , Eichstaedt Christina A.
Published: November 2021

Background

Iron deficiency affects up to 50% of patients with pulmonary arterial hypertension (PAH) but iron markers such as ferritin and serum iron are confounded by several non-disease related factors like acute inflammation and diet. The aim of this study was to identify a new marker for iron deficiency and clinical outcome in PAH patients.

Methods

In this single-center, retrospective study we assessed indicators of iron status and clinical parameters specifying the time to clinical worsening (TTCW) and survival in PAH patients at time of initial diagnosis and at 1-year follow-up using univariable and multivariable analysis.

Results

In total, 150 patients were included with an invasively confirmed PAH and complete data on iron metabolism. The proportion of hypochromic erythrocytes > 2% at initial diagnosis was identified as an independent predictor for a shorter TTCW (p = 0.0001) and worse survival (p = 0.002) at initial diagnosis as well as worse survival (p = 0.016) at 1-year follow-up. Only a subset of these patients (64%) suffered from iron deficiency. Low ferritin or low serum iron neither correlated with TTCW nor survival. Severe hemoglobin deficiency at baseline was significantly associated with a shorter TTCW (p = 0.001).

Conclusions

The presence of hypochromic erythrocytes > 2% was a strong and independent predictor of mortality and shorter TTCW in this cohort of PAH patients. Thus, it can serve as a valuable indicator of iron homeostasis and prognosis even in patients without iron deficiency or anemia. Further studies are needed to confirm the results and to investigate therapeutic implications.
Functional pre-therapeutic evaluation by genome editing of variants of uncertain significance of essential tumor suppressor genes
Authors: Billaud Amandine , Chevalier Louise-Marie , Augereau Paule , Frenel Jean-Sebastien , Passot Christophe , Campone Mario , Morel Alain
Published: November 2021

Background

Targeted therapies in oncology are promising but variants of uncertain significance (VUS) limit their use for clinical management and necessitate functional testing in vitro. UsingBRCA1andBRCA2variants, which have consequences on PARP inhibitor sensitivity, andPOLEvariants, potential biomarkers of immunotherapy response, we developed a rapid functional assay based on CRISPR-Cas9 genome editing to determine the functional consequences of these variants having potentially direct implications on patients’ access to targeted therapies.

Methods

We first evaluated the functional impact of 26BRCA1and 7BRCA2variants by editing and comparing NGS results between the variant of interest and a silent control variant. Ten of these variants had already been classified as benign or pathogenic and were used as controls. Finally, we extended this method to the characterization ofPOLEVUS.

Results

For the 23 variants that were unclassified or for which conflicting interpretations had been reported, 15 were classified as functionally normal and 6 as functionally abnormal. Another two variants were found to have intermediate consequences, both with potential impacts on splicing. We then compared these scores to the patients’ responses to PARP inhibitors when possible. Finally, to prove the application of our method to the classification of variants from other tumor suppressor genes, we exemplified with threePOLEVUS. Among them, two were classified with an intermediate functional impact and one was functionally abnormal. Eventually, fourPOLEvariants previously classified in databases were also evaluated. However, we found evidence of a discordance with the classification, variant p.Leu424Val being found here functionally normal.

Conclusions

Our new rapid functional assay can be used to characterize the functional implication ofBRCA1andBRCA2variants, giving patients whose variants were evaluated as functionally abnormal access to PARP inhibitor treatment. Retrospective analysis of patients’ responses to PARP inhibitors, where accessible, was consistent with our functional score evaluation and confirmed the accuracy of our protocol. This method could potentially be extended to the classification of VUS from all essential tumor suppressor genes and can be performed within a timeframe compatible with clinical applications, thereby having a direct theranostic impact.
Gummatous neurosyphilis in an elderly patient in the Australian outback: a case report
Authors: Devanand Nilesh Anand , Sundararajan Krishnaswamy
Published: November 2021

Introduction

Neurosyphilis is an infection caused by the spirochete Treponema pallidum, which causes infiltration and thickening of brain meninges. Despite being an Old World disease, the rates of infection continue to rise. This clinical challenge involves early and accurate diagnosis, as neurosyphilis masquerades with various clinical symptoms and is often missed during initial presentation to the hospital. A comprehensive history and clinical examination are essential to detect suspicious cases early for further cerebrospinal fluid examination and neuroimaging. Patients treated with benzylpenicillin for a specific duration often show promising clinical and cognitive improvement, thus emphasizing the need for constant vigilance in our day-to-day practice.

Case presentation

A 77-year-old Caucasian gentleman presented to our hospital repeatedly with multiple episodes of presyncope and cognitive impairment. He also demonstrated bilateral deafness, tabes dorsalis, and left sixth cranial nerve palsy. His cerebrospinal fluid examination showed a nonreactive venereal disease research laboratory test, and magnetic resonance imaging of the brain revealed a gumma.

