bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen avoidance and outcome of nonfibrotic and fibrotic hypersensitivity pneumonitis
Authors: Nishida Takashi , Kawate Eriko , Ishiguro Takashi , Kanauchi Tetsu , Shimizu Yoshihiko , Takayanagi Noboru
Published: November 2021

Background

Hypersensitivity pneumonitis (HP) is classified into nonfibrotic and fibrotic phenotypes. Patients with nonfibrotic HP often experience recurrence and develop fibrosis, whereas those with fibrotic HP have a poor prognosis. Although antigen avoidance has long been the first line of treatment for HP, its impact on prognosis has been poorly reported.

Methods

Medical records of 121 patients with HP diagnosed by new diagnostic criteria of American Thoracic Society/Japanese Respiratory Society/Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) guidelines and treated at our institution in Saitama, Japan, were retrospectively analysed. HP was classified into nonfibrotic and fibrotic phenotypes and six HP subtypes: summer-type, bird-related, home-related and occupational HP, humidifier lung, and hot tub lung. Achievement of reduced exposure to inciting agents was divided into complete antigen avoidance (CAA) and incomplete antigen avoidance (IAA) by HP subtype.

Results

Of the 74 patients with nonfibrotic HP, 30 achieved CAA and experienced no recurrence or development of fibrosis. In the remaining 44 patients with IAA, 24 (54.5%) experienced recurrence and/or development of fibrosis. The all-cause 5-year mortality rate in the 47 patients with fibrotic HP was 47.8%. Negative prognostic factors of HP-related mortality in these patients were <50% lymphocytes in bronchoalveolar lavage (BAL) and honeycombing. Multivariate analysis showed a tendency for IAA to be related to poorer survival (hazard ratio 3.452, 95% CI 0.964–12.359, p=0.057).

Conclusions

In the patients with nonfibrotic HP, CAA resulted in no recurrence or development of fibrosis and longer survival. In the patients with fibrotic HP, <50% lymphocytes in BAL and honeycombing were negative prognostic factors for mortality.
International consensus on lung function testing during the COVID-19 pandemic and beyond
Authors: McGowan Aisling , Laveneziana Pierantonio , Bayat Sam , Beydon Nicole , Boros P.W. , Burgos Felip , Fležar Matjaž , Franczuk Monika , Galarza Maria-Alejandra , Kendrick Adrian H. , Lombardi Enrico , Makonga-Braaksma Jellien , McCormack Meredith C. , Plantier Laurent , Stanojevic Sanja , Steenbruggen Irene , Thompson Bruce , Coates Allan L. , Wanger Jack , Cockcroft Donald W. , Culver Bruce , Sylvester Karl , De Jongh Frans
Published: November 2021

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance.

This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond.

Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals.

The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.
Arms and ammunitions: effectors at the interface of rice and it’s pathogens and pests
Authors: Deb Sohini , Madhavan Vishnu Narayanan , Gokulan C. G. , Patel Hitendra K. , Sonti Ramesh V.
Published: November 2021

The plant immune system has evolved to resist attack by pathogens and pests. However, successful phytopathogens deliver effector proteins into plant cells where they hijack the host cellular machinery to suppress the plant immune responses and promote infection. This manipulation of the host cellular pathways is done by the pathogen using various enzymatic activities, protein- DNA or protein- protein interactions. Rice is one the major economically important crops and its yield is affected by several pathogens and pests. In this review, we summarize the various effectors at the plant- pathogen/ pest interface for the major pathogens and pests of rice, specifically, on the mode of action and target genes of the effector proteins. We then compare this across the major rice pathogens and pests in a bid to understand probable conserved pathways which are under attack from pathogens and pests in rice. This analysis highlights conserved patterns of effector action, as well as unique host pathways targeted by the pathogens and pests.
Synergistic effect of folate-conjugated polymers and 5-fluorouracil in the treatment of colon cancer
Authors: Siemiaszko Gabriela , Niemirowicz-Laskowska Katarzyna , Markiewicz Karolina H. , Misztalewska-Turkowicz Iwona , Dudź Ewelina , Milewska Sylwia , Misiak Paweł , Kurowska Izabela , Sadowska Anna , Car Halina , Wilczewska Agnieszka Z.
Published: November 2021

Background

In recent years, targeted drug delivery strategies have received special attention from the scientific world due to advantages such as more effective therapy and reduction of side effects. The principle of operation is delayed excretion from the bloodstream of the drug delivery system compared to the drug itself, as well as facilitated penetration into diseased cells thanks to the use of ligands recognized by appropriate receptors. Particularly interesting drug carriers are amphiphilic copolymers that form nano-sized micelles with a drug, which can release the drug at a specific place in the body under the influence of appropriate stimuli.

