bluuebunny/crossref_metadata_2025 huggingface dataset:
The Feasibility of High-Intensity Interval Training in Patients with Intensive Care Unit-Acquired Weakness Syndrome Following Long-Term Invasive Ventilation
Authors: Wernhart Simon , Hedderich Jürgen , Wunderlich Svenja , Schauerte Kunigunde , Weihe Eberhard , Dellweg Dominic , Siemon Karsten
Published: February 2021

Background

Intensive care unit-acquired weakness syndrome (ICUAWS) can be a consequence of long-term mechanical ventilation. Despite recommendations of early patient mobilisation, little is known about the feasibility, safety and benefit of interval training in early rehabilitation facilities (ERF) after long-term invasive ventilation.

Methods and Results

We retrospectively analysed two established training protocols of bicycle ergometry in ERF patients after long-term (> 7 days) invasive ventilation (n = 46). Patients conducted moderate continuous (MCT, n = 24, mean age 70.3 ± 10.1 years) or high-intensity interval training (HIIT, n = 22, mean age 63.6 ± 12.6 years). The intensity of training was monitored with the BORG CR10 scale (intense phases ≥ 7/10 and moderate phases ≤ 4/10 points). The primary outcome was improvement (∆-values) of six-minute-walk-test (6 MWT), while the secondary outcomes were improvement of vital capacity (VCmax), forced expiratory volume in 1 s (FEV1), maximal inspiratory pressure (PImax) and functional capabilities (functional independence assessment measure, FIM/FAM and Barthel scores) after 3 weeks of training. No adverse events were observed. There was a trend towards a greater improvement of 6 MWT in HIIT than MCT (159.5 ± 64.9 m vs. 120.4 ± 60.4 m; p = .057), despite more days of invasive ventilation (39.6 ± 16.8 days vs. 26.8 ± 16.2 days; p = .009). VCmax (∆0.5l ± 0.6 vs. ∆0.5l ± 0.3; p = .462), FEV1 (∆0.2l ± 0.3 vs. ∆0.3l ± 0.2; p = .218) PImax (∆0.8 ± 1.1 kPa vs. ∆0.7 ± 1.3pts; p = .918) and functional status (FIM/FAM: ∆29.0 ± 14.8pts vs. ∆30.9 ± 16.0pts; p = .707; Barthel: ∆28.9 ± 16.0 pts vs. ∆25.0 ± 10.5pts; p = .341) improved in HIIT and MCT.

Conclusions

We demonstrate the feasibility and safety of HIIT in the early rehabilitation of ICUAWS patients. Larger trials are necessary to find adequate dosage of HIIT in ICUAWS patients.
The practice of active patient involvement in rare disease research using ICT: experiences and lessons from the RUDY JAPAN project
Authors: Hamakawa Nao , Kogetsu Atsushi , Isono Moeko , Yamasaki Chisato , Manabe Shirou , Takeda Toshihiro , Iwamoto Kazumasa , Kubota Tomoya , Barrett Joe , Gray Nathanael , Turner Alison , Teare Harriet , Imamura Yukie , Yamamoto Beverley Anne , Kaye Jane , Hide Michihiro , Takahashi Masanori P. , Matsumura Yasushi , Javaid Muhammad Kassim , Kato Kazuto
Published: February 2021

Background

The role of patients in medical research is changing, as more emphasis is being placed on patient involvement, and patient reported outcomes are increasingly contributing to clinical decision-making. Information and communication technology provides new opportunities for patients to actively become involved in research. These trends are particularly noticeable in Europe and the US, but less obvious in Japan. The aim of this study was to investigate the practice of active involvement of patients in medical research in Japan by utilizing a digital platform, and to analyze the outcomes to clarify what specific approaches could be put into practice.

Methods

We developed the RUDY JAPAN system, an ongoing rare disease medical research platform, in collaboration with the Rare and Undiagnosed Diseases Study (RUDY) project in the UK. After 2 years of preparation, RUDY JAPAN was launched in December 2017. Skeletal muscle channelopathies were initially selected as target diseases, and hereditary angioedema was subsequently added. Several approaches for active patient involvement were designed through patient-researcher collaboration, namely the Steering Committee, questionnaire development, dynamic consent, and other communication strategies. We analyzed our practices and experiences focusing on how each approach affected and contributed to the research project.

Results

RUDY JAPAN has successfully involved patients in this research project in various ways. While not a part of the initial decision-making phase to launch the project, patients have increasingly been involved since then. A high level of patient involvement was achieved through the Steering Committee, a governance body that has made a major contribution to RUDY JAPAN, and the process of the questionnaire development. The creation of the Patient Network Forum, website and newsletter cultivated dialogue between patients and researchers. The registry itself allowed patient participation through data input and control of data usage through dynamic consent.

Conclusions

We believe the initial outcomes demonstrate the feasibility and utility of active patient involvement in Japan. The collaboration realized through RUDY JAPAN was enabled by digital technologies. It allowed busy patients and researchers to find the space to meet and work together for the Steering Committee, questionnaire development and various communication activities. While the practice of active patient involvement in Japan is still in its early stages, this research confirms its viability if the right conditions are in place. (331 words).
Estimating the prevalence of text overlap in biomedical conference abstracts
Authors: Kinney Nick , Wubah Araba , Roig Miguel , Garner Harold R.
Published: February 2021

Background

Scientists communicate progress and exchange information via publication and presentation at scientific meetings. We previously showed that text similarity analysis applied to Medline can identify and quantify plagiarism and duplicate publications in peer-reviewed biomedical journals. In the present study, we applied the same analysis to a large sample of conference abstracts.