Conclusion

The diagnosis of neurosyphilis in the elderly requires a combination of clinical vigilance and a high index of suspicion, along with multimodal investigations, including cerebrospinal fluid examination and brain imaging.
Clinical application of mesenchymal stem cells in rheumatic diseases
Authors: Wang Yajing , Ma Dan , Wu Zewen , Yang Baoqi , Li Rong , Zhao Xingxing , Yang Helin , Zhang Liyun
Published: November 2021

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm during early development that are characterized by high self-renewal ability and multidirectional differentiation potential. These cells are present various tissues in the human body and can be cultured in vitro. Under specific conditions, MSCs can differentiate into osteoblasts, neuron-like cells, adipocytes and muscle cells and so on, therefore, have a great application value in cell replacement therapy and tissue repair. In recent years, the application of MSCs in rheumatic diseases has received increasing attention. On the one hand, MSCs have the ability to differentiate into bone and cartilage cells; on the other hand, these stem cells are also involved in immune regulation, resulting in the alleviation of inflammation and anti-fibrotic properties and the promotion of vascular repair, thus bringing new hope for the treatment of rheumatic diseases. This article reviews the clinical progress in MSC application for the treatment of rheumatic diseases.
Are wheezing, asthma and eczema in children associated with mother’s health during pregnancy? Evidence from an Australian birth cohort
Authors: Ahmad Kabir , Kabir Enamul , Ormsby Gail M. , Khanam Rasheda
Published: November 2021

Background

This study investigated the prevalence of wheezing, asthma, and eczema among Australian children using longitudinal data from birth to 15 years of age. This study also examined the association between maternal health status during pregnancy and their offspring’s respiratory and allergic morbidities using sex-segregated data.

Methods

This study used data from the Longitudinal Study of Australian Children (LSAC) where approximately 5000 children of a birth cohort across Australia were surveyed in 2004. These children were followed biennially in eight waves up to their age of 15 years until 2018. The status of the children’s wheezing, asthma, and eczema were reported by the mothers upon doctors’ diagnosis (for asthma) or self-assessment (for wheezing or eczema). Binomial logistic regression models were used to analyse associations between maternal health during pregnancy and their children’s health outcomes.

Results

Asthma prevalence among 0–1-year aged children was 11.7%, increased to 15.4% when the children were 10–11 years old, and then decreased to 13.6% when they were 14–15 years old. Wheezing and eczema were most prevalent when the children were 2–3 years old (26.0 and 17.8% respectively) and were least prevalent when the children were 14–15 years old (7.3 and 9.5% respectively). Maternal asthma, smoking during pregnancy, and pre-pregnancy obesity were significantly associated with an increased risk of wheezing and asthma in Australian children. Childhood eczema was associated only with maternal asthma. These associations were stronger among male children up to age 10–11 and during adolescence (12–15 years of age), female children were more prone to wheezing, asthma, and eczema.

Conclusion

This is a comprehensive longitudinal study of Australian children (0–15 years of age) to assess the prevalence (with sex-specific differences) of wheezing, asthma and eczema as well as the association between these respiratory and allergic morbidities and maternal health during pregnancy. The study findings suggest that careful medical and obstetric monitoring, improved specific age-sex wise risk factor prevention for children and health promotion for pregnant women would help protect child health.
Time to first antenatal care visit among pregnant women in Ethiopia: secondary analysis of EDHS 2016; application of AFT shared frailty models
Authors: Fentaw Kenaw Derebe , Fenta Setegn Muche , Biresaw Hailegebrael Birhan , Mulugeta Solomon Sisay
Published: November 2021

Background

The survival of pregnant women is one of great interest of the world and especially to a developing country like Ethiopia which had the highest maternal mortality ratios in the world due to low utilization of maternal health services including antenatal care (ANC). Survival analysis is a statistical method for data analysis where the outcome variable of interest is the time to occurrence of an event. This study demonstrates the applications of the Accelerated Failure Time (AFT) model with gamma and inverse Gaussian frailty distributions to estimate the effect of different factors on time to first ANC visit of pregnant women in Ethiopia.

Methods

This study was conducted by using 2016 EDHS data about factors associated with the time to first ANC visit of pregnant women in Ethiopia. A total of 4328 women from nine regions and two city administrations whose age group between 15 and 49 years were included in the study AFT models with gamma and inverse Gaussian frailty distributions have been compared using Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) to select the best model.