Results

We describe the synthesis of the diblock polymer, poly(2-hydroxyethyl acrylate)-b-poly(N-vinylcaprolactam) using RAFT/MADIX (Reversible Addition-Fragmentation chain Transfer/MAcromolecular Design by Interchange of Xanthate) controlled polymerization affording polymers with good dispersity according to SEC (Size-Exclusion Chromatography). Some post-modifications of the polymer with folic acid were then performed as evidenced by NMR (Nuclear Magnetic Resonance), UV–Vis (UltraViolet–Visible) and FT-IR (Fourier-Transform Infrared) spectroscopy, and TGA (ThermoGravimetric Analysis). The formation of stable micellar systems from polymers with and without the drug, 5-fluorouracil, was confirmed by DLS (Dynamic Light Scattering) and zeta potential measurements, and TEM (Transmission Eelectron Microscopy) imaging. Finally, the cloud point of the polymers was investigated, which turned out to be close to the temperature of the human body. Most importantly, these micellar systems have been explored as a drug delivery system against colon cancer, showing increased cytotoxicity compared to the drug alone. This effect was achieved due to the easier cellular uptake by the interaction of folic acid and its receptors on the surface of cancer cells.

Conclusions

The presented results constitute a solid foundation for the implementation of a nano-sized drug delivery system containing folic acid for practical use in the treatment of drug-resistant cancer, as well as more effective therapy with fewer side effects.

Graphical Abstract
Comparative genomic analysis of the tricarboxylic acid cycle members in four Solanaceae vegetable crops and expression pattern analysis in Solanum tuberosum
Authors: Liu Yongming , Qu Jingtao , Shi Ziwen , Zhang Peng , Ren Maozhi
Published: November 2021

Background

The tricarboxylic acid (TCA) cycle is crucial for energy supply in animal, plant, and microbial cells. It is not only the main pathway of carbohydrate catabolism but also the final pathway of lipid and protein catabolism. Some TCA genes have been found to play important roles in the growth and development of tomato and potato, but no comprehensive study of TCA cycle genes in Solanaceae crops has been reported.

Results

In this study, we analyzed TCA cycle genes in four important Solanaceae vegetable crops (potato (Solanum tuberosum), tomato (Solanum lycopersicum), eggplant (Solanum melongena), and pepper (Capsicum annuum)) based on comparative genomics. The four Solanaceae crops had a total of 180 TCA cycle genes: 43 in potato, 44 in tomato, 40 in eggplant, and 53 in pepper. Phylogenetic analysis, collinearity analysis, and tissue expression patterns revealed the conservation of and differences in TCA cycle genes between the four Solanaceae crops and found that there were unique subgroup members in Solanaceae crops that were independent of Arabidopsis genes. The expression analysis of potato TCA cycle genes showed that (1) they were widely expressed in various tissues, and some transcripts like Soltu.DM.01G003320.1(SCoAL) and Soltu.DM.04G021520.1 (SDH) mainly accumulate in vegetative organs, and some transcripts such as Soltu.DM.12G005620.3 (SDH) and Soltu.DM.02G007400.4 (MDH) are preferentially expressed in reproductive organs; (2) several transcripts can be significantly induced by hormones, such as Soltu.DM.08G023870.2 (IDH) and Soltu.DM.06G029290.1 (SDH) under ABA treatment, and Soltu.DM.07G021850.2 (CSY) and Soltu.DM.09G026740.1 (MDH) under BAP treatment, and Soltu.DM.02G000940.1 (IDH) and Soltu.DM.01G031350.4 (MDH) under GA treatment; (3) Soltu.DM.11G024650.1 (SDH) can be upregulated by the three disease resistance inducers including Phytophthora infestans, acibenzolar-S-methyl (BTH), and DL-β-amino-n-butyric acid (BABA); and (4) the levels of Soltu.DM.01G045790.1 (MDH), Soltu.DM.01G028520.3 (CSY), and Soltu.DM.12G028700.1 (CSY) can be activated by both NaCl and mannitol. The subcellular localization results of three potato citrate synthases showed that Soltu.DM.01G028520.3 was localized in mitochondria, while Soltu.DM.12G028700.1 and Soltu.DM.07G021850.1 were localized in the cytoplasm.

Conclusions

This study provides a scientific foundation for the comprehensive understanding and functional studies of TCA cycle genes in Solanaceae crops and reveals their potential roles in potato growth, development, and stress response.
Hyperoxia during extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest is associated with severe circulatory failure and increased mortality
Authors: Bonnemain Jean , Rusca Marco , Ltaief Zied , Roumy Aurélien , Tozzi Piergiorgio , Oddo Mauro , Kirsch Matthias , Liaudet Lucas
Published: November 2021

Background

High levels of arterial oxygen pressures (PaO2) have been associated with increased mortality in extracorporeal cardiopulmonary resuscitation (ECPR), but there is limited information regarding possible mechanisms linking hyperoxia and death in this setting, notably with respect to its hemodynamic consequences. We aimed therefore at evaluating a possible association between PaO2, circulatory failure and death during ECPR.

Methods

We retrospectively analyzed 44 consecutive cardiac arrest (CA) patients treated with ECPR to determine the association between the mean PaO2 over the first 24 h, arterial blood pressure, vasopressor and intravenous fluid therapies, mortality, and cause of deaths.

