bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of centre volume on atrial fibrillation ablation outcomes in Europe: a report from the ESC EHRA EORP Atrial Fibrillation Ablation Long-Term (AFA LT) Registry
Authors: Vassilikos Vassilios P , Pagourelias Efstathios D , Laroche Cécile , Blomström-Lundqvist Carina , Kautzner Josef , Maggioni Aldo P , Tavazzi Luigi , Dagres Nikolaos , Brugada Josep , Stühlinger Markus , Arbelo Elena ,   the AFA LT registry investigators group
Published: July 2020

Aims 

The aim of the study was to investigate differences in clinical outcomes and complication rates among European atrial fibrillation (AF) ablation centres related to the volume of AF ablations performed.

Methods and results 

Data for this analysis were extracted from the ESC EHRA EORP European AF Ablation Long-Term Study Registry. Based on 33rd and 67th percentiles of number of AF ablations performed, the participating centres were classified into high volume (HV) (≥ 180 procedures/year), medium volume (MV) (<180 and ≥74/year), and low volume (LV) (<74/year). A total of 91 centres in 26 European countries enrolled in 3368 patients. There was a significantly higher reporting of cardiovascular complications and stroke incidence in LV centres compared with HV and MV (P = 0.039 and 0.008, respectively) and a lower success rate after AF ablation (55.3% in HV vs. 57.2% in LV vs. 67.4% in MV centres, P < 0.001), despite lower CHA2DS2-VASc score of patients, enrolled in LVs and less complex ablation techniques used. Adjustments of confounding factors (including type of AF ablation) led to elimination of these differences.

Conclusion 

Low-volume centres tended to present slightly higher cardiovascular complications’ and stroke incidence and a lower unadjusted success rate after AF ablation, despite the fact that ablation procedures and patients were of lower risk compared with MV and HV centres. On the other hand, adjusted overall complication and recurrence rates were non-significantly different among different volume centres, a fact reflecting the heterogeneity of patient and procedural profiles, and a counterbalance between expertise and risk level among participating centres.
Predictive role of early recurrence of atrial fibrillation after cryoballoon ablation
Authors: Stabile Giuseppe , Iacopino Saverio , Verlato Roberto , Arena Giuseppe , Pieragnoli Paolo , Molon Giulio , Manfrin Massimiliano , Rovaris Giovanni , Curnis Antonio , Bertaglia Emanuele , Mantica Massimo , Sciarra Luigi , Landolina Maurizio , Tondo Claudio
Published: July 2020

Aims

The aims of this study were to determine the rate and the predictors of early recurrences of atrial fibrillation (ERAF) after cryoballoon (CB) ablation and to evaluate whether ERAF correlate with the long-term outcome.

Methods and results

Three thousand, six hundred, and eighty-one consecutive patients (59.9 ± 10.5 years, female 26.5%, and 74.3% paroxysmal AF) were included in the analysis. Atrial fibrillation recurrence, lasting at least 30 s, was collected during and after the 3-month blanking period. Three-hundred and sixteen patients (8.6%) (Group A) had ERAF during the blanking period, and 3365 patients (Group B) had no ERAF. Persistent AF and number of tested anti-arrhythmic drugs ≥2 resulted as significant predictors of ERAF. After a mean follow-up of 16.8 ± 16.4 months, 923/3681 (25%) patients had at least one AF recurrence. The observed freedom from AF recurrence, at 24-month follow-up from procedure, was 25.7% and 64.8% in Groups A and B, respectively (P < 0.001). ERAF, persistent AF, and number of tested anti-arrhythmic drugs ≥2 resulted as significant predictors of AF. In a propensity score matching, the logistic model showed that ERAF 1 month after ablation are the best predictor of long-term AF recurrence (P = 0.042).

Conclusion

In patients undergoing CB ablation for AF, ERAF are rare and are a strong predictor of AF recurrence in the follow-up, above all when occur >30 days after the ablation.
Seismic and hydroacoustic observations from recent underwater events in the South Atlantic Ocean
Authors: Heyburn Ross , Bowers David , N. Green David
Published: July 2020

To study the location and characterize two underwater events in the South Atlantic Ocean, we analyse both seismic and hydroacoustic signals. The first event (2017 November 15) occurred around 550 km east of Argentina, near the last reported position of the Argentine Navy submarine the ARA San Juan, the seafloor wreck of which was found one year later. The second event (2017 December 1) was due to an aircraft-dropped depth charge, detonated as part of the search for the ARA San Juan. We use signal arrival times and azimuths recorded at two seismic and two hydroacoustic stations to estimate epicentres for both events; our estimates were within 10 km of the ground-truth locations. We used geophysical models and databases to determine the sound-speed structure of the water and the presence of sea-ice to help interpret differences in the frequency content and dispersion of signals at the two hydrophone stations. Hydrophone signals for the 2017 November 15 event contain significant energy at high frequencies, which is inconsistent with an earthquake source. Hydrophone signals for the 2017 December 1 event show frequency modulations consistent with those expected from the known depth and explosive energy. Hydrophone signals from the 2017 November 15 event also show frequency modulations, though differences between these for the two events suggest differences in the details of the source mechanisms. Using estimates of the local seismic magnitudes, the peak pressures recorded on the hydrophones, and the known charge weight for the 2017 December 1 event, we estimate that the 2017 November 15 event had an acoustic energy release equivalent to around 428 kg of trinitrotoluene. This analysis demonstrates the importance of high-precision traveltime predictions from models of seismic and ocean acoustic velocities when analysing low-magnitude underwater events.
Source modelling and strong ground motion simulations for the 24 January 2020, Mw 6.8 Elazığ earthquake, Turkey
Authors: Cheloni Daniele , Akinci Aybige
Published: July 2020