Results

The factors residence, media exposure, wealth index, education level of women, education level of husband and husband occupation are found to be statistically significant (P-value < 0.05) for the survival time of time to first ANC visit of pregnant women in Ethiopia. Inverse Gaussian shared frailty model with Weibull as baseline distribution is found to be the best model for the time to first ANC visit of pregnant women in Ethiopia. The model also reflected there is strong evidence of the high degree of heterogeneity between regions of pregnant women for the time to first ANC visit.

Conclusion

The median time of the first ANC visit for pregnant women was 5 months. From different candidate models, Inverse Gaussian shared frailty model with Weibull baseline is an appropriate approach for analyzing time to first ANC visit of pregnant women data than without frailty model. It is essential that maternal and child health policies and strategies better target women’s development and design and implement interventions aimed at increasing the timely activation of prenatal care by pregnant women. The researchers also recommend using more powerful designs (such as cohorts) for the research to establish timeliness and reduce death.
Brass products in the coronet excavated from an M2-numbered Sui-Tang-dynasty tomb situated in Kun Lun Company in Xi'an, Shaanxi
Authors: Shao Yanbing , Jiang Fengrui , Du Jingnan , Yang Junchang , Zhang Quanmin
Published: November 2021

Ancient Chinese brass smelting technology has promoted the invention of zinc smelting, thus becoming an important part of the metallurgical history. However, the information concerning its origin and development is still controversial. In that regard, thorough analysis of composition and structure of the early brass is crucial for studying various stages of the ancient brass smelting technology history. This study aimed to investigate brass artifacts from Kunlun M2 tomb in Xi'an, Shaanxi, dating back during Sui to early Tang Dynasty (581–712 AD). The composition and metallographic characterization of the materials was performed using XRF, SEM–EDS and metallographic analysis. According to the results, brass was composed of 83 wt% of copper, 12 wt% of zinc, and 3 wt% of tin. Furthermore, its microstructure consisted of α-isometric single crystals with some slip lines and a few twinned grains. This indicated that brass was obtained by melting an appropriate mixture of zinc ores and copper ores at a temperature above 920 °C. Furthermore, brass support components were installed on the coronet after integral hot forging and partial cold shaping. Besides, the use of brass in the coronet was in conformity with the social hierarchy of that historical period, and also reflected the attention paid to the properties of materials.
How confident are pharmacists in providing pharmaceutical care on anticoagulants? A cross-sectional, self-administered questionnaire study in Borneo, Malaysia
Authors: Tan Sze Ling , Yong Zai Yang , Liew Jerry Ee Siung , Zainal Hadzliana , Siddiqui Sania
Published: November 2021

Background

Anticoagulants are the cornerstone therapy for the management of venous thromboembolism (VTE) and atrial fibrillation (AF). Pharmacists should be confident and equipped with the skill and updated knowledge in managing anticoagulation therapy.

Objective

To explore self-reported confidence level of pharmacists, perceived reasons influencing their confidence and socio-demographic associated with high confidence level in the area of anticoagulation.

Methods

A cross-sectional, self-administered questionnaire survey was carried out among fully registered pharmacists who work in selected government hospitals and clinics in Borneo, Malaysia, from January 2019 to February 2020.

Results

Overall, responses from 542 fully registered pharmacists were obtained. Proportion of respondents who claimed confident in providing necessary information to patient receiving warfarin (n = 479, 88.3%) was significantly higher (p < 0.001) compared to low molecular weight heparins (n = 317, 58.5%) and direct oral anticoagulants (n = 211, 38.9%). Respondents’ perceived reasons that may influence their confidence level include experience in dealing with anticoagulants’ cases (n = 469, 86.5%), knowledge on anticoagulants (n = 394, 72.7%) and knowledge on diseases needing anticoagulation therapy (n = 311, 57.4%). Practising as ward pharmacist and “always” dealing with anticoagulants during their practice were the socio-demographic that significantly associated with high confidence level of pharmacist in providing pharmaceutical care on all types of anticoagulants (p < 0.05).

Conclusion

Pharmacists were found more confident in providing pharmaceutical care on warfarin compared to low molecular weight heparins and direct oral anticoagulants. Continuous educational and training programmes on the use of anticoagulants should be carried out to enhance pharmacists’ confidence in supporting patients’ care.
Linking strike directions to invariant TE and TM impedances of the magnetotelluric impedance tensor
Authors: Arellano-Castro Rocío F. , Gómez-Treviño Enrique
Published: November 2021