Results

Eleven patients (25%) survived to hospital discharge. The main causes of death were refractory circulatory shock (46%) and neurological damage (24%). Compared to survivors, non survivors had significantly higher mean 24 h PaO2 (306 ± 121 mmHg vs 164 ± 53 mmHg, p < 0.001), lower mean blood pressure and higher requirements in vasopressors and fluids, but displayed similar pulse pressure during the first 24 h (an index of native cardiac recovery). The mean 24 h PaO2 was significantly and positively correlated with the severity of hypotension and the intensity of vasoactive therapies. Patients dying from circulatory failure died after a median of 17 h, compared to a median of 58 h for patients dying from a neurological cause. Patients dying from neurological cause had better preserved blood pressure and lower vasopressor requirements.

Conclusion

In conclusion, hyperoxia is associated with increased mortality during ECPR, possibly by promoting circulatory collapse or delayed neurological damage.
Methodological aspects for accelerometer-based assessment of physical activity in heart failure and health
Authors: Schwendinger Fabian , Wagner Jonathan , Infanger Denis , Schmidt-Trucksäss Arno , Knaier Raphael
Published: November 2021

Background

For valid accelerometer-assessed physical activity (PA) data, several methodological aspects should be considered. We aimed to 1) visualize the applicability of absolute accelerometer cut-offs to classify PA intensity, 2) verify recommendations to measure PA over 7 days by examining inter-day variability and reactivity, 3) examine seasonal differences in PA, and 4) recommend during which 10 h day period accelerometers should be worn to capture the most PA in patients with heart failure (HEART) and healthy individuals (HEALTH).

Methods

Fifty-six HEART (23% female; mean age 66 ± 13 years) and 299 HEALTH (51% female; mean age 54 ± 19 years) of the COmPLETE study wore accelerometers for 14 days. Aim 1 was analyzed descriptively. Key analyses were performed using linear mixed models.

Results

The results yielded poor applicability of absolute cut-offs. The day of the week significantly affected PA in both groups. PA-reactivity was not present in either group. A seasonal influence on PA was only found in HEALTH. Large inter-individual variability in PA timing was present.

Conclusions

Our data indicated that absolute cut-offs foster inaccuracies in both populations. In HEART, Sunday and four other days included in the analyses seem sufficient to estimate PA and the consideration of seasonal differences and reactivity seems not necessary. For healthy individuals, both weekend days plus four other days should be integrated into the analyses and seasonal differences should be considered. Due to substantial inter-individual variability in PA timing, accelerometers should be worn throughout waking time. These findings may improve future PA assessment.

Trial registration

The COmPLETE study was registered at clinicaltrials.gov (NCT03986892).
Advancing data science in drug development through an innovative computational framework for data sharing and statistical analysis
Authors: Mallon Ann-Marie , Häring Dieter A. , Dahlke Frank , Aarden Piet , Afyouni Soroosh , Delbarre Daniel , El Emam Khaled , Ganjgahi Habib , Gardiner Stephen , Kwok Chun Hei , West Dominique M. , Straiton Ewan , Haemmerle Sibylle , Huffman Adam , Hofmann Tom , Kelly Luke J. , Krusche Peter , Laramee Marie-Claude , Lheritier Karine , Ligozio Greg , Readie Aimee , Santos Luis , Nichols Thomas E. , Branson Janice , Holmes Chris
Published: November 2021

Background

Novartis and the University of Oxford’s Big Data Institute (BDI) have established a research alliance with the aim to improve health care and drug development by making it more efficient and targeted. Using a combination of the latest statistical machine learning technology with an innovative IT platform developed to manage large volumes of anonymised data from numerous data sources and types we plan to identify novel patterns with clinical relevance which cannot be detected by humans alone to identify phenotypes and early predictors of patient disease activity and progression.

Method

The collaboration focuses on highly complex autoimmune diseases and develops a computational framework to assemble a research-ready dataset across numerous modalities. For the Multiple Sclerosis (MS) project, the collaboration has anonymised and integrated phase II to phase IV clinical and imaging trial data from ≈35,000 patients across all clinical phenotypes and collected in more than 2200 centres worldwide. For the “IL-17” project, the collaboration has anonymised and integrated clinical and imaging data from over 30 phase II and III Cosentyx clinical trials including more than 15,000 patients, suffering from four autoimmune disorders (Psoriasis, Axial Spondyloarthritis, Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA)).

Results

A fundamental component of successful data analysis and the collaborative development of novel machine learning methods on these rich data sets has been the construction of a research informatics framework that can capture the data at regular intervals where images could be anonymised and integrated with the de-identified clinical data, quality controlled and compiled into a research-ready relational database which would then be available to multi-disciplinary analysts. The collaborative development from a group of software developers, data wranglers, statisticians, clinicians, and domain scientists across both organisations has been key. This framework is innovative, as it facilitates collaborative data management and makes a complicated clinical trial data set from a pharmaceutical company available to academic researchers who become associated with the project.

Conclusions

An informatics framework has been developed to capture clinical trial data into a pipeline of anonymisation, quality control, data exploration, and subsequent integration into a database. Establishing this framework has been integral to the development of analytical tools.
Association between multiple sclerosis and dietary patterns based on the traditional concept of food nature: a case-control study in Iran
Authors: Sharifi Mohammad Hossein , Keshani Parisa , Salehi Alireza , Jaladat Amir Mohammad , Mirzaei Zahra , Nikseresht Alireza
Published: November 2021

Introduction

It remains a matter of debate whether traditional concepts regarding the nature of food affect the development and progression of multiple sclerosis (MS).To date, there are limited studies that have investigated the association between MS and dietary patterns based on the categories of food nature (hot, cold, or balanced) defined in traditional medicine.