On 24 January 2020 an Mw 6.8 earthquake occurred at 20:55 local time (17:55 UTC) in eastern Turkey, close to the town of Sivrice in the Elazığ province, causing widespread considerable seismic damage in buildings. In this study, we analyse the main features of the rupture process and the seismic ground shaking during the Elazığ earthquake. We first use Interferometric Synthetic Aperture Radar (InSAR) interferograms (Sentinel-1 satellites) to constrain the fault geometry and the coseismic slip distribution of the causative fault segment. Then, we utilize this information to analyse the ground motion characteristics of the main shock in terms of peak ground acceleration (PGA), peak ground velocity (PGV) and spectral accelerations. The absence of seismic registrations in near-field for this earthquake imposes major constraints on the computation of seismic ground motion estimations in the study area. To do this, we have used a stochastic finite-fault simulation method to generate high-frequency ground motions synthetics for the Mw 6.8 Elazığ 2020 earthquake. Finally, we evaluate the potential state of stress of the unruptured portions of the causative fault segment as well as of adjacent segments, using the Coulomb stress failure function variations. Modelling of geodetic data shows that the 2020 Elazığ earthquake ruptured two major slip patches (for a total length of about 40 km) located along the Pütürge segment of the well-known left-lateral strike-slip East Anatolian Fault Zone (EAFZ), with up to 2.3 m of slip and an estimated geodetic moment of 1.70 $\,\, \times $ 1019 Nm (equivalent to a Mw 6.8). The position of the hypocentre supports the evidence of marked WSW rupture directivity during the main shock. In terms of ground motion characteristics, we observe that the high-frequency stochastic ground motion simulations have a good capability to reproduce the source complexity and capture the ground motion attenuation decay as a function of distance, up to the 200 km. We also demonstrate that the design spectra corresponding to 475 yr return period, provided by the new Turkish building code is not exceeded by the simulated seismograms in the epicentral area where there are no strong motion stations and no recordings available. Finally, based on the Coulomb stress distribution computation, we find that the Elazığ main shock increased the stress level of the westernmost part of the Pütürge fault and of the adjacent Palu segment and as a result of an off-fault lobe.
It Takes Two to Tango: Including a Female Perspective in Reproductive Biology
Authors: Orr Teri J , Burns Mercedes , Hawkes Kristen , Holekamp Kay E , Hook Kristin A , Josefson Chloe C , Kimmitt Abigail A , Lewis A Kelsey , Lipshutz Sara E , Lynch Kathleen S , Sirot Laura K , Stadtmauer Daniel J , Staub Nancy L , Wolfner Mariana F , Hayssen Virginia
Published: July 2020

Synopsis

Like many scientific disciplines, the field of reproductive biology is subject to biases in terminology and research foci. For example, females are often described as coy and passive players in reproductive behaviors and are termed “promiscuous” if they engage in extra-pair copulations. Males on the other hand are viewed as actively holding territories and fighting with other males. Males are termed “multiply mating” if they mate with multiple females. Similarly, textbooks often illustrate meiosis as it occurs in males but not females. This edition of Integrative and Comparative Biology (ICB) includes a series of papers that focus on reproduction from the female perspective. These papers represent a subset of the work presented in our symposium and complementary sessions on female reproductive biology. In this round table discussion, we use a question and answer format to leverage the diverse perspectives and voices involved with the symposium in an exploration of theoretical, cultural, pedagogical, and scientific issues related to the study of female biology. We hope this dialog will provide a stepping-stone toward moving reproductive science and teaching to a more inclusive and objective framework.
The Female Snark Is Still a Boojum: Looking toward the Future of Studying Female Reproductive Biology
Authors: Orr Teri J , Hayssen Virginia
Published: July 2020

Synopsis

Philosophical truths are hidden in Lewis Carroll’s nonsense poems, such as “The hunting of the snark.” When the poem is used as a scientific allegory, a snark stands for the pursuit of scientific truth, while a boojum is a spurious discovery. In the study of female biology, boojums have been the result of the use of cultural stereotypes to frame hypotheses and methodologies. Although female reproduction is key for the continuation of sexually reproducing species, not only have females been understudied in many regards, but also data have commonly been interpreted in the context of now-outdated social mores. Spurious discoveries, boojums, are the result. In this article, we highlight specific gaps in our knowledge of female reproductive biology and provide a jumping-off point for future research. We discuss the promise of emerging methodologies (e.g., micro-CT scanning, high-throughput sequencing, proteomics, big-data analysis, CRISPR-Cas9, and viral vector technology) that can yield insights into previously cryptic processes and features. For example, in mice, deoxyribonucleic acid sequencing via chromatin immunoprecipitation followed by sequencing is already unveiling how epigenetics lead to sex differences in brain development. Similarly, new explorations, including microbiome research, are rapidly debunking dogmas such as the notion of the “sterile womb.” Finally, we highlight how understanding female reproductive biology is well suited to the National Science Foundation’s big idea, “Predicting Rules of Life.” Studies of female reproductive biology will enable scholars to (1) traverse levels of biological organization from reproductive proteins at the molecular level, through anatomical details of the ovum and female reproductive tract, into physiological aspects of whole-organism performance, leading to behaviors associated with mating and maternal care, and eventually reaching population structure and ecology; (2) discover generalizable rules such as the co-evolution of maternal-offspring phenotypes in gestation and lactation; and (3) predict the impacts of changes to reproductive timing when the reliability of environmental cues becomes unpredictable. Studies in these key areas relative to female reproduction are sure to further our understanding across a range of diverse taxa.
Quantum Q-Systems and Fermionic Sums—The Non-Simply Laced Case
Authors: Simon Lin Mingyan
Published: July 2020