Estimation of the traditional transverse electric (TE) and transverse magnetic (TM) impedances of the magnetotelluric tensor for two-dimensional structures can be decoupled from the estimation of the strike direction with significant implications when dealing with galvanic distortions. Distortion-free data are obtainable by combining a quadratic equation with the phase tensor. In the terminology of Groom–Bailey, the quadratic equation provides amplitudes and phases that are immune to twist, and the phase tensor provides phases immune to both, twist and shear. On the other hand, distortion-free strike directions can be obtained using Bahr's approach or the phase tensor. In principle, this is all that is needed to proceed to a two-dimensional (2D) interpretation. However, the resulting impedances are strike ignorant because they are invariant under coordinate system rotation, and if they are to be related to a geological strike, they must be linked to a particular direction. This is an additional ambiguity to the one of 90° arising in classic strike-determination methods, which must be resolved independently. In this work, we use the distortion model of Groom–Bailey to resolve the ambiguity by bringing back the coupling between impedances and strike in the presence of galvanic distortions. Our approach is a hybrid between existing numerical and analytical methods that reduces the problem to a binary decision, which involves associating the invariant impedances with the correct TE and TM modes. To determine the appropriate association, we present three algorithms. Two of them require optimizing the fit to the data, and the third one requires a comparison of phases. All three keep track of possible crossings of the phase curves providing a clear-cut solution. Synthetic and field data illustrate the performance of the three schemes.

Graphical Abstract
Breeding biology of the Green-backed Tit (Parus monticolus) in southwest China
Authors: Ye Ping , Yao Xiaogang , Bi Jianli , Li Guangrong , Liang Wei , Yang Canchao
Published: November 2021

Studies on breeding biology enable us to broaden our understanding of the evolution of life history strategies. We studied the breeding biology of the Green-backed Tit (Parus monticolus) to provide comprehensive data on nest and egg characteristics, parental behavior throughout egg laying and nestling periods, and reproductive outcome. Our study reveals adaptive behavioral patterns and reproductive strategies forP. monticolus.
Impact of Spirulina corn soy blend on Iron deficient children aged 6–23 months in Ndhiwa Sub-County Kenya: a randomized controlled trial
Authors: Othoo Dorothy Apondi , Ochola Sophie , Kuria Elizabeth , Kimiywe Judith
Published: November 2021

Background

Iron deficiency anemia (IDA) remains high in Kenya despite interventions. Twenty-seven percent of children aged 6 months-14 years are anemic, with low iron intake (7%) among children aged 6–23 months. Standard food interventions involve a corn soy blend (CSB), which is limited in micronutrients, and fortifiers are not accessible locally. Moreover, the use of spirulina as a strategy for mitigating IDA has not been adequately documented. This study compared the impact of a spirulina corn soy blend (SCSB) on IDA among children aged 6–23 months.

Methods

A total of 240 children with IDA were randomly assigned to study groups at a ratio of 1:1:1 through lotteries, and caregivers and research assistants were blinded to group assignment. Dry-take-home SCSB, CSB and placebo flour (1.7 kg) was given to caregivers to prepare porridges using a flour water ratio of 1:4, producing 600 ml–700 ml of porridge to feed children 200 ml of porridge three times a day for 6 months. Impact was assessed as plasma hematocrit at baseline and after the study. Blood drawing, preparation and analysis were performed in accordance with approved procedures by the EthicsResearchCommittee. Monthly follow-up and data collection on dietary intake, anthropometry, morbidity and infant feeding practices were performed using questionnaires. Relative risk, magnitude of change and log-rank tests were used to compare the impact of the intervention, and significant differences were determined at P < 0.05.

Results

The survival probabilities for children consuming SCSB were significantly higher than those consuming CSB (log-rank-X2 = 0.978; CI: 0.954–1.033, P = 0.001) and the placebo (log-rankX2 = 0.971; CI: 0.943–0.984, P = 0.0001). Children consuming SCSB had a mean recovery time of 8 days (CI: 7–12 days) compared to those consuming CSB (19 days; CI: 20–23 days) and placebo (33 days; CI: 3 1–35 days). The recovery rate was 15.4 per 100 persons per day for children who consumed SCSB as opposed to 4.6 and 1.8 per 100 persons per day for those who consumed CSB and the placebo, respectively.

Conclusion

Management of IDA with SCSB compared to CSB and the placebo led to faster reversal and large numbers of recoveries from IDA. The recovery rates were above the World Health Organizations (WHO) minimums standards for food interventions. Efforts to realize high and faster recoveries from IDA should be heightened by fortifying CSB with spirulina powder.
Melanin production and laccase mediated oxidative stress alleviation during fungal-fungal interaction among basidiomycete fungi
Authors: Dullah Samim , Hazarika Dibya Jyoti , Goswami Gunajit , Borgohain Tanushree , Ghosh Alokesh , Barooah Madhumita , Bhattacharyya Ashok , Boro Robin Chandra
Published: November 2021