Method

This case-control study was conducted from October 2019 to February 2020. In total, 60 patients diagnosed with MS within the preceding 6 months and referred to our neurology outpatient clinic were included in our case group. The control group included 180 patients who were referred to the same center for general or orthopedic surgery. Dietary intake was assessed in both groups through a reliable and valid semi-quantitative food frequency questionnaire. Data were assessed using principal component analysis.

Results

The mean age of the participants was 44.9 ± 17.33 years. The analysis showed that four food patterns were distinguished (eigenvalue > 1), namely “additives and cold-natured foods”, “hot and balanced foods and nuts”, “dairy and legumes”, and “hot and balanced starches”. These food patterns explained 57.8% of the total variance.

After adjusting all confounding factors, individuals in the highest quartile and medium quartile of “additives and cold-natured foods” had an elevated MS risk compared with the lowest quartile (OR = 7.21, 95%CI = 2.01–12.38 and OR = 3.37, 95%CI = 1.02–11.35, respectively). Furthermore, individuals in the highest quartile of the “hot and balanced foods and nuts” group were protected against MS compared with its lowest quartile (OR = 0.28, 95%CI = 0.08–0.90). Moreover, a protective effect against MS was seen in the highest quartile of the “hot and balanced starches” group relative to its lowest quartile (OR = 0.34, 95%CI = 0.12–0.98). No significant association was found between “dairy and legumes” and the risk of MS.

Conclusion

This study revealed that dietary patterns based on the traditional concept of food nature might be associated with the risk of developing MS. This represents the first work in this area, so further research is recommended.
Lymphatic leakage after pelvic lymphadenectomy for cervical cancer: a retrospective case-control study
Authors: Chen Li , Lin Liang , Li Ling , Xie Zuolian , He Haixin , Lin Cuibo , Chen Jian , Lin An
Published: November 2021

Background

The study aims to evaluate the clinical features and management of postoperative lymphatic leakage (PLL) in patients with cervical cancer who received pelvic lymphadenectomy.

Methods

This retrospective study screened consecutive patients with cervical cancer (stage Ia2-IIb).

Results

Among 3427 cases screened, 63 patients (1.8%) were diagnosed with PLL, which manifested as persistent abdominal drainage (42/63, 66.7%), chylous ascites (12/63, 19.0%) or vaginal drainage (9/63, 14.3%). Median time from surgery to onset of PLL was 6 days (range, 4–21 days). All cases resolved in a median 10 days (range, 3–56 days) after conservative treatment; although one case experienced recurrence of vaginal drainage after 26 days, this also resolved after conservative therapy. Multivariate analysis showed that two cycles of neoadjuvant chemotherapy (odds ratio [OR], 3.283; 95% confidence interval [95%CI], 1.289–8.360; P = 0.013), a decrease in hemoglobin level of ≥20 and < 30 g/L (OR, 6.175; 95%CI, 1.033–10.919; P = 0.046) or ≥ 30 g/L (OR, 8.467; 95%CI, 1.248–17.426; P = 0.029), and postoperative albumin level ≥ 30 and < 35 g/L (OR, 2.552; 95%CI, 1.112–5.857; P = 0.027) or < 30 g/L (OR, 5.517; 95%CI, 2.047–18.148; P = 0.012) were associated with PLL.

Conclusion

Neoadjuvant chemotherapy, postoperative anemia and postoperative hypoproteinemia are risk factors for PLL.
A novel rat model of interbody fusion based on anterior lumbar corpectomy and fusion (ALCF)
Authors: Kang Yu , Liu Chao , Wang Ming , Wang Cheng , Yan Yi-Guo , Wang Wen-Jun
Published: November 2021

Background

Rats have been widely used as experimental animals when performing fundamental research because they are economical, rapidly reproducing, and heal quickly. While the rat interbody fusion model has been applied in basic studies, existing rat models generally have shortcomings, such as insufficiently simulating clinical surgery. The purpose of this study was to develop a novel rat model of interbody fusion which more closely represents clinical surgery.

Methods

The internal fixation was designed based on physical measurements of the rats’ lumbar spine. Then, ten rats divided into two groups (A and B) underwent anterior lumbar corpectomy and fusion of the L5 vertebrae. Groups A and B were sacrificed four and 8 weeks post-surgery, respectively. Micro-CT and histological examination were used to evaluate the model. Fusion rate, bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), and the area ratio of newly formed bone (NB) were calculated for quantitative analysis.