Methods

We downloaded 144,149 abstracts from 207 national and international meetings of 63 biomedical conferences. Pairwise comparisons were made using eTBLAST: a text similarity engine. A domain expert then reviewed random samples of highly similar abstracts (1500 total) to estimate the extent of text overlap and possible plagiarism.

Results

Our main findings indicate that the vast majority of textual overlap occurred within the same meeting (2%) and between meetings of the same conference (3%), both of which were significantly higher than instances of plagiarism, which occurred in less than .5% of abstracts.

Conclusions

This analysis indicates that textual overlap in abstracts of papers presented at scientific meetings is one-tenth that of peer-reviewed publications, yet the plagiarism rate is approximately the same as previously measured in peer-reviewed publications. This latter finding underscores a need for monitoring scientific meeting submissions – as is now done when submitting manuscripts to peer-reviewed journals – to improve the integrity of scientific communications.
Production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair
Authors: McNeil Brooke L. , Robertson Andrew K. H. , Fu Winnie , Yang Hua , Hoehr Cornelia , Ramogida Caterina F. , Schaffer Paul
Published: February 2021

Background

Lead-212 (212Pb, t1/2 = 10.6 h) and lead-203 (203Pb, t1/2 = 51.9 h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both203Pb and212Pb using TRIUMF’s TR13 (13 MeV) and 500 MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane).

Results

Proton irradiation (12.8 MeV) of natural and enriched thallium-203 (203Tl) targets gave203Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/μA, respectively. Thorium-228 (228Th, t1/2 = 1.9 y), a by-product of232Th proton spallation on TRIUMF’s main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a228Th/212Pb generator with the ability to deliver up to 9–10 MBq of212Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([203/212Pb]Pb(OAc)2) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both203Pb and212Pb. All chelates incorporated212Pb/203Pb efficiently, with higher radiolabeling yields observed for the212Pb-complexes.

Conclusion

The production of203Pb and212Pb was established using TRIUMF 13 MeV and 500 MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic212Pb/203Pb studies.
Factors associated with self-rated health among mineworkers in Zambia: a cross-sectional study
Authors: Ohnishi Mayumi , Tembo Backsion , Nakao Rieko , Matsuura Emi , Fujita Wakako
Published: February 2021

Background

This study aims to examine miners’ working conditions and self-rated health status in copper mines in Zambia and to identify the conditions and factors necessary to improve the safety and health of mineworkers.

Methods

A cross-sectional study using a self-administered questionnaire was conducted anonymously among copper mineworkers in Zambia in 2015 and 2016. Five targeted mining companies among 33 were introduced by the Mineworkers’ Union of Zambia. Study participants were recruited at the waiting space for underground work, waiting rooms of company clinics/hospitals, and/or at training sessions, which were places permitted by the target companies to perform data collection via convenience sampling. Bivariate analyses (e.g., t tests, Kruskal-Wallis tests, chi-square tests, or Cochran-Armitage tests) and logistic regression analysis were used to analyze differences in demographic characteristics and to compare their working conditions, health conditions, safety management at the workplace, and training opportunities by employment status.

Results

In total, 338 responses were analyzed. Regular employees had better working conditions, including higher incomes (P = 0.001), more likely to be guaranteed sickness insurance by the company (P < 0.001), paid holidays (P = 0.094), and sick leave (P = 0.064), although the difference was not statistically significant. Mineworkers’ decreased self-rated health was determined by job category (adjusted odds ratio [AOR], 0.41; 95% confidence interval [CI], 0.21, 0.82; P = 0.012). Having experienced violence from the boss/manager (AOR, 0.54; 95% CI, 0.32, 0.91; P = 0.020) was negatively associated with better self-rated health in the crude odds ratio.

Conclusions

Among mineworkers in Zambia, nonunderground work and not having experienced violence from their boss/manager contributed to increased self-rated health. From the perspective of psychological safety and human security, the management of safety and the working environment, including human resource management and preventing harassment/violence, should be assured, especially for underground mineworkers.
Intra-articular Adenosine, Lidocaine and Magnesium (ALM) solution decreases postoperative joint fibrosis in an experimental knee implant model
Authors: Morris Jodie L. , Letson Hayley L. , McEwen Peter , Biros Erik , Dlaska Constantin , Hazratwala Kaushik , Wilkinson Matthew , Dobson Geoffrey P.
Published: February 2021

Background

There is currently no drug therapy to prevent arthrofibrosis following knee surgery. We aimed to determine if the anti-ischemic and anti-inflammatory drug adenosine, lidocaine and Mg2+(ALM), reduces surgery-related arthrofibrosis in a rat model of knee implant surgery.