Fungal-fungal interaction often leads to the change in metabolite profile of both the interacting fungus which may have potential implication in industry or agriculture. In the present study, we performed two sets of fungal-fungal interaction—Trametes coccinea (F3) with Leiotrametes lactinea (F9) and T. coccinea (F3) with T. versicolor (F1) to understand the changes in the metabolite profile during the interaction process and how this process impacts the hyphal/mycelial morphology of the participating fungi. The metabolites produced during interaction of T. coccinea (F3) with L. lactinea (F9) and T. coccinea (F3) with T. versicolor (F1) was analysed through liquid chromatography coupled to mass spectroscopy (LC-MS). Most of the metabolites secreted or produced during interaction are associated with defensive response. Further, visualization with scanning electron microscopy revealed that interaction between the tested fungi led to the changes in the hyphal morphology. The bipartite fungal interaction resulted in the production of a dark brown colour pigment—melanin as confirmed by the LC-MS, FTIR and NMR analysis. Moreover, the fungal–fungal interaction also led to increase in the production of laccase, a group of multicopper oxidases involved in detoxification of toxic compounds. Further, increased activity of superoxide dismutase, an enzyme that catalyzes the dismutation of the superoxide anion to hydrogen peroxide was also recorded during fungal–fungal interaction. Quantitative real-time PCR revealed upregulation of lcc1 (encoding a laccase enzyme) and few other stress related genes of T. versicolor during its hyphal interaction with T. coccinea, suggesting a direct correlation between laccase production and melanin production.
Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin
Authors: Fontana Elisa , Meyers Jeff , Sobrero Alberto , Iveson Timothy , Shields Anthony F. , Taieb Julien , Yoshino Takayuki , Souglakos Ioannis , Smyth Elizabeth C. , Lordick Florian , Moehler Markus , Giraut Anne , Harkin Andrea , Labianca Roberto , Meyerhardt Jeffrey , André Thierry , Boukovinas Ioannis , Lonardi Sara , Saunders Mark , Vernerey Dewi , Oki Eiji , Georgoulias Vassilis , Ben-Aharon Irit , Shi Qian
Published: November 2021

PURPOSE

Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years).

MATERIALS AND METHODS

Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered.

RESULTS

Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85).

CONCLUSION

Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
Intraoperative Management for Left Ventricular Assist Device Implantation With Concurrent Laparoscopic Sleeve Gastrectomy: A Case Series
Authors: Kumar Rishi , Ellis Sarah , Salas De Armas Ismael A. , Patel Manish K. , Akay Mehmet H. , Bajwa Kulvinder S. , Liang Yafen , Gregoric Igor D.
Published: November 2021

The increasing coincidence of obesity with heart failure may preclude eligibility for orthotopic heart transplantation, requiring continuous-flow left ventricular assist devices (LVADs) as destination therapy. This report describes intraoperative considerations for patients who underwent LVAD implantation with concurrent laparoscopic sleeve gastrectomy (LSG) to promote weight loss. In particular, right ventricular dysfunction associated with acute left ventricular unloading may be compounded by pneumoperitoneum for LSG due to the difficulty in ventilating patients with obesity, hypercarbia-mediated increase in pulmonary vascular resistance, and variable cardiac loading conditions. We identify specific anesthetic challenges and discuss methods of monitoring and management.
A Framework for Estimating Migrant Stocks Using Digital Traces and Survey Data: An Application in the United Kingdom
Authors: Rampazzo Francesco , Bijak Jakub , Vitali Agnese , Weber Ingmar , Zagheni Emilio
Published: November 2021

An accurate estimation of international migration is hampered by a lack of timely and comprehensive data, and by the use of different definitions and measures of migration in different countries. In an effort to address this situation, we complement traditional data sources for the United Kingdom with social media data: our aim is to understand whether information from digital traces can help measure international migration. The Bayesian framework proposed is used to combine data from the Labour Force Survey (LFS) and the Facebook Advertising Platform to study the number of European migrants in the United Kingdom, with the aim of producing more accurate estimates of the numbers of European migrants. The overarching model is divided into a Theory-Based Model of migration and a Measurement Error Model. We review the quality of the LFS and Facebook data, paying particular attention to the biases of these sources. The results indicate visible yet uncertain differences between model estimates using the Bayesian framework and individual sources. Sensitivity analysis techniques are used to evaluate the quality of the model. The advantages and limitations of this approach, which can be applied in other contexts, are discussed. We cannot necessarily trust any individual source, but combining them through modeling offers valuable insights.
NF-κB determines Paneth versus goblet cell fate decision in the small intestine
Authors: Brischetto Cristina , Krieger Karsten , Klotz Christian , Krahn Inge , Kunz Séverine , Kolesnichenko Marina , Mucka Patrick , Heuberger Julian , Scheidereit Claus , Schmidt-Ullrich Ruth
Published: November 2021