Results

Based on the L5 body dimensions of individual rats, 3D-printed titanium cage of the appropriate size were printed. The operations were successfully completed in all ten rats, and X-ray confirmed that internal fixation was good without migration. Micro-CT suggested that fusion rates in group B (100%) were greater than group A (40%, P < 0.05). The BV/TV (B: 42.20 ± 10.50 vs. A: 29.02 ± 3.25, P < 0.05) and Tb.N (B: 4.66 ± 1.23 vs. A: 1.97 ± 0.40, P < 0.05) were greater in group B than A, and the Tb.Th in group B was lower than group A (B: 0.10 ± 0.04 vs. A: 0.15 ± 0.02, P < 0.05). Histomorphometry results demonstrated that the area ratio of NB in group B were greater than group A (B: 35.72 ± 12.80 vs. A: 12.36 ± 16.93, P < 0.05).

Conclusion

A rat interbody fusion model based on anterior lumbar corpectomy and fusion has successfully been constructed and verified. It could provide a new choice for fundamental research using animal models of spinal fusion.
State of the practice of health information systems: a survey study amongst health care professionals in intellectual disability care
Authors: Tummers Joep , Tobi Hilde , Schalk Bianca , Tekinerdogan Bedir , Leusink Geraline
Published: November 2021

Background

Care for people with an Intellectual Disability (ID) is complex: multiple health care professionals are involved and use different Health Information Systems (HISs) to store medical and daily care information on the same individuals. The objective of this study is to identify the HISs needs of professionals in ID care by addressing the obstacles and challenges they meet in their current HISs.

Methods

We distributed an online questionnaire amongst Dutch ID care professionals via different professional associations and care providers. 328 respondents answered questions on their HISs. An inventory was made of HIS usage purposes, problems, satisfaction and desired features, with and without stratification on type of HIS and care professional.

Results

Typical in ID care, two types of HISs are being used that differ with respect to their features and users: Electronic Client Dossiers (ECDs) and Electronic Patient Dossiers (EPDs). In total, the respondents mentioned 52 unique HISs. Groups of care professionals differed in their satisfaction with ECDs only. Both HIS types present users with difficulties related to the specifics of care for people with an ID. Particularly the much needed communication between the many unique HISs was reported a major issue which implies major issues with inter-operability. Other problems seem design-related as well.

Conclusion

This study can be used to improve current HISs and design new HISs that take ID care professionals requirements into account.
Pilot study of dogs with suppurative and non-suppurative Malassezia otitis: A case series
Authors: Nunes Rodrigues Tania C. , Vandenabeele Sophie I.
Published: November 2021

Background

Rarely,Malasseziaotitis presents as a painful, erosive otitis with an otic discharge containingMalasseziaand neutrophils on cytology. There are no published reports of this type of suppurativeMalasseziaotitis (SMO). The role ofMalasseziahypersensitivity in otitis is still unknown, and no association has been demonstrated with SMO. We comparedMalasseziaIgE levels, intradermal test and histology changes in SMO dogs with the more conventionalMalasseziaotitis (MO) presentation.

Results

Three dogs (case 1, case 2 and case 3) were diagnosed with SMO, one dog (case 4) was diagnosed with unilateral MO and unilateral SMO, and one dog (case 5) was diagnosed with MO. Only one case (case 4) with SMO/MO had a positive Intradermal Allergy Test (IDAT) and elevated IgE levels forMalassezia. Histopathology findings from SMO revealed: interface dermatitis (case 1 and 3), lymphocytic dermatitis (case 2) and chronic hyperplastic eosinophilic and lymphoplasmacytic dermatitis (case 4). Histopathology findings from MO showed perivascular dermatitis (case 4 and 5). All the cases were treated successfully.

Conclusions

SMO presents with a distinct clinical phenotype in comparison with conventional MO. No consistent aetiology could be isolated. In these clinical cases it is possible that previous treatments could have influenced the results. More research is needed to understand the possible aetiologies and the pathogenesis of SMO.
Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia
Authors: Wang Ching-Yuan , Tang Yen-An , Lee I-Wen , Chang Fong-Ming , Chien Chun-Wei , Pan Hsien-An , Sun H. Sunny
Published: November 2021

Background

Skeletal dysplasia (SD) is one of the most common inherited neonatal disorders worldwide, where the recurrent pathogenic mutations in the FGFR2, FGFR3, COL1A1, COL1A2 and COL2A1 genes are frequently reported in both non-lethal and lethal SD. The traditional prenatal diagnosis of SD using ultrasonography suffers from lower accuracy and performed at latter gestational stage. Therefore, it remains in desperate need of precise and accurate prenatal diagnosis of SD in early pregnancy. With the advancements of next-generation sequencing (NGS) technology and bioinformatics analysis, it is feasible to develop a NGS-based assay to detect genetic defects in association with SD in the early pregnancy.

Methods

An ampliseq-based targeted sequencing panel was designed to cover 87 recurrent hotspots reported in 11 common dominant SD and run on both Ion Proton and NextSeq550 instruments. Thirty-six cell-free and 23 genomic DNAs were used for assay developed. Spike-in DNA prepared from standard sample harboring known mutation and normal sample were also employed to validate the established SD workflow. Overall performances of coverage, uniformity, and on-target rate, and the detecting limitations on percentage of fetal fraction and read depth were evaluated.