Methods

Male Sprague-Dawley rats (n = 24) were randomly divided into ALM or saline groups. The right knee of each animal was implanted with custom titanium (femur) and polyethylene (tibia) implants, and the left knee served as a non-operated control. An intra-articular ALM or saline bolus (0.1 ml) was administered at the end of surgery, and animals monitored for 4 weeks. Fibrotic changes were assessed by macroscopic examination, histopathology, and expression of key inflammatory and fibrotic markers in the joint capsule and infrapatellar fat pad (IFP).

Results

Knee swelling was evident in both groups at 4 weeks. However, range of motion was 2-fold higher in the ALM-treated knees, and differences in macroscopic pathology indicated improved healing, compared to the control group. Histologically, ALM treatment also led to significantly decreased synovitis and fibrotic pathology in the joint capsule and IFP compared to saline controls. RNA and protein expression profiles of pro-fibrotic mediators (α-SMA, TGF-β1, FGF1, PDGFA) were also significantly lower in knees from ALM-treated animals. In addition, the expression of inflammatory mediators was lower in plasma (IL-1β, IL-10) and joint tissue (NFκB, IL-1β, IL-12), 4 weeks after surgery.

Conclusion

We show that intra-articular administration of a single ALM bolus significantly decreased fibrotic pathology and synovitis in an experimental model of knee implant surgery, by blunting inflammation and modulating essential genes of fibrosis. ALM has the therapeutic potential for translation into humans undergoing knee replacement surgery.
Abundance and diversity of soil invertebrate macro-fauna in different land uses at Shenkolla watershed, South Central Ethiopia
Authors: Bufebo Belayneh , Elias Eyasu , Getu Emana
Published: February 2021

Background

Land use can exert a strong influence on the abundance, diversity, and community composition of soil macro-fauna. This study was conducted to evaluate the effects of four land use types on the abundance and diversity of soil invertebrate macro-fauna communities. These land uses include forest land, grazing land, crop cultivated outfields, and homestead garden fields present at Shenkolla watershed, south central Ethiopia. Monolith sampling of soil macro-fauna was done according to the standard of Tropical Soils Biology and Fertility Institute (TSBF) procedure. Five sampling points were chosen in each land use type and small monolith (25 × 25 × 30 cm) was dug out at 5-m interval along a transect with randomly positioned starting point, but perpendiculars to the slope. A total of 20 monoliths (4 treatments × 5 replications) were taken across all the land use types. Sampling of SIMF was carried out in April 2019 where soil macro-faunas are known to be more active. To evaluate the SIMF community eight parameters were measured: Shannon-Wiener index, Simpson diversity index, Pielou’s measure of evenness, Margalef’s diversity index, the Number of Occurrence Index, Relative abundance, Density (individuals per square meter) of each taxon and density of all SIMF and Bray-Curtis similarity index. The data were further analyzed using ANOVA and a general linear model to determine the variation and the influence of land use type, respectively.

Results

In general, 332 individuals, 10 orders, 12 families, and 15 species were identified, from the collected samples. There were significant differences (p < 0.05) among the four land use types for SIMF except wireworm, spiders, and millipedes. Overall abundance and diversity were lowest in the crop cultivated outfields and highest in homestead garden fields and forest land. Bray-Curtis’ similarity was highest between the sampled sites s16 and s19 with in the forest land, and lowest (2%) between sites s1 (crop cultivated out fields) and s14 (homestead garden fields).

Conclusion

The results revealed that the diversity of SIMF was positively influenced by forest land and homestead garden fields and negatively influenced in grazing land and cultivated outfields. Therefore, maintenance of a continuous litter cover at the surface and application of a wide range of organic fertilizers (farmyard manure, household refuse, and compost) is very much critical to prevent the decrease in diversity of SIMF.
Post-stroke dementia: frequency, predictors, and health impact
Authors: Al Fawal Bastawy , Ibrahim Ahmed , Abd Elhamed Mohamed
Published: February 2021

Background

Cognitive impairment is an important aspect for stroke survivors. Little data are available about the frequency and risk factors of post-stroke dementia in Egypt.

Objectives

The aim of this study is to evaluate the frequency and predictors of post-stroke dementia and its impact on outcome.

Methods

A total of 380 patients with acute stroke were included. Patients were subjected to demographic data collection, neurological examination, and assessment of vascular risk factors. Furthermore, assessment of stroke severity by Barthel Index was done. After 6 months, patients were assessed for outcome and development of post-stroke dementia.

Results

Post-stroke dementia was detected in 20.8% of patient. It was recorded more in old ages, illiterates, unmarried, unemployed, and those with recurrent stroke and with cerebral infarction (significantly with cardio-embolic).

Conclusion

Post-stroke dementia is high in Egypt, especially in those with illiteracy, atrial fibrillation, brain atrophy, severe strokes, and those presented with hemiplegia, sphincter affection, abnormal gait, and psychotic features. Assessment for post-stroke dementia should be done during follow up of stroke patients.
Prospective study of thyroid functions in multiple sclerosis patients treated with interferon beta in Alexandria University MS clinic
Authors: Talaat Farouk , Eldeeb Hany
Published: February 2021

Background

The incidence of thyroid dysfunction in multiple sclerosis (MS) patients on interferon (as a disease-modifying line) has been reported in many studies performed on patients already on interferon therapy. Our study adopted a prospective follow-up of the thyroid profile in those patients newly starting interferon beta therapy over 1 year trying to find a correlation between the start of therapy and the occurrence of this dysfunction.