Although the role of the transcription factor NF-κB in intestinal inflammation and tumor formation has been investigated extensively, a physiological function of NF-κB in sustaining intestinal epithelial homeostasis beyond inflammation has not been demonstrated. Using NF-κB reporter mice, we detected strong NF-κB activity in Paneth cells, in ‘+4/+5’ secretory progenitors and in scattered Lgr5+ crypt base columnar stem cells of small intestinal (SI) crypts. To examine NF–κB functions in SI epithelial self-renewal, mice or SI crypt organoids (‘mini-guts’) with ubiquitously suppressed NF-κB activity were used. We show that NF-κB activity is dispensable for maintaining SI epithelial proliferation, but is essential for ex vivo organoid growth. Furthermore, we demonstrate a dramatic reduction of Paneth cells in the absence of NF-κB activity, concomitant with a significant increase in goblet cells and immature intermediate cells. This indicates that NF-κB is required for proper Paneth versus goblet cell differentiation and for SI epithelial homeostasis, which occurs via regulation of Wnt signaling and Sox9 expression downstream of NF-κB. The current study thus presents evidence for an important role for NF-κB in intestinal epithelial self-renewal.
Inflammatory Arthropathy in the Elite Sports Athlete
Authors: Kin-Hoo Koo Kenneth , Chinoy Hector , Creaney Leon , Hayton Mike
Published: November 2021

Elite athletes commonly present with joint pains that are attributed to overuse injuries though on occasion it can be due to an inflammatory arthropathy. The diagnostic challenge is that presenting symptoms of benign injuries are similar to inflammatory arthropathies. A holistic review of the athlete can provide clues suggestive of inflammatory arthropathy, before requesting further investigations to confirm the diagnosis. Current imaging modalities are not specific in differentiating inflammatory arthritis with other causes of joint inflammation. Prompt treatment is required to restore the athlete to an optimum level of activity and prevent career ending disability, all in adherence to the regulations of the sporting governing bodies. This review aims to highlight the importance of inflammatory arthropathy in the differentials for an athlete presenting with joint pains.
Overview of positron emission tomography in functional imaging of the lungs for diffuse lung diseases
Authors: Gulhane Avanti V , Chen Delphine L
Published: November 2021

Positron emission tomography (PET) is a quantitative molecular imaging modality increasingly used to study pulmonary disease processes and drug effects on those processes. The wide range of drugs and other entities that can be radiolabeled to study molecularly targeted processes is a major strength of PET, thus providing a noninvasive approach for obtaining molecular phenotyping information. The use of PET to monitor disease progression and treatment outcomes in DLD has been limited in clinical practice, with most of such applications occurring in the context of research investigations under clinical trials. Given the high costs and failure rates for lung drug development efforts, molecular imaging lung biomarkers are needed not only to aid these efforts but also to improve clinical characterization of these diseases beyond canonical anatomic classifications based on computed tomography. The purpose of this review article is to provide an overview of PET applications in characterizing lung disease, focusing on novel tracers that are in clinical development for DLD molecular phenotyping, and briefly address considerations for accurately quantifying lung PET signals.
Implementation challenges from a prospective, interventional biopsy-based study of Environmental Enteropathy in rural Pakistan
Authors: Ahmed Sheraz , Iqbal Najeeha , Sadiq Kamran , Umrani Fayaz , Rizvi Arjumand , Jamil Zehra , Syed Sana , Khan Marium , Iqbal Junaid , Qureshi Shahida , Hotwani Aneeta , Rahman Najeeb , Moore Sean , Ali Asad
Published: November 2021

The Study of Environmental Enteropathy (EE) and Malnutrition in Pakistan (SEEM) is a community intervention trial designed to understand the pathophysiology of EE and its associated clinical phenotypes in children less than two years of age. Undernutrition is the underlying cause of three million deaths worldwide annually, accounting for 45% of all deaths among children under five years of age. Linear growth stunting affects a further 165 million, especially in low- and middle-income countries. In Pakistan,  an estimated one in three children are underweight and nearly half are stunted. This manuscript summarizes the challenges faced by the field team and the solutions employed for achieving our research objectives at the rural Matiari field site.

Our study design involved a longitudinal collection of field data and biological samples which required constant engagement of field staff with the participating families. Challenges faced in SEEM included: 1) quality assurance parameters of anthropometry data; 2) 24-hour food recall data collection; 3) clinical management of sick enrolled children; 4) obtaining informed consent for upper gastrointestinal (UGI)endoscopy (an invasive procedure); and 5) biological sample collection (blood, urine, stool) from enrolled children.