In this paper, we seek to prove the equality of the $q$-graded fermionic sums conjectured by Hatayama et al. [ 14] in its full generality, by extending the results of Di Francesco and Kedem [ 9] to the non-simply laced case. To this end, we will derive explicit expressions for the quantum $Q$-system relations, which are quantum cluster mutations that correspond to the classical $Q$-system relations, and write the identity of the $q$-graded fermionic sums as a constant term identity. As an application, we will show that these quantum $Q$-system relations are consistent with the short exact sequence of the Feigin–Loktev fusion product of Kirillov–Reshetikhin modules obtained by Chari and Venkatesh [ 5].
Interventions to improve the review of antibiotic therapy in acute care hospitals: a systematic review and narrative synthesis
Authors: Matuluko Ayodeji , Macdonald Jennifer , Ness Valerie , Currie Kay
Published: July 2020

Objectives

To synthesize current evidence for the effectiveness of interventions to ensure the timely review of antibiotics in acute care hospitals.

Methods

Five databases were searched from 1 January 2015 to 8 March 2019 for studies in English, focused on the timely review of antibiotics in acute care hospitals. Randomized controlled trials, non-randomized studies, case–control and cohort study designs were eligible. Intervention strategies were categorized according to the Cochrane Effective Practice and Organisation of Care taxonomy of health interventions, then mapped to the intervention functions of the behaviour change wheel.

Results

Fourteen studies were included. Most studies (11 out of 14) were conducted in single sites. Nine out of 14 reported intervention delivery by more than one healthcare professional. Physicians were the main targets of interventions in all studies. Thirteen out of 14 studies tested interventions comprising more than one strategy. The three most commonly utilized strategies within interventions were clinical practice guidelines, audit and feedback, and educational materials. Only one study employed theory in intervention evaluation. Reported interventions led to timely review and switch of IV antibiotic therapy, and shortened durations of overall antibiotic therapy.

Conclusions

Interventions to improve the review of antibiotics were found to be effective in the short to medium term, with limited evidence of long-term sustainability in multiple sites. Future research may benefit from the application of theory to intervention design and detailed specifications of interventions to aid their easy replication and implementation in different contexts.
Use of word and graph embedding to measure semantic relatedness between Unified Medical Language System concepts
Authors: Mao Yuqing , Fung Kin Wah
Published: July 2020

Objective

The study sought to explore the use of deep learning techniques to measure the semantic relatedness between Unified Medical Language System (UMLS) concepts.

Materials and Methods

Concept sentence embeddings were generated for UMLS concepts by applying the word embedding models BioWordVec and various flavors of BERT to concept sentences formed by concatenating UMLS terms. Graph embeddings were generated by the graph convolutional networks and 4 knowledge graph embedding models, using graphs built from UMLS hierarchical relations. Semantic relatedness was measured by the cosine between the concepts’ embedding vectors. Performance was compared with 2 traditional path-based (shortest path and Leacock-Chodorow) measurements and the publicly available concept embeddings, cui2vec, generated from large biomedical corpora. The concept sentence embeddings were also evaluated on a word sense disambiguation (WSD) task. Reference standards used included the semantic relatedness and semantic similarity datasets from the University of Minnesota, concept pairs generated from the Standardized MedDRA Queries and the MeSH (Medical Subject Headings) WSD corpus.

Results

Sentence embeddings generated by BioWordVec outperformed all other methods used individually in semantic relatedness measurements. Graph convolutional network graph embedding uniformly outperformed path-based measurements and was better than some word embeddings for the Standardized MedDRA Queries dataset. When used together, combined word and graph embedding achieved the best performance in all datasets. For WSD, the enhanced versions of BERT outperformed BioWordVec.