Results

The established targeted-seq workflow enables a single-tube multiplex PCR for library construction and shows high amplification efficiency and robust reproducibility on both Ion Proton and NextSeq550 platforms. The workflow reaches 100% coverage and both uniformity and on-target rate are > 96%, indicating a high quality assay. Using spike-in DNA with different percentage of known FGFR3 mutation (c.1138 G > A), the targeted-seq workflow demonstrated the ability to detect low-frequency variant of 2.5% accurately. Finally, we obtained 100% sensitivity and 100% specificity in detecting target mutations using established SD panel.

Conclusions

An expanded panel for rapid and cost-effective genetic detection of SD has been developed. The established targeted-seq workflow shows high accuracy to detect both germline and low-frequency variants. In addition, the workflow is flexible to be conducted in the majority of the NGS instruments and ready for routine clinical application. Taken together, we believe the established panel provides a promising diagnostic or therapeutic strategy for prenatal genetic testing of SD in routine clinical practice.
A school-based nutrition education program involving children and their guardians in Japan: facilitation of guardian-child communication and reduction of nutrition knowledge disparity
Authors: Asakura Keiko , Mori Sachie , Sasaki Satoshi , Nishiwaki Yuji
Published: November 2021

Background

Since the risk of noncommunicable diseases is closely associated with dietary intake, it is important to establish healthy dietary habits in childhood. Although several dietary education programs for children have been attempted, their implementation at school was often difficult due to overcrowded study curricula. We developed a new program which included homework for children and guardians, and evaluated its effect. Determinants of the effect were also investigated.

Methods

The school-based nutrition education program including a 45-min lecture, a series of homework assignments involving children and guardians, and two handouts was implemented in 14 public primary schools in Japan. Seven schools each underwent the intervention in an alternating manner. Nutrition knowledge (percentage (%) of correct answers in the nutrition knowledge questionnaire) and attitude/behavior toward diet was evaluated three times (May (baseline), October, February) as outcomes. These factors and their changes following the intervention were assessed by linear mixed models to adjust for individual factors, with consideration to clustering of the participants and repeated measurements.

Results

In total, 2227 children aged 10–12 years and their guardians participated. All schools completed the program. Children’s nutrition knowledge level was significantly increased (8.7%, 95% confidence interval [7.7–9.7]) following the intervention. Communication between children and their guardians, which was positively related with nutrition knowledge, was facilitated by the intervention. The increase in nutrition knowledge was greater among children with a lower knowledge level at baseline.

Conclusions

This school-based nutrition education program was effective and feasible. Appropriate teaching materials for homework can reduce the burden on schools and facilitate communication between children and guardians. Public schools can be crucial venues for decreasing disparities in nutrition knowledge.

Trial registration

This study was registered as an intervention study in the UMIN Clinical Trials Registry (trial ID: UMIN000029252) on Sep 22, 2017.
Fus2Net: a novel Convolutional Neural Network for classification of benign and malignant breast tumor in ultrasound images
Authors: Ma He , Tian Ronghui , Li Hong , Sun Hang , Lu Guoxiu , Liu Ruibo , Wang Zhiguo
Published: November 2021

Background

The rapid development of artificial intelligence technology has improved the capability of automatic breast cancer diagnosis, compared to traditional machine learning methods. Convolutional Neural Network (CNN) can automatically select high efficiency features, which helps to improve the level of computer-aided diagnosis (CAD). It can improve the performance of distinguishing benign and malignant breast ultrasound (BUS) tumor images, making rapid breast tumor screening possible.

Results

The classification model was evaluated with a different dataset of 100 BUS tumor images (50 benign cases and 50 malignant cases), which was not used in network training. Evaluation indicators include accuracy, sensitivity, specificity, and area under curve (AUC) value. The results in the Fus2Net model had an accuracy of 92%, the sensitivity reached 95.65%, the specificity reached 88.89%, and the AUC value reached 0.97 for classifying BUS tumor images.

Conclusions

The experiment compared the existing CNN-categorized architecture, and the Fus2Net architecture we customed has more advantages in a comprehensive performance. The obtained results demonstrated that the Fus2Net classification method we proposed can better assist radiologists in the diagnosis of benign and malignant BUS tumor images.

Methods

The existing public datasets are small and the amount of data suffer from the balance issue. In this paper, we provide a relatively larger dataset with a total of 1052 ultrasound images, including 696 benign images and 356 malignant images, which were collected from a local hospital. We proposed a novel CNN named Fus2Net for the benign and malignant classification of BUS tumor images and it contains two self-designed feature extraction modules. To evaluate how the classifier generalizes on the experimental dataset, we employed the training set (646 benign cases and 306 malignant cases) for tenfold cross-validation. Meanwhile, to solve the balance of the dataset, the training data were augmented before being fed into the Fus2Net. In the experiment, we used hyperparameter fine-tuning and regularization technology to make the Fus2Net convergence.
How different domains of quality of life are associated with latent dimensions of mental health measured by GHQ-12
Authors: Nouri Fatemeh , Feizi Awat , Roohafza Hamidreza , Sadeghi Masoumeh , Sarrafzadegan Nizal
Published: November 2021

Background and objectives

A short form of the General Health Questionnaire (GHQ-12) is a useful screening instrument for assessing mental health. Furthermore, Quality of life (QoL) is a critical treatment outcome in many clinical and health care research settings. This study aimed to reassess the dimensionality of GHQ-12 using Multidimensional Graded Response Model (MGRM) and evaluate how its extracted dimensions are associated with the QoL's domains.