We enrolled 350 malnourished children(Weight for Height Z (WHZ) score <-2) and 50 well-nourished children(WHZ score ≥ 0 and height-for-age Z (HAZ) score ≥ -1)   with more than 95% success rate of collecting blood, urine and stool specimens. We collected 72% microbiome stool samples within 30 minutes of the child passing stool. We conducted a UGI biopsy in 63 children.  

Solutions to these challenges included good project governance, the establishment of credibility, and the development of a longitudinal bidirectional relationship embedded in trust and effective communication with the caretakers of the enrolled children.    

Continuous monitoring, regular training of staff, and effective teamwork were key factors that led to the successful execution of our study.
Detection of herpes simplex virus 2: a SYBR-Green-based real-time PCR assay
Authors: Shaha Modhusudon , Roy Bithi , Islam Mohammad Ariful
Published: November 2021

The prevalence of Herpes simplex virus 2 (HSV2) is increasing at an alarming rate in the world. Most of the HSV2 cases are not diagnosed properly, although a range of molecular and serological diagnoses exist. Herein, we have reported a very rapid detection method specific for HSV2 using real-time PCR. The primers specific for HSV2 were designed using the Primer-BLAST tool and 120 base pairs of the polymerase gene were amplified using real-time PCR with SYBR Green dye. The designed primer pair was found highly efficient in detecting only HSV2 DNA, but not HSV1. The threshold cycle (Ct) value for HSV2 reactions by designed primers was found to be an average of 22.55 for a standard copy number of viral DNA that may denote the efficiency of the primers. The melting temperature (Tm) of the amplicon using designed primers (82.60C) was also higher than that using reference primers (about 780C), indicating the high GC content of the amplified template. The designed primer pair will help clinicians to detect the HSV2 DNA specifically and diagnose the associated disease rapidly.
The CUSSH programme: supporting cities’ transformational change towards health and sustainability
Authors: Davies Michael , Belesova Kristine , Crane Melanie , Hale Joanna , Haines Andy , Hutchinson Emma , Kiesewetter Gregor , Mberu Blessing , Mohajeri Nahid , Michie Susan , Milner James , Moore Gemma , Osrin David , Pineo Helen , Pluchinotta Irene , Prasad Aarathi , Salvia Giuseppe , Symonds Phil , Taylor Jonathon , Turcu Catalina , Tsoulou Ioanna , Zimmermann Nici , Wilkinson Paul
Published: November 2021

This paper describes a global research programme on the complex systemic connections between urban development and health. Through transdisciplinary methods the Complex Urban Systems for Sustainability and Health (CUSSH) project will develop critical evidence on how to achieve the far-reaching transformation of cities needed to address vital environmental imperatives for planetary health in the 21st Century. CUSSH’s core components include: (i) a review of evidence on the effects of climate actions (both mitigation and adaptation) and factors influencing their implementation in urban settings; (ii) the development and application of methods for tracking the progress of cities towards sustainability and health goals; (iii) the development and application of models to assess the impact on population health, health inequalities, socio-economic development and environmental parameters of urban development strategies, in order to support policy decisions; (iv) iterative in-depth engagements with stakeholders in partner cities in low-, middle- and high-income settings, using systems-based participatory methods, to test and support the implementation of the transformative changes needed to meet local and global health and sustainability objectives; (v) a programme of public engagement and capacity building. Through these steps, the programme will provide transferable evidence on how to accelerate actions essential to achieving population-level health and global climate goals through, amongst others, changing cities’ energy provision, transport infrastructure, green infrastructure, air quality, waste management and housing.
Логопедическое обследование детей с нарушением произносительной стороны речи (ринолалия, ринофония, дизартрия, ДЦП) : учеб.-метод. пособие
Authors: Larina Elena A.
Published: November 2021

Еducational methodical manual guide is intended for full-time and part-time students enrolled in special (defectological) education 44.03.03, training profile Speech therapy. The manual consists of two sections, they contain a description of the sequence of stages of speech therapy examination of children with SSD (severe speech disorders), the structure of drawing up a speech therapy opinion, a summary on the topic, questions and control tasks for independent work, a list of references and a glossary. The educational-methodical is intended for students of the defectology department of the university, practicing speech therapists, specialists in the field of speech pathology. Published by the decision of the educational and methodological commission of the university.
INVESTIGATING THE INFLUENCE OF ENVIRONMENTAL CONDITIONING ON EPOXY RESINS AT QUASISTATIC AND HIGH STRAIN RATES FOR MATERIAL OPERATING LIMIT
Authors: SAGAR M. DOSHI, SAGAR M. DOSHI, , MANOHARAN NITHINKUMAR , HAQUE, BAZLE Z. (GAMA) , DEITZEL JOSEPH , GILLESPIE, JR. JOHN W.
Published: November 2021