Conclusions

Word and graph embedding techniques can be used to harness terms and relations in the UMLS to measure semantic relatedness between concepts. Concept sentence embedding outperforms path-based measurements and cui2vec, and can be further enhanced by combining with graph embedding.
A refined methodology for validation of information models derived from flowsheet data and applied to a genitourinary case
Authors: Westra Bonnie L , Lytle , Kay S , Whittenburg Luann , Adams Mischa , Ali Samira , Furukawa Meg , Hartleben Stephanie , Hook Mary , Johnson Steve , Collins Rossetti Sarah , Settergren Tess (Theresa)
Published: July 2020

Use of electronic health record data is expanding to support quality improvement and research; however, this requires standardization of the data and validation within and across organizations. Information models (IMs) are created to standardize data elements into a logical organization that includes data elements, definitions, data types, values, and relationships. To be generalizable, these models need to be validated across organizations. The purpose of this case report is to describe a refined methodology for validation of flowsheet IMs and apply the revised process to a genitourinary IM created in one organization. The refined IM process, adding evidence and input from experts, produced a clinically relevant and evidence-based model of genitourinary care. The refined IM process provides a foundation for optimizing electronic health records with comparable nurse sensitive data that can add to common data models for continuity of care and ongoing use for quality improvement and research.
Clinical informatics accelerates health system adaptation to the COVID-19 pandemic: examples from Colorado
Authors: Lin Chen-Tan , Bookman Kelly , Sieja Amber , Markley Katie , Altman Richard L , Sippel Jeffrey , Perica Katharine , Reece Lori , Davis Christopher , Horowitz Edward , Pisney Larissa , Sottile Peter D , Kao David , Adrian Bonnie , Szkil Melissa , Griffin Julie , Youngwerth Jeanie , Drew Brendan , Pell Jonathan
Published: July 2020

Objective

Large health systems responding to the coronavirus disease 2019 (COVID-19) pandemic face a broad range of challenges; we describe 14 examples of innovative and effective informatics interventions.

Materials and Methods

A team of 30 physician and 17 nurse informaticists with an electronic health record (EHR) and associated informatics tools.

Results

To meet the demands posed by the influx of patients with COVID-19 into the health system, the team built solutions to accomplish the following goals: 1) train physicians and nurses quickly to manage a potential surge of hospital patients; 2) build and adjust interactive visual pathways to guide decisions; 3) scale up video visits and teach best-practice communication; 4) use tablets and remote monitors to improve in-hospital and posthospital patient connections; 5) allow hundreds of physicians to build rapid consensus; 6) improve the use of advance care planning; 7) keep clinicians aware of patients’ changing COVID-19 status; 8) connect nurses and families in new ways; 9) semi-automate Crisis Standards of Care; and 10) predict future hospitalizations.

Discussion

During the onset of the COVID-19 pandemic, the UCHealth Joint Informatics Group applied a strategy of “practical informatics” to rapidly translate critical leadership decisions into understandable guidance and effective tools for patient care.

Conclusion

Informatics-trained physicians and nurses drew upon their trusted relationships with multiple teams within the organization to create practical solutions for onboarding, clinical decision-making, telehealth, and predictive analytics.
“There’s a problem, now what’s the solution?”: suggestions for technologies to support the menopausal transition from individuals experiencing menopause and healthcare practitioners
Authors: Backonja Uba , Taylor-Swanson Lisa , Miller Andrew D , Jung Se-Hee , Haldar Shefali , Woods Nancy Fugate
Published: July 2020

Objective

To elicit novel ideas for informatics solutions to support individuals through the menopausal transition. (Note: We use “individuals experiencing menopause” and “experiences” rather than “symptoms” when possible to counter typical framing of menopause as a cisgender women’s medical problem.)

Methods

A participatory design study was conducted 2015–2017 in the Western US. Two sessions were held with individuals experiencing menopause recruited from the general public; and 3 sessions with healthcare practitioners (HCPs) including nurses, physicians, and complementary and integrative health (CIH) practitioners were held. Participants designed technologies addressing informational needs and burdensome experiences. HCPs reflected on designs from participants experiencing menopause. Directed content analysis was used to analyze transcripts.

Results

Eight individuals experiencing menopause (n = 4 each session) and 18 HCPs (n = 10 CIH, n = 3 nurses, n = 5 physicians) participated. All participants provided ideas for solution purpose, hardware, software, features and functions, and data types. Individuals experiencing menopause designed technologies to help understand and prevent burdensome menopause experiences. HCPs designed technologies for tracking and facilitating communication. Compared to nurses and physicians, CIH practitioners suggested designs reframing menopause as a positive experience and accounted for the complex lives of individuals experiencing menopause, including stigma; these ideas corresponded to comments made by participants experiencing menopause. Participants from both populations were concerned about data confidentiality and technology accessibility.

Conclusions

Participant generated design ideas included novel ideas and incorporated existing technologies. This study can inform the development of new technologies or repurposing of existing technologies to support individuals through the menopausal transition.
Sensitive Derivative Synchronous and Micellar Enhanced Ecofriendly Spectrofluorimetric Methods for the Determination of Atenolol, Diclofenac, and Triclosan in Drinking Tap Water
Authors: Safwat Nardine , Abdel-Ghany Maha F , Ayad Miriam F
Published: July 2020

Background

Nowadays, emergence of unexpected contaminants in drinking water is a challenging environmental problem facing humanity.

Objective

Two eco-friendly spectrofluorimetric methods were proposed for the determination of three unexpected contaminants in drinking tap water.

Methods

The first method is first derivative synchronous spectrofluorimetric method which was developed for simultaneous determination of atenolol (ATN) and diclofenac (DCF) without prior separation at Δλ = 70 nm and at Δλ = 80 nm for ATN and DCF, respectively. The second method was based on using sodium dodecyl sulfate (SDS) as fluorescent enhancer of triclosan (TCS) native fluorescence. TCS exhibits enhanced fluorescence at λ emission = 600 nm upon excitation at λ excitation = 299.4 nm. Solid phase extraction was carried out in both methods.