Methods

Isfahan Cohort Study 2 (ICS2) is a population-based, ongoing prospective cohort study among adults aged 35 years and older who were free of cardiovascular diseases (CVDs) at the beginning of the study in 2013. A total of 1316 participants, all living in urban and rural areas of Isfahan and Najafabad, Iran was completed the GHQ-12 and WHO QoL-brief version at baseline. Five competing MGRMs with different latent structures were specified for GHQ-12. Factor scores derived from the best fitted model were used to associate with various domains of QoL. Results: The Three-Dimensional model for GHQ-12 was the best-fitted model explaining the Social Function (SF), Self Confidence (SC), and Anxiety/Depression (A/D) as three correlated yet different latent dimensions of mental health. Our findings in full adjusted multivariate regression models showed that a one-SD increase in dimensions of SC and SF was associated with a 38- to 48%-SD and 27- to 38%-SD increase in the domains scores of QoL, respectively. Moreover, for each one‐SD increase in score of A/D dimension, the domains scores of QoL decreased by 29- to 40%-SD. The highest to the lowest standardized coefficients for all latent dimensions of mental health were respectively related to the psychological, physical health, social relationships, and environmental condition domains of QoL. Furthermore, SC, A/D, and SF dimensions of GHQ-12 showed the highest to the lowest degree of association with all domains of QoL.

Conclusions

Our findings confirm that the GHQ-12 as a multidimensional rather than unitary instrument measures distinct dimensions of mental health. Furthermore, all aspects of QoL changed when the intensity of latent dimensions of mental health increased. Moreover, the psychological domain of QoL is the most affected by all latent dimensions of mental health, followed by physical health, social relationships, and environmental condition domains. It seems that in an attempt to full recovery as assessed by improved QoL outcomes, treatment of clinical symptoms may not be sufficient. Identifying and differentiating the structures of mental health in each community as well as implementing intervention programs aimed at focusing on specific dimensions may help in the prevention of further deterioration of mental health and improved QoL in the community.
Screening of CXC chemokines in the microenvironment of ovarian cancer and the biological function of CXCL10
Authors: Li Weiyuan , Ma Ji-Ao , Sheng Xun , Xiao Chunjie
Published: November 2021

Background

This study aims to screen and identify the biological functions and prognostic value of CXC chemokines in ovarian cancer (OC) through bioinformatics and molecular biology methods, and to provide data support for the selection of biomarkers and prognostic analysis of OC.

Methods

In this study, GEO, ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, STRING, TRRUST, and TIMER databases were used to study CXC chemokines. Angiogenesis and T cell killing assay were used to detect the effect of CXCL10 on tumor cell immunity and angiogenesis. Real-time quantitative PCR (qRT-PCR), immunoblotting, and ectopic tumor formation experiments were used to verify the effect of CXCL10 on ovarian cancer tumors.

Results

We found that CXCL1, CXCL10, CXCL11, CXCL13, and CXCL14 were significantly upregulated in OC samples compared with normal tissues. Our data showed that there was a relationship between the expression of CXC chemokines and the infiltration of six types of immune cells significant correlation. In vitro assay confirmed that overexpression of CXCL10 could enhance the killing effect of T cells and inhibit angiogenesis. Further in vivo assay had shown that CXCL10 could affect the progression of ovarian cancer by increasing the expression of cytotoxic T cells and inhibiting angiogenesis.

Conclusion

In conclusion, we hope that our data will provide new insights into the development of immunotherapy and the selection of prognostic markers for patients with OC.
Monitoring the tissue perfusion during hemorrhagic shock and resuscitation: tissue-to-arterial carbon dioxide partial pressure gradient in a pig model
Authors: Endo Yusuke , Hirokawa Taku , Miyasho Taku , Takegawa Ryosuke , Shinozaki Koichiro , Rolston Daniel M. , Becker Lance B. , Hayashida Kei
Published: November 2021

Background

Despite much evidence supporting the monitoring of the divergence of transcutaneous partial pressure of carbon dioxide (tcPCO2) from arterial partial pressure carbon dioxide (artPCO2) as an indicator of the shock status, data are limited on the relationships of the gradient between tcPCO2 and artPCO2 (tc-artPCO2) with the systemic oxygen metabolism and hemodynamic parameters. Our study aimed to test the hypothesis that tc-artPCO2 can detect inadequate tissue perfusion during hemorrhagic shock and resuscitation.

Methods

This prospective animal study was performed using female pigs at a university-based experimental laboratory. Progressive massive hemorrhagic shock was induced in mechanically ventilated pigs by stepwise blood withdrawal. All animals were then resuscitated by transfusing the stored blood in stages. A transcutaneous monitor was attached to their ears to measure tcPCO2. A pulmonary artery catheter (PAC) and pulse index continuous cardiac output (PiCCO) were used to monitor cardiac output (CO) and several hemodynamic parameters. The relationships of tc-artPCO2 with the study parameters and systemic oxygen delivery (DO2) were analyzed.