Objectives

To evaluate the incidence of thyroid dysfunction in MS patients before and 1 year after of interferon beta.

Methods

A prospective cohort study on 48 MS patients newly receiving interferon beta therapy through MS clinic were subjected to assessment of thyroid profile including serum TSH, free T3, and T4 at the start of treatment; they were followed-up at 6- and 12-month intervals after the start of therapy.

Results and conclusion

There was a statistically significant increase in serum-free T3 levels in those treated with interferon beta therapy in a follow-up of 1 year. Our work also showed a decrease in serum-free T4 levels without statistical significance. TSH levels showed a tendency towards increase without statistical significance.
Spheno-orbital meningiomas: surgical techniques and results
Authors: Elborady Mohamed Abdelrahman , Nazim Wael Mohamed
Published: February 2021

Introduction

Spheno-orbital meningiomas are characterized by bone invasion with extensive hyperostosis and possible encroachment into the orbit, infra-temporal fossa, and/or the cavernous sinus that render total surgical excision challenging. The surgical technique utilized is a key factor facilitating complete resection and hence improvement of proptosis and accompanying visual symptoms.

Methods

This is a retrospective study of twenty-two patients (including 4 recurrent cases) with meningioma en-plaque, presenting with hyperostosis and proptosis. We describe the surgical approaches used, technique, and extent of resection in addition to postoperative outcome.

Results

In twenty patients, the pterional approach was used, while two patients were operated on via the mini orbito-zygomatic approach. Total resection of the tumor was achieved in 10 cases (45.5%), subtotal in 6 (27.3%), partial in 5 (22.7%), and in 1 case, injury to the internal carotid artery lead to premature termination of surgery. Seventeen patients (77.3%) had improvement of proptosis, 2 (9.1%) had partial improvement, and 2 (9.1%) had no improvement at 3 months of follow-up. Post-operative morbidities include cerebrospinal fluid leak, infection, and hydrocephalus, each occurred in one (4.5%) different case.

Conclusions

Proper drilling of the lateral and superior orbital walls with excision of any intra-orbital soft tissue components is all key points for better surgical resection and clinical regression of proptosis. However, factors such as extension of the hyperostosis to the infra-temporal fossa or medial orbital wall, tumor invasion of the cavernous sinus, or adherence of tumor to the orbital muscles, prevent total excision.
Classification of renal cell tumors – current concepts and use of ancillary tests: recommendations of the Brazilian Society of Pathology
Authors: Athanazio Daniel Abensur , Amorim Luciana Schultz , da Cunha Isabela Werneck , Leite Katia Ramos Moreira , da Paz Alexandre Rolim , de Paula Xavier Gomes Regina , Tavora Fabio Rocha Fernandes , Faraj Sheila Friedrich , Cavalcanti Marcela Santos , Bezerra Stephania Martins
Published: February 2021

Classification of renal cell carcinomas has become more challenging. The 2016 WHO classification included 14 different subtypes and 4 emerging/provisional entities, and recent literature indicates new entities to be incorporated. Nomenclature is based on cytoplasmic appearance, architecture, combination of morphologies, anatomic location, underlying disease, familial syndromes, and specific genetic alterations. Immunohistochemistry is useful in selected cases while it can be insufficient in entities that require molecular confirmation of a specific gene alteration. The aim of these recommendations is to provide a reasonable and optimized approach for the use of ancillary tests in subtyping renal tumors, particularly in resource-limited settings.
A PLS blockchain for IoT applications: protocols and architecture
Authors: Shafarenko Alex
Published: February 2021

This paper proposes an architecture and a protocol suite for a permissioned blockchain for a local IoT network. The architecture is based on a sealed Sequencer and a Fog Server running (post-quantum) Guy Fawkes protocols. The blocks of the blockchain are stored in networked Content Addressable Storage alongside any user data and validity proofs. We maintain that a typical IoT device can, despite its resource limitations, use our blockchain protocols directly, without a trusted intermediary. This includes posting and monitoring transactions as well as off-chain (post-quantum) emergency communications without an explicit public key.
Quantifying the variability between multiple multiplanar reconstructions of computed tomography scans
Authors: Miles James E. , Buelund Lene E.
Published: February 2021

Background

Multiplanar reconstructions of computed tomography (CT) scans can alleviate issues with bone or joint positioning during scan acquisition. The repeatability of these reconstructions is dependent on human operators applying reconstruction criteria, and therefore is subject to error, which could affect measurement reliability for angular or spatial measurements made for orthopaedic surgery.

We describe a method for quantifying inter-reconstruction variability numerically and graphically using metadata from the CT header to find vectors describing reconstruction axis alignment. The approach is demonstrated using 3 sets of computed tomographic reconstructions of 24 vulpine femorotibial joints.

Results

Vectors describing axis alignments permitted identification and subsequent analysis of deviations from optimal alignment between reconstruction sets. For the worked example, alignment deviations equivalent to femoral abduction/adduction were nearly twice those for extension/flexion, and simulation of the effects of these deviations on measurements closely matched published data.