Results

Linear calibration curves were obtained in concentration range of (4–3000 ng/mL) for ATN and (4–2000 ng/mL) for DCF, by measuring first derivative signal of fluorescence at 300 nm and 375.2 nm, respectively. TCS exhibits linear range (0.1–1 ng/mL) at 600 nm. Mean percentage recoveries were 101.04 ± 0.571, 99.66 ± 1.443, and 99.73 ± 0.566 for ATN, DCF, and TCS, respectively.

Conclusions

Validation of both methods were performed according to the International Conference on Harmonization guidelines. Results obtained were statistically compared with published methods and no significant differences were found. The proposed methods’ greenness is evaluated using analytical Eco-scale and Green Analytical Procedure Index. A greenness comparison with previously published methods has been performed.

Highlights

Both methods were found to be eco-friendly and were successfully applied for the determination of the emerging contaminants in drinking tap water.
The direct and difference procedures result in similar estimates for amino acid digestibility in feed ingredients fed to growing pigs
Authors: Oliveira Maryane S F , Htoo John K , Stein Hans H
Published: July 2020

An experiment was conducted to test the hypothesis that values for standardized ileal digestibility (SID) of amino acids (AA) in corn, wheat, and wheat middlings obtained using the direct procedure are not different from values obtained using the difference procedure. Sixteen ileal-cannulated barrows (initial BW: 69.5 ± 5.0 kg) were allotted to a replicated 8 × 4 Youden Square design with 8 diets and 4 periods. Each period consisted of 5 d of adaptation to the diet and 2 d of collection of ileal digesta. Four diets were based on soybean meal (SBM), corn, wheat, or wheat middlings as the only AA-containing ingredients. Three additional diets were based on a mixture of SBM and corn, SBM and wheat, or SBM and wheat middlings, and an N-free diet was also used. The apparent ileal digestibility (AID) and the SID of crude protein (CP) and AA for the 4 diets containing SBM, corn, wheat, or wheat middlings as the sole source of AA were calculated using the direct procedure. The AID and SID of CP and AA for the 3 mixed diets containing SBM and corn, wheat, or wheat middlings were also calculated and the contribution of digestible AA from SBM was subtracted from the AID or SID values for the diets. The AID or SID of AA in corn, wheat, and wheat middlings were subsequently calculated by difference. Results indicated that the AID values for a few AA were lower (P < 0.05) if the direct procedure was used instead of the difference procedure, regardless of ingredient. The AID of Trp was greater in corn and wheat middlings, and the SID of Trp in corn and wheat middlings tended to be greater, if the direct procedure rather than the difference procedure was used, but that was not the case for wheat (interaction, P < 0.05 and P < 0.10, respectively). However, for all other indispensable AA, and for most of the dispensable AA, the SID of AA in corn, wheat, and wheat middlings was not different between the difference procedure and the direct procedure. Therefore, values for SID of AA in cereal grains and fiber-rich ingredients may be determined using either the direct or the difference procedure.
Supplemental effects of dietary lysophospholipids in lactation diets on sow performance, milk composition, gut health, and gut-associated microbiome of offspring
Authors: Jang Ki Beom , Purvis Jerry M , Kim Sung Woo
Published: July 2020

Dietary lysophospholipids (LPL) would influence milk composition of sows, thus positively affect intestinal health of offspring. The objective of this study was to determine effects of dietary LPL fed to lactating sows on performance, milk characteristics, gut health, and gut-associated microbiome of offspring. Sixty pregnant sows were allotted to 2 treatments in a randomized complete block design with parity and BW as blocks on day 110 of gestation. Treatments were CON (no added LPL) and LPL (0.05% LPL; Lipidol-Ultra, Pathway Intermediates, Shrewsbury, UK). Sows were fed 2 kg/d from day 110 of gestation until farrowing and ad libitum after farrowing. Diets were formulated to meet NRC requirement for lactating sows. Colostrum and milk samples from 12 sows per treatment were collected to measure nutrients and immunoglobulins on days 1 and 18 of lactation, respectively. Twelve piglets per treatment (1 piglet per litter) were euthanized on day 18 to collect tissues to measure tumor necrosis factor-α, interleukin-8 (IL-8), malondialdehyde, protein carbonyl, IgA, histomorphology, crypt cell proliferation rate, and microbiota in the jejunum and colon. Data were analyzed using the MIXED procedure of SAS, and the mortality was analyzed using the GLIMMIX procedure of SAS. There was no difference in sow BW, parity, and litter size between treatments on day 0 of lactation. Sows fed LPL had increased (P < 0.05) litter BW gain (53.9 vs. 59.4 kg) and decreased piglet mortality (13.9% vs. 10.6%) on day 18 of lactation. Sows fed LPL had increased (P < 0.05) omega-6:omega-3 (22.1 vs. 23.7) and unsaturated:saturated (1.4 vs. 1.6) fatty acids ratios with increased oleic acid (29.1% vs. 31.4%) and tended to have increased (P = 0.092) IgG (1.14 vs. 1.94 g/L) and linoleic acid (17.7% vs. 18.7%) in the milk on day 18 of lactation. Piglets from sows fed LPL had increased (P < 0.05) IL-8 (184 vs. 245 pg/mg) and crypt cell proliferation rate (39.4% vs. 40.9%) and tended to have increased (P = 0.095) Firmicutes:Bacteroidetes ratio (1.0 vs. 3.5) in the jejunum. In conclusion, sows fed with LPL had milk with increased IgG, oleic acids, and linoleic acids without changes in BW and backfat during lactation. These changes could contribute to improved survivability and intestinal health of piglets by increasing IL-8 concentration, enhancing balance among gut-associated microbiome, and increasing enterocyte proliferation in the jejunum.
A novel site-specific chemical conjugation of IgG antibodies by affinity peptide for immunoassays
Authors: Mori Satoka , Abe Arisa , Ishikawa Naoto , Rafique Abdur , Ito Yuji
Published: July 2020