Epoxy resin-based composite panels used for armors may be subjected to a wide range of operating temperatures (-55°C to 76°C) and high strain rates on the order of 103-104 s-1. Over the life cycle, various environmental factors also affect the resin properties and hence influence the performance of the composites. Therefore, it is critical to determine the stress-strain behavior of the epoxy resin over a wide range of strain rates and temperatures for accurate multi-scale modeling of composites and to investigate the influence of environmental aging on the resin properties. Additionally, the characterization of key mechanical properties such as yield stress, modulus, and energy absorption (i.e. area under the stress-strain curve) at varying temperatures and moisture can provide critical data to calculate the material operating limits. In this study, we characterize mechanical properties of neat epoxy resin, SC-15 (currently used in structural armor) and RDL-RDC using uniaxial compression testing. RDL-RDC, developed by Huntsman Corporation, has a glass transition temperature of ~ 120°C, compared to ~ 85°C of SC-15. A split Hopkinson pressure bar is used for high strain rate testing. Quasistatic testing is conducted using a screw-driven testing machine (Instron 4484) at 10-3 s-1 and 10-1 s-1 strain rates and varying temperatures. The yield stress is fit to a modified Eyring model over the varying strain rates at room temperature. For rapid investigation of resistance to environmental aging, accelerated aging tests are conducted by immersing the specimens in 100°C water for 48 hours. Specimens are conditioned in an environmental chamber at 76 °C and 88% RH until they reach equilibrium. Tests are then conducted at five different temperatures from 0°C to 95°C, and key mechanical properties are then plotted vs. temperature. The results presented are an important step towards developing a methodology to identify environmental operating conditions for composite ground vehicle applications.
MODELING AND CALIBRATION OF UNCERTAINTY IN MATERIAL PROPERTIES OF ADDITIVELY MANUFACTURED COMPOSITES
Authors: PITZ EMIL , ROONEY SEAN , POCHIRAJU KISHORE
Published: November 2021

Simulations quantifying the uncertainty in structural response and damage evolution require accurate representation of the randomness of the underlying material stiffness and strength behaviors. In this paper, the mean and variance descriptions of variability of strength and stiffness of additively manufactured composite specimens are augmented with random field correlation descriptors that represent the process dependence on the property heterogeneity through microstructure variations. Two correlation lengths and a rotation parameter are introduced into randomized stiffness and strength distribution fields to capture the local heterogeneities in the microstructure of Additively Manufactured (AM) composites. We formulated a simulation and Artificial Intelligence (AI)-based technique to calibrate the correlation length and rotation parameter measures from relatively few samples of experimentally obtained strain field observations using Digital Image Correlation (DIC). The neural networks used for calibrating the correlation lengths of Karhunen-Loève Expansion (KL expansion) from the DIC images are trained using simulated stiffness and strength fields that have known correlation coefficients. A virtual DIC filter is used to add the noise and artifacts from typical DIC analysis to the simulated strain fields. A Deep Neural Network (DNN), whose architecture is optimized using Efficient Neural Architecture Search (ENAS), is trained on 150,000 simulated DIC images. The trained DNN is then used for calibration of KL expansion correlation lengths for additively manufactured composite specimens. The AM composites are loaded in tension and DIC images of the strain fields are generated and presented to the DNNs, which produce the correlation coefficients for the random fields as outputs. Compared to classical optimization methods to calibrate model parameters iteratively, neural networks, once trained, efficiently and quickly predict parameters without the need for a robust simulator and optimization methods.
A SIZE EFFECT STUDY ON THE SPLITTING CRACK INITIATION AND PROPAGATION IN OFF-AXIS LAYERS OF COMPOSITE LAMINATES
Authors: QIAO YAO , ZHANG QIWEI , NAKAGAWA TROY , SALVIATO MARCO
Published: November 2021

This work proposes an investigation on size effects in micro-scale splitting crack initiation and propagation and their consequences on the macro-scale structural behavior carbon-fiber reinforced polymers under transverse tension. Towards this goal, size effect tests were experimentally conducted on both notch-free [90]n composites and specimens with different notch types under three-point bending. The mechanical tests were followed by morphological studies to identify the micro-scale damage mechanisms and their evolution. The results clearly show that splitting crack initiation in the transverse direction of composites not only happens at the fiber/matrix interface but also in the matrix. Moreover, the subsequent development of these damage mechanisms can depend on the structure size. This interesting phenomenon inherently leads to size-dependent structural behavior which can be described through Baznt’s Size Effect Laws. This study on the splitting crack initiation and propagation can provide unprecedented information for the calibration and validation of micromechanical models for the damage behavior of fiber composites at the microscale.