Conclusions

The method presented here is straightforward and permits numerical and graphical analysis of reconstruction variability. Reconstruction alignment variability should be considered before adopting new reconstruction criteria for clinical use, and evaluated whenever there is suspicion that reconstruction variability could unduly influence subsequent measurements. These evaluations may help drive improvements in reconstruction criteria. The methods described here could also be employed for comparing patient positioning between scans and between different scan modalities.
Can bilirubin/albumin ratio predict neurodevelopmental outcome in severe neonatal hyperbilirubinemia? A 3-month follow up study
Authors: Soliman Reem M. , Iskander Iman F. , Elmazzahy Esraa A. , Abdellatif May A. K.
Published: February 2021

Background

The risk of kernicterus and BIND may be in part determined by total serum bilirubin (TSB) and by the level of non-albumin bound free bilirubin, which can easily pass the blood–brain barrier. Free bilirubin (Bf) seems a more reliable predictor for bilirubin neurotoxicity. Bilirubin/albumin ratio (B/A) is considered a surrogate parameter for Bf and has been more useful than TSB. The aim of the study is to determine whether B/A ratio correlates with BIND in newborns with severe hyperbilirubinemia and if it can predict poor neurologic outcome at 3 months follow up.

Results

This prospective study included one hundred seventeen outborn neonates ≥ 35 weeks admitted in a tertiary care neonatal intensive care unit, between May and December 2012, with TSB ≥ 20 mg/dl or necessitating exchange transfusion. Total serum bilirubin and serum albumin were done on admission and bilirubin/albumin ratio was calculated. BIND score was calculated. At the age of 3 months, 112 neonates were followed up with a detailed neurological assessment. Babies who depicted any abnormal motor examination were subjected to brain stem auditory evoked response and MRI examination. Seven infants (6.2%) presented with kernicterus on follow up. BIND scores on admission, mean TSB, and bilirubin/albumin ratio was significantly higher in kernicteric infants compared with those having normal neurological outcome at 3 months of age (P0.001). The lowest TSB level at which kernicterus occurred in our study was 31 mg/dl. Receiver operation characteristics analysis identified B/A ratio cut off value for predicting kernicterus of 9.6 with sensitivity of 100% and specificity of 91.4%, whereas TSB cut off value of 30 mg/dl showed sensitivity of 100% and specificity of 83%.

Conclusion

B/A ratio is a strong indicator for the risk of kernicterus. B/A is more specific than TSB and should be used in the early management of neonatal hyperbilirubinemia.
NS34A resistance-associated substitutions in chronic hepatitis C in Upper Egypt and regression of liver fibrosis after direct-acting antiviral therapy
Authors: Makhlouf Nahed A. , Farouk Mohamed , Nafeh Hanan Mohamed , Hasanain Ahmad Farooq Alsayed , El-Mokhtar Mohamed Ahmed , Hetta Helal F. , Mekky Mohamed A. , Alboraie Mohamed , ELamin Hussein , Nasr Ahmed Medhat
Published: February 2021

Background

Viral resistance-associated substitutions (RASs) can develop in the setting of DAAs therapy (i.e., emerging RASs). Long-term monitoring of fibrosis regression after achieving SVR to simiprevir (SMV)/sofosbuvir (SOF) is essential. The aim of this study was to determine the prevalence of baseline and emerging NS34A RASs in chronic HCV patients in Upper Egypt and to assess the impact of SMV/SOF therapy on liver stiffness.

Results

The enrolled 59 patients had HCV genotype 4a without any baseline RASs in the NS34A region. 96.6% (57/59) of patients achieved sustained virological response (SVR12). Of the two patients who failed to achieve SVR12, one of them developed emerging RASs Q80K in the NS34A region. Seventy-two weeks after SMV/SOF therapy, the percentage of patients with liver fibrosis stage (F2, F3, and F4) decreased from 75.4% before treatment to 42.1% after treatment. The combination of SOF and SMV appeared to be well tolerated.

Conclusions

All patients had HCV genotype 4a without any baseline RASs in the NS34A region. In addition, there was improvement of non-invasive measures of liver fibrosis in patients who achieved SVR, 72 weeks after SMV/SOF therapy.
Toll-like receptor-4 gene variations in Egyptian children with familial Mediterranean fever
Authors: Farag Yomna , Salah Samia , Tawfik Hanan , Hamed Mai , Marzouk Huda
Published: February 2021

Background

Familial Mediterranean fever (FMF) is an autosomal recessive disorder affecting people in the region of the Mediterranean Sea. It is usually associated with mutation in Mediterranean fever (MEFV) gene that encodes the pyrin protein, which affects the innate inflammatory response. Toll-like receptors (TLR) are a family of pattern recognition receptors that recognize pathogenic microbes and activate antimicrobial defense mechanisms. Toll-like receptor 4 (TLR-4) is concerned with recognition of gram-negative organisms. There is growing clinical evidence suggesting a role for expression of TLRs in the immune pathogenesis of FMF. Thus, the aim of the current study was to evaluate the presence of TLR-4 (p.Asp299Gly) and TLR-4 (p.Thr399Ile) gene variants in association with Egyptian children having FMF, furthermore, its effect on disease course and severity.