Recently, there has been an increasing interest in site-specific modifications of antibodies used in immunoassays for disease diagnosis and as antibody therapeutics, such as antibody−drug conjugates. Previously, we established a site-specific chemical conjugation system using an IgG-Fc binding chemical conjugation affinity peptide (CCAP). CCAP could be used only for the modification of human IgG owing to the lack of affinity of CCAP to rodent IgG molecules. In this study, novel CCAP reagents are proposed, which can be used for both human and mouse IgG, based on the Staphylococcus aureus protein A domain-derived affinity peptides Z34C and Z33. Compared with the activity of a conventional randomly modified antibody, mouse IgG modified using this method had favourable features in two immunoassays, demonstrating the advantages of the proposed CCAP method in preserving antibody functionality during conjugation.
GTP metabolic reprogramming by IMPDH2: unlocking cancer cells’ fuelling mechanism
Authors: Kofuji Satoshi , Sasaki Atsuo T
Published: July 2020

Growing cells increase multiple biosynthetic processes in response to the high metabolic demands needed to sustain proliferation. The even higher metabolic requirements in the setting of cancer provoke proportionately greater biosynthesis. Underappreciated key aspects of this increased metabolic demand are guanine nucleotides and adaptive mechanisms to regulate their concentration. Using the malignant brain tumour, glioblastoma, as a model, we have demonstrated that one of the rate-limiting enzymes for guanosine triphosphate (GTP) synthesis, inosine monophosphate dehydrogenase-2 (IMPDH2), is increased and IMPDH2 expression is necessary for the activation of de novo GTP biosynthesis. Moreover, increased IMPDH2 enhances RNA polymerase I and III transcription directly linking GTP metabolism to both anabolic capacity as well as nucleolar enlargement historically observed as associated with cancer. In this review, we will review in detail the basis of these new discoveries and, more generally, summarize the current knowledge on the role of GTP metabolism in cancer.
Cd(II)-binding transcriptional regulator interacts with isoniazid and regulates drug susceptibility in mycobacteria
Authors: Yang Min , Jia Shi-Hua , Tao Hui-Ling , Zhu Chen , Jia Wan-Zhong , Hu Li-Hua , Gao Chun-Hui
Published: July 2020

It is urgent to understand the regulatory mechanism of drug resistance in widespread bacterial pathogens. In Mycobacterium tuberculosis, several transcriptional regulators have been found to play essential roles in regulating its drug resistance. In this study, we found that an ArsR family transcription regulator encoded by Rv2642 (CdiR) responds to isoniazid (INH), a widely used anti-tuberculosis (TB) drug. CdiR negatively regulates self and adjacent genes, including arsC (arsenic-transport integral membrane protein ArsC). CdiR directly interacts with INH and Cd(II). The binding of INH and Cd(II) both reduce its DNA-binding activity. Disrupting cdiR increased the drug susceptibility to INH, whereas overexpressing cdiR decreased the susceptibility. Strikingly, overexpressing arsC increased the drug susceptibility as well as cdiR. Additionally, both changes in cdiR and arsC expression caused sensitivity to other drugs such as rifamycin and ethambutol, where the minimal inhibitory concentrations in the cdiR deletion strain were equal to those of the arsC-overexpressing strain, suggesting that the function of CdiR in regulating drug resistance primarily depends on arsC. Furthermore, we found that Cd(II) enhances bacterial resistance to INH in a CdiR-dependent manner. As a conclusion, CdiR has a critical role in directing the interplay between Cd(II) metal ions and drug susceptibility in mycobacteria.
Quasi-oppositional-based Rao algorithms for multi-objective design optimization of selected heat sinks
Authors: Rao R V , Pawar R B
Published: July 2020