Results

Hemorrhage and blood transfusion precisely impacted hemodynamic and laboratory data as expected. The tc-artPCO2 level markedly increased as CO decreased. There were significant correlations of tc-artPCO2 with DO2 and COs (DO2: r = − 0.83, CO by PAC: r = − 0.79; CO by PiCCO: r = − 0.74; all P < 0.0001). The critical level of oxygen delivery (DO2crit) was 11.72 mL/kg/min according to transcutaneous partial pressure of oxygen (threshold of 30 mmHg). Receiver operating characteristic curve analyses revealed that the value of tc-artPCO2 for discrimination of DO2crit was highest with an area under the curve (AUC) of 0.94, followed by shock index (AUC = 0.78; P < 0.04 vs tc-artPCO2), and lactate (AUC = 0.65; P < 0.001 vs tc-artPCO2).

Conclusions

Our observations suggest the less-invasive tc-artPCO2 monitoring can sensitively detect inadequate systemic oxygen supply during hemorrhagic shock. Further evaluations are required in different forms of shock in other large animal models and in humans to assess its usefulness, safety, and ability to predict outcomes in critical illnesses.
Serotype-dependent recombinant adeno-associated vector (AAV) infection of Epstein–Barr virus-positive B-cells, towards recombinant AAV-based therapy of focal EBV + lymphoproliferative disorders
Authors: Ahmadi Elham , Ravanshad Mehrdad , Xie Jun , Panigrahi Rajesh , Jubbal Sandeep S. , Guru Santosh Kumar , Guangping Gao , Ziyaeyan Mazyar , Fingeroth Joyce
Published: November 2021

Background

B-cell proliferative disorders, such as post-transplant lymphoproliferative disease (PTLD), are increased among persons afflicted by T-cell compromise. Most are Epstein–Barr virus (EBV) + and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy, immunotherapy and radiation therapy by reducing systemic toxicity. Despite extensive study as a vehicle for gene therapy, adeno-associated viruses (AAV) have rarely been applied to human cancer research due to technical and theoretical obstacles. Moreover, human B-cells have historically been described as resistant to AAV infection. Nonetheless, advances using different recombinant (r)AAV serotypes with unique tropisms to deliver cytotoxic therapy suggested a localized anti-tumor approach was feasible.

Methods

As a prelude to the development of a therapeutic vehicle, the ability of fifteen distinct EGFP-bearing rAAV serotypes to transduce human B-cells, including primary, immortalized, and B-cell tumor lines ± EBV was assessed by confocal microscopy, flow cytometry and subsequently cell viability assay.

Results

Rank order analysis revealed augmented transduction by rAAV6.2 and closely related virions. EBV infection of EBV-negative B-cell tumor lines and EBV immortalization of primary B-cells increased susceptibility to rAAV6.2 transduction. As a proof of concept, transduction by rAAV6.2 encoding herpes simplex virus type 1 (HSV1)-thymidine kinase (TK) eliminated TK-negative rhabdomyosarcoma cells and diminished viability of transduced B-cell lines upon incubation with ganciclovir.

Conclusions

rAAV serotypes differentially transduce human B-cell lines reversing the dogma that human B-cells are refractory to AAV infection. EBV + B-cells display increased susceptibility to rAAV6.2 infection, uncovering a new method for improved nucleic acid transfer into transfection-resistant B-cell lines. The introduction of a functional suicide gene into the rAAV6.2 genome identifies a candidate vector for the development of rAAV-based oncolytic therapy targeting focal EBV-bearing B-lymphoproliferative disorders.
Explore association of genes in PDL1/PD1 pathway to radiotherapy survival benefit based on interaction model strategy
Authors: Shen Junjie , Liu Jingfang , Li Huijun , Bai Lu , Du Zixuan , Geng Ruirui , Cao Jianping , Sun Peng , Tang Zaixiang
Published: November 2021

Purpose

To explore the association of genes in “PD-L1 expression and PD-1 check point pathway in cancer” to radiotherapy survival benefit.

Methods and materials

Gene expression data and clinical information of cancers were downloaded from TCGA. Radiotherapy survival benefit was defined based on interaction model. Fast backward multivariate Cox regression was performed using stacking multiple interpolation data to identify radio-sensitive (RS) genes.

Results

Among the 73 genes in PD-L1/PD-1 pathway, we identified 24 RS genes in BRCA data set, 25 RS genes in STAD data set and 20 RS genes in HNSC data set, with some crossover genes. Theoretically, there are two types of RS genes. The expression level of Type I RS genes did not affect patients' overall survival (OS), but when receiving radiotherapy, patients with different expression level of Type I RS genes had varied survival benefit. Oppositely, Type II RS genes affected patients' OS. And when receiving radiotherapy, those with lower OS could benefit a lot. Type II RS genes in BRCA had strong positive correlation and closely biological interactions. When performing cluster analysis using these related Type II RS genes, patients could be divided into RS group and non-RS group in BRCA and METABRIC data sets.

Conclusions

Our study explored potential radio-sensitive biomarkers of several main cancer types in an important tumor immune checkpoint pathway and revealed a strong association between this pathway and radiotherapy survival benefit. New types of RS genes could be identified based on expanded definition to RS genes.