Results

Seventy Egyptian children diagnosed as having FMF, together with 50 age and gender-matched controls were enrolled in the study. The TLR-4 (p.Asp299Gly) and (Thr399Ile) gene variants were determined by PCR-RFLP analysis for all studied patients and controls. TLR-4 p.Asp299Gly gene variant was detected in 1 (1.4%) of the patients and p.Thr399Ile gene variant was detected in 2 (2%). None of the controls had any of the two tested gene variants. All found variations were heterozygous. We could not find a statistically significant association with disease severity in cases with or without TLR-4 gene variants (P = 0.568). Patients with M694V gene mutation showed a higher disease severity (P = 0.035).

Conclusion

TLR-4 (p.Asp299Gly) and (p.Thr399Ile) gene variants were not found to have a link with the occurrence, the clinical picture of FMF, its severity, and response to colchicine treatment in Egyptian children. M694V gene mutation seems to be associated with higher disease severity. Further larger studies are needed to verify these results.
Physics-driven deep-learning inversion with application to transient electromagnetics
Authors: Colombo Daniele , Turkoglu Ersan , Li Weichang , Sandoval-Curiel Ernesto , Rovetta Diego
Published: February 2021

Machine learning, and specifically deep-learning (DL) techniques applied to geophysical inverse problems, is an attractive subject, which has promising potential and, at the same time, presents some challenges in practical implementation. Some obstacles relate to scarce knowledge of the searched geologic structures, a problem that can limit the interpretability and generalizability of the trained DL networks when applied to independent scenarios in real applications. Commonly used (physics-driven) least-squares optimization methods are very efficient local optimization techniques but require good starting models close to the correct solution to avoid local minima. We have developed a hybrid workflow that combines both approaches in a coupled physics-driven/DL inversion scheme. We exploit the benefits and characteristics of both inversion techniques to converge to solutions that typically outperform individual inversion results and bring the solution closer to the global minimum of a nonconvex inverse problem. The completely data-driven and self-feeding procedure relies on a coupling mechanism between the two inversion schemes taking the form of penalty functions applied to the model term. Predictions from the DL network are used to constrain the least-squares inversion, whereas the feedback loop from inversion to the DL scheme consists of the network retraining with partial results obtained from inversion. The self-feeding process tends to converge to a common agreeable solution, which is the result of two independent schemes with different mathematical formalisms and different objective functions on the data and model misfit. We determine that the hybrid procedure is converging to robust and high-resolution resistivity models when applied to the inversion of the synthetic and field transient electromagnetic data. Finally, we speculate that the procedure may be adopted to recast the way we solve inverse problems in several different disciplines.
The Role of Metabolic Syndrome and its Components in Incident Fracture: A 15-Year Follow-Up Among the Iranian Population
Authors: Amouzegar Atieh , Asgari Samaneh , Azizi Fereidoun , Momenan Amir Abbas , Bozorgmanesh Mohammadreza , Hadaegh Farzad
Published: February 2021

Context

The relationship between metabolic syndrome (MetS) and the risk of fracture is a matter of debate.

Objective

This work aimed to determine the impact of MetS and its components on the risk of hospitalized fractures, during a median follow-up of 15.9 years.

Methods

A total of 7,520 participants (4,068 women) 30 years or older entered the study. Multivariable Cox proportional hazards regression were applied for data analysis.

Results

The prevalence of MetS was 40.0% and 40.4% in men and women, respectively. During the follow-up, hospitalized fracture was observed in 305 cases (men = 152). The multivariable hazard ratio (HR) and 95% confidence interval (CI) of MetS for incident fracture for men and women was 0.72 (0.49-1.05, P = .08) and 1.38 (0.96-1.98, P = .08), respectively. In the fully adjusted model, high fasting plasma glucose (FPG) among men tended to be associated with a lower risk of fracture [0.67 (0.44-1.02, P = .06)]; among women, high waist circumference (WC) was associated with a greater risk [2.40 (1.55-3.73)]. Among the population 50 years and older in the pooled sample, MetS was not accompanied by the risk of fracture, but high WC was associated with a higher risk [1.58 (1.07-2.33)]. For incident hip/pelvic fracture, abdominal obesity—but not MetS per se—was also a strong and independent risk factor.

Conclusion

A significant sex difference in the association between MetS and its components with incident fracture was observed. Women with central adiposity were at increased risk of hospitalized fracture, whereas men with high FPG were at decreased risk.
Hardship Among Immigrants and the Native-born in the United States
Authors: Iceland John
Published: February 2021

This study examines the prevalence of several types of hardship (e.g., bill paying and housing hardships) among immigrants by race and ethnicity in the United States using data from the 2008 and 2014 panels of the Survey of Income and Program Participation and logistic regressions. I find that Blacks, and to some extent Hispanics, are more likely to report hardships than Whites and Asians, who are about equally likely to report hardships. Exploring results by nativity and citizenship status, I find that immigrants who became U.S. citizens are less likely than the native-born population to report some kinds of hardship. Undocumented immigrants, however, are more likely to report some kinds of hardships, particularly in the 2008 panel conducted at the time of the Great Recession, which hit immigrants especially hard; this relationship, however, is explained by the lower incomes of undocumented immigrant households in the 2008 panel. Results within racial and ethnic groups are generally in the same direction but are less frequently statistically significant. Overall, these findings suggest that immigrants are not particularly prone to hardship, especially when other characteristics are controlled for. In fact, the lower likelihood of some hardships among foreign-born citizens suggests that they are positively selected: they may have unobserved characteristics that are protective, such as better health, stronger social networks, or money management skills. Because the foreign-born are less likely to be disadvantaged vis-à-vis the native-born when hardship rather than the official income poverty measure is used, this study highlights the importance of using multiple measures when assessing the well-being of immigrants.
The many bits of positional information
Authors: Tkačik Gašper , Gregor Thomas
Published: February 2021

Half a century after Lewis Wolpert's seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to?
APETALA2 functions as a temporal factor together with BLADE-ON-PETIOLE2 and MADS29 to control flower and grain development in barley
Authors: Shoesmith Jennifer R. , Solomon Charles Ugochukwu , Yang Xiujuan , Wilkinson Laura G. , Sheldrick Scott , van Eijden Ewan , Couwenberg Sanne , Pugh Laura M. , Eskan Mhmoud , Stephens Jennifer , Barakate Abdellah , Drea Sinéad , Houston Kelly , Tucker Matthew R. , McKim Sarah M.
Published: February 2021

Cereal grain develops from fertilised florets. Alterations in floret and grain development greatly influence grain yield and quality. Despite this, little is known about the underlying genetic control of these processes, especially in key temperate cereals such as barley and wheat. Using a combination of near-isogenic mutant comparisons, gene editing and genetic analyses, we reveal that HvAPETALA2 (HvAP2) controls floret organ identity, floret boundaries, and maternal tissue differentiation and elimination during grain development. These new roles of HvAP2 correlate with changes in grain size and HvAP2-dependent expression of specific HvMADS-box genes, including the B-sister gene, HvMADS29. Consistent with this, gene editing demonstrates that HvMADS29 shares roles with HvAP2 in maternal tissue differentiation. We also discovered that a gain-of-function HvAP2 allele masks changes in floret organ identity and grain size due to loss of barley LAXATUM.A/BLADE-ON-PETIOLE2 (HvBOP2) gene function. Taken together, we reveal novel pleiotropic roles and regulatory interactions for an AP2-like gene controlling floret and grain development in a temperate cereal.
Fibronectin Extra Domains tune cellular responses and confer topographically distinct features to fibril networks
Authors: Efthymiou Georgios , Radwanska Agata , Grapa Anca-Ioana , Beghelli-de la Forest Divonne Stéphanie , Grall Dominique , Schaub Sébastien , Hattab Maurice , Pisano Sabrina , Poet Mallorie , Pisani Didier F. , Counillon Laurent , Descombes Xavier , Blanc-Féraud Laure , Van Obberghen-Schilling Ellen
Published: February 2021

Cellular fibronectin (FN; also known as FN1) variants harboring one or two alternatively spliced so-called extra domains (EDB and EDA) play a central bioregulatory role during development, repair processes and fibrosis. Yet, how the extra domains impact fibrillar assembly and function of the molecule remains unclear. Leveraging a unique biological toolset and image analysis pipeline for direct comparison of the variants, we demonstrate that the presence of one or both extra domains impacts FN assembly, function and physical properties of the matrix. When presented to FN-null fibroblasts, extra domain-containing variants differentially regulate pH homeostasis, survival and TGF-β signaling by tuning the magnitude of cellular responses, rather than triggering independent molecular switches. Numerical analyses of fiber topologies highlight significant differences in variant-specific structural features and provide a first step for the development of a generative model of FN networks to unravel assembly mechanisms and investigate the physical and functional versatility of extracellular matrix landscapes.

This article has an associated First Person interview with the first author of the paper.
The 20S proteasome activator PA28γ controls the compaction of chromatin
Authors: Fesquet Didier , Llères David , Grimaud Charlotte , Viganò Cristina , Méchali Francisca , Boulon Séverine , Coux Olivier , Bonne-Andrea Catherine , Baldin Véronique
Published: February 2021

PA28γ (also known as PSME3), a nuclear activator of the 20S proteasome, is involved in the degradation of several proteins regulating cell growth and proliferation and in the dynamics of various nuclear bodies, but its precise cellular functions remain unclear. Here, using a quantitative FLIM-FRET based microscopy assay monitoring close proximity between nucleosomes in living human cells, we show that PA28γ controls chromatin compaction. We find that its depletion induces a decompaction of pericentromeric heterochromatin, which is similar to what is observed upon the knockdown of HP1β (also known as CBX1), a key factor of the heterochromatin structure. We show that PA28γ is present at HP1β-containing repetitive DNA sequences abundant in heterochromatin and, importantly, that HP1β on its own is unable to drive chromatin compaction without the presence of PA28γ. At the molecular level, we show that this novel function of PA28γ is independent of its stable interaction with the 20S proteasome, and most likely depends on its ability to maintain appropriate levels of H3K9me3 and H4K20me3, histone modifications that are involved in heterochromatin formation. Overall, our results implicate PA28γ as a key factor involved in the regulation of the higher order structure of chromatin.
Influence of rumen bypass fat fed with total mixed ration on growth performance in Nili-Ravi buffalo calves
Authors: AHMED S. , AAMIR M. , UL-HAQUE M. N. , AHMAD N. , MARGHAZANI I.B. , KHAN M. I.
Published: February 2021

This study was conducted to know the influence of rumen bypass fat supplement on growth performance of Nili-Ravi mal buffalo calves. Nili Ravi buffalo male calves (n=12) were randlomly selected and divided into two groups i.e., A and B based on two different levels of age. These groups (A and B) were further divided into two respective subgroups i.e., A1, A2 and B1, B2. Sub groups A1 and BI served as control (without supplement) whilst subgroups A2 and B2 were fed RBF supplement (at the rate of 2.35% of dry matter intake) with basel diet with total mixed ration. Results showed no statistical difference (P>0.05) in dry matter intake, body weight gain and body condition score on rumen bypass fat supplementation. In blood metabolites, rumen bypass fat supplementation increased (P<0.05) blood triglyceride and cholesterol levels, however, it reduced (P<0.05) blood glucose level in Nili-Ravi buffalo male calves. This study suggests that supplementation of rumen bypass fat at the rate of 2.35% per day in TMR possess no impact on growth performance parameters in Nili Ravi buffalo male calves.
Effects of Housing Locations on Feather Damages of Laying Hens in a Free-Range Housing System
Authors: PETEK METIN
Published: February 2021

This study was made to evaluate the effects of different locations of a free range housing system on feather damages of laying hens. The experimental house consisted of three different locations as closed indoor plastic slats, closed indoor litter and outdoor range area. The birds were able to move freely between the locations of the experimental house and they had continuous access to outdoor range during the day. The feather damages of the birds was evaluated with a distance scoring system at 64 weeks of age. Five area in each location of the experimental house were determined at first and then feather damages of five body parts of ten birds in each location were scored to measure plumage quality. Total feather score was defined as the sum of the scores of five body parts of the birds. Best plumage quality was measured in neck in all housing locations (P<0.01, P<0.05 and P<0.01) and total feather score of the birds was significantly greatest (worst) in slats (P<0.05).
Molecular Investigation and Genotyping of Theileria equi and Babesia caballi in Horses in Mus Province, Turkey
Authors: OGUZ B. , ÖZDAL N. , DEGER M.S. , BICEK K.
Published: February 2021

Equine Piroplasmosis (EP) is a tick-borne disease caused by Theileria equi and Babesia caballi of the phylum Apicomplexa. In this study, 102 blood samples were randomly collected from the horses in Mus province of Turkey. PCR analysis, gene sequences, and phylogenetic analyses were carried out for detecting the presence and genotypic characteristics of species that cause piroplasmosis. Four (3.9%) of the 102 horses that were examined were found to be positive for T. equi, while B. caballi was not detected. Theileria equi isolates that were detected in the sequence analyses were found to be 100% identical to the isolates that were isolated from the horses in Turkey, the United States, and South Africa as well. In the phylogenetic analysis, all of the isolates were found to cluster with T. equi sequences in the genotype A. This study, in which we revealed intraspecies sequence heterogeneity of the parasite using the 18S rRNA gene region, provides important epidemiological data for equine piroplasmosis. However, we think that determining the characterization of genotypes that are common in different parts of our country is extremely important in terms of developing new diagnostic tools and vaccines.
Benchmarking of long-read assemblers for prokaryote whole genome sequencing
Authors: Wick Ryan R. , Holt Kathryn E.
Published: February 2021

Background: Data sets from long-read sequencing platforms (Oxford Nanopore Technologies and Pacific Biosciences) allow for most prokaryote genomes to be completely assembled – one contig per chromosome or plasmid. However, the high per-read error rate of long-read sequencing necessitates different approaches to assembly than those used for short-read sequencing. Multiple assembly tools (assemblers) exist, which use a variety of algorithms for long-read assembly.

Methods: We used 500 simulated read sets and 120 real read sets to assess the performance of eight long-read assemblers (Canu, Flye, Miniasm/Minipolish, NECAT, NextDenovo/NextPolish, Raven, Redbean and Shasta) across a wide variety of genomes and read parameters. Assemblies were assessed on their structural accuracy/completeness, sequence identity, contig circularisation and computational resources used.

Results: Canu v2.1 produced reliable assemblies and was good with plasmids, but it performed poorly with circularisation and had the longest runtimes of all assemblers tested. Flye v2.8 was also reliable and made the smallest sequence errors, though it used the most RAM. Miniasm/Minipolish v0.3/v0.1.3 was the most likely to produce clean contig circularisation. NECAT v20200803 was reliable and good at circularisation but tended to make larger sequence errors. NextDenovo/NextPolish v2.3.1/v1.3.1 was reliable with chromosome assembly but bad with plasmid assembly. Raven v1.3.0 was reliable for chromosome assembly, though it did not perform well on small plasmids and had circularisation issues. Redbean v2.5 and Shasta v0.7.0 were computationally efficient but more likely to produce incomplete assemblies.

Conclusions: Of the assemblers tested, Flye, Miniasm/Minipolish, NextDenovo/NextPolish and Raven performed best overall. However, no single tool performed well on all metrics, highlighting the need for continued development on long-read assembly algorithms.