In this paper, an endeavor is made to enhance the convergence speed of the recently proposed Rao algorithms. The new upgraded versions of Rao algorithms named as “quasi-oppositional-based Rao algorithms” are proposed in this paper. The quasi-oppositional-based learning is incorporated in the basic Rao algorithms to diversify the searching process of the algorithms. The performance of the proposed algorithms is tested on 51 unconstrained benchmark functions. Also, three multi-objective optimization case studies of different heat sinks such as a single-layered microchannel heat sink (SL-MCHS), a double-layered microchannel heat sink (DL-MCHS), and a plate-fin heat sink (PFHS) are attempted to investigate the effectiveness of the proposed algorithms in solving real-world complex engineering optimization problems. The results obtained using the proposed algorithms are compared with the results obtained using the well-known advanced optimization algorithms such as genetic algorithm (GA), artificial bee colony (ABC), differential evolution (DE), particle swarm optimization (PSO), teaching-learning-based algorithm (TLBO), Jaya algorithm, multi-objective genetic algorithm (MOGA), non-dominated sorting genetic algorithm (NSGA-II), real-coded GA (RCGA), direction-based GA, self-adaptive multi-population (SAMP) Rao algorithms, and basic Rao algorithms. The proposed quasi-oppositional-based Rao algorithms are found superior or competitive to the other optimization algorithms considered.
Verification and Utility in the Arabic Commentaries on the Canon of Medicine: Examples from the Works of Fakhr al-Dīn al-Rāzī (d. 1210) and Ibn al-Nafīs (d. 1288)
Authors: Fancy Nahyan
Published: July 2020

Although over two dozen Arabic commentaries on the Canon of Medicine were composed between the twelfth and fourteenth centuries, historians of medicine have paid scant attention to them. Instead, these commentaries have often been dismissed as being uncritical expositions that further entrenched the dogma of Galenic/Avicennan medical theory. In this article, I shall show that in fact the opposite was the case for at least a subset of the Canon commentaries from this period. Fakhr al-Dīn al-Rāzī developed a new style of verification commentary across his philosophical corpus that he also deployed in his Canon commentary. Even though Fakhr al-Dīn largely adhered to Galenic/Avicennan medical theory, his commitment to verification (taḥqīq) led him to challenge and critically assess many facets of medical theory based on systematic, philosophical investigations. Ibn al-Nafīs, following in Fakhr al-Dīn’s footsteps, undertook a similar, systematic investigation into medical theory in his own Commentary on the Canon. However, in this case, verification led Ibn al-Nafis to challenge and modify several facets of medical theory. Moreover, as a trained, practicing physician, Ibn al-Nafīs also wanted to ensure that his commentary was useful for other practicing physicians. His commentary thus shows how a post-classical physician committed to the principles of verification and utility could employ philosophical argumentation, empirical observations and even occasional experiments to modify key aspects of Galenic/Avicennan medical theory and practice.
A Systematic Review of External Validity in Pediatric Integrated Primary Care Trials
Authors: Callejo-Black Alicia , Wagner David V , Ramanujam Krishnapriya , Manabat Ann Jeline , Mastel Sarah , Riley Andrew R
Published: July 2020

Objective

We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to conduct a systematic review of external validity reporting in integrated primary care (IPC) interventions for mental health concerns.

Methods

We searched Medline, CINAHL, PsycINFO, the Cochrane Center Register of Controlled Trials, and relevant literature to identify publications from 1998 to 2018 reporting on open, randomized, or quasi-randomized trials of IPC interventions that targeted child (ages 0–18 years) psychological symptoms. For each publication, we extracted the information reported in each RE-AIM domain and calculated the proportion of the total studies reviewed.

Results

Thirty-nine publications describing 25 studies were included in the review. Publications rarely reported some indicators of external validity, including the representativeness of participants (12%), rate of adoption clinics or providers (16%), cost of implementation (8%), or evidence of maintenance (16%). Few studies reported on key pragmatic factors such as cost or organizational change processes related to implementation and maintenance. Strengths of some studies included comparisons of multiple active treatments, use of tailorable interventions, and implementation in “real world” settings.

Conclusions

Although IPC interventions appear efficacious under research conditions, there are significant knowledge gaps regarding the degree to which they reach and engage target recipients, what factors impact adoption and implementation of IPC interventions by clinicians, how fidelity can be maintained over time, and cost-effectiveness. Pediatric IPC researchers should embrace dissemination and implementation science methods to balance internal and external validity concerns moving forward.
A Puzzling Silence: James 2:24 before the Reformation
Authors: Mooney Christopher R
Published: July 2020

Since the Reformation, James 2:24, ‘justified by works and not by faith alone’, has been the source of special controversy within an already contested epistle. But in the patristic and medieval period it was almost entirely unemployed and ignored, despite the widespread use, both approvingly and critically, of the expression sola fide. This article offers a pre-Reformation reception history of James 2:24. It begins with Origen and Augustine’s broader interpretation of James 2, then turns to the key pre-Reformation references to James: the earliest references (fifth–seventh century), Bede the Venerable (eighth), the Glossa Ordinaria (twelfth), Nicholas of Gorran (thirteenth), John Wyclif and Ps-Jan Hus (fourteenth), and Dionysius the Carthusian (fifteenth). Surprisingly, James 2:24 is at times explicitly harmonized with the expression sola fide, and only rarely used to critique it, because most read the Vulgate’s language in James 2:24 (non ex fide tantum) to refer solely to the need for later good works. At the same time, ‘justified by works’ was generally interpreted as referring to a confirmation or manifestation of justification until the scholastic period, when we find the earliest instances of interpreting ‘justified by works’ as a further justification. These results provide a theologically rich historical perspective on the reception of James 2:24 with respect to the development of sola fide and the scholastic interpretation of ‘justified by works’ as a subsequent increase in justification.
Using GC Content to Compare Recombination Patterns on the Sex Chromosomes and Autosomes of the Guppy,Poecilia reticulata, and Its Close Outgroup Species
Authors: Charlesworth Deborah , Zhang Yexin , Bergero Roberta , Graham Chay , Gardner Jim , Yong Lengxob
Published: July 2020

Genetic and physical mapping of the guppy (Poecilia reticulata) have shown that recombination patterns differ greatly between males and females. Crossover events occur evenly across the chromosomes in females, but in male meiosis they are restricted to the tip furthest from the centromere of each chromosome, creating very high recombination rates per megabase, as in pseudoautosomal regions of mammalian sex chromosomes. We used GC content to indirectly infer recombination patterns on guppy chromosomes, based on evidence that recombination is associated with GC-biased gene conversion, so that genome regions with high recombination rates should be detectable by high GC content. We used intron sequences and third positions of codons to make comparisons between sequences that are matched, as far as possible, and are all probably under weak selection. Almost all guppy chromosomes, including the sex chromosome (LG12), have very high GC values near their assembly ends, suggesting high recombination rates due to strong crossover localization in male meiosis. Our test does not suggest that the guppy XY pair has stronger crossover localization than the autosomes, or than the homologous chromosome in the close relative, the platyfish (Xiphophorus maculatus). We therefore conclude that the guppy XY pair has not recently undergone an evolutionary change to a different recombination pattern, or reduced its crossover rate, but that the guppy evolved Y-linkage due to acquiring a male-determining factor that also conferred the male crossover pattern. We also identify the centromere ends of guppy chromosomes, which were not determined in the genome assembly.
Prolonged (6-Month) Shedding of Middle East Respiratory Syndrome Coronavirus RNA in the Sputum of a Lymphoma Patient
Authors: Choe Pyoeng Gyun , Park Wan Beom , Choi Su-Jin , Kang Chang Kyung , Koh Yongil , Kim Nam Joong , Oh Myoung-don
Published: July 2020

During the 2015 Korea Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, a lymphoma patient developed MERS pneumonia. His pneumonia improved by 45 days after illness onset, but the polymerase chain reaction tests remained (+) for 6 months. However, replication-competent virus was detected by 60 days after illness onset.
Intradiscal Platelet-Rich Plasma Injection for Discogenic Low Back Pain and Correlation with Platelet Concentration: A Prospective Clinical Trial
Authors: Jain Dhruv , Goyal Titiksha , Verma Nimisha , Paswan Anil Kumar , Dubey Rajeev Kumar
Published: July 2020

Objective

Discogenic pain is common cause of low back ache and may result in significant morbidity. Platelet-rich plasma (PRP) is an upcoming regenerative therapy that has treatment potential for this condition. The objective of this study was to correlate platelet concentration in intradiscal PRP injection with improvement in low back pain and functional status at three and six months.

Design

Prospective single-arm interventional study.

Setting

Outpatient pain clinic and operation theater.

Subjects

Twenty-five patients with discogenic pain diagnosed by clinical means and imaging with confirmation by provocative discography were recruited.

Methods

The patients received PRP injection at a single or multiple disc levels. Preprocedure numerical rating scale (NRS) pain scores and Oswestry Disability Index (ODI) scores were calculated. Platelet counts of patients and PRP samples were measured. At three and six months postprocedure, NRS and ODI scores were measured, and improvement in these scores was correlated with platelet concentrations in the PRP sample.

Results

Twenty patients completed the study. The improvement in NRS and ODI scores positively correlated with platelet concentrations in the PRP sample. We determined the correlation coefficient (r) of platelet concentrations with a reduction in NRS at three months (r = 0.65) and six months (r = 0.73) and in ODI score at three months (r = 0.72) and six months (r = 0.7).

Conclusions

This study supports the use of intradiscal PRP for treatment of discogenic pain with preferably higher platelet counts to elicit a favorable response.
EFFECT OF WORKING CONDITIONS AND NATURAL RADIOACTIVITY LEVELS ON OCCUPATIONAL DOSES TO WORKERS OF AN OLD MANGANESE MINE
Authors: Monged Mohamed H E
Published: July 2020

The aim of this work was to use RESRAD-Build model to predict the resulting external and internal radiological doses received by the workers of manganese mine located in Southern Sinai. In order to achieve that goal, measurement of the activity concentrations of natural radionuclides in rock samples collected from the inside gallery of such mine, using hyper pure germanium (HPGe) detector. Radon gas concentrations were also measured. The average activity concentrations of 238U, 226Ra, 232Th, 40K and 210Pb in rock samples were 207.3, 155.5, 59.7, 304.5 and 119.3 Bq kg–1, respectively. The average radon activity concentration was 1254.6 Bqm−3, which is equivalent to 0.135 WL. The radon concentration increases further as going deep inside the mine up to 6238 Bqm−3. RESRAD-Build model occupational effective dose equivalent (EDE) received by the workers, from natural radionuclides, dominated by 222Rn emanated from the parent nuclide 226Ra.There was good agreement between the occupational annual EDE calculated from the measured rock samples and that predicted by modeling, with estimated values of 83.8 and 82.1 mSvy−1, respectively. This radiological dose assessment indicated the predominance of internal pathways owing to radon decay products, in both cases (measured and modeled). The occupational radiological dose from the inhalation of radon and radon decay products resulted in a high lung cancer risk based on the current measurements and ventilation conditions within the